Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 726
Filtrar
1.
J Surg Oncol ; 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285659

RESUMEN

The 2022 PSOGI (Peritoneal Surface Oncology Group International) and RENAPE (French Network for Rare Peritoneal Malignancies) consensus on hyperthermic intraperitoneal chemotherapy (HIPEC) was a comprehensive effort aimed at standardizing treatment protocols for various peritoneal malignancies. This initiative is critical due to the wide range of technical variations in HIPEC procedures and the resulting need for standardization to ensure consistent and effective patient care and meaningful audit of multicenter data.

2.
Rev Esp Enferm Dig ; 1192024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39087669

RESUMEN

Intestinal mucormycosis is a rare manifestation of the Mucor fungus, associated with high mortality and typically found in immunocompromised patients, though it has also been described in immunocompetent individuals. The mode of acquisition is digestive. It usually presents as abdominal pain, with ischemia and intestinal perforation, and the diagnosis is often histopathological after surgical resection. We present the case of a 54-year-old female patient with recurrent acute myeloid leukemia undergoing treatment with daunorubicin-cytarabine and experiencing febrile neutropenia. She developed patchy and progressive intestinal ischemia that evolved into intestinal necrosis, which was treated with antifungal medications and surgery. Examination of the surgical specimen revealed aseptate wide hyphae with branching at right angles, suggestive of Mucor fungus. This is a rare but highly mortal pathology in which clinical, radiological, and surgical suspicion is essential for early diagnosis and treatment, thus improving the patient's prognosis.

3.
Biomedicines ; 12(8)2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39200310

RESUMEN

Despite remarkable improvement in the human immunodeficiency virus (HIV) and hepatitis C virus (HCV) care continuum, the rate of late diagnosis of HIV and HCV in high-income countries remains unacceptably high. Testing relies mainly on primary care physicians' identification of risk factors. We aimed to adapt an analogic to an online questionnaire to help HIV and HCV screening and perform a pilot study to assess its accuracy and acceptability. We used the Delphi method to adapt a previously validated analogical questionnaire to a user-friendly online tool. It aimed to identify participants who should be screened for HIV or HCV and those who should be referred for pre-exposure prophylaxis (PrEP). We then designed a proof-of-concept pilot study from July to October 2022 to test its feasibility and suitability for use on a larger scale and to assess its accuracy in identifying patients at risk for HIV or HCV or with indication for PrEP. The final questionnaire consisted of 37 questions. A total of 142 participants provided informed consent, and 102 completed the questionnaire: 41 random patients recruited at the primary care level, 10 participants recently diagnosed with HIV, 20 participants with HIV on follow-up, 21 participants from the PrEP program, and 10 patients diagnosed with HCV. The tool adequately indicated the need for testing in more than 98% of participants with confirmed HIV/HCV infections or in the PrEP program. Furthermore, it adequately assessed PrEP referral in 94% of participants already on PrEP or with known HIV infection. Participants were highly satisfied with the tool, and 98% of them recommended its use. A self-administered web-based tool to identify patients who should be tested for HIV or HCV or referred to PrEP could simplify patient selection and help reduce late diagnosis.

4.
Oncoimmunology ; 13(1): 2384667, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39108501

RESUMEN

Deficient (d) DNA mismatch repair (MMR) is a biomarker predictive of better response to PD-1 blockade immunotherapy in solid tumors. dMMR can be caused by mutations in MMR genes or by protein inactivation, which can be detected by sequencing and immunohistochemistry, respectively. To investigate the role of dMMR in diffuse large B-cell lymphoma (DLBCL), MMR gene mutations and expression of MSH6, MSH2, MLH1, and PMS2 proteins were evaluated by targeted next-generation sequencing and immunohistochemistry in a large cohort of DLBCL patients treated with standard chemoimmunotherapy, and correlated with the tumor immune microenvironment characteristics quantified by fluorescent multiplex immunohistochemistry and gene-expression profiling. The results showed that genetic dMMR was infrequent in DLBCL and was significantly associated with increased cancer gene mutations and favorable immune microenvironment, but not prognostic impact. Phenotypic dMMR was also infrequent, and MMR proteins were commonly expressed in DLBCL. However, intratumor heterogeneity existed, and increased DLBCL cells with phenotypic dMMR correlated with significantly increased T cells and PD-1+ T cells, higher average nearest neighbor distance between T cells and PAX5+ cells, upregulated immune gene signatures, LE4 and LE7 ecotypes and their underlying Ecotyper-defined cell states, suggesting the possibility that increased T cells targeted only tumor cell subsets with dMMR. Only in patients with MYC¯ DLBCL, high MSH6/PMS2 expression showed significant adverse prognostic effects. This study shows the immunologic and prognostic effects of genetic/phenotypic dMMR in DLBCL, and raises a question on whether DLBCL-infiltrating PD-1+ T cells target only tumor subclones, relevant for the efficacy of PD-1 blockade immunotherapy in DLBCL.


Asunto(s)
Reparación de la Incompatibilidad de ADN , Linfoma de Células B Grandes Difuso , Microambiente Tumoral , Humanos , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/inmunología , Linfoma de Células B Grandes Difuso/patología , Reparación de la Incompatibilidad de ADN/genética , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Masculino , Femenino , Mutación , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Pronóstico , Adulto , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/genética , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo
5.
Case Reports Plast Surg Hand Surg ; 11(1): 2393819, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39170854

RESUMEN

Intramuscular hemangiomas (IMH) are extremely rare, accounting for 0.8% of all hemangiomas. IMH must be included in the differential diagnosis of soft tissue masses, and unexplained muscular pain. We herein describe the case of a patient who presented with an atypical localization of IMH in the infraspinatus muscle.

6.
Age Ageing ; 53(8)2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39141079

RESUMEN

BACKGROUND: Advanced age has been widely identified as a risk factor for recurrent Clostridioides difficile infection (CDI), but most related studies were performed before the introduction of novel therapies. The aim of this study was to compare CDI characteristics and outcomes in patients over and under 80 years old with CDI and their outcomes in the era of new treatments. METHODS: This was a retrospective cohort study of patients diagnosed with CDI from January 2021 to December 2022 in an academic hospital. We compared recurrence and mortality at 12 weeks after the end of treatment. An extension of the Fine and Grey model adjusted for competing events was used to assess the effect of age on recurrence. RESULTS: Four hundred seventy-six patients were considered to have CDI (320 in patients <80 years and 156 in ≥80 years). CDI in older patients was more frequently healthcare-associated and was more severe. Although the Charlson index was almost identical between populations, comorbidities clearly differed. New treatments (bezlotoxumab, fidaxomicin and faecal microbiota transplantation) were more frequently used in older patients without statistical significance (41.3% vs. 33.4%, P = .053). There were 69 (14.5%) recurrences, with no differences by age group after adjusting for competing events. Mortality was greater in the oldest (35.3%) than in the youngest (13.1%); P < .001. CONCLUSIONS: No differences in CDI recurrence rates were found between age groups. However, there was a high mortality rate in patients ≥80 years old, which emphasises the urgent need to improve the prevention and treatment of CDI in this group.


Asunto(s)
Infecciones por Clostridium , Recurrencia , Humanos , Masculino , Anciano de 80 o más Años , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/mortalidad , Infecciones por Clostridium/microbiología , Infecciones por Clostridium/terapia , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/tratamiento farmacológico , Femenino , Estudios Retrospectivos , Factores de Riesgo , Anciano , Factores de Edad , Trasplante de Microbiota Fecal , Antibacterianos/uso terapéutico , Clostridioides difficile , Persona de Mediana Edad , Fidaxomicina/uso terapéutico , Anticuerpos ampliamente neutralizantes/uso terapéutico , Anticuerpos Monoclonales
8.
J Clin Med ; 13(13)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38999359

RESUMEN

Background: Cisplatin is employed in hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) for peritoneal surface malignancies (PSMs). The main concern regarding intraperitoneal cisplatin administration is nephrotoxicity. Numerous reports in this context are available. Our objective was to conduct a systematic review and meta-analysis to assess cisplatin-based HIPEC-related nephrotoxicity (CHRN). Methods: A systematic literature review on CHRN after CRS for the treatment of PSMs was performed. The literature search was carried out using Medline, Cochrane, and Embase. The last day of the search was 23 October 2023. PRISMA guidelines were used. A meta-analysis was then conducted. The main endpoint was the incidence of acute and chronic renal impairment after CHRN. Secondary endpoints included the potential impact of several clinical variables on the primary endpoint and a critical appraisal of the different renal impairment scales employed. Results: Our study included 26 articles with a total sample of 1473 patients. The incidence of acute kidney injury (AKI) was 18.6% (95% CI: 13.6-25%, range of true effects 3-59%). For chronic kidney disease, it was 7% (95% CI: 3-15.3%, range of true effects 1-53%). The variables that statistically influenced these results were the scale used to measure renal insufficiency, the use of nephroprotective agents, and the presence of pre-existing renal disease. Conclusions: The reported incidence of renal impairment following cisplatin-based HIPEC is highly variable. The incidence of renal failure obtained in this meta-analysis should be used as a reference for subsequent reports on this topic. Further prospective studies are warranted to establish optimal and standardized management.

9.
Lancet Reg Health Eur ; 44: 100989, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39036304

RESUMEN

Background: All-cause and AIDS-mortality in Europe has been decreasing between 1996 and 2020. However, regional differences as well as their drivers remain unclear. This study investigates mortality differences and their drivers, including usage of and response to antiretroviral therapy (ART) and active tuberculosis (TB), among people with HIV across Europe. Methods: People with HIV enrolled in EuroSIDA were followed from 2001 through 2020. Immunologic-virologic status (IVS) was categorized as poor (CD4-cell count ≤350 cells/mm3 and viral load (VL) > 200 copies/ml), good (CD4 ≥ 500 and VL < 200), or intermediate (remaining combinations). Participants missing either CD4-cell count or VL were categorized as unknown. Regional differences in mortality were analyzed using multivariable Poisson regression with interaction analyses between regions of Europe and IVS, ART, or TB status. Findings: 20,364 people with HIV were included: 13,715/20,346 (67.3%) from Western, 3020/20,364 (14.8%) from Central Eastern, and 3629/20,364 (17.8%) from Eastern Europe. At enrolment, median age was 40 years (inter-quartile range (IQR): 33-48), median CD4-cell count 449 cells/mm3 (IQR: 291-638), and most were male 14,993/20,346 (73.3%). A total of 2639 died during 192,591 person-years of follow-up (crude mortality rate 13.7/1000 person-years, 95% CI: 13.2-14.2), 519/2639 (19.7%) from AIDS (2.7/1000 person-years, 2.5-2.9). All-cause and AIDS-mortality rates decreased over time but remained higher in Eastern Europe after adjusting for confounders. Being off ART (aIRR 2.42; 95% CI 2.14-2.74), poor IVS (aIRR 4.2; 95% CI 3.39-5.20) and prior TB (aIRR 3.33; 95% CI 2.75-4.03) were associated with higher all-cause mortality. For all-cause mortality the effect of ART (test for interaction: p < 0.001) and IVS (p = 0.02), but not TB (p = 0.5) varied across regions. Interpretation: Overall mortality and AIDS-mortality rates decreased over time, but remained higher in Eastern Europe. A poor IVS, being off ART and prior active TB were related to higher mortality. Eastern Europe had the highest proportion of people with poor or unknown IVS, emphasizing the continued need to improve HIV care with a focus on early diagnosis, ART initiation, and adherence. Funding: EuroSIDA has received funding from ViiV Healthcare LLC, Janssen Scientific Affairs, Janssen R&D, Bristol-Myers Squibb Company, Merck Sharp & Dohme Corp, Gilead Sciences and the European Union's Seventh Framework Programme for research, technological development and demonstration under EuroCoord grant agreement n˚ 260694. The study is also supported by a grant from the Danish National Research Foundation and by the International Cohort Consortium of Infectious Disease (RESPOND).

10.
Ann Surg Oncol ; 31(10): 7090-7110, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39037523

RESUMEN

This manuscript reports the results of an international consensus on technologies of hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) performed with the following goals: To provide recommendations for the technological parameters to perform HIPEC. To identify the role of heat and its application forms in treating peritoneal metastases. To provide recommendations regarding the correct dosimetry of intraperitoneal chemotherapy drugs and their carrier solutions. To identify for each intraperitoneal chemotherapy regimen the best dosimetry and fractionation. To identify areas of future research pertaining to HIPEC technology and regimens. This consensus was performed by the Delphi technique and comprised two rounds of voting. In total, 96 of 102 eligible panelists replied to both Delphi rounds (94.1%) with a consensus of 39/51 questions on HIPEC technical aspects. Among the recommendations that met with the strongest consensus were those concerning the dose of HIPEC drug established in mg/m2, a target temperature of at least 42°C, and the use of at least three temperature probes to pursue hyperthermia. Ninety minutes as the ideal HIPEC duration seemed to make consensus. These results should be considered when designing new clinical trials in patients with peritoneal surface malignancies.


Asunto(s)
Consenso , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneales , Humanos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/secundario , Terapia Combinada , Hipertermia Inducida/métodos , Técnica Delphi
11.
Sci Rep ; 14(1): 13980, 2024 06 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886484

RESUMEN

Maraviroc (MVC) is an antiretroviral drug capable of binding to CCR5 receptors and block HIV entry into target cells. Moreover, MVC can activate NF-kB pathway and induce viral transcription in HIV-infected cells, being proposed as a latency reversal agent (LRA) in HIV cure strategies. However, the evaluation of immunological and metabolic parameters induced by MVC concentrations capable of inducing HIV transcription have not been explored in depth. We cultured isolated CD4 T cells in the absence or presence of MVC, and evaluated the frequency of CD4 T cell subpopulations and activation markers levels by flow cytometry, and the oxidative and glycolytic metabolic rates of CD4 T cells using a Seahorse Analyzer. Our results indicate that a high concentration of MVC did not increase the levels of activation markers, as well as glycolytic or oxidative metabolic rates in CD4 T cells. Furthermore, MVC did not induce significant changes in the frequency and activation levels of memory cell subpopulations. Our data support a safety profile of MVC as a promising LRA candidate since it does not induce alterations of the immunological and metabolic parameters that could affect the functionality of these immune cells.


Asunto(s)
Linfocitos T CD4-Positivos , Maraviroc , Maraviroc/farmacología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Humanos , Glucólisis/efectos de los fármacos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , Infecciones por VIH/inmunología , Células Cultivadas , Triazoles/farmacología , VIH-1/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Masculino , Antagonistas de los Receptores CCR5/farmacología , Ciclohexanos/farmacología , Adulto
12.
Lancet HIV ; 11(7): e470-e478, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38824937

RESUMEN

BACKGROUND: Ending AIDS by 2030 requires improvements across all stages of the HIV care continuum. We used a longitudinal approach to assess changes in the HIV care continuum in Spain and transition probabilities across different stages. METHODS: We used data from the prospective Cohort of the Spanish HIV/AIDS Research Network to analyse the time from diagnosis to linkage to care, linkage to care to antiretroviral therapy (ART), and ART to viral suppression in five calendar periods defined by milestones in ART, from 2005 to 2022. We used the Kaplan-Meier method and Cox proportional hazard models to estimate cumulative probabilities of stage transition within 1, 3, 6, and 12 months of stage eligibility, by period. FINDINGS: We included 18 529 participants. Comparing the initial (2005-09) and final (2020-22) periods, time to linkage to care decreased from a median of 6·0 weeks to 1·3 weeks, time to ART initiation from 15·9 weeks to 0·4 weeks, and time to viral suppression from 13·3 weeks to 7·1 weeks. Adjusted hazard ratios for the comparison between the last period and the initial period were 3·1 (95% CI 2·8-3·4) for linkage to care within 1 month, 11·4 (10·1-12·3) for ART initiation within 1 month, and 2·2 (1·2-2·4) for viral suppression within 3 months. The aggregate proportion of late diagnoses was 38·6%, increasing after 2012 to 46·4% in the 2020-22 period. Same-day ART initiation increased from 18% to 39% from 2005 to 2022. The overall incidence rate of virological failure was 1·05 failures per 1000 person-years and showed a non-significant decline throughout the study. INTERPRETATION: The great improvement in transition times through the HIV care cascade might put Spain on the verge of achieving the UNAIDS targets for HIV elimination. However, late diagnosis remains a challenge that should be addressed. FUNDING: Instituto de Salud Carlos III and Spanish AIDS Research Network.


Asunto(s)
Fármacos Anti-VIH , Continuidad de la Atención al Paciente , Infecciones por VIH , Humanos , España/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Masculino , Femenino , Adulto , Estudios Longitudinales , Estudios Prospectivos , Persona de Mediana Edad , Fármacos Anti-VIH/uso terapéutico , Carga Viral/efectos de los fármacos , Factores de Tiempo , Modelos de Riesgos Proporcionales , Adulto Joven
13.
AIDS Patient Care STDS ; 38(7): 305-314, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38916077

RESUMEN

We assessed the prevalence and factors associated with HIV-infected patients' interest in trying long-acting injectable antiretroviral treatment (LAI-ART) along with its expected benefits and concerns, and evaluated physicians' opinions about LAI-ART. This study was set within the multi-center prospective CoRIS cohort, comprising HIV-positive adults, naïve to antiretroviral treatment (ART) at study entry, recruited from 2004 onward in 48 centers in Spain. In June 2022, we conducted a 2-day cross-sectional survey among patients across 34 CoRIS centers and sent an online questionnaire to all physicians prescribing ART in 39 CoRIS centers. Of the 271 patients included, 83.3% [95% confidence interval (CI)]: 78.0 - 87.0%) expressed interest in receiving LAI-ART. This interest was higher among men (adjusted odds ratio: 2.96; 95% CI: 1.4-6.12), those aged <50 years (2.41; 1.23 - 4.73), and individuals inconvenienced by oral ART (5.03; 1.47 - 17.15), daily intake (14.65; 3.44-62.46), carrying HIV pills constantly (7.19; 2.88 - 17.96), and taking multiple medications (3.94; 1.58 - 9.85). Among the 154 physicians surveyed, 45.5% believed LAI-ART would be the preferred option for patients. Although most physicians (92.9%) thought LAI-ART could improve patients' quality of life (QoL), concerns were raised by 37.7% and 44.2% of them regarding injection site pain and visit rescheduling, respectively. Interest in LAI-ART was higher among men, those aged <50 years, and individuals finding their oral ART inconvenient. Physicians believed LAI-ART could improve QoL and overcome treatment challenges, yet concerns were raised about its potential usage difficulties. Although most patients were interested in receiving LAI-ART, only less than half of the physicians considered it their preferred option, likely owing to concerns about missed visits and injection site pain.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Inyecciones , Médicos , Humanos , Masculino , Infecciones por VIH/tratamiento farmacológico , España , Femenino , Persona de Mediana Edad , Adulto , Estudios Transversales , Médicos/psicología , Encuestas y Cuestionarios , Estudios Prospectivos , Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Aceptación de la Atención de Salud/estadística & datos numéricos , Preparaciones de Acción Retardada , Actitud del Personal de Salud
14.
Clin Cancer Res ; 30(17): 3704-3714, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-38900037

RESUMEN

PURPOSE: This phase II clinical trial evaluated the combination of ibrutinib with rituximab, gemcitabine, and oxaliplatin (R-GemOx) in patients with nongerminal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: The IBDCL trial (NCT02692248) included patients with histologic diagnosis of non-GCB DLBCL with relapsed or refractory disease and non-candidates for stem-cell transplantation. Patients received an induction treatment consisting of six or eight cycles of R-GemOx at standard doses every 2 weeks, in combination with ibrutinib (560 mg daily), followed by a maintenance treatment with ibrutinib for a maximum of 2 years. The primary objective was to evaluate the overall response rate after four cycles. RESULTS: Sixty-four patients were included, 72% of them refractory to the last regimen. The overall response rate and complete remission rate after the fourth cycle were 53% [95% confidence interval (CI), 41-65] and 34% (95% CI, 24-46), respectively. Twenty-four (37%) patients started maintenance, and 7 (11%) completed the planned 2 years. After a median follow-up of 29.7 months (range: 0.4-48.6), the estimated 2-year progression-free survival and overall survival were 18% (95% CI, 8-28) and 26% (95% CI, 14-37), respectively. The most common grade ≥3 treatment-related adverse events were thrombocytopenia (44%), neutropenia (30%), and anemia (14%). Grade ≥3 infectious and cardiovascular treatment-related adverse events were reported in 6 (9%) and 1 (2%) patient, respectively. CONCLUSIONS: Ibrutinib in combination with R-GemOx, followed by ibrutinib maintenance, demonstrated encouraging antitumor activity with durable responses and a manageable toxicity in patients with non-GCB DLBCL.


Asunto(s)
Adenina , Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Piperidinas , Humanos , Adenina/análogos & derivados , Adenina/administración & dosificación , Masculino , Femenino , Piperidinas/administración & dosificación , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/patología , Linfoma de Células B Grandes Difuso/mortalidad , Anciano , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Anciano de 80 o más Años , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Gemcitabina , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/patología , Resistencia a Antineoplásicos , Rituximab/administración & dosificación , Rituximab/efectos adversos , Oxaliplatino/administración & dosificación , Oxaliplatino/efectos adversos , Resultado del Tratamiento , España/epidemiología , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico
15.
Mol Genet Genomic Med ; 12(5): e2471, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38803233

RESUMEN

BACKGROUND: Bone tissue homeostasis relies on the coordinated activity of the bone-forming osteoblasts and bone-resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown. METHODS: We present a case report encompassing clinical assessments, imaging studies, and whole-exome sequencing analysis, complemented by functional in vitro experiments. RESULTS: This new case of osteomesopyknosis was associated with a missense ALOX5 variant predicted to induce protein misfolding and proteasomal degradation. Transfection experiments demonstrated that the variant was associated with reduced protein levels restored by proteasomal inhibition with bortezomib. Likewise, gene expression analysis showed that the mutated gene was associated with a decreased RANKL/OPG ratio, which is a critical driver of osteoclast precursor differentiation. CONCLUSION: Our data indicate impaired bone resorption as the underlying mechanism of this rare osteosclerosis, implicating ALOX5 pathogenic variants as potential etiological factors.


Asunto(s)
Araquidonato 5-Lipooxigenasa , Mutación Missense , Ligando RANK , Femenino , Humanos , Araquidonato 5-Lipooxigenasa/genética , Araquidonato 5-Lipooxigenasa/metabolismo , Osteoclastos/metabolismo , Osteoclastos/patología , Osteosclerosis/genética , Osteosclerosis/patología , Osteosclerosis/metabolismo , Ligando RANK/metabolismo , Ligando RANK/genética , Transducción de Señal , Persona de Mediana Edad
16.
Clin Proteomics ; 21(1): 37, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38778280

RESUMEN

BACKGROUND: Information on the microbiome's human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied a unique collection of samples harvested from April to June 2020 from unvaccinated patients. METHODS: We compared 10 infected and hospitalized patients with severe (n = 5) and moderate (n = 5) coronavirus disease (COVID-19) with 10 uninfected individuals, including non-COVID-19 but susceptible individuals (n = 5) and non-COVID-19 and nonsusceptible healthcare workers with repeated high-risk exposures (n = 5). RESULTS: By performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤ 0.05) out of 3376 unambiguously identified proteins (false discovery rate ≤ 1%). Major differences were observed between the non-COVID-19 and nonsusceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with the saliva of SARS-CoV-2-infected patients (p-value ≤ 0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression levels of two human proteins related to protein transport in the cytoplasm, DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that were overrepresented in the infected group. CONCLUSION: Our study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility, although further studies in larger cohorts will be necessary.

17.
Artículo en Inglés | MEDLINE | ID: mdl-38763865

RESUMEN

INTRODUCTION: HIV infection has become a chronic disease with a good long-term prognosis, necessitating a change in the care model. For this study, we applied a proposal for an Optimal Care Model (OCM) for people with HIV (PHIV), which includes tools for assessing patient complexity and their classification into profiles to optimize care provision. METHODS: Observational, cross-sectional, and retrospective study. Adult PHIV treated at the Tropical Medicine consultations at Ramón y Cajal Hospital from January 1 to June 30, 2023, were included. The complexity calculation and the stratification into profiles for each patient were done according to the OCM. RESULTS: Ninety-four participants were included, 76.6% cisgender men, with a median age of 41 years (range 23-76). Latin America and Africa were the main regions of origin (72.4%). 98% had an undetectable HIV viral load. The degree of complexity was 78.7% low, 11.7% medium, 1% high, and 8.5% extreme. The predominant profile was blue (64.9%), followed by lilac (11.7%), purple (6.3%), and green (4.3%). 7.4% were unclassifiable, of whom 57.2% had high/extreme complexity. Among the unclassifiable, mental health problems were the most common. CONCLUSIONS: The OCM tools for People Living with HIV (PLWH) allow for the classification and stratification of most patients in a consultation with a non-standard population. Patients who did not fit into the pre-established profiles presented high complexity. Creating a profile focused on mental health or mixed profiles could facilitate the classification of more patients.

18.
Hepatología ; 5(2)mayo-ago. 2024. fig, tab
Artículo en Español | LILACS, COLNAL | ID: biblio-1556417

RESUMEN

La enfermedad vascular porto-sinusoidal es una causa infrecuente de hipertensión portal no cirrótica, fue descrita recientemente y es poco diagnosticada por el desconocimiento entre los médicos. Se considera en casos de hipertensión portal clínicamente significativa, en ausencia de cirrosis. El diagnóstico se basa en los hallazgos de la biopsia. El pronóstico de la enfermedad es mejor que el de los pacientes cirróticos, y el tratamiento es similar al de la hipertensión portal y al de las complicaciones que presentan los pacientes con cirrosis. Se presenta el caso de una paciente con várices esofágicas con estudios de imágenes no compatibles con cirrosis y hallazgos específicos en la biopsia de enfermedad vascular porto-sinusoidal. Este caso muestra el ejercicio diagnóstico en un caso de enfermedad vascular porto-sinusoidal de una paciente de Colombia, así como el resultado de las intervenciones terapéuticas y la evolución en el tiempo.


Porto-sinusoidal vascular disease is an uncommon cause of non-cirrhotic portal hypertension. It was recently described and is rarely diagnosed due to lack of knowledge among doctors. It is considered in cases of clinically significant portal hypertension in the absence of cirrhosis, and the diagnosis is based on biopsy findings. The prognosis of the disease is better than that of cirrhotic patients, and the treatment is similar to that of portal hypertension, including the management of complications associated with cirrhosis. We present the case of a patient with esophageal varices, whose imaging studies were not compatible with cirrhosis, alongside specific biopsy findings of porto-sinusoidal vascular disease. This case illustrates the diagnostic process in a patient from Colombia with portosinusoidal vascular disease, as well as the outcomes of therapeutic interventions and the patient´s evolution over time.

19.
J Infect Dis ; 230(2): 421-425, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-38557859

RESUMEN

We studied the association of mitochondrial DNA (mtDNA) haplogroups with weight and body mass index (BMI) gain at 96 weeks in 1019 treatment-naive persons with HIV (PWH) who initiated first-line antiretroviral therapy (ART) since 2014. The mean increase in weight and BMI over the study period was 2.90 kg and 0.98 kg/m2, respectively. We found a significant adjusted association between the major UK mtDNA haplogroup and lower weight and BMI increase at 96 weeks after ART initiation. Our findings reveal a potential role for mitochondrial genetics in the complex phenomenon of weight gain after initial ART in PWH.


Asunto(s)
Índice de Masa Corporal , ADN Mitocondrial , Infecciones por VIH , Haplotipos , Aumento de Peso , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Aumento de Peso/efectos de los fármacos , Aumento de Peso/genética , Masculino , Femenino , Adulto , ADN Mitocondrial/genética , Persona de Mediana Edad , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/efectos adversos , Mitocondrias/genética , Mitocondrias/efectos de los fármacos , Reino Unido/epidemiología
20.
Rev. esp. patol ; 57(1): 42-47, ene.-mar. 2024. ilus, tab
Artículo en Inglés | IBECS | ID: ibc-229921

RESUMEN

Subsequent to mass vaccination programs against COVID-19, diverse side effects have been described, both at the injection site, such as pain, redness and swelling, and systemic effects such as fatigue, headache, muscle or joint pain. On rare occasions, a lymphadenopathic syndrome may develop, raising the clinical suspicion of a lymphoproliferative disorder. We present the case of a 30-year-old woman who developed self-limiting left axillary lymphadenopathy following COVID-19 vaccination. To date, only seven similar cases with a complete clinicopathological description have been published, and fourteen cases have been notified to the European adverse events databases (Eudravigilance) in relationship with vaccination against COVID-19. It is important to be aware of this potential complication when a lymphadenopathic syndrome develops following vaccination, to avoid unnecessary treatment. (AU)


Tras la vacunación masiva frente a la COVID-19 se han comenzado a describir diversos efectos adversos incluyendo efectos locales en el lugar de la inyección, como dolor, enrojecimiento, hinchazón, etc., y efectos sistémicos como fatiga, dolor de cabeza, dolor muscular o articular. Más infrecuentemente se pueden desarrollar cuadros linfadenopáticos sospechosos clínicamente de proceso linfoproliferativo. Presentamos el caso de una mujer de 30 años que desarrolló linfadenopatía axilar izquierda tras la vacunación contra la COVID-19 con hallazgos histopatológicos de linfadenopatía necrotizante de tipo Kikuchi y resolución espontánea. Hasta el momento se han publicado 7 casos con descripción clinicopatológica completa en la literatura y notificado 14 casos en la Red Europea de Farmacovigilancia en relación con la vacunación. Es importante tener en cuenta esta entidad en linfadenopatías sospechosas de procesos linfoproliferativos en este contexto, para evitar un tratamiento innecesario. (AU)


Asunto(s)
Humanos , Femenino , Adulto , Infecciones por Coronavirus/epidemiología , Vacunación Masiva/efectos adversos , Linfadenitis Necrotizante Histiocítica
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA