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1.
J Clin Med ; 13(17)2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39274191

RESUMEN

The treatment of complex aortic pathologies requires specialized techniques and tailored approaches due to each patient's unique anatomical and clinical challenges. The European Association for Cardiothoracic Surgery (EACTS) and the Society of Thoracic Surgeons (STS) new guidelines identify the aorta as the body's 24th organ and reiterate that multidisciplinary aortic teams are recommended for shared decision-making to determine optimal treatment strategies. Patients treated for conditions such as aneurysms, dissections, intramural hematomas, or penetrating aortic ulcers may develop complex forms over time, necessitating careful follow-up and timely corrective actions. Endovascular solutions can be favorable for older patients with complex anatomies and multiple comorbidities. However, when endovascular treatment is not feasible, hybrid treatments or open surgery must be considered if the patient's condition allows it. The risk-benefit ratio of each procedure must be carefully evaluated; choosing the best intervention or deciding not to intervene becomes a critical and challenging decision. At our Cardiac Surgery Center in Verona, a multidisciplinary team with over 20 years of experience in treating complex aortic arch pathologies extensively discussed different cases of complex aortic pathologies treated with endovascular, hybrid, or surgical approaches, emphasizing the importance of considering both anatomical and patient-specific characteristics. The decisions and treatments were often challenging, and unanimity was not always achieved, reflecting the complexity of finding the best solutions.

2.
Int J Mol Sci ; 25(16)2024 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-39201407

RESUMEN

Proliferative vitreoretinopathy (PVR) has traditionally been managed with vitreoretinal surgery. Although there have been several recent innovations in this surgery to make the retinal approach as uninvasive as possible, the outcomes remain unsatisfactory. Significant complications remain and the complexity of the surgical approach is challenging. The focus of this review was to investigate and discuss the effectiveness of nanomedicine, featuring a wide range of drugs and molecules, as a novel potential treatment for PVR. To date, ocular drug delivery remains a significant issue due to the physiological and anatomical barriers, dynamic or static, which prevent the entry of exogenous molecules. We tried to summarize the nanotechnology-based ophthalmic drugs and new nanoparticles currently under research, with the intention of tackling the onset and development of PVR. The purpose of this review was to thoroughly and analytically examine and assess the potential of nano-based techniques as innovative strategies to treat proliferative vitreoretinopathy (PVR). This study aimed to emphasize the breakthroughs in nanomedicine that provide promising therapeutic options to enhance the results of vitreoretinal surgery and halt disease progression, considering the complexity and difficulty of PVR treatment. The future directions of the nanoparticles and nanotherapies applied to PVR highlight the importance of investing in the development of better designs and novel ophthalmic formulations in order to accomplish a mini-invasive ocular approach, replacing the standard-of-care vitreoretinal surgery.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas , Cirugía Vitreorretiniana , Vitreorretinopatía Proliferativa , Vitreorretinopatía Proliferativa/tratamiento farmacológico , Vitreorretinopatía Proliferativa/cirugía , Humanos , Cirugía Vitreorretiniana/métodos , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Animales , Nanomedicina/métodos
3.
Helicobacter ; 29(4): e13126, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39143948

RESUMEN

BACKGROUND: The optimal duration of regimens for tailored therapy based on genotypic resistance for clarithromycin has yet to be established. AIM: This study was a nationwide, multicenter, randomized trial comparing empirical therapy with tailored therapy based on genotypic resistance for first-line eradication of Helicobacter pylori. We also compared the eradication rates of 7- and 14-day regimens for each group. PATIENTS AND METHODS: Patients with H. pylori infection were first randomized to receive empirical or tailored therapy. Patients in each group were further randomized into 7- or 14-day regimens. Empirical therapy consisted of a triple therapy (TT) regimen (twice-daily doses of pantoprazole 40 mg, amoxicillin 1 g, and clarithromycin 500 mg) for 7 or 14 days. Tailored therapy consisted of TT of 7 or 14 days in patients without genotypic resistance. Patients with genotypic resistance were treated with bismuth quadruple therapy (BQT) regimens (twice-daily doses of pantoprazole 40 mg, three daily doses of metronidazole 500 mg, and four times daily doses of bismuth 300 mg and tetracycline 500 mg) for 7 or 14 days. A 13C-urea breath test assessed eradication rates. The primary outcome was eradication rates of each group. RESULTS: A total of 593 patients were included in the study. The eradication rates were 65.7% (201/306) in the empirical therapy group and 81.9% (235/287) in the tailored therapy group for intention-to-treat analysis (p < 0.001). In the per-protocol analysis, the eradication rates of the empirical therapy and tailored groups were 70.3% (201/286) and 85.5% (235/274) (p < 0.001), respectively. There was no difference in compliance between the two groups. The rate of adverse events was higher in the tailored group compared to the empirical group (p < 0.001). DISCUSSION: Our study confirmed that tailored therapy based on genotypic resistance was more effective than empirical therapy for H. pylori eradication in Korea. However, no significant difference was found between 7- and 14-day regimens for each group. Future studies are needed to determine the optimal duration of therapy for empirical and tailored therapy regimens.


Asunto(s)
Antibacterianos , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/efectos de los fármacos , Helicobacter pylori/genética , Masculino , Femenino , Persona de Mediana Edad , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , República de Corea , Adulto , Anciano , Resultado del Tratamiento , Farmacorresistencia Bacteriana , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Claritromicina/uso terapéutico , Metronidazol/uso terapéutico , Pantoprazol/uso terapéutico , Genotipo , Adulto Joven
4.
J Clin Med ; 13(16)2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39201046

RESUMEN

Non-bacterial thrombotic endocarditis (NBTE) is a form of non-infective endocarditis characterized by the deposition of sterile fibrin and platelets on cardiac valves. Even though some studies have identified important pathophysiological features, many aspects remain poorly understood. Given its wide availability, transthoracic echocardiography is typically the initial diagnostic approach to the patient. Additionally, recent technological advancements in transesophageal echocardiography, such as three-dimensional and multiplanar reconstruction analysis, have significantly improved diagnostic accuracy over time. By presenting our case series and performing a literature review, we focused on the main pathophysiologic, diagnostic, and therapeutic aspects of this rare but potentially life-threatening disease.

5.
J Clin Med ; 13(13)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38999202

RESUMEN

Transcatheter aortic valve implantation (TAVI) now represents the mainstay of treatment for severe aortic stenosis. Owing to its exceptional procedural efficacy and safety, TAVI has been extended to include patients at lower surgical risk, thus now encompassing a diverse patient population receiving this treatment. Yet, long-term outcomes also depend on optimal medical therapy for secondary vascular prevention, with antithrombotic therapy serving as the cornerstone. Leveraging data from multiple randomized controlled trials, the current guidelines generally recommend single antithrombotic therapy, with either single antiplatelet therapy (SAPT) or oral anticoagulation (OAC) alone in those patients without or with atrial fibrillation, respectively. Yet, individualization of this pattern, as well as specific case uses, may be needed based on individual patient characteristics and concurrent procedures. This review aims to discuss the evidence supporting antithrombotic treatments in patients treated with TAVI, indications for a standardized treatment, as well as specific considerations for an individualized approach to treatment.

6.
J Hematol Oncol ; 17(1): 48, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38915117

RESUMEN

It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Fragilidad , Lenalidomida , Mieloma Múltiple , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/terapia , Anciano , Estudios Prospectivos , Masculino , Femenino , Anciano de 80 o más Años , Dexametasona/uso terapéutico , Dexametasona/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Lenalidomida/uso terapéutico , Lenalidomida/administración & dosificación , Bortezomib/uso terapéutico , Bortezomib/administración & dosificación , Medicina de Precisión/métodos , Anciano Frágil , Evaluación Geriátrica/métodos , Anticuerpos Monoclonales
7.
Helicobacter ; 29(2): e13076, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38680067

RESUMEN

BACKGROUND: The systematic use of susceptibility testing and tailored first-line treatment for Helicobacter pylori eradication has yet to be established. AIM: To compare 14-day tailored PCR-guided triple therapy to 14-day non-Bismuth concomitant quadruple therapy for first-line Helicobacter pylori eradication. PATIENTS AND METHODS: We performed a multicenter, parallel-group, randomized noninferiority controlled trial. Naive adult patients with Helicobacter pylori infection were treated with 14-day tailored PCR-guided triple therapy (esomeprazole 40 mg and amoxicillin 1000 mg b.d. plus clarithromycin 500 mg or levofloxacin 500 mg b.d. according to clarithromycin susceptibility) or 14-day non-Bismuth concomitant quadruple therapy (esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg b.d.). The primary endpoint was H. pylori eradication. RESULTS: We screened 991 patients for eligibility and randomized 241 patients. The first-line eradication rate was 99.2% in the tailored PCR-guided group and 95.9% in the control group (ITT population; absolute difference of +3.30%, with a lower bound of CI at -0.68%). Both first-line therapies were well tolerated, with a formally significant difference in favor of the tailored PCR-guided group (61.4% vs. 41.2%, p = 0.003). Economic analyses revealed a lower cost of the tailored PCR-guided arm, with a 92% chance of being jointly more effective and less expensive than the control arm in the ITT population. CONCLUSION: In a country with a high level of clarithromycin resistance, the results of our study demonstrated the noninferiority of 14-day tailored PCR-guided triple therapy as a first-line H. pylori eradication therapy compared to 14-day non-Bismuth quadruple therapy (ClinicalTrials.gov NCT02576236).


Asunto(s)
Antibacterianos , Claritromicina , Quimioterapia Combinada , Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Masculino , Femenino , Persona de Mediana Edad , Helicobacter pylori/efectos de los fármacos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Adulto , Claritromicina/uso terapéutico , Claritromicina/administración & dosificación , Reacción en Cadena de la Polimerasa/métodos , Amoxicilina/uso terapéutico , Amoxicilina/administración & dosificación , Anciano , Resultado del Tratamiento , Metronidazol/uso terapéutico , Metronidazol/administración & dosificación , Levofloxacino/uso terapéutico , Levofloxacino/administración & dosificación , Adulto Joven
8.
Eur J Pharm Sci ; 195: 106727, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38360153

RESUMEN

Fentanyl transdermal patches are widely implemented for cancer-induced pain treatment due to the high potency of fentanyl and gradual drug release. However, transdermal fentanyl up-titration for opioid-naïve patients is difficult, which is why opioid treatment is often started with oral/iv morphine. Based on the daily dose of morphine, the initial dose of the fentanyl patch is decided upon. After reaching a stable level of pain, the switch is made from oral/iv morphine to transdermal fentanyl. There are standard calculation tools for transferring from oral/iv morphine to transdermal fentanyl, which is the same for all patients. By considering the variations in the physiology of the patients, a unique switching strategy cannot meet the needs of different patients. This study explores the outcome in terms of pain relief and minute ventilation during opioid therapy. For this, we used physics-based simulations on a virtually-generated population of patients, and we applied the same therapy to all patients. We could show that patients' physiology, such as gender, age, and weight, greatly impact the outcome of the therapy; as such, the correlation coefficient between pain intensity and age is 0.89, and the correlation coefficient between patient's weight and maximum plasma concentration of morphine and fentanyl is -0.98 and -0.97. Additionally, a different combination of the duration of overlap between morphine and fentanyl therapy with different doses of fentanyl was considered for the virtual patients to find the best opioid-switching strategy for each patient. We explored the impact of combining physiological features to determine the best-suited strategy for virtual patients. Our findings suggest that tailoring morphine and fentanyl therapy only based on a limited number of features is insufficient, and increasing the number of impactful physiological features positively influences the outcome of the therapy.


Asunto(s)
Fentanilo , Neoplasias , Humanos , Fentanilo/efectos adversos , Analgésicos Opioides , Morfina/uso terapéutico , Dolor/tratamiento farmacológico , Manejo del Dolor , Administración Cutánea , Neoplasias/tratamiento farmacológico
9.
J Dig Dis ; 25(1): 36-43, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38323705

RESUMEN

OBJECTIVES: We aimed to explore the efficacy and safety of tailored therapy guided by genotypic resistance in the first-line treatment of Helicobacter pylori (H. pylori) infection in treatment-naive patients. METHODS: Gastric mucosal specimens were taken during gastroscopy, and main mutations of clarithromycin- and levofloxacin-resistant genes were detected by polymerase chain reaction (PCR). Sensitive antibiotics were selected individually for treating H. pylori infection with tailored bismuth-containing quadruple therapy (BQT) consisting of esomeprazole 20 mg twice daily, bismuth potassium citrate 220 mg twice daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily, or levofloxacin 500 mg once daily, or metronidazole 400 mg four times daily. Safety and patient compliance were assessed 1-3 days after eradication. Treatment outcome was evaluated by urea breath test 4-8 weeks after eradication. RESULTS: One hundred and thirty-two treatment-naive patients with H. pylori infection were included. PCR results suggested resistance rates of 47.7% and 34.9% for clarithromycin and levofloxacin, respectively, and a dual resistance rate of 18.2%. Eradication rates of tailored BQT were 87.1% and 95.8% by intention-to-treat (ITT) analysis and per-protocol (PP) analysis, respectively. There was no statistically significant difference in the efficacy of 7-day clarithromycin-containing, 7-day levofloxacin-containing, and 14-day full-dose metronidazole-containing BQT (ITT analysis: P = 0.488; PP analysis: P = 0.833). The incidence of adverse events was 19.7%, and patient compliance was 97.7%. CONCLUSION: Tailored BQT guided by genotypic resistance can achieve satisfactory efficacy, safety, and patient compliance in the first-line treatment of H. pylori infection.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Claritromicina/farmacología , Claritromicina/uso terapéutico , Levofloxacino/efectos adversos , Helicobacter pylori/genética , Bismuto/uso terapéutico , Metronidazol/uso terapéutico , Quimioterapia Combinada , Antibacterianos/efectos adversos , Amoxicilina/uso terapéutico , Resultado del Tratamiento , Reacción en Cadena de la Polimerasa
10.
Curr Obes Rep ; 13(1): 51-70, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38172476

RESUMEN

PURPOSE OF REVIEW: The goal of the present review is to address the main adiposity-related alterations in Polycystic Ovary Syndrome (PCOS) focusing on hypothalamic-pituitary-ovarian (H-P-O) axis and to provide an overview of nutraceutical and pharmacological therapeutic strategies. RECENT FINDINGS: Female reproduction is a complex and delicate interplay between neuroendocrine signals involving the H-P-O axis. Elements that disrupt the balance of these interactions can lead to metabolic and reproductive disorders, such as PCOS. This disorder includes menstrual, metabolic, and biochemical abnormalities as well as hyperandrogenism, oligo-anovulatory menstrual cycles, insulin resistance, and hyperleptinemia which share an inflammatory state with other chronic diseases. Moreover, as in a self-feeding cycle, high androgen levels in PCOS lead to visceral fat deposition, resulting in insulin resistance and hyperinsulinemia, further stimulating ovarian and adrenal androgen production. In fact, regardless of age and BMI, women with PCOS have more adipose tissue and less lean mass than healthy women. Excessive adiposity, especially visceral adiposity, is capable of affecting female reproduction through direct mechanisms compromising the luteal phase, and indirect mechanisms as metabolic alterations able to affect the function of the H-P-O axis. The intricate crosstalk between adiposity, inflammatory status and H-P-O axis function contributes to the main adiposity-related alterations in PCOS, and alongside currently available hormonal treatments, nutraceutical and pharmacological therapeutic strategies can be exploited to treat these alterations, in order to enable a more comprehensive synergistic and tailored treatment.


Asunto(s)
Hiperandrogenismo , Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Femenino , Humanos , Síndrome del Ovario Poliquístico/terapia , Adiposidad , Andrógenos , Obesidad/terapia , Obesidad/metabolismo
11.
Front Oncol ; 13: 1203994, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38094610

RESUMEN

Background: Intracranial mesenchymal tumors are a rare type of neoplasm (0.3% of all soft tissue tumors) characterized by a fusion of a FET family gene (usually EWSR1, rarely FUS) to CREB family genes (CREB1, ATF1, and CREM) with a slow-growing and favorable prognosis. Mesenchymal tumors are most frequently localized in the subcutaneous tissue (typically in the limbs and hands) of young adults and have rarely been diagnosed in the central nervous system. Surgery is the gold standard treatment; adjuvant radiation therapy and chemotherapy with sarcoma-based regimens have been used in rare cases when complete surgical excision was not recommended. In terms of prognosis, these tumors show a tendency for local relapse. The longest patient outcomes reported in the literature are five years. Case description: This case describes a 27-year-old woman with unconventional extracranial metastatic sites of myxoid intracranial mesenchymal tumor FET::CREB fusion-positive and high expression of PD-1 (40%) and PD-L1 (30%). Based on clinical, molecular, and histological characteristics, she underwent various local and systemic therapies, including surgery, proton beam therapy, the use of immune checkpoint inhibitors, and chemotherapy. These treatments led to a complete remission of the disease after eight years from tumor diagnosis. Conclusions: Our case sheds light on the importance of precision medicine and tailored therapy to explore new treatment opportunities for rare or unknown tumor entities.

12.
J Clin Med ; 12(21)2023 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-37959382

RESUMEN

Background: The role of tailored immunosuppression (IS) in the development of the humoral response (HR) to SARS-CoV-2 mRNA-based vaccination in liver transplant (LT) recipients is unknown. Methods: This is a single-centre prospective study of patients who underwent LT between January 2015 and December 2021 and who have received three doses of mRNA-based SARS-CoV-2 vaccination. Patients undergoing Tacrolimus-based immunosuppression (TAC-IS) were compared with those undergoing Everolimus-based immunosuppression (EVR-IS). Patients receiving the TAC-EVR combination were divided into two groups based on trough TAC concentrations, i.e., above or below 5 ng/mL. HR (analysed with ECLIA) was assessed at 30 to 135 days after vaccination. The primary outcome was the presence of a positive antibody titre (≥0.8 U/mL). Secondary outcomes were the presence of a highly protective antibody titre (≥142 U/mL), median antibody titre, and incidence of COVID-19. Results: Sixty-one participants were included. Twenty-four (40%) were receiving TAC-IS and thirty-seven (60%) were receiving EVR-IS. At the median follow-up of 116 (range: 89-154) days, there were no significant differences in positive antibody titre (95.8% vs. 94.6%; p = 0.8269), highly-protective antibody titre (83.3% vs. 81.1%; p = 0.8231), median antibody titre (2410 [IQ range 350-2500] vs. 1670 [IQ range 380-2500]; p = 0.9450), and COVID-19 incidence (0% vs. 5.4%; p = 0.5148). High serum creatinine and low estimated glomerular filtration rate were risk factors for a weak or absent HR. Conclusions: Three doses of mRNA-based SARS-CoV-2 vaccination yielded a highly protective HR in LT recipients. The use of TAC or EVR-based IS does not appear to influence HR or antibody titre, while renal disease is a risk factor for a weak or null HR.

13.
Clin Ter ; 174(Suppl 2(6)): 37-45, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37994747

RESUMEN

Abstract: Lung cancer is a complex disease, with a wide range of genetic alterations and clinical presentations. Understanding the natural and clinical history of the disease is crucial for developing effective diagnostic and treatment strategies. Omics approaches, such as genomics, transcriptomics, proteomics, and metabolomics, have emerged as powerful tools for understanding the molecular mechanisms underlying lung cancer and for identifying novel biomarkers and therapeutic targets. These approaches enable researchers to examine the entire genome, transcriptome, proteome, or metabolome of a cell or tissue, providing a comprehensive view of the biological processes involved in lung cancer development and progression. Targeted therapies that address specific genetic mutations and pathways hold promise for improving the diagnosis and treatment of this disease.


Asunto(s)
Neoplasias Pulmonares , Medicina de Precisión , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Genómica , Proteómica , Metabolómica
14.
Clin Ter ; 174(Suppl 2(6)): 236-242, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37994770

RESUMEN

Background: Genodermatoses are rare heterogeneous genetic skin diseases with multiorgan involvement. They severely impair an individual's well-being and can also lead to early death. Methods: During the progress of this review, we have implemented a targeted research approach, diligently choosing the most relevant and exemplary articles within the subject matter. Our method entailed a systematic exploration of the scientific literature to ensure a compre-hensive and accurate compilation of the available sources. Results: Among genodermatoses, X-linked ones are of particular importance and should always be considered when pediatric males are affected. Regardless of other syndromic forms without prevalence of skin symptoms, X-linked genodermatoses can be classified in three main groups: keratinization defects, pigmentation defects, and inflammatory skin diseases. Typical examples are dyskeratosis congenita, keratosis follicularis spinulosa decalvans, hypohidrotic ectodermal dysplasia, chondrodysplasia punctata, hypohidrotic ectodermal dysplasia, incontinentia pigmenti, chronic granulomatous disease, CHILD syndrome and ichthyosis. In this field, genetic diagnosis of the specific disease is important, also considering that numerous clinical trials of orphan drugs and genetic therapies are being proposed for these rare genetic diseases. Conclusions: Thus, this chapter starts from clinical to molecular testing and ends with a review of all clinical trials on orphan drugs and gene therapy for genodermatoses.


Asunto(s)
Displasia Ectodermal Anhidrótica Tipo 1 , Enfermedades Genéticas Ligadas al Cromosoma X , Ictiosis , Enfermedades Cutáneas Genéticas , Neoplasias Cutáneas , Masculino , Humanos , Niño , Ictiosis/genética , Enfermedades Cutáneas Genéticas/diagnóstico , Enfermedades Cutáneas Genéticas/genética , Enfermedades Cutáneas Genéticas/terapia
15.
J Clin Med ; 12(22)2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-38002756

RESUMEN

Dual antiplatelet therapy (DAPT), comprising aspirin and a P2Y12 receptor inhibitor, is the cornerstone of post-percutaneous coronary intervention treatment to prevent stent thrombosis and reduce the risk of adverse cardiovascular events. The selection of an optimal DAPT regimen, considering the interplay of various antiplatelet agents, patient profiles, and procedural characteristics, remains an evolving challenge. Traditionally, a standard duration of 12 months has been recommended for DAPT in most patients. While contemporary guidelines provide general frameworks, DAPT modulation with longer or shorter treatment courses followed by aspirin or P2Y12 inhibitor monotherapy are evolving towards an individualized strategy to optimize the balance between efficacy and safety. This review comprehensively examines the current landscape of DAPT strategies after coronary stenting, with a focus on emerging evidence for treatment individualization.

16.
JACC Case Rep ; 22: 101978, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37790775

RESUMEN

Ischemia with no obstructive coronary artery disease (INOCA) is not an uncommon diagnosis in patients presenting with chest pain who undergo clinically indicated coronary angiography. However, the symptoms reported by patients with INOCA may be heterogeneous, leading to misdiagnosis and undertreatment. Herein we report 3 clinical cases of INOCA misdiagnosis and describe how the cases were reinvestigated following the appropriate diagnostic pathway. (Level of Difficulty: Advanced.).

17.
Expert Rev Clin Pharmacol ; 16(11): 1035-1051, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37874608

RESUMEN

INTRODUCTION: The growing spread of infections caused by multidrug-resistant pathogens makes the need of tailoring antimicrobial therapies by means of a 'patient-centered' approach fundamental. In this scenario, therapeutic drug monitoring (TDM) of emerging antimicrobial candidates may be a valuable approach, but expert interpretation of TDM results should be granted for making them more clinically useful. The MD Clinical Pharmacologist may take over this task since this specialist may couple PK/PD expertise on drugs with a medical background and may provide expert interpretation of TDM results of antimicrobials for tailoring therapy on real-time in each single patient based on specific both drug/pathogen issues and patient issues. AREAS COVERED: This article aims to highlight the main key-points and organizational aspects for implementing a successful TDM-based expert clinical pharmacological advice (ECPA) program for tailoring antimicrobial therapies on real-time in different hospitalized patient special populations. EXPERT OPINION: TDM-based ECPA programs lead by the MD Clinical Pharmacologist may represent a way forward for maximizing clinical efficacy and for minimizing the risk of resistance developments and/or toxicity of antimicrobials. Stakeholders should be aware of the fact that this innovative approach may be cost-effective.


Asunto(s)
Anseriformes , Antiinfecciosos , Farmacología Clínica , Humanos , Animales , Monitoreo de Drogas/métodos , Antiinfecciosos/efectos adversos
18.
Front Genet ; 14: 1213283, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37662840

RESUMEN

We report a case of Klippel Trenaunay Syndrome that was monitored both clinically and molecularly over a period of 9 years. A somatic mosaic mutation of PIK3CA (p(E545G)) was identified using both cfDNA NGS liquid biopsy and tissue biopsy. At the age of 56, due to intervening clonal mutations in PIK3CA background, she developed a squamous cell carcinoma in the right affected leg which was treated surgically. Nine years later, lung bilateral adenocarcinoma arose on PIK3CA mutated tissues supported by different clonal mutations. One year later, the patient died from metastases led by a new FGFR3 clone unresponsive to standard-of-care, immunotherapy-based. Our results highlight the presence of a molecular hallmark underlying neoplastic transformation that occurs upon an angiodysplastic process and support the view that PIK3CA mutated tissues must be treated as precancerous lesions. Importantly, they remark the effectiveness of combining cfDNA NGS liquid and tissue biopsies to monitor disease evolution as well as to identify aggressive clones targetable by tailored therapy, which is more efficient than conventional protocols.

19.
Int J Mol Sci ; 24(17)2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37686338

RESUMEN

There is an ongoing need for patient-specific chemotherapy for pancreatic cancer. Tumour cells isolated from human tissues can be used to predict patients' response to chemotherapy. However, the isolation and maintenance of pancreatic cancer cells is challenging because these cells become highly vulnerable after losing the tumour microenvironment. Therefore, we investigated whether the cells retained their original characteristics after lentiviral transfection and expansion. Three human primary pancreatic cancer cell lines were lentivirally transduced to create expandable (Ex) cells which were then compared with primary (Pri) cells. No obvious differences in the morphology or epithelial-mesenchymal transition (EMT) were observed between the primary and expandable cell lines. The two expandable cell lines showed higher proliferation rates in the 2D and 3D models. All three expandable cell lines showed attenuated migratory ability. Differences in gene expression between primary and expandable cell lines were then compared using RNA-Seq data. Potential target drugs were predicted by differentially expressed genes (DEGs), and differentially expressed pathways (DEPs) related to tumour-specific characteristics such as proliferation, migration, EMT, drug resistance, and reactive oxygen species (ROS) were investigated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We found that the two expandable cell lines expressed similar chemosensitivity and redox-regulatory capability to gemcitabine and oxaliplatin in the 2D model as compared to their counterparts. In conclusion, we successfully generated expandable primary pancreatic cancer cell lines using lentiviral transduction. These expandable cells not only retain some tumour-specific biological traits of primary cells but also show an ongoing proliferative capacity, thereby yielding sufficient material for drug response assays, which may provide a patient-specific platform for chemotherapy drug screening.


Asunto(s)
Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Páncreas , Línea Celular , Fenotipo , Microambiente Tumoral/genética , Neoplasias Pancreáticas
20.
Helicobacter ; 28(6): e13015, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37634236

RESUMEN

BACKGROUND AND AIM: The prevalence of antibiotic resistance for Helicobacter pylori (H. pylori) has been increasing over the year, making it more difficult for traditional empirical therapy to successfully eradicate H. pylori. Thus, tailored therapy (TT) guided by molecular-based antibiotic susceptibility testing (AST) has been frequently recommended. We conducted a single-arm meta-analysis to determine the efficacy of tailored therapy guided by molecular-based AST. METHODS: A systematic literature review was performed on multiple databases, and studies on molecular-based TT were included. The eradication rates of TT by intention-to-treat (ITT) and per-protocol (PP) analyses were pooled respectively. RESULTS: A total of 35 studies from 31 literature (4626 patients) were included in the single-arm meta-analysis. Overall, the pooled eradication rate of TT was 86.9% (95% CI:84.7%-89.1%) by the ITT analysis, and 91.5% (95% CI:89.8%-93.2%) by PP analysis. The pooled eradication rates of first-line TT and rescue TT were 86.6% and 85.1% by ITT analysis and 92.0% and 87.9% by PP analysis, respectively. When tailored rescue therapy was based on the genotypic resistance to at least four antibiotics, the pooled eradication rates reached 89.4% by ITT analysis and 92.1% by PP analysis. For genotype-susceptive strains, the pooled eradication rate of TT with targeted antibiotics was 93.1% (95% CI:91.3%-94.9%), among which the pooled eradication rate of tailored bismuth quadruple therapy was the highest (94.3%). Besides, the eradication rate of 7-day TT or tailored triple therapy without bismuth for genotype-susceptive strains could both reach more than 93.0%. CONCLUSION: Tailored therapy guided by molecular-based AST can achieve somewhat ideal therapeutic outcomes. TT with a 7-day duration or without bismuth for genotype-susceptible strains can achieve good eradication efficacy. The effectiveness of TT can be improved to some extent by expanding the coverage of AST or by adding bismuth.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Humanos , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/genética , Bismuto/uso terapéutico , Metronidazol/uso terapéutico , Quimioterapia Combinada , Antibacterianos/uso terapéutico , Genotipo , Resultado del Tratamiento , Amoxicilina/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéutico
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