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2.
Endocrinol Diabetes Nutr (Engl Ed) ; 71(3): 96-102, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38493010

RESUMO

INTRODUCTION: To establish whether glycemic variability (GV) parameters used when gestational diabetes mellitus (GDM) has been diagnosed could help predict the probability that a patient will need pharmacological treatment, and to analyze the link of these parameters to the development of maternal-fetal complications. MATERIALS AND METHODS: A prospective study of 87 women with GDM who underwent retrospective continuous glucose monitoring (CGM) for six days between weeks 26 and 32 of gestation, following diagnosis. The mean glycemia levels and GV variables were analyzed together with their link to maternal-fetal complications, and the need for pharmacological treatment. ROC (receiver operating characteristic) curves were developed to determine validity to detect the need for pharmacological treatment. RESULTS: Patients with higher mean glycemia (p < 0.001) and continuous overlapping of net glycemic action in a period of n-hours (CONGAn) (p = 0.001) required pharmacological treatment. The ROC curves showed cut-off points of 98.81 mg/dL for mean glycemia, and 86.70 mg/dL for CONGAn, with 83.3% sensitivity and 67.8% specificity for both parameters. No relation between the GV parameters and development of maternal-fetal complications was observed. CONCLUSIONS: The use of CGM, once GDM is diagnosed, enables us to identify those patients who would benefit from closer monitoring during gestation, and facilitate a speedier take-up of pharmacological treatment. However, prospective studies involving a higher number of patients are needed, as well as a cost assessment for recommending the use of CGM following GDM diagnosis.


Assuntos
Diabetes Gestacional , Hiperglicemia , Gravidez , Humanos , Feminino , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/tratamento farmacológico , Estudos Prospectivos , Glicemia , Estudos Retrospectivos , Automonitorização da Glicemia
3.
J Alzheimers Dis ; 98(2): 601-618, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427484

RESUMO

Background: Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPß1, a surface receptor that triggers amyloid-ß(Aß) phagocytosis via TYROBP. Objective: To analyze the impact of this copy-number variant in SIRPß1 expression and how it affects AD molecular etiology. Methods: Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPß1 isoform-specific phagocytosis assays were performed in HEK393T cells. Results: The insertion alters the SIRPß1 protein isoform landscape compromising its ability to bind oligomeric Aß and its affinity for TYROBP. SIRPß1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aß ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPß1 duplication allele correlates with higher TREM2 expression and an increased microglial activation. Conclusions: The SIRPß1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aß. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPß1 structural variant might be considered as a potential modulator of this causative pathway.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Receptores de Superfície Celular , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Microglia/metabolismo , Fagocitose , Receptores de Superfície Celular/metabolismo
4.
Crit Care ; 28(1): 91, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515193

RESUMO

BACKGROUND: Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster. METHODS: Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3. RESULTS: Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3. CONCLUSIONS: During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Análise por Conglomerados , Unidades de Terapia Intensiva , Estudos Prospectivos , Síndrome do Desconforto Respiratório/terapia , Estudos Retrospectivos
5.
Arq Bras Oftalmol ; 87(2): e20220091, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38451678

RESUMO

Hepatitis C virus infection may be implicated in 12.7% of ocular adnexal marginal zone lymphomas. We present the first case of an orbital-systemic mucosa-associated lymphoid tissue lymphoma that responded to hepatitis C virus medical treatment. A 62-year-old male with a right-sided orbital mass was diagnosed with stage IIA orbital marginal zone lymphoma in addition to hepatitis C virus infection based on clinical, imaging, laboratory, and histological examinations. The systemic and orbital responses were achieved 1 year after undergoing hepatitis C virus treatment with glecaprevir/pibrentasvir. The association between the hepatitis C virus infection and orbital-systemic mucosa-associated lymphoid tissue lymphoma is relevant. Accordingly, patients with orbital mucosa-associated lymphoid tissue lymphoma should be assessed for hepatitis C virus seroreactivity for therapeutic and prognostic purposes.


Assuntos
Hepatite C , Linfoma de Zona Marginal Tipo Células B , Masculino , Humanos , Pessoa de Meia-Idade , Hepacivirus , Linfoma de Zona Marginal Tipo Células B/complicações , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Tecido Linfoide , Mucosa
6.
Contact Dermatitis ; 90(5): 486-494, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38348533

RESUMO

BACKGROUND: Current frequency and features for positivity to textile dye mix (TDM) in Spain are unknown. OBJECTIVES: To study the frequency, clinical features and simultaneous positivity between TDM, para-phenylenediamine (PPD) and specific disperse dyes. MATERIALS AND METHODS: We analysed all consecutive patients patch-tested with TDM from the Spanish Contact Dermatitis Registry (REIDAC), from 1 January 2019 to 31 December 2022. Within this group, we studied all selected patients patch-tested with a textile dye series. RESULTS: Out of 6128 patients analysed, 3.3% were positive to the TDM and in 34% of them, the sensitization was considered currently relevant. TDM positivity was associated with working as a hairdresser/beautician and scalp, neck/trunk and arm/forearm dermatitis. From TDM-positive patients, 57% were positive to PPD. One hundred and sixty-four patients were patch-tested with the textile dye series. Disperse Orange 3 was the most frequent positive dye (16%). One of every six cases positive to any dye from the textile dye series would have been missed if patch-tested with the TDM alone. CONCLUSIONS: Positivity to TDM is common in Spain and often associated with PPD sensitization. TDM is a valuable marker of disperse dyes allergy that should be part of the Spanish and European standard series.


Assuntos
Dermatite Alérgica de Contato , Humanos , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Espanha/epidemiologia , Têxteis/efeitos adversos , Testes do Emplastro , Corantes/efeitos adversos
7.
Contact Dermatitis ; 90(5): 507-513, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38351475

RESUMO

BACKGROUND: A global epidemic of allergic contact dermatitis to (meth)acrylates has been described in relation to the widespread use of manicure products. OBJECTIVES: To evaluate the frequency of sensitization to 2-hydroxyethyl methacrylate (2-HEMA) among consecutively patch tested patients with eczema in Spain; the percentage of current relevance; the MOAHLFA index; and, the potential sources of exposure to (meth)acrylates. METHODS: From January 2019 to December 2022, 2-HEMA 2% pet. was prospectively patch tested in 24 REIDAC (Spanish Allergic Contact Dermatitis Registry) centres. RESULTS: Six thousand one hundred thirty-four patients were consecutively patch tested with 2-HEMA 2% pet. 265/6134 (4.3%) were positive. Positive reactions of current relevance were identified to involve 184/265 (69%). The efficiency (number of patch tests needed to detect relevant positive patch test reactions) was 34 (6134/184). The variable 'occupational' was found to be significantly associated with a higher risk for relevant positive reactions to 2-HEMA (OR: 10.9; 95% CI: 8.1-14.9). CONCLUSION: (Meth)acrylate sensitization is a prevalent health issue in Spain. 2-HEMA 2% pet. has been identified to be a highly effective (meth)acrylate allergy marker in the GEIDAC baseline series. The responsible authorities should implement policies guaranteeing accurate labelling of industrial, medical, and consumer materials while ensuring the enforcement of said labelling through appropriate legal means.


Assuntos
Dermatite Alérgica de Contato , Dermatite Ocupacional , Humanos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Espanha/epidemiologia , Metacrilatos/efeitos adversos , Acrilatos , Testes do Emplastro
8.
Artigo em Inglês | MEDLINE | ID: mdl-38411353

RESUMO

BACKGROUND: There is still limited clinical-practice data on specific clinical and patch test features, as well as on allergen clusters in polysensitization (PS). OBJECTIVES: To determine the frequency, relevance, symptoms duration and risk factors in polysensitized patients and to assess possible allergen aggregation. METHODS: Prospective multicentric study (January 2019-December 2022) conducted in setting of the Spanish Contact Dermatitis Register (REIDAC). Clinical and patch test data of polysensitized and oligosensitized patients were compared, and risk factors of PS were investigated with logistic multivariate regression. Unsupervised hierarchical clustering and network analysis were used to study allergen aggregation in PS. RESULTS: A total of 10,176 patients were analysed. PS was found in 844 (8.3%). Current relevance was significantly higher in polysensitized patients (p < 0.01). Risk factors for PS were atopic dermatitis (OR: 1.58, 95% CI: 1.24-2.02), age (≥60 years vs. ≤24 years, OR: 1.75, 95% CI: 1.25-2.44) and some special locations (legs vs. face OR: 1.54, 95% CI: 1.05-2.25, hands vs. face OR: 1.46, 95% CI:1.15-1.85, arms vs. face OR: 1.49, 95% CI:1.01-2.20, trunk vs. face OR: 1.40, 95% CI:1.06-1.85). Cluster and network analyses revealed specific-allergen clusters and significant associations, including allergens belonging to metals group, fragrances and botanicals group, topical drugs group, rubber allergens and biocides. CONCLUSIONS: This study confirms that PS is structured by discernible patterns of specific-allergen clusters and reinforces significant allergen associations in PS. Cross-reactivity and/or concomitant sensitization could explain the formation of allergen clusters in PS.

9.
Biomolecules ; 14(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38254726

RESUMO

(1) Background: Eosinophilia has traditionally been linked to eosinophilic asthma, for which it is the gold-standard prognostic biomarker. However, the association between eosinophilia and the presence of other diseases and comorbidities is yet unclear. (2) Methods: For this retrospective study, we reviewed the electronic medical records of 49,909 subjects with blood eosinophilia to gather data on the presence of asthma, COPD, sleep apnea, tuberculosis, dyslipidemia, hypertension, and other cardiovascular diseases and severe CRSwNP among these subjects. Demographic features including age, sex, and smoking habits were collected, as well as the number of hospitalizations and emergency department visits. T-tests, ANOVA, Fisher test, and logistic regression models were used. (3) Results: For all age groups studied, eosinophilia was significantly more prevalent among asthmatic subjects than nonasthmatics, especially in patients also presenting CRSwNP, hypertension, and dyslipidemia. The likelihood of developing asthma, COPD, and CRSwNP, and hospitalization, was increased when BEC was above 600 eosinophils/µL. The association between asthma, CRSwNP, and BEC was corroborated by multiple logistic regressions models. (4) Conclusions: We demonstrated the association of having over 600 blood eosinophils/µL with a higher number of hospitalizations and comorbidities (CRSwNP and COPD), which proves that BEC is a highly useful parameter to consider in subjects who present blood eosinophilia.


Assuntos
Asma , Dislipidemias , Hipertensão , Mustelidae , Doença Pulmonar Obstrutiva Crônica , Eosinofilia Pulmonar , Humanos , Animais , Estudos Retrospectivos , Asma/complicações , Asma/epidemiologia , Hospitalização , Dislipidemias/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia
10.
Vet Res Commun ; 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38263503

RESUMO

Shiga toxin-producing Escherichia coli (STEC) are recognized as being responsible for many cases of foodborne diseases worldwide. Cattle are the main reservoir of STEC, shedding the microorganisms in their feces. The serogroup STEC O91 has been associated with hemorrhagic colitis and hemolytic uremic syndrome. Locus of Adhesion and Autoaggregation (LAA) and its hes gene are related to the pathogenicity of STEC and the ability to form biofilms. Considering the frequent isolation of STEC O91, the biofilm-forming ability, and the possible role of hes in the pathogenicity of STEC, we propose to evaluate the ability of STEC to form biofilms and to evaluate the expression of hes before and after of biofilm formation. All strains were classified as strong biofilm-forming. The hes expression showed variability between strains before and after biofilm formation, and this may be due to other genes carried by each strain. This study is the first to report the relationship between biofilm formation, and hes expression and proposes that the analysis and diagnosis of LAA, especially hes as STEC O91 virulence factors, could elucidate these unknown mechanisms. Considering that there is no specific treatment for HUS, only supportive care, it is necessary to know the survival and virulence mechanisms of STEC O91.

11.
Contact Dermatitis ; 90(4): 402-410, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38010086

RESUMO

BACKGROUND: There is speculation that some environmental factors may be impacting the increasing incidence of frontal fibrosing alopecia (FFA). In a recent publication, sensitisation to benzyl salicylate was shown to be prevalent among 36 patients with FFA. Ethylhexyl salicylate (EHS), a light stabiliser, ultraviolet (UV) B absorber and UV filter, frequently found in photoprotectors/cosmetics and, rarely reported as a sensitiser, was not patch tested in said research. METHODS: From January 2021 to February 2022, 33 patients with FFA were patch-tested with the European Photopatch Series, including EHS 10% pet. in two hospitals. In addition, we conducted a literature review and a market survey. RESULTS: Patch test reactions to EHS were identified in 9 of 33 (27.3%). Four of nine also reacted to their personal sunscreens (containing EHS). All involved women with a mean age of 54 (30-65). Five patients had been diagnosed with FFA before the patch tests; and, four were diagnosed with FFA during the patch test investigations. CONCLUSION: Sensitisation to EHS was frequently found in a selected population of patients with FFA. We propose to expand the spectrum of contact allergens described in patients with FFA to include EHS and discuss the possible need for optimization of the patch test preparation.


Assuntos
Cosméticos , Dermatite Alérgica de Contato , Humanos , Feminino , Pessoa de Meia-Idade , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/epidemiologia , Protetores Solares/efeitos adversos , Alopecia/complicações , Testes do Emplastro/efeitos adversos , Salicilatos/efeitos adversos
12.
Clin J Pain ; 40(2): 72-81, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37942728

RESUMO

OBJECTIVE: Randomized controlled trials indicate regional anesthesia (RA) improves postoperative outcomes with reduced pain and opioid consumption. Therefore, we hypothesized children who received RA, regardless of technique, would have reduced pain/opioid use in routine practice. METHODS: Using a retrospective cohort, we assessed the association of RA with perioperative outcomes in everyday practice at our academic pediatric hospital. Patients 18 years or below undergoing orthopedic, urologic, or general surgeries with and without RA from May 2014 to September 2021 were categorized as single shot, catheter based, or no block. Outcomes included intraoperative opioid exposure and dose, preincision anesthesia time, postanesthesia care unit (PACU) opioid exposure and dose, PACU antiemetic/antipruritic administration, PACU/inpatient pain scores, PACU/inpatient lengths of stay, and cumulative opioid exposure. Regression models estimated the adjusted association of RA with outcomes, controlling for multiple variables. RESULTS: A total of 11,292 procedures with 3160 RAs were included. Compared with no-block group, single-shot and catheter-based blocks were associated with opioid-free intraoperative anesthesia and opioid-free PACU stays. Post-PACU (ie, while inpatient), single-shot blocks were not associated with improved pain scores or reduced opioid use. Catheter-based blocks were associated with reduced PACU and inpatient opioid use until 24 hours postop, no difference in opioid use from 24 to 36 hours, and a higher probability of use from 36 to 72 hours. RA was not associated with reduced cumulative opioid consumption. DISCUSSION: Despite adjustment for confounders, the association of RA with pediatric pain/opioid use outcomes was mixed. Further investigation is necessary to maximize the benefits of RA.


Assuntos
Analgésicos Opioides , Anestesia por Condução , Humanos , Criança , Estudos Retrospectivos , Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Anestesia por Condução/métodos , Anestésicos Locais
14.
Contact Dermatitis ; 90(3): 245-252, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37987093

RESUMO

BACKGROUND: Monitoring of adverse events induced by cosmetics performed by health authorities, known as cosmetovigilance, has been relied on the collection of case notifications. OBJECTIVES: We aimed to show how a contact dermatitis registry can contribute to the cosmetovigilance of emerging allergens. We used the example of phenylethyl resorcinol, an infrequent allergen with only 6 previous cases reported in Europe and Japan since 2013. METHODS: A systematic search in the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC) database was performed to identify patients with positive patch test to phenylethyl resorcinol or cosmetics that contains it between June 2018 and January 2023. We collected the main clinical features of these patients and compared them with those of patients recorded in the registry with similar epidemiological features. RESULTS: Thirteen patients with positive patch test to phenylethyl resorcinol were identified. All the patients were women with a mean age of 42 years (range 32-59) and their lesions were mainly in the face. CONCLUSION: Assessing the importance of infrequent allergens based solely on a case series is difficult. Multicentre registries facilitate the collection of cases and provide appropriate background information for new allergens.


Assuntos
Compostos Benzidrílicos , Cosméticos , Dermatite Alérgica de Contato , Resorcinóis , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Alérgenos/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Espanha/epidemiologia , Estudos Retrospectivos , Cosméticos/efeitos adversos , Testes do Emplastro/efeitos adversos , Sistema de Registros
15.
Arq. bras. oftalmol ; 87(2): e2022, 2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1533801

RESUMO

ABSTRACT Hepatitis C virus infection may be implicated in 12.7% of ocular adnexal marginal zone lymphomas. We present the first case of an orbital-systemic mucosa-associated lymphoid tissue lymphoma that responded to hepatitis C virus medical treatment. A 62-year-old male with a right-sided orbital mass was diagnosed with stage IIA orbital marginal zone lymphoma in addition to hepatitis C virus infection based on clinical, imaging, laboratory, and histological examinations. The systemic and orbital responses were achieved 1 year after undergoing hepatitis C virus treatment with glecaprevir/pibrentasvir. The association between the hepatitis C virus infection and orbital-systemic mucosa-associated lymphoid tissue lymphoma is relevant. Accordingly, patients with orbital mucosa-associated lymphoid tissue lymphoma should be assessed for hepatitis C virus seroreactivity for therapeutic and prognostic purposes.

16.
IJID Reg ; 9: 63-71, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37928802

RESUMO

Objectives: To determine the incidence and factors associated with SARS-CoV-2 infection and seroconversion among healthcare workers (HCWs) during the COVID-19 pandemic in a university hospital in Colombia. Methods: We analyzed the CoVIDA-Fundación Santa Fe de Bogotá (FSFB) cohort, consisting of 419 HCWs from the FSFB university hospital. The cohort was followed during active surveillance (June 25, 2020, to April 30, 2021) and passive surveillance (May 01, 2021, to March 16, 2022) periods. Incidence rates for SARS-CoV-2 infection, reinfection, and seroconversion were estimated, considering pre- and post-COVID-19 vaccination. Cox proportional-hazards models were used to identify factors related to infection and seroconversion during the active surveillance period. Results: COVID-19 incidence rate ranged between 16-52 cases per 1000 person-month. SARS-CoV-2 reinfections were rare, ranging between less than one case to 13 cases per 1000 person-month. The seroconversion rates ranged between 52-55 cases per 1000 person-month. High socioeconomic level was a protective factor for SARS-CoV-2 infection, while SARS-CoV-2 infection was the main factor associated with seroconversion. Conclusion: This study provides insights into the incidence and risk factors of SARS-CoV-2 infection among HCWs in a Colombian university hospital. The findings may offer valuable guidance for reducing virus spread within healthcare settings.

17.
J Clin Haematol ; 4(1): 35-42, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38009096

RESUMO

Introduction: During the past two decades, new therapeutic agents have greatly improved the treatment landscape in multiple myeloma (MM). Treatments such as proteasome inhibitors, immunomodulatory agents, targeted monoclonal antibody therapy, and chimeric antigen receptor (CAR) T-cell therapy have improved outcomes with less toxicity. Advances in laboratory testing have accompanied this change, performing faster and more accurate assessments of treatment response. Despite these advances, however, disparities in MM outcomes persist. Objective: The purpose of this study was to review epidemiological trends in MM over the past two decades and to identify disparities that may impact MM identification and survival. Methods: Retrospective analysis was conducted on adult patients diagnosed with MM between the years 2000-2019 using the November 2021 Surveillance, Epidemiology, and End Results (SEER) program database. Joinpoint models were used to calculate annual percent changes (APCs) and average annual percent change (AAPC). Results: There were a total of 111,328 diagnoses of MM extracted from the SEER database. Most patients were male (55.17%) and white (76.7%). Age-adjusted rate analysis found a significantly higher incidence among black patients compared to white patients. The APC between 2000-2015 was 1.46, and the APC between 2015-2019 was -1.34. Relative survival also increased from 2000 to 2014. The 5-year cancer survival in MM also increased at an average of 1.8% for every year after diagnosis. The annual probability of MM-related mortality at the 1-year mark also decreased from 28.5% in 2000 to 16.7% in 2018. Conclusion: Novel advances in MM therapeutic agents and diagnostic testing have paved the way for significant improvements in patient survival outcomes. Disparities persist along racial lines. Further research is needed to evaluate responses to specific MM treatment in the age of newly developed targeted therapies to overcome these disparities.

18.
Res Sq ; 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37790525

RESUMO

Hematopoietic stem cell transplantation can deliver therapeutic proteins to the CNS through donor-derived hematopoietic cells that become microglia-like cells. However, using standard conditioning approaches, hematopoietic stem cell transplantation is currently limited by low and slow engraftment of microglia-like cells. We report an efficient conditioning regimen based on Busulfan and a six-day course of microglia depletion using the colony-stimulating factor receptor 1 inhibitor PLX3397. Combining Busulfan-myeloablation and transient microglia depletion results in robust, rapid, and persistent microglia replacement by bone marrow-derived microglia-like cells throughout the CNS. Adding PLX3397 does not affect neurobehavior or has adverse effects on hematopoietic reconstitution. Through single-cell RNA sequencing and high-dimensional CyTOF mass cytometry, we show that microglia-like cells are a heterogeneous population and describe six distinct subpopulations. Though most bone-marrow-derived microglia-like cells can be classified as homeostatic microglia, their gene signature is a hybrid of homeostatic/embryonic microglia and border associated-macrophages. Busulfan-myeloablation and transient microglia depletion induce specific cytokines in the brain, ultimately combining myeloid proliferative and chemo-attractive signals that act locally to repopulate microglia from outside the niche. Importantly, this conditioning approach demonstrates therapeutic efficacy in a mouse model of GRN deficiency. Transplanting wild-type bone marrow into Grn-/- mice conditioned with Busulfan plus PLX3397 results in high engraftment of microglia-like cells in the brain and retina, restoring GRN levels and normalizing lipid metabolism.

19.
Front Microbiol ; 14: 1240891, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37869670

RESUMO

Background: Saliva modulates the environment of the oral biofilm through pH buffer, microbial attachment to host surfaces, and nutritional source. The ecology of stress occurs when a physical factor adversely impacts an ecosystem or its biotic components. Therefore, reduced salivary flow can affect oral-host balance. The leading causes of hyposalivation include disease-associated Sjögren's syndrome (SS) and menopausal women as aging-associated. However, little is known about the oral microbiome integrated with sex hormones in hyposalivation. This study aimed to characterize the hyposalivation microbiome caused by aging or disease affecting the salivary glands in women. Methods: We included 50 women older than 40 years of age in any menopausal phase. We collected stimulated saliva from 25 women diagnosed with SS (SS) and 25 without SS (non-SS). The bacterial profile of the patients was obtained by 16S rRNA sequencing. Bioinformatics analysis used machine learning to analyze the cohort's signs, symptoms, and bacterial profile. Salivary estradiol as a sex hormone variation level was determined. Results: We obtained that 79% of the SS group, and 52% of the non-SS group had hyposalivation. We found a negatively correlated Prevotella-age and Rothia-estradiol in the SS group. Highlight, we found that the cause of the hyposalivation in the study did not explain differences in microbial diversity comparing non-SS and SS groups. Therefore, microbial communities found in hyposalivation but not related to systemic conditions suggest that changes in the oral environment might underpin host-microbial balance. Conclusion: The salivary microbiome was similar in women with and without SS. However, hyposalivation showed two distinctive clusters associated with the bacterial population profiles. Our study suggests that local ecological disturbances could drive the change in the microbiome.

20.
Cancers (Basel) ; 15(17)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37686518

RESUMO

BACKGROUND: The rising incidence of colorectal cancer (CRC) among young patients is alarming. We aim to characterize the clinico-pathological features and outcomes of patients with early-onset CRC (EOCRC), as well as the impacts of COVID-19 pandemic. METHODS: We included all patients with pathologically confirmed diagnoses of CRC at Hospital Universitario La Paz from October 2016 to December 2021. The EOCRC cut-off age was 50 years old. RESULTS: A total of 1475 patients diagnosed with CRC were included, eighty (5.4%) of whom had EOCRC. Significant differences were found between EOCRC and later-onset patients regarding T, N stage and metastatic presentation at diagnosis; perineural invasion; tumor budding; high-grade tumors; and signet ring cell histology, with all issues having higher prevalence in the early-onset group. More EOCRC patients had the RAS/ BRAF wild type. Chemotherapy was administered more frequently to patients with EOCRC. In the metastatic setting, the EOCRC group presented a significantly longer median OS. Regarding the COVID-19 pandemic, more patients with COVID-19 were diagnosed with metastatic disease (61%) in the year after the lockdown (14 March 2020) than in the pre-pandemic EOCRC group (29%). CONCLUSIONS: EOCRC is diagnosed at a more advanced stage and with worse survival features in localized patients. More patients with EOCRC were diagnosed with metastatic disease in the year after the COVID-19 pandemic lockdown. The long-term consequences of COVID-19 are yet to be determined.

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