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1.
J Vasc Surg Cases Innov Tech ; 10(4): 101525, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38966820

RESUMO

Dysphagia lusoria occurs due to compression of the esophagus as an aberrant right subclavian artery (ARSA) crosses the mediastinum. Surgical management includes open, hybrid, and endovascular techniques, with no consensus gold standard. There are few reports of robotic-assisted ARSA resection. We describe the innovative technique and outcomes for two patients who successfully underwent robotic-assisted transthoracic resection of an ARSA after right carotid-subclavian bypass for dysphagia lusoria. Both patients experienced improvement or resolution of their dysphagia and no major complications. In select patients with a noncalcified origin of the ARSA without aneurysmal degeneration, the robotic-assisted approach represents a viable option.

2.
Clin Lung Cancer ; 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38879395

RESUMO

INTRODUCTION: Lung cancer resection has largely focused on perioperative outcomes (eg, mortality) to benchmark performance. While variations in perioperative outcomes and in utilization of services (eg, ambulatory procedures, hospitalization) have been independently demonstrated, there has been limited evaluation of associations between these outcomes. We evaluated the association between perioperative outcomes and utilization of services to evaluate provider performance across a broader context of care. PATIENTS AND METHODS: This was a retrospective cohort study of patients undergoing lung cancer resection in 2017 to 2019. We utilized hierarchical logistic regression models to determine risk- and reliability-adjusted mortality and risk-adjusted utilization of services, at the hospital-level. We then evaluated utilization of services across quartiles of perioperative mortality. RESULTS: A total of 15,168 patients across 297 hospitals underwent lung cancer resection. Mean risk- and reliability-adjusted 90-day mortality varied between 1.58% (95% CI, 1.54%-1.62%) and 2.74% (95% CI, 2.59%-2.90%) across quartiles. Risk-adjusted utilization of all ambulatory procedures was highest in the best performing (lowest mortality) quartile at 37.7% (95% CI, 33.6%-41.8%). Additionally, risk-adjusted inpatient utilization prior to and after surgery was lowest in the best performing quartile at 15% (95% CI, 13.7%-16.3%) and 19.3% (95% CI, 17.5%-21.0%), respectively. CONCLUSIONS: Hospitals with the lowest perioperative mortality demonstrated trends towards using more outpatient resources prior to surgery, but fewer inpatient services surrounding lung cancer resection. This correlation highlights the importance of incorporating utilization of services in addition to other metrics to profile the efficiency and effectiveness of centers performing lung cancer resection across a broader spectrum of care.

4.
Ann Thorac Surg ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38815847

RESUMO

BACKGROUND: We aimed to investigate the incidence of extrapulmonary findings identified on low-dose computed tomography (CT) that may warrant evaluation by cardiothoracic surgeons and describe their management and referral patterns at our institution. METHODS: We conducted a retrospective cohort study of patients who underwent low-dose CT through a centralized Lung Cancer Screening Program at Thomas Jefferson University Hospital between January 2018 and December 2022. An electronic medical record review was performed for patients with incidental findings. Demographic, workup, referral, and management data were collected. RESULTS: Of 2285 patients who underwent low-dose CT, 368 (16%) had an extrapulmonary finding that may have an indication for clinical evaluation by a cardiothoracic surgeon. The most common incidental finding was a hiatal hernia, with a prevalence of 6.3% (144 of 2285), followed by ascending thoracic aneurysms, with a prevalence of 3.6% (82 of 2285), and small pericardial effusions, with a prevalence of 1.2% (28 of 2285). Of the patients with symptomatic hiatal hernias, 29% (14 of 48) were referred to a cardiothoracic surgeon compared with only 6.25% (6 of 96) in the asymptomatic group. Of the patients with thoracic aneurysms, 48% (39 of 82) had aneurysms ≥4.2 cm. Of the ≥4.2 cm group, 18% (7 of 39) were monitored by a cardiothoracic surgeon compared with 11.6% (5 of 43) in patients with aneurysms <4.2 cm. CONCLUSIONS: Hiatal hernias and ascending thoracic aneurysms were the 2 most prevalent incidental findings identified on low-dose CT during lung cancer screening. We demonstrated potential gaps in hiatal hernia referral patterns. Referring patients with thoracic aneurysms to cardiothoracic surgeons may not be initially warranted.

5.
Euro Surveill ; 29(16)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639093

RESUMO

BackgroundMpox, caused by monkeypox virus (MPXV), was considered a rare zoonotic disease before May 2022, when a global epidemic of cases in non-endemic countries led to the declaration of a Public Health Emergency of International Concern. Cases of mpox in Ireland, a country without previous mpox reports, could reflect extended local transmission or multiple epidemiological introductions.AimTo elucidate the origins and molecular characteristics of MPXV circulating in Ireland between May 2022 and October 2023.MethodsWhole genome sequencing of MPXV from 75% of all Irish mpox cases (182/242) was performed and compared to sequences retrieved from public databases (n = 3,362). Bayesian approaches were used to infer divergence time between sequences from different subclades and evaluate putative importation events from other countries.ResultsOf 242 detected mpox cases, 99% were males (median age: 35 years; range: 15-60). All 182 analysed genomes were assigned to Clade IIb and, presence of 12 distinguishable subclades suggests multiple introductions into Ireland. Estimation of time to divergence of subclades further supports the hypothesis for multiple importation events from numerous countries, indicative of extended and sustained international spread of mpox. Further analysis of sequences revealed that 92% of nucleotide mutations were from cytosine to thymine (or from guanine to adenine), leading to a high number of non-synonymous mutations across subclades; mutations associated with tecovirimat resistance were not observed.ConclusionWe provide insights into the international transmission dynamics supporting multiple introductions of MPXV into Ireland. Such information supported the implementation of evidence-informed public health control measures.


Assuntos
Monkeypox virus , Mpox , Masculino , Humanos , Adulto , Feminino , Irlanda/epidemiologia , Monkeypox virus/genética , Teorema de Bayes , Mpox/diagnóstico , Mpox/epidemiologia , Surtos de Doenças
6.
J Gastrointest Surg ; 28(7): 1027-1032, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38593866

RESUMO

BACKGROUND: Peripancreatic fluid collections after distal pancreatectomy and splenectomy are commonly identified on postoperative cross-sectional imaging. This study aimed to determine the incidence, natural history, and indications for intervention. METHODS: We conducted a retrospective review of patients with peripancreatic fluid collections after distal pancreatectomy with or without splenectomy between 2013 and 2018, approved by our institutional review board. The chi-square test was used for categorical variables, the Mann-Whitney U test for continuous variables, and Fisher's exact test was used for values in which the sample size was less than 5 to compare data. RESULTS: During the study period, 235 patients underwent distal pancreatectomy with or without splenectomy, and 182 patients with postoperative imaging were included. In the cohort of patients with postoperative imaging, 83 (46%) had peripancreatic fluid collections, of which 46 (55%) were symptomatic fluid collections (SFCs) and 37 (45%) were asymptomatic fluid collections (AFCs). Those with SFC had a higher incidence of postoperative morbidity (46% vs 8%; P = .0002), most commonly postoperative pancreatic fistula (90%). Of patients with SFC, 34 (74%) underwent treatment via percutaneous drainage (n = 26), endoscopic drainage (n = 7), or antibiotics alone (n = 1). AFCs (n = 37) were observed. Collections that were intervened upon resolved significantly faster than those observed, 3.5 months vs 13.2 months (P < .0001), respectively. CONCLUSION: Asymptomatic patients may be observed with or without serial imaging and the AFC will typically resolve spontaneously with time. Patients who develop symptoms should generally be intervened upon with drainage if deemed feasible, given that this reduces the time to resolution.


Assuntos
Drenagem , Pancreatectomia , Fístula Pancreática , Complicações Pós-Operatórias , Esplenectomia , Humanos , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Esplenectomia/métodos , Esplenectomia/efeitos adversos , Estudos Retrospectivos , Feminino , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Drenagem/métodos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Idoso , Adulto , Incidência
8.
Atherosclerosis ; 391: 117492, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38461759

RESUMO

BACKGROUND AND AIMS: Obesity increases the risk for abdominal aortic aneurysms (AAA) in humans and enhances angiotensin II (AngII)-induced AAA formation in C57BL/6 mice. We reported that deficiency of Serum Amyloid A (SAA) significantly reduces AngII-induced inflammation and AAA in both hyperlipidemic apoE-deficient and obese C57BL/6 mice. The aim of this study is to investigate whether SAA plays a role in the progression of early AAA in obese C57BL/6 mice. METHODS: Male C57BL/6J mice were fed a high-fat diet (60% kcal as fat) throughout the study. After 4 months of diet, the mice were infused with AngII until the end of the study. Mice with at least a 25% increase in the luminal diameter of the abdominal aorta after 4 weeks of AngII infusion were stratified into 2 groups. The first group received a control antisense oligonucleotide (Ctr ASO), and the second group received ASO that suppresses SAA (SAA-ASO) until the end of the study. RESULTS: Plasma SAA levels were significantly reduced by the SAA ASO treatment. While mice that received the control ASO had continued aortic dilation throughout the AngII infusion periods, the mice that received SAA-ASO had a significant reduction in the progression of aortic dilation, which was associated with significant reductions in matrix metalloprotease activities, decreased macrophage infiltration and decreased elastin breaks in the abdominal aortas. CONCLUSIONS: We demonstrate for the first time that suppression of SAA protects obese C57BL/6 mice from the progression of AngII-induced AAA. Suppression of SAA may be a therapeutic approach to limit AAA progression.


Assuntos
Angiotensina II , Aneurisma da Aorta Abdominal , Humanos , Masculino , Animais , Camundongos , Angiotensina II/farmacologia , Proteína Amiloide A Sérica/genética , Oligonucleotídeos Antissenso/uso terapêutico , Camundongos Endogâmicos C57BL , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/prevenção & controle , Aorta Abdominal , Obesidade , Modelos Animais de Doenças , Camundongos Knockout , Apolipoproteínas E
9.
Influenza Other Respir Viruses ; 18(2): e13225, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38322196

RESUMO

The Eastern Mediterranean Region (EMR) faces ongoing challenges in its public health system due to limited resources, logistical issues, and political disruptions. The COVID-19 pandemic accelerated the need for stronger laboratory capacities to handle the increased demand for testing. In a phased response, EMR countries utilized the National Influenza Centers to rapidly establish and scale molecular testing for SARS-CoV-2, the causative agent of COVID-19. The expansion of capacity included strong collaborations between public health bodies and private and academic sectors to decentralize and expand testing to the subnational level. To ensure that the quality of testing was not impacted by rapid expansion, national and subnational laboratories were enrolled in external quality assurance programs for the duration of the response. Implementation of genomic surveillance was prioritized for variant tracking, leading to the establishment of regional sequencing reference laboratories and the distribution of MinION sequencing platforms to complex emergency countries who previously had limited experience with pathogen sequencing. Challenges included a lack of technical expertise, including in implementing novel diagnostic assays and sequencing, a lack of bioinformatics expertise in the region, and significant logistical and procurement challenges. The collaborative approach, coordinated through the WHO Eastern Mediterranean Regional Office, enabled all 22 countries to achieve SARS-CoV-2 diagnostic capabilities, highlighting the pivotal role of laboratories in global health security.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Laboratórios , Pandemias , Região do Mediterrâneo/epidemiologia
10.
Int J Mol Sci ; 24(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38139330

RESUMO

Serum amyloid A (SAA) is a family of proteins, the plasma levels of which may increase >1000-fold in acute inflammatory states. We investigated the role of SAA in sepsis using mice deficient in all three acute-phase SAA isoforms (SAA-TKO). SAA deficiency significantly increased mortality rates in the three experimental sepsis mouse models: cecal ligation and puncture (CLP), cecal slurry (CS) injection, and lipopolysaccharide (LPS) treatments. SAA-TKO mice had exacerbated lung pathology compared to wild-type (WT) mice after CLP. A bulk RNA sequencing performed on lung tissues excised 24 h after CLP indicated significant enrichment in the expression of genes associated with chemokine production, chemokine and cytokine-mediated signaling, neutrophil chemotaxis, and neutrophil migration in SAA-TKO compared to WT mice. Consistently, myeloperoxidase activity and neutrophil counts were significantly increased in the lungs of septic SAA-TKO mice compared to WT mice. The in vitro treatment of HL-60, neutrophil-like cells, with SAA or SAA bound to a high-density lipoprotein (SAA-HDL), significantly decreased cellular transmigration through laminin-coated membranes compared to untreated cells. Thus, SAA potentially prevents neutrophil transmigration into injured lungs, thus reducing exacerbated tissue injury and mortality. In conclusion, we demonstrate for the first time that endogenous SAA plays a protective role in sepsis, including ameliorating lung injury.


Assuntos
Lesão Pulmonar , Sepse , Animais , Camundongos , Lesão Pulmonar/patologia , Proteína Amiloide A Sérica/genética , Sepse/patologia , Pulmão/patologia , Quimiocinas , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças
11.
Influenza Other Respir Viruses ; 17(12): e13233, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38098648

RESUMO

Introduction: Severe acute respiratory illness (SARI) is a potentially lethal condition, necessitating thorough medical care. COVID-19 underscored the SARI threat, but other high-risk pathogens require monitoring alongside SARS-CoV-2. Oman instituted a comprehensive testing system to gauge the prevalence of these pathogens between 2017 and 2021, aiding resource allocation and public health responses to potential respiratory pathogen outbreaks. Methods: Samples from SARI cases admitted to ICU were tested for pathogens using the Fast-Track Diagnostic (FTD) molecular assay, a respiratory virus panel (RVP) that tests for 21 pathogens, including 20 viruses, by qPCR. Results: Between 2017 and 2022, ~30 000 samples were analysed using the RVP panel. Among SARI patients, 8%-42% tested positive for respiratory pathogens, with 4% showing multiple infectious agents, especially in children under 10. A drop in positivity during 2020-2021 can be attributed to SARS-CoV-2 control measures, followed by a rebound in infections in early 2022. Discussion: The COVID-19 pandemic heightened awareness of respiratory pathogens' spread without adequate control measures. Influenza A/B, human rhinoviruses and respiratory syncytial virus constituted over 50% of severe acute respiratory illness cases in Oman over the past 5 years. During the pandemic, the incidence of these infections significantly declined, demonstrating the efficacy of COVID-19 prevention measures in reducing spread of other pathogens.


Assuntos
COVID-19 , Influenza Humana , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Vírus , Criança , Humanos , COVID-19/epidemiologia , Pandemias , Omã/epidemiologia , Infecções Respiratórias/epidemiologia , SARS-CoV-2 , Vírus/genética , Influenza Humana/epidemiologia
12.
Influenza Other Respir Viruses ; 17(11): e13210, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37964989

RESUMO

Background: Afghanistan experienced various outbreaks before and during the Covid-19 pandemic, including dengue, Crimean Congo hemorrhagic fever (CCHF), measles, and acute watery diarrhea (AWD). Diagnostic and surveillance support was limited, with only the Central Public Health Laboratory equipped to handle outbreak responses. This article highlights initiatives taken to improve diagnostic capabilities for COVID-19 and other outbreaks of public health concern encountered during the pandemic. Background: The World Health Organization (WHO) Afghanistan Country Office collaborated with the WHO Eastern Mediterranean Regional Office (EMRO), Central Public Health Laboratory (CPHL), and National Influenza Center (NIC) to enhance COVID-19 diagnostic capacity at national and subnational facilities. To alleviate pressure on CPHL, a state-of-the-art laboratory was established at the National Infectious Disease Hospital (NIDH) in Kabul in 2021-2022, while WHO EMRO facilitated the regionalization of testing to subnational facilities for dengue, CCHF, and AWD in 2022-2023. Results: COVID-19 testing capacity expanded nationwide to 34 Biosafety Level II labs, improving diagnosis time. Daily testing rose from 1000 in 2020 to 9200 in 2023, with 848,799 cumulative tests. NIDH identified 229 CCHF cases and 45 cases nationally. Dengue and CCHF testing, decentralized to Nangarhar and Kandahar labs, identified 338 dengue and 18 CCHF cases. AWD testing shifted to NIDH and five subnational facilities (Kandahar, Paktia, Balkh, Herat, and Nangarhar labs), while measles testing also decentralized to nine subnational facilities. Conclusion: Afghanistan implemented a remarkable, multisectoral response to priority pathogens. The nation now possesses diagnostic expertise at national and subnational levels, supported by genomic surveillance. Future efforts should concentrate on expanding and sustaining this capacity to enhance public health responses.


Assuntos
COVID-19 , Doenças Transmissíveis Emergentes , Dengue , Vírus da Febre Hemorrágica da Crimeia-Congo , Febre Hemorrágica da Crimeia , Sarampo , Humanos , Febre Hemorrágica da Crimeia/diagnóstico , Febre Hemorrágica da Crimeia/epidemiologia , Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Doenças Transmissíveis Emergentes/epidemiologia , Afeganistão/epidemiologia , Teste para COVID-19 , Patologia Molecular , Pandemias , COVID-19/diagnóstico , COVID-19/epidemiologia , Sarampo/diagnóstico , Sarampo/epidemiologia , Sarampo/prevenção & controle , Dengue/epidemiologia
13.
Influenza Other Respir Viruses ; 17(11): e13217, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38019698

RESUMO

INTRODUCTION: The COVID-19 pandemic placed unprecedented stress on laboratories in the Eastern Mediterranean Region. Building on existing capacity for influenza diagnostics, countries introduced COVID-19 diagnostic support to ~100% regional coverage. A key challenge during the expansion was maintaining quality testing in laboratories, ensuring that correct results were shared with medical facilities. METHODS: WHO organized two rounds of independently monitored severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) external quality assurance programs (EQAP). The Public Health Laboratory (PHL) division of WHO supplied external quality assurance (EQA) panels, from the Royal College of Pathologists of Australasia Quality Assurance Programme (RCPAQAP) Australia to laboratories not enrolled in recurring Global Influenza Surveillance and Response System (GISRS) quality assurance programs, in which national influenza centers routinely participate. RESULTS: Fifteen and 14 countries participated in PHL/EQAP for SARS-CoV-2 between 2020 and 2022. Concordance was consistent between rounds, reaching 96.4% and 89.9%. A separate assessment of GISRS/EQAP to national-level laboratories identified high levels of response and concordance for SARS-CoV-2 (100% response, 93% concordance), which was reduced for influenza (50% response rate, 80% concordance), reflecting the challenge of prioritizing pathogens during outbreaks. CONCLUSION: The proliferation of laboratories in response to COVID-19 was a success story from the pandemic. However, monitoring the quality of laboratories was challenging via existing EQAP. The addition of PHL/EQAP provided a mechanism to monitor performance of laboratories that were not designated as national influenza centers. While a high proportion of laboratories attained good results, continual emphasis on quality and enrollment in EQAP is key to ensuring sustainability of laboratory testing in future.


Assuntos
COVID-19 , Influenza Humana , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Laboratórios , Pandemias , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Patologia Molecular , Região do Mediterrâneo/epidemiologia , Teste para COVID-19
14.
Influenza Other Respir Viruses ; 17(10): e13205, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37859974

RESUMO

The COVID-19 pandemic highlighted the critical role of pathogen sequencing in making informed public health decisions. Initially, the Eastern Mediterranean Region faced limitations in sequencing capacity. However, with robust WHO and stakeholder support, the situation significantly improved. By 2022, COVID-19 sequencing was underway in 22 out of 23 regional countries, with varying throughput and capacity. Notably, three genomic hubs were established in Oman, UAE, and Morocco, playing a key role in providing expanded genomics training and support across the region. While primarily for COVID-19 surveillance, this sequencing capacity offers an opportunity to integrate genomic surveillance into existing networks. This integration can enable early detection and response to high-threat pathogens with pandemic potential. To advance this, WHO/EMRO collaborated with stakeholders to formulate the Eastern Mediterranean Regional Genomic Surveillance Strategy for Emerging Pathogens of Pandemic Concern. Consultative meetings with regional and international genomic surveillance experts identified strategy focal points, key partners, priority pathogens, and implementation steps. As the strategy awaits member states' ratification in Q4 2023, this manuscript outlines pivotal facets defined by member states and the strategic document's key deliverables and opportunities. These efforts aim to yield a substantial positive impact within the region.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Saúde Pública , Genômica , Região do Mediterrâneo/epidemiologia
15.
Influenza Other Respir Viruses ; 17(10): e13209, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37885370

RESUMO

INTRODUCTION: The global COVID-19 pandemic overwhelmed national public health and laboratory capacity in Jordan and globally. In response, Biolab, a private laboratory group with 27 branches across Jordan, assisted with testing. Biolab was equipped to quickly increase molecular testing capacity without compromising quality or turnaround time, allowing them to contribute to national COVID-19 surveillance efforts. METHODS: Biolab expanded testing in Jordan by operationalizing automated testing platforms at various locations, including 16 branches, 2 drive-through and 2 walk-through centres, and entry points for airports and marine passenger arrivals. Genomic and molecular testing were implemented to track variants. Information technology platforms were introduced for sample management, registration, and commercial sample payments. Data were directly provided to the Ministry of Health through these platforms to support public health decision-making and responses. Biolab prioritized staff well-being by providing mental, financial, and physical health support during the pandemic. RESULTS: Biolab processed more than two million samples, with a turnaround time of ~1.5 h. Results were transmitted directly to key stakeholders in near real time. Biolab conducted variant evaluations on >1.4 million samples using molecular variant testing and >1000 samples using whole genome sequencing. Biolab prioritized staff well-being, improving staff satisfaction from 74% to 91%, a remarkable achievement when many laboratory systems experienced staff burnout and dissatisfaction. CONCLUSION: The collaboration between public and private laboratories during COVID-19 established a model for future joint efforts to prevent outbreaks from becoming pandemics. Biolab's focus on efficiency, quality, and staff well-being enabled consistent, high-quality performance. The introduction of innovative information technology platforms ensured swift information dissemination. Biolab plans to continue investing in these platforms and expand pathogen testing, creating a top-tier testing infrastructure in Jordan with a demonstrated ability to cooperate with the government for public benefit.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Pandemias/prevenção & controle , Laboratórios , Jordânia/epidemiologia , Parcerias Público-Privadas
16.
bioRxiv ; 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37662383

RESUMO

OBJECTIVE: Obesity increases the risk for abdominal aortic aneurysms (AAA) in humans and enhances angiotensin II (AngII)-induced AAA formation in C57BL/6 mice. Obesity is also associated with increases in serum amyloid A (SAA). We previously reported that deficiency of SAA significantly reduces AngII-induced inflammation and AAA in both hyperlipidemic apoE-deficient and obese C57BL/6 mice. In this study, we investigated whether SAA plays a role in the progression of early AAA in obese C57BL/6 mice. APPROACH AND RESULTS: Male C57BL/6J mice were fed a high-fat diet (60% kcal as fat) throughout the study. After 4 months of diet, the mice were infused with angiotensin II (AngII) until the end of the study. Mice with at least a 25% increase in the luminal diameter of the abdominal aorta after 4 weeks of AngII infusion were stratified into 2 groups. The first group received a control antisense oligonucleotide (Ctr ASO), and the second group received ASO that suppresses SAA (SAA-ASO) until the end of the study. Plasma SAA levels were significantly reduced by the SAA ASO treatment. While mice that received the control ASO had continued aortic dilation throughout the AngII infusion periods, the mice that received SAA-ASO had a significant reduction in the progression of aortic dilation, which was associated with significant reductions in matrix metalloprotease activities, decreased macrophage infiltration and decreased elastin breaks in the abdominal aortas. CONCLUSION: We demonstrate for the first time that suppression of SAA protects obese C57BL/6 mice from the progression of AngII-induced AAA. Suppression of SAA may be a therapeutic approach to limit AAA progression.

17.
BMC Infect Dis ; 23(1): 446, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37400776

RESUMO

BACKGROUND: Due to practical challenges associated with genetic sequencing in low-resource environments, the burden of hepatitis C virus (HCV) in forcibly displaced people is understudied. We examined the use of field applicable HCV sequencing methods and phylogenetic analysis to determine HCV transmission dynamics in internally displaced people who inject drugs (IDPWID) in Ukraine. METHODS: In this cross-sectional study, we used modified respondent-driven sampling to recruit IDPWID who were displaced to Odesa, Ukraine, before 2020. We generated partial and near full length genome (NFLG) HCV sequences using Oxford Nanopore Technology (ONT) MinION in a simulated field environment. Maximum likelihood and Bayesian methods were used to establish phylodynamic relationships. RESULTS: Between June and September 2020, we collected epidemiological data and whole blood samples from 164 IDPWID (PNAS Nexus.2023;2(3):pgad008). Rapid testing (Wondfo® One Step HCV; Wondfo® One Step HIV1/2) identified an anti-HCV seroprevalence of 67.7%, and 31.1% of participants tested positive for both anti-HCV and HIV. We generated 57 partial or NFLG HCV sequences and identified eight transmission clusters, of which at least two originated within a year and a half post-displacement. CONCLUSIONS: Locally generated genomic data and phylogenetic analysis in rapidly changing low-resource environments, such as those faced by forcibly displaced people, can help inform effective public health strategies. For example, evidence of HCV transmission clusters originating soon after displacement highlights the importance of implementing urgent preventive interventions in ongoing situations of forced displacement.


Assuntos
Infecções por HIV , Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Hepacivirus/genética , Ucrânia/epidemiologia , Estudos Transversais , Filogenia , Estudos Soroepidemiológicos , Teorema de Bayes , Infecções por HIV/complicações , Abuso de Substâncias por Via Intravenosa/complicações , Abuso de Substâncias por Via Intravenosa/epidemiologia , Prevalência
18.
Plast Surg (Oakv) ; 31(2): 132-137, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37188129

RESUMO

Introduction: The increasing prevalence of obesity in patients with breast cancer has prompted a reappraisal of the role of the latissimus dorsi flap (LDF) in breast reconstruction. Although the reliability of this flap in obese patients is well-documented, it is unclear whether sufficient volume can be achieved through a purely autologous reconstruction (eg, extended harvest of the subfascial fat layer). Additionally, the traditional combined autologous and prosthetic approach (LDF + expander/implant) is subject to increased implant-related complication rates related to flap thickness in obese patients. The purpose of this study is to provide data on the thicknesses of the various components of the latissimus flap and discuss the implications for breast reconstruction in patients with increasing body mass index (BMI). Methods: Measurements of back thickness in the usual donor site area of an LDF were obtained in 518 patients undergoing prone computed tomography-guided lung biopsies. Thicknesses of the soft tissue overall and of individual layers (e.g., muscle, subfascial fat) were obtained. Patient, demographics including age, gender, and BMI were obtained. Results: A range of BMI from 15.7 to 65.7 was observed. In females, total back thickness (skin, fat, muscle) ranged from 0.6 to 9.4 cm. Every 1-point increase in BMI resulted in an increase of flap thickness by 1.11 mm (adjusted R2 of 0.682, P < .001) and an increase in the thickness of the subfascial fat layer by 0.513 mm (adjusted R2 of 0.553, P < .001). Mean total thicknesses for each weight category were 1.0, 1.7, 2.4, 3.0, 3.6, and 4.5 cm in underweight, normal weight, overweight, and class I, II, III obese individuals, respectively. The average contribution of the subfascial fat layer to flap thickness was 8.2 mm (32%) overall and 3.4 mm (21%), 6.7 mm (29%), 9.0 mm (30%), 11.1 mm (32%), and 15.6 mm (35%) in normal weight, overweight, class I, II, III obese individuals, respectively. Conclusion: The above findings demonstrate that the thickness of the LDF overall and of the subfascial layer closely correlated with BMI. The contribution of the subfascial layer to overall flap thickness tends to increase as a percentage of overall flap thickness with increasing BMI, which is favourable for extended LDF harvests. Because this layer cannot be separated from overall thickness on examination, these results are useful in estimating the amount of additional volume obtained from an extended latissimus harvest technique.


Introduction: La prévalence croissante d'obésité chez les patientes atteintes du cancer du sein a suscité une réévaluation du rôle du lambeau du grand dorsal (LGD) en reconstruction mammaire. La fiabilité de ce lambeau est bien établie en cas d'obésité, mais on ne sait pas si le volume suffit pour effectuer une reconstruction purement autologue (p. ex., prélèvement élargi de la couche adipeuse sous-aponévrotique). De plus, en cas d'obésité, la combinaison habituelle de l'approche autologue et prothétique (LGD+expanseur et implant) est liée à un taux de complications plus élevé lié aux implants à cause de l'épaisseur du lambeau. La présente étude visait à obtenir des données sur l'épaisseur des diverses parties du grand dorsal et à traiter des conséquences de la reconstruction mammaire chez les patientes ayant un IMC plus élevé. Méthodologie: Les chercheurs ont mesuré l'épaisseur du dos au siège habituel de prélèvement du LGD chez 518 patientes dans le cadre d'une biopsie pulmonaire orientée par tomodensitométrie en position couchée. Ils ont mesuré l'épaisseur globale du dos et l'épaisseur de chaque couche dans cette région. Ils ont également obtenu les données démographiques des patientes, y compris l'âge, le genre et l'IMC. Résultats: Les chercheurs ont observé une fourchette d'IMC de 15,7 à 65,7. Chez les femmes, l'épaisseur totale du dos (peau, adiposité, muscle) variait entre 0,6 et 9,4 cm. Chaque point ajouté à l'IMC est associé à une augmentation de l'épaisseur du lambeau de 1,11 mm (rapport de cote rajusté [RCR] de 0,682, p<0,001) et à une augmentation de l'épaisseur de la couche adipeuse sous-aponévrotique de 0,513 mm (RCR de 0,553, p<0,001). L'épaisseur totale moyenne pour chaque catégorie de poids correspondait à 1,0, 1,7, 2,4, 3,0, 3,6 et 4, cm chez les patientes en insuffisance pondérale, de poids normal, en surpoids et obèses de classe I, II et III, respectivement. L'apport moyen de la couche adipeuse sous-aponévrotique à l'épaisseur du lambeau était de 8,2 mm (32 %) globalement et de 3,4 mm (21 %), 6,7 mm (29 %), 9,0 mm (30 %), 11,1 (32 %) et 15,6 mm (35 %) chez les patientes de poids normal, en surpoids et obèses de classe I, II, III, respectivement. Conclusion: Les résultats précédents démontrent que l'épaisseur globale du LGD et de la couche sous-aponévrotique est étroitement liée à l'IMC. L'apport de la couche sous-aponévrotique a tendance à être proportionnel à l'IMC en pourcentage de l'épaisseur globale du lambeau, ce qui est favorable à un prélèvement étendu du LGD. Puisque cette couche ne peut pas être séparée de l'épaisseur globale à l'examen, ces résultats sont utiles pour évaluer le volume supplémentaire obtenu à partir de la technique de prélèvement élargi du grand droit.

19.
Diagn Pathol ; 18(1): 45, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37041531

RESUMO

BACKGROUND: Malignant perivascular epithelioid cell tumors (PEComas) are exceedingly rare malignant mesenchymal neoplasms with characteristic morphological and immunohistochemical (IHC) patterns. However, some malignant PEComas are poorly differentiated with atypical histopathological features, making a definitive diagnosis difficult. PEComas are most commonly found in females and often show either TSC1 or TSC2 alterations, which result in the activation of the mTOR pathway, or TFE3 fusions. Given these molecular characteristics, mTOR inhibitors have recently been approved by the FDA in the treatment of malignant PEComas, particularly in those with TSC1/2 alterations. Therefore, molecular analyses may be helpful for both the diagnostic workup of and predicting response to mTOR inhibitors in cases of malignant PEComas. CASE PRESENTATION: Here, we report a case of an aggressive, 23 cm mesenteric malignant PEComa with multiple peritoneal metastases in a young male patient. Pathological examination of the initial biopsy showed a malignant epithelioid neoplasm with high-grade morphology and atypical immunoprofile, which precluded a definitive diagnosis. Because of the patient's excessive transfusion requirements due to intra-tumoral hemorrhage, a palliative R2 resection was performed. Histopathological examination of the tumor revealed focal immunoreactivity for Melan-A, HMB-45, desmin, and CD117. Although a diagnosis of malignant PEComa was favored, other entities such as epithelioid gastrointestinal stromal tumor (GIST) or melanoma could not be definitively ruled out. Given the favored diagnosis, the patient was started on sirolimus, an mTOR inhibitor, rather than chemotherapy. Molecular analyses were performed and the tumor was found to harbor mutations in TP53 and TSC2, supporting a definitive diagnosis of malignant PEComa. The patient was then switched to nab-sirolimus, with initial stabilization of the disease. CONCLUSIONS: This report details a multidisciplinary approach for the diagnosis and management of a highly aggressive, metastatic malignant PEComa in a young male patient. The basis for the treatment of malignant PEComas with the recently FDA-approved mTOR inhibitor, nab-sirolimus, is also reviewed. In summary, this case highlights the importance of molecular analysis, particularly TSC1/2 alterations, for both the definitive diagnosis of malignant PEComas and predicting their response to nab-sirolimus.


Assuntos
Neoplasias de Células Epitelioides Perivasculares , Sarcoma , Humanos , Masculino , Inibidores de MTOR , Mutação , Neoplasias de Células Epitelioides Perivasculares/tratamento farmacológico , Neoplasias de Células Epitelioides Perivasculares/metabolismo , Neoplasias de Células Epitelioides Perivasculares/patologia , Sirolimo/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo
20.
PNAS Nexus ; 2(3): pgad008, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36896134

RESUMO

Internally displaced persons are often excluded from HIV molecular epidemiology surveillance due to structural, behavioral, and social barriers in access to treatment. We test a field-based molecular epidemiology framework to study HIV transmission dynamics in a hard-to-reach and highly stigmatized group, internally displaced people who inject drugs (IDPWIDs). We inform the framework by Nanopore generated HIV pol sequences and IDPWID migration history. In June-September 2020, we recruited 164 IDPWID in Odesa, Ukraine, and obtained 34 HIV sequences from HIV-infected participants. We aligned them to publicly available sequences (N = 359) from Odesa and IDPWID regions of origin and identified 7 phylogenetic clusters with at least 1 IDPWID. Using times to the most recent common ancestors of the identified clusters and times of IDPWID relocation to Odesa, we infer potential post-displacement transmission window when infections likely to happen to be between 10 and 21 months, not exceeding 4 years. Phylogeographic analysis of the sequence data shows that local people in Odesa disproportionally transmit HIV to the IDPWID community. Rapid transmissions post-displacement in the IDPWID community might be associated with slow progression along the HIV continuum of care: only 63% of IDPWID were aware of their status, 40% of those were in antiviral treatment, and 43% of those were virally suppressed. Such HIV molecular epidemiology investigations are feasible in transient and hard-to-reach communities and can help indicate best times for HIV preventive interventions. Our findings highlight the need to rapidly integrate Ukrainian IDPWID into prevention and treatment services following the dramatic escalation of the war in 2022.

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