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1.
Immunol Lett ; : 106864, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38705481

ABSTRACT

Tumor-associated myeloid cells, including macrophages and myeloid-derived suppressor cells, can be highly prevalent in solid tumors and play a significant role in the development of the tumor. Therefore, myeloid cells are being considered potential targets for cancer immunotherapies. In this review, we focused on strategies aimed at targeting tumor-associated macrophages (TAMs). Most strategies were studied preclinically but we also included a limited number of clinical studies based on these strategies. We describe possible underlying mechanisms and discuss future challenges and prospects.

2.
PLOS Glob Public Health ; 4(5): e0003061, 2024.
Article in English | MEDLINE | ID: mdl-38709753

ABSTRACT

Men who have sex with men (MSM) and transgender women (TW) are disproportionally affected by HIV infection. This cross-sectional study evaluated the HIV-1/2 prevalence, risk factors and HIV molecular features of MSM and TW from Midwest Brazil. Four hundred and thirty participants (278 MSM and 152 TW) from Mato Grosso do Sul, Brazil, were interviewed and tested for HIV-1/2 infection between November 2011 and September 2013. Participants who were assigned male at birth, older than 18 years old and self-declared as MSM or TW were recruited from LGBT+ associations, as well as public (parks, square, streets, etc) and private [nightclubs, saunas, brothels, etc] places. The prevalence of HIV-1 was 14.4% (9.0% among MSM and 24% among TW; p<0.001). The factor independently associated with HIV-1 infection among MSM was being 30 years-old or older. Among TW, having suffered sexual coercion, lifetime syphilis infection and hepatitis C virus exposure were associated with HIV-1 infection. Phylogenetic analyses classified 65% sequences as subtype B and 35% as possible recombinants. All but one recombinant sample were from TW individuals. High HIV-1 prevalences were observed in both groups, highlighting the urgent need to devise specific HIV interventions targeting these key populations. Notably, TWs are more vulnerable to HIV infection, which was associated with sexual violence and co-infection with other STIs. With regard to MSM, being 30 years old or older was significanty associated to HIV, reinforcing the idea that MSM are less exposed [or exposed later] to STIs than TWs, although MSM are clearly more vulnerable than the general population.

3.
Int J Oral Maxillofac Implants ; 0(0): 1-17, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38717353

ABSTRACT

PURPOSE: to determine the relationship between bone loss that occurs during the peri-implantitis process and variations in implant stability using resonance frequency analysis measurement methods. MATERIAL & METHODS: 40 self- tapping implants were placed in cow ribs. For each group of 10 implants, a bone loss of 0 mm, 4 mm (simulating 1/3 of bone loss) and 8 mm (simulating 2/3 of bone loss) was established. Osteotomy measurements were made with a periodontal probe. For each implant, RFA was measured using the OSSTELL BEACON system by the same operator. RESULTS: The initial ISQ value of the 40 implants placed exceeded values of 70, reflecting an average of 73 in the VL direction and 74.8 in the MD direction. ISQ measurements in the 10 implants in which bone dehiscence was performed on the vestibular aspect reflected a decrease in ISQ values as bone loss deepens. When generating bone loss in two opposite faces (V and L), a greater decrease in ISQ values was observed when 2/3 of the implant were affected. The average value of the measurements in the VL direction was less than 70 when the loss is 2/3. CONCLUSIONS: when bone loss occurs on only one side of the implant, the ISQ values decrease,but the implant maintains good stability. The same occurs when two opposite sides of the implant are affected, the unaffected side has the least decrease in ISQ value.

4.
Int J Periodontics Restorative Dent ; 0(0): 1-22, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38717438

ABSTRACT

OBJECTIVE: This study aims to collect data on implant survival, bone volume maintenance, and complications associated with the socket shield technique. BACKGROUND DATA: The socket shield technique was introduced in 2010. Since then, several systematic reviews have been published, showing good clinical outcomes. The behaviour of the buccal bone plate is so far not completely understood. METHODS: The study involved the placement of 23 implants using the socket shield technique in 20 patients. AstraTech EV implants were used, and no bone substitutes or connective tissue grafts were applied. Patients were monitored for 18 months, recording implant survival, volumetric bone analysis on CBCT scans, interproximal bone levels, bone sounding, pink esthetic scores, and complications. Prosthetic procedures were also described, including temporary and final restorations. RESULTS: A 95.7% cumulative 18-month implant survival rate was obtained using the socket shield technique, with a significant but limited reduction in buccal bone thickness (BBT) after implant placement. One implant did not integrate and two shields were partially exposed. The mean pink esthetic score, 1 year after loading was 12.93 ± 1.22. CONCLUSION: The study suggests that the socket shield technique can result in limited reduction of the buccal bone volume, with a high implant survival rate. Re-entry studies are recommended to investigate the causes of bone resorption.

5.
AIDS Behav ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38720109

ABSTRACT

Despite the effectiveness of antiretroviral therapy (ART), human immunodeficiency virus (HIV) infection remains a global public health concern. However, weaknesses in its management regarding access to integrated HIV care include treatment gaps and loss to follow-up (LTFU) from antiretroviral treatment (ART). This study aimed to characterize the epidemiological and clinical profiles of people living with HIV/AIDS (PLHA) in LTFU from HIV care in Campo Grande, Central Brazil. This retrospective cross-sectional study was conducted between January 2021 and April 2022 using secondary data from PLHA who had LTFU in Campo Grande. A total of 852 patients with PLHA were included in this study. The majority of participants in LTFU were male (63.1%), had a CD4 cell count > 200 cells/mm3 (68.2%), and had been treated for ≥ 3 months (86.4%). Only 287 (33.7%) participants had undetectable HIV viral load. Of the total number of patients who returned to treatment during the study period, 448 (54.3%) were LTFU-positive. The tracking strategy was not applied to 556 (65.26%) patients, and 44.4% of the participants had been in spontaneous demand. These results highlight the relevance of patient-centered interventions and the need to ensure early treatment and promote retention in care systems with consequent viral suppression, impacting the healthcare indicators of the population, with emphasis on health managers and stakeholders in HIV care.

7.
NPJ Breast Cancer ; 10(1): 26, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38575691

ABSTRACT

To evaluate the role of chemotherapy in stage IA triple-negative breast cancer, we conducted a retrospective population-based study including 8601 patients. The use of chemotherapy significantly increased from 2010 to 2019 in patients with T1b and T1c tumors (p = 0.001 and p < 0.001, respectively). Receipt of chemotherapy was associated with improved breast cancer-specific survival (BCSS, adjusted hazard ratio = 0.70; p = 0.006), particularly in patients with T1c tumors (5-year BCSS 94.5% vs. 91.2%).

8.
J. Am. Coll. Cardiol ; 83(13 Suppl. A)Apr. 2024. graf.
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1551732

ABSTRACT

BACKGROUND: Selective cardiac myosin inhibitors (CMI) are promising therapies for obstructive hypertrophic cardiomyopathy (HCM). Yet, the extent of their benefits remains unclear due to the limited population studied. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing CMI vs. placebo in patients with obstructive HCM. PubMed, Cochrane, and embase were searched. We calculated risk ratios (RRs), mean differences (MDs) and standardized mean differences (SMDs) with 95% confidence intervals (CI). RESULTS: Four RCTs with 485 patients with obstructive HCM were included, of whom 261 (53.8%) were prescribed CMI (10.7% were aficamten and 89.3% were mavacamten). CMI significantly reduced resting left ventricular outflow tract (LVOT) gradient (SMD -1.4, 95% CI -1.6,-1.2, p<0.001), but also reduced left ventricular ejection fraction (LVEF) (MD -5.1%, 95% CI -7.6,-2.6, p<0,001). Patients receiving CMI had a higher rate of study-defined complete hemodynamic response (RR 16.8, CI 95% 5.5, 51.4, p<0,001; Figure 1A) with a number needed to treat (NNT) of 8; and improvement of at least one point in NYHA functional class (RR 2.29, CI 95% 1.8,2.9, p<0,001; Figure 1B). Conclusion: In this meta-analysis of RCTs including patients with obstructive HCM, CMI led to a significant reduction in LVOT gradient and symptomatic improvement. The NNT to achieve one complete hemodynamic response was 8. There was a significant, albeit modest, decrease in LVEF in the CMI group.

9.
J. Am. Coll. Cardiol ; 83(13 Suppl. A)Apr. 2024. tab.
Article in English | CONASS, Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1551748

ABSTRACT

BACKGROUND: The use of anabolic androgenic steroids (AAS) among athletes has been linked to pathological structural and functional cardiac changes. However, the studies are small, and the results are inconsistent. METHODS: We conducted a systematic review and meta-analysis of echocardiographic outcomes comparing athletes with prolonged use of AAS (at least 2 years of use) versus sex and age- matched athletes who were did not use AAS. PubMed, Cochrane, and embase were searched. A random-effects model was used to calculate mean differences (MDs), with 95% confidence intervals (CI). Statistical analyses were performed using Review Manager 5.4.1. RESULTS: We included 17 studies comprising 1,023 athletes, of whom 543 (53%) were AAS users. The mean age ranged to 24.2 to 43 years. Compared with non-AAS users, athletes who used AAS exhibited a significant increase in interventricular septal wall thickness (MD 1.33 mm; 95% CI [0.8,1.89], p<0.001), a reduction in left ventricular ejection fraction (MD 2.77 %; 95% CI [-4.2,-1.34], p<0.001;Figure 1B) , and worsening of global longitudinal strain (MD 3.39%; 95% CI [2.88,3.91], p<0.001;Figure 1B). Additionally, there was a significant reduction in the E/A ratio (MD -0.21; 95% CI [-0.35,-0.07], p=0.003) and an increase in the E/e' ratio (MD 1.71; 95% CI [0.96,2.46], p<0.001). CONCLUSION: Our findings suggest that prolonged use of AAS in athletes is associated with increased left ventricular wall thickness and worsening of systolic and diastolic parameters.


Subject(s)
Ventricular Dysfunction, Left , Athletes , Anabolic Androgenic Steroids
10.
J Med Internet Res ; 26: e54934, 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38684088

ABSTRACT

BACKGROUND: Falls and their consequences are a serious public health problem worldwide. Each year, 37.3 million falls requiring medical attention occur. Therefore, the analysis of fall risk is of great importance for prevention. Artificial intelligence (AI) represents an innovative tool for creating predictive statistical models of fall risk through data analysis. OBJECTIVE: The aim of this review was to analyze the available evidence on the applications of AI in the analysis of data related to postural control and fall risk. METHODS: A literature search was conducted in 6 databases with the following inclusion criteria: the articles had to be published within the last 5 years (from 2018 to 2024), they had to apply some method of AI, AI analyses had to be applied to data from samples consisting of humans, and the analyzed sample had to consist of individuals with independent walking with or without the assistance of external orthopedic devices. RESULTS: We obtained a total of 3858 articles, of which 22 were finally selected. Data extraction for subsequent analysis varied in the different studies: 82% (18/22) of them extracted data through tests or functional assessments, and the remaining 18% (4/22) of them extracted through existing medical records. Different AI techniques were used throughout the articles. All the research included in the review obtained accuracy values of >70% in the predictive models obtained through AI. CONCLUSIONS: The use of AI proves to be a valuable tool for creating predictive models of fall risk. The use of this tool could have a significant socioeconomic impact as it enables the development of low-cost predictive models with a high level of accuracy. TRIAL REGISTRATION: PROSPERO CRD42023443277; https://tinyurl.com/4sb72ssv.


Subject(s)
Accidental Falls , Artificial Intelligence , Accidental Falls/prevention & control , Humans , Risk Assessment/methods , Postural Balance
11.
Biol Sport ; 41(2): 163-174, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38524817

ABSTRACT

Although studies have demonstrated the effectiveness of exercise in controlling systemic arterial hypertension (SAH), the mechanisms involved in this effect are still poorly understood. Thus, this study investigated the impact of aerobic training on the relationship between platelet-activating factor (PAF) circulating levels and blood pressure in hypertensives. Seventy-seven hypertensive subjects were enrolled in this randomized controlled trial (age 66.51 ± 7.53 years, body mass 76.17 ± 14.19 kg). Participants were randomized to two groups: the intervention group (IG, n = 36), composed of hypertensive individuals submitted to an aerobic training protocol, and the control group (CG, n = 41), composed of non-exercised hypertensives. Body mass index, arterial blood pressure, quality of life, respiratory muscle strength, and functional capacity were assessed before and after 12 weeks. PAF and plasma cytokine levels were also evaluated respectively by liquid chromatography coupled with mass spectrometry and enzyme-linked immunosorbent assay. Aerobic training promoted a significant reduction in blood pressure while functional capacity, expiratory muscle strength, and quality of life, PAFC16:0 and PAFC18:1 plasma levels were increased in comparison to the CG (p < 0.05). In addition, multiple correlation analysis indicated a positive correlation [F (3.19) = 6.322; p = 0.001; R2adjusted = 0.499] between PAFC16:0 levels and expiratory muscle strength after aerobic training. Taken together, our findings indicate that PAF may be involved in the indirect mechanisms that control SAH, being mainly associated with increased respiratory muscle strength in hypertensive subjects undergoing aerobic training.

12.
Article in English | MEDLINE | ID: mdl-38501552

ABSTRACT

Accessible Summary What is known on the subject? Functioning is one of the most affected areas in schizophrenia. Social, occupational and personal domains are affected, and these deficits are responsible for a major part of the disability associated with the disorder. There are several instruments to measure functioning, but the HoNOS provides a wide assessment of impairment in 12 areas of functioning. What does the paper add to existing knowledge? The Spanish version of the HoNOS shows good properties in terms of reliability and validity for use in schizophrenia patients. Although some authors divide the scale according to proposed underlying dimensions, in schizophrenia this division may not be appropriate. What are the implications for practice? A reliable and easy-to-use measure of impairment in different areas of functioning is useful for optimizing the treatment and rehabilitation of patients with schizophrenia. ABSTRACT: INTRODUCTION: The HoNOS scale was designed for the assessment of psychosocial impairment in various domains. While it is widely used in psychiatric settings, it has not been validated in Spanish for use in patients with schizophrenia. AIM: To examine the psychometric properties of the Spanish version of the HoNOS scale in a sample of schizophrenia patients. METHOD: A total of 194 individuals aged 18 to 65 with schizophrenia spectrum diagnoses were evaluated using the HoNOS. Illness severity and level of functioning were also assessed. RESULTS: The HoNOS showed moderate internal consistency, good inter-observer reliability and good test-retest reliability. Factor analysis revealed an internal structure consisting of four factors, with item distribution differing from the theoretical dimensions proposed for the original scale. DISCUSSION: The Spanish version of the HoNOS scale is a reliable and valid instrument for assessing psychosocial impairment in individuals diagnosed with schizophrenia spectrum disorders. However, further research is needed to determine its internal structure more accurately. IMPLICATIONS FOR PRACTICE: The HoNOS scale provides researchers and clinicians with a valid measure of impairment in twelve different domains, which can facilitate and guide the treatment of schizophrenia patients.

13.
BJUI Compass ; 5(3): 345-355, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38481669

ABSTRACT

Background: Foley catheters have been subject to limited development in the last few decades. They fulfil their basic function of draining urine from the bladder but cause other associated problems. T-Control is a new silicone Foley catheter with an integrated fluid control valve whose design aims to reduce the risks associated with bladder catheterization by a multifactorial approach. The general purpose of this study is to determine the effectiveness, comfort, and experience of the patient catheterized with T-Control® compared with patients with a conventional Foley catheter. Study Design: This trial is a mixed-method study comprising a two-arm, pilot comparative study with random allocation to T-Control catheter or traditional Foley catheter in patients with long-term catheterization and a study with qualitative methodology, through discussion groups. Endpoints: The comfort and acceptability of the T-Control® device (qualitative) and the quality of life related to self-perceived health (quantitative) will be analysed as primary endpoints. As secondary endpoints, the following will be analysed: magnitude and rate of infections (symptomatic and asymptomatic); days free of infection; indication of associated antibiotic treatments; determination of biofilm; number of catheter-related adverse events; use of each type of catheterization's healthcare resources; and level of satisfaction and workload of health professionals. Patients and Methods: Eligible patients are male and female adults aged ≥18 years, who require a change of long-term bladder catheter. The estimated sample size is 50 patients. Patient follow-up includes both the time of catheter insertion and its removal or change 4 weeks later, plus the time until the discussion groups take place.

14.
Nat Prod Res ; : 1-9, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38425178

ABSTRACT

Smilax fluminensis Steud. is distributed in Central and South America, commonly named as 'salsaparilha' or 'japicanga'. In the present work, the chemical composition was determined, antioxidant and cytotoxic effects were evaluated for the ethanol extract (EE) and fractions from leaves. Fatty acid esters and phytol were characterised in the hexane (HEX) fraction. O-glycosylated flavonols and flavones, caffeic acid derivatives, and steroidal saponins were annotated for EE, and dichloromethane (DCM), ethyl acetate (AC), and hydroethanol (HE) fractions. The samples contain flavonoids and phenolic compounds, and the AC fraction displayed the biggest concentration of these substances. Antioxidant potential was observed in all samples, being especially pronounced in the AC fraction by DPPH and FRAP assays, with IC50 values of 8.18 and 2.35 µg/mL, respectively. AC and HEX fractions showed 35% and 5% lethality at 1000 µg/mL, in the Artemia salina assay, and the other samples did not show a toxic effect.

15.
Pathogens ; 13(3)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38535549

ABSTRACT

Daptomycin is one of the last therapeutic resources for multidrug-resistant gram-positive bacteria. Despite its structural similarities with glycopeptides, its mechanisms of action and resistance are different and in some respects are not completely understood. Mutations in several genes have been associated with daptomycin resistance, especially in mprF, walkR, rpoB and rpoC, but their role and importance remain to be elucidated. We have studied mutations in 11 genes, which have been previously associated with daptomycin non-susceptibility, in nine daptomycin-non-susceptible Staphylococcus aureus clinical isolates (daptomycin MIC: >1 mg/L). Susceptibility to daptomycin, vancomycin, linezolid, oxacillin, telavancin and dalbavancin was studied. walkR, agrA, cls1, cls2, fakA, pnpA, clpP, prs, rpoB, rpoC and mprF were amplified by PCR and sequenced. The sequences were compared with the S. aureus ATCC 25923 complete genome (GenBank gi: 685631213) by using BLAST® software. We did not find any changes in walkR, pnpA, prs and clpP. All isolates excepting isolate MSa5 showed a high number of significant mutations (between 13 and 25 amino acid changes) in mprF. Most isolates also showed mutations in the rpo genes, the cls genes and fakA. Daptomycin non-susceptibility in S. aureus clinical isolates seems to be reached through different mutation combinations when compared to S. aureus ATCC 25293. Especially mprF and cls1 showed very high polymorphism in most isolates. Meanwhile, one isolate, MSa5, showed only single mutation in mprF (P314T).

16.
Arch. argent. pediatr ; 122(1): e202302992, feb. 2024. tab
Article in English, Spanish | LILACS, BINACIS | ID: biblio-1525290

ABSTRACT

La resistencia a los antirretrovirales (ARV) es un problema de salud pública. Con el uso de inhibidores de la integrasa (INSTI) en pediatría, también comienzan a aparecer resistencias. El objetivo de esta comunicación es describir 3 casos con resistencia a los INSTI. Se describen 3 pacientes pediátricos con transmisión vertical del virus de la inmunodeficiencia humana (VIH). Iniciaron ARV de lactantes y preescolares, con mala adherencia al tratamiento, cursaron con diferentes planes secundarios a comorbilidades asociadas y fallas virológicas por resistencia. Los 3 casos clínicos describen la rápida aparición de resistencia frente a la falla virológica y el compromiso de los INSTI. La adherencia debe ser supervisada para detectar precozmente el aumento de la viremia. La falla virológica en un paciente tratado con raltegravir obliga a un rápido cambio de esquema ARV, ya que continuar utilizándolo podría favorecer nuevas mutaciones y resistencia a los INSTI de segunda generación.


Antiretroviral (ARV) drug resistance is a public health issue. Resistance has also been observed in the case of integrase strand transfer inhibitors (INSTIs) used in pediatrics. The objective of this article is to describe 3 cases of INSTI resistance. These are the cases of 3 children with vertically-transmitted human immunodeficiency virus (HIV). They were started on ARVs as infants and preschoolers, with poor treatment adherence, and had different management plans due to associated comorbidities and virological failure due to resistance. In the 3 cases, resistance developed rapidly as a result of virological failure and INSTI involvement. Treatment adherence should be monitored so that any increase in viremia can be detected early. Virological failure in a patient treated with raltegravir forces to a rapid change in ARV therapy because its continued use may favor new mutations and resistance to second-generation INSTIs.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , HIV Infections/drug therapy , HIV-1/genetics , HIV Integrase Inhibitors/therapeutic use , HIV Integrase Inhibitors/pharmacology , Anti-HIV Agents/therapeutic use , Uruguay , Raltegravir Potassium/therapeutic use , Raltegravir Potassium/pharmacology , Mutation
17.
J Pediatr Gastroenterol Nutr ; 78(4): 836-845, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38344848

ABSTRACT

OBJECTIVE: Analyze fecal and blood samples at point of diagnosis in IgE mediated cow's milk protein allergy (CMPA) and non-IgE mediated (NIM)-CMPA patients to look for potential new biomarkers. PATIENTS AND METHODS: Fourteen patients with IgE mediated CMPA and 13 with NIM-CMPA were recruited in three hospitals in the north of Spain, and were compared with 25 infants from a control group of the same age range. To characterize intestinal microbiota, 16S rDNA gene and internal transcribed spacer amplicons of bifidobacteria were sequenced with Illumina technology. Fatty acids were analyzed by gas chromatography, meanwhile intestinal inflammation markers were quantified by enzyme-linked immunosorbent assay and a multiplex system. Immunological analysis of blood was performed by flow cytometry. RESULTS: The fecal results obtained in the NIM-CMPA group stand out. Among them, a significant reduction in the abundance of Bifidobacteriaceae and Bifidobacterium sequences with respect to controls was observed. Bifidobacterial species were also different, highlighting the lower abundance of Bifidobacterium breve sequences. Fecal calprotectin levels were found to be significantly elevated in relation to IgE mediated patients. Also, a higher excretion of IL-10 and a lower excretion of IL-1ra and platelet derived growth factor-BB was found in NIM-CMPA patients. CONCLUSIONS: The differential fecal parameters found in NIM-CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins.


Subject(s)
Food Hypersensitivity , Gastrointestinal Microbiome , Milk Hypersensitivity , Infant , Female , Animals , Humans , Cattle , Immunoglobulin E , Milk Hypersensitivity/diagnosis , Milk Proteins
18.
Rev Soc Bras Med Trop ; 57: e007022024, 2024.
Article in English | MEDLINE | ID: mdl-38359311

ABSTRACT

BACKGROUND: Syphilis is associated with social and behavioral factors. METHODS: This cross-sectional study determined the prevalence of syphilis and its associated risk factors among recyclable waste collectors in Central Brazil. RESULTS: A lifetime syphilis prevalence rate of 7.91% (95% confidence interval: 5.25-11.75) was found among 278 participants. Low educational level, history of sexually transmitted infection, and age ≥ 36 years were associated with a high prevalence of lifetime syphilis. CONCLUSIONS: These findings emphasize the need for syphilis prevention, screening, and treatment among recyclable waste collectors, highlighting the potential for the spread of infection in vulnerable populations.


Subject(s)
HIV Infections , Syphilis , Humans , Adult , Syphilis/epidemiology , Brazil/epidemiology , Prevalence , Cross-Sectional Studies , Risk Factors , HIV Infections/epidemiology
19.
Eur J Cancer ; 201: 113920, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38368741

ABSTRACT

INTRODUCTION: We have previously found that HER2 expression is dynamic, and can change from the primary breast tumor to matched recurrences. With this work, we aimed to assess the dynamics of HER2 during neoadjuvant treatment.(NAT). METHODS: We reviewed HER2 expression in pre- and post-treatment samples from consecutive patients with early-stage breast cancer that received NAT and underwent surgery at Dana-Farber Brigham Cancer Center between 01/2016-08/2022. The primary outcome was evolution of HER2 expression from pre- to post-NAT specimens in patients with residual disease. RESULTS: Among 1613 patients receiving NAT, 1080 had residual disease at surgery. A total of 319 patients (29.5%) experienced a change in HER2 expression (HER2 0 vs. HER2-low vs. HER2-positive) from the pre-treatment sample to residual disease, with roughly equal distribution between decreased (50.5%) and increased HER2 expression (49.5%). Similar rates of change in HER2 expression were observed with anthracycline-based (31.8%) or taxane/platinum-based regimens (32.4%). Patients with HER2-0 or HER2-low tumors at diagnosis were likelier to experience a change in HER2 expression post-NAT compared to HER2-positive (32.3% vs. 21.3%, p < 0.001). Changes in HER2 expression post-NAT were prognostic among patients with HER2-positive tumors at diagnosis (3-year recurrence-free survival for change vs. no change: 71.6% vs. 89.6%, p = 0.006) but not among those with HER2-negative tumors at diagnosis (3-year recurrence-free survival for change vs. no change: 79.3% vs. 81.1%, p = 0.31). CONCLUSIONS: Nearly 30% of patients with early-stage breast cancer showed a change in HER2 expression after NAT. Changes in HER2 expression post-NAT were only prognostic in the setting of HER2-positive tumors becoming HER2-negative at surgery.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Breast Neoplasms/metabolism , Neoadjuvant Therapy , Receptor, ErbB-2/metabolism , Prognosis , Biopsy , Antineoplastic Combined Chemotherapy Protocols/adverse effects
20.
Zebrafish ; 2024 Feb 20.
Article in English | MEDLINE | ID: mdl-38386543

ABSTRACT

In fish species, heterochromatinization is one process that could trigger sex chromosome differentiation. The present article describes a nascent XX/XY sex chromosome system evidenced by heterochromatin accumulation and microsatellite (GATA)8 in Hypostomus albopunctatus from two populations of the Paraná River basin. The specimens of H. albopunctatus from the Campo and Bossi Rivers share the same karyotype. The species exhibits 74 chromosomes (8m+14sm +16st +36a, fundamental number = 112). The C-banding technique suggests male heterogamety in H. albopunctatus, where the Y-chromosome is morphologically like the X-chromosome but differs from it for having long arms that are entirely heterochromatic. Double fluorescence in situ hybridization (FISH) with 18S and 5S rDNA probes confirmed the Ag-nucleolus organizer region sites in a single pair for both populations, and minor rDNA clusters showed interpopulational variation. FISH with the microsatellite (GATA)8 probe showed a dispersed pattern in the karyotype, accumulating these sequences of sex chromosomes of both populations. FISH with microsatellite (CGC)10 probe showed interpopulational variation. The absence of differentiated sex chromosomes in H. albopunctatus is described previously, and a new variant is documented herein where XY chromosomes can be seen in an early stage of differentiation.

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