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BACKGROUND: Recent research identified that cancer bereavement can lead to post-traumatic growth (PTG). Although PTG and its correlates are well explored in cancer patients and survivors, persons bereaved from cancer have received scant attention. Therefore, the present review attempts to identify the correlates of PTG among persons bereaved from cancer. METHODS: A systematic search in PubMed, Web of Science, APA PsycNet, Science Direct, Scopus, and Wiley was conducted to identify quantitative studies published in English, resulting in 12 eligible reports being included in the final analysis. JBI critical checklists were employed to appraise the risk of bias. RESULTS: The review identified 17 correlates, which were classified into four categories: demographic factors (age, gender, religious status, level of education), loss-related factors (time since death, quality of death, prolonged grief symptoms), interpersonal factors (relationship to the deceased, social support, attachment style, bereavement behaviours) and intrapersonal factors (resilience, coping, rumination, benevolence, meaningfulness, self-worth). Random effects meta-analyses on six correlates revealed correlation coefficients of age = -0.02 (95% CI: -0.35-0.31), gender = 0.27 (95% CI: 0.08-0.45), time since death = 0.09 (95% CI: -0.02-0.20), quality of death = 0.29 (95% CI: -0.01-0.54), prolonged grief symptoms = 0.22 (95% CI: 0.08-0.35) and relationship to the deceased = 0.13 (95% CI: -0.03-0.29). Fixed effects meta-analysis was performed for social support (r = 0.13, 95% CI: 0.04-0.21). However, PTG was found to be significantly associated with gender, prolonged grief symptoms, and social support. CONCLUSIONS: Very few studies examined PTG among persons bereaved from cancer, highlighting the need for increased attention, understanding, and conceptualisation of PTG in the population.
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Luto , Neoplasias , Crescimento Psicológico Pós-Traumático , Apoio Social , Humanos , Neoplasias/psicologia , Adaptação Psicológica , Masculino , FemininoRESUMO
Hypoxia-Inducible Factor-1α (HIF-1α) has presented a new direction for ischemic preconditioning of surgical flaps to promote their survival. In a previous study, we demonstrated the effectiveness of HIF-1a DNA plasmids in this application. In this study, to avoid complications associated with plasmid use, we sought to express HIF-1α through mRNA transfection and determine its biological activity by measuring the upregulation of downstream angiogenic genes. We transfected six different HIF-1a mRNAs-one predominant, three variant, and two novel mutant isoforms-into primary human dermal fibroblasts using Lipofectamine, and assessed mRNA levels using RT-qPCR. At all time points examined after transfection (3, 6, and 10 h), the levels of HIF-1α transcript were significantly higher in all HIF-1α transfected cells relative to the control (all p < 0.05, unpaired Student's T-test). Importantly, the expression of HIF-1α transcription response genes (VEGF, ANG-1, PGF, FLT1, and EDN1) was significantly higher in the cells transfected with all isoforms than with the control at six and/or ten hours post-transfection. All isoforms were transfected successfully into human fibroblast cells, resulting in the rapid upregulation of all five downstream angiogenic targets tested. These findings support the potential use of HIF-1α mRNA for protecting ischemic dermal flaps.
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Subunidade alfa do Fator 1 Induzível por Hipóxia , Fator A de Crescimento do Endotélio Vascular , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , RNA Mensageiro/metabolismo , Transfecção , Peptídeos e Proteínas de Sinalização Intercelular/genética , Isoformas de Proteínas/genéticaRESUMO
BACKGROUND: Tenosynovial giant cell tumor (TGCT) may be misdiagnosed as osteoarthritis (OA), or the chronic course of TGCT may lead to development of secondary OA. However, little is known about the effect of comorbid OA on long-term surgical patterns and costs among TGCT patients. METHODS: This cohort study used claims data from the Merative MarketScan Research Databases. The study included adults diagnosed with TGCT from January 1, 2014, to June 30, 2019, who have at least 3 years of continuous enrollment before and after the first TGCT diagnosis (date of the first TGCT diagnosis = index date) and no other cancer diagnosis during the study period. Patients were stratified by the presence of an OA diagnosis relative to the index date. Outcomes included surgical procedure patterns, healthcare resource utilization, and costs in the 3-year pre- and postindex periods. Multivariable models were used to assess the effect of OA on the study outcomes, controlling for baseline characteristics. RESULTS: The study included 2856 TGCT patients: 1153 (40%) had no OA before or after index (OA[-/-]), 207 (7%) had OA before index but not after (OA[+/-]), 644 (23%) had OA after index but not before (OA[-/+]), and 852 (30%) had OA before and after index (OA[+/+]). The mean age was 51.6 years, and 61.7% were female. During the postperiod, joint surgery was more common among OA(-/+) and OA(+/+) patients compared with OA(-/-) and OA(+/-) patients (55.7% vs 33.2%). The mean all-cause total costs in the 3-year postperiod were $19,476 per patient per year. Compared with OA(-/-) patients, OA(-/+) and OA(+/+) patients had a higher risk of undergoing recurrent surgery and higher total healthcare costs postindex. DISCUSSION: Higher rates of surgery and increased healthcare cost observed in TGCT patients with postindex OA underscore the need for effective treatment options to reduce joint damage, especially among patients with comorbid OA.
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Tumor de Células Gigantes de Bainha Tendinosa , Osteoartrite , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos de Coortes , Tumor de Células Gigantes de Bainha Tendinosa/epidemiologia , Tumor de Células Gigantes de Bainha Tendinosa/cirurgia , Tumor de Células Gigantes de Bainha Tendinosa/patologia , Osteoartrite/epidemiologia , Osteoartrite/cirurgia , Aceitação pelo Paciente de Cuidados de Saúde , Custos de Cuidados de SaúdeRESUMO
OBJECTIVES: As few large studies identify correlative biomarkers in chordoma, our objective was to use our large, single-center chordoma tumor bank to identify novel signaling pathways. METHODS: Clinical and pathologic data for 73 patients with chordoma were retrospectively collected. Tumor microarrays were built from 61 archived chordoma specimens; immunohistochemistry for TOMM20, TIGAR, and MCT1 were performed; and semiquantitative analysis of staining intensity and percentage of positive tumor cells was performed. Average composite scores of MCT1, TIGAR, and TOMM20 expression were compared by disease status and anatomic location. RESULTS: Higher expression of TOMM20 was seen in recurrent and metastatic chordomas compared with primary lesions. Comparing composite scores of primary lesions in patients with primary disease only vs those with recurrent disease showed that TIGAR and TOMM20 expressions are significantly higher in primary lesions, followed by a history of recurrence. A TOMM20 composite score of greater than or equal to 3 significantly decreased overall survival (hazard ratio [HR], 5.83) and recurrence-free survival (HR, 8.95). CONCLUSIONS: Identifying novel signaling pathways that promote chordoma growth and recurrence is critical for developing targeted therapy for chordoma. TOMM20 may be a biomarker associated with chordoma disease progression.
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Cordoma , Humanos , Cordoma/patologia , Estudos Retrospectivos , Prognóstico , Receptores de Superfície Celular/metabolismo , Modelos de Riscos Proporcionais , Proteínas do Complexo de Importação de Proteína Precursora MitocondrialRESUMO
[This corrects the article DOI: 10.36469/jheor.2022.32485.].
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INTRODUCTION: Esophageal cancer is an aggressive malignancy with high mortality. Optimal treatment of esophageal cancer remains an elusive goal. Ribonucleic acid (RNA) interference is a novel potential targeted approach to treat esophageal cancer. Targeting oncogenes that can alter critical cellular functions with silencing RNA molecules is a promising approach. The silencing of specific oncogenes in esophageal cancer cells in the experimental setting has been shown to decrease the expression of oncogenic proteins. This has resulted in cell apoptosis, reduction in cell proliferation, reduced invasion, migration, epithelial-mesenchymal transition, decrease in tumor angiogenesis and metastasis, and overcoming drug resistance. The Hedgehog (Hh) signaling pathway has been shown to be involved in esophageal adenocarcinoma formation in a reflux animal model. In addition to Hh, we will focus on other targets with clinical potential in the treatment of esophageal cancer. MATERIALS AND METHODS: We searched for articles published from 2005 to August 2020 that studied the siRNA effects on inhibiting esophageal cancer formation in experimental settings. We used combinations of the following terms for searching: "esophageal cancer," "RNA interference," "small interfering RNA," "siRNA," "silencing RNA," "Smoothened (Smo)," "Gli," "Bcl-2," "Bcl-XL," "Bcl-W,â³ "Mcl-1," "Bfl-1," "STAT3,"and "Hypoxia inducible factor (HIF)". A total of 21 relevant articles were found. RESULTS AND CONCLUSIONS: Several proto-oncogenes/oncogenes including Hh pathway mediators, glioma-associated oncogene homolog 1 (Gli-1), Smoothened (Smo), and antiapoptotic Bcl-2 have potential as targets for silencing RNA in the treatment of esophageal cancer.
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Neoplasias Esofágicas , Proteínas Hedgehog , Animais , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA Interferente Pequeno/metabolismo , Proteína GLI1 em Dedos de Zinco/genéticaRESUMO
Background: Tenosynovial giant cell tumors (TGCT) are rare and locally aggressive neoplasms in synovium, bursae, and tendon sheaths, which cause pain, joint dysfunction, and damage to the affected joints. Objective: To evaluate the surgical patterns and economic burden among patients with TGCT who underwent joint surgery in the United States. Methods: Patients newly diagnosed with TGCT, aged 18-64 years, who underwent joint surgery post-TGCT diagnosis were identified from the OptumHealth Care Solutions, Inc database (Q1/1999-Q1/2017). Patients were required to be continuously enrolled for ≥1 year before and ≥3 years after the first TGCT diagnosis (index date). Surgical patterns were assessed post-index. Healthcare resource utilization and associated healthcare costs, and indirect costs related to work loss in year 1, year 2, and year 3 post-index, were compared with those at baseline. Results: Of 835 eligible TGCT patients, 462 (55%) patients who had ≥1 joint surgery post-index were included. During a median follow-up of 5.7 years, 78% of patients underwent their first joint surgery in year 1 and 41% had ≥1 repeat surgery. Magnetic resonance imaging utilization was highest during baseline (46%) and declined afterward (28%, 17%, and 19% in years 1, 2, and 3, respectively). Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), and physical therapy, occupational therapy, and rehabilitation services, were commonly used during baseline (45%, 40%, and 30%, respectively). More patients used opioids in year 1 vs baseline (78% vs 45%; P<0.0001), while its utilization return to baseline levels in year 2 (41%) and year 3 (42%). A similar pattern was observed for NSAIDs and physical/occupational therapy/rehabilitation services. Healthcare resource utilization and associated healthcare costs surged in year 1 and returned to baseline or lower in years 2 and 3. A similar pattern was observed for indirect costs associated with work loss. Discussion: The high proportion of patients undergoing repeat surgeries and prevalent use of opioids, NSAIDs, and physical/occupational therapy/rehabilitation services suggests an unmet medical need after surgical treatment. Conclusions: Surgical resection alone might be inadequate to control TGCT. New treatment options may complement surgery and alleviate the clinical and economic burden experienced by patients with TGCT who had received prior surgery.
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BACKGROUND: This study evaluated the incidence of de novo bone metastasis across all primary cancer sites and their impact on survival by primary cancer site, age, race, and sex. QUESTIONS/PURPOSES: Our objectives were (I) characterize the epidemiology of de novo bone metastasis with respect to patient demographics, (II) characterize the incidence by primary site, age, and sex (2010-2015), and (III) compare survival of de novo metastatic cancer patients with and without bone metastasis. METHODS: This is a retrospective, population-based study using nationally representative data from the Surveillance, Epidemiology, and End Results program, 2010-2015. Incidence rates by year of diagnosis, annual percentage changes, Kaplan-Meier, univariate and multiple Cox regression models are included in the analysis. RESULTS: Of patients with cancer in the SEER database, 5.1% were diagnosed with metastasis to bone, equaling ~18.8 per 100,000 bone metastasis diagnoses in the US per year (2010-2015). For adults >25, lung cancer is the most common primary site (2015 rate: 8.7 per 100,000) with de novo bone metastases, then prostate and breast primaries (2015 rates: 3.19 and 2.38 per 100,000, respectively). For patients <20 years old, endocrine cancers and soft tissue sarcomas are the most common primaries. Incidence is increasing for prostate (Annual Percentage Change (APC) = 4.6%, P < 0.001) and stomach (APC = 5.0%, P = 0.001) cancers. The presence of de novo bone metastasis was associated with a limited reduction in overall survival (HR = 1.02, 95%, CI = [1.01-1.03], p < 0.001) when compared to patients with other non-bone metastases. CONCLUSION: The presence of bone metastasis versus metastasis to other sites has disease site-specific impact on survival. The incidence of de novo bone metastasis varies by age, sex, and primary disease site.
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Neoplasias Ósseas , Neoplasias Pulmonares , Adulto , Neoplasias Ósseas/epidemiologia , Neoplasias Ósseas/patologia , Humanos , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Estudos Retrospectivos , Programa de SEER , Adulto JovemRESUMO
Venous thromboembolism (VTE), including both deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major complication of musculoskeletal surgery in general, and the risk is heightened in musculoskeletal oncology surgery. Despite the well-known association between cancer and VTE, the mechanism promoting this pathology is not entirely well understood. It is estimated that nearly all cancer patients will experience from some form of VTE, whether or not clinically relevant, during the course of their disease. Nonetheless, numerous studies have analyzed the occurrence and prevention of VTE in patients with cardiovascular disease or suffering trauma, but very few have specifically examined the safety or efficacy of preventing VTE in cancer patients with metastatic skeletal disease. This review will examine the various types of prophylactic treatment, timing of administration, risk stratification for determining the appropriate course of anticoagulation (AC), and discuss current views on chemical prophylaxes relativity to wound complications and excessive bleeding in orthopedic oncology patients. Overall, careful choice of anticoagulant and timing of administration must be made in order to avoid bleeding complications. A risk stratification system to determine which chemical prophylaxis to administered could be beneficial in both reducing the occurrence of VTE and decreasing associated wound complications or mortality. Further study should be conducted to tailor chemical prophylaxes recommendations to this largely affected population and effectively reduce the occurrence of VTE.
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BACKGROUND: Whether arthroscopic or open surgical management for diffuse-type tenosynovial giant cell tumor (D-TGCT) of the knee is associated with a lower rate of recurrence is unknown. METHODS: PubMed, Scopus, Web of Science, Cochrane, and EMBASE were searched on December 3, 2020. Retrospective studies that reported on recurrence rates for arthroscopic versus open management of D-TGCT were included. A total of 16 studies evaluating 1143 patients with D-TGCT of the knee were included (nopen = 551, narthroscopic = 350 patients, and narthroscopic/open = 23 patients). Random-effects meta-analyses were used to summarize and compare the reported recurrence rates, stratified by approach and overall recurrence. The meta-analysis was registered with PROSPERO. RESULTS: The recurrence rate per year (incidence) for arthroscopic procedures was 0.11 (95% CI 0.08 to 0.16, P < 0.0001) and for open procedures was 0.07 (95% CI 0.04 to 0.13, P < 0.0001). There was a 1.56 times (95% CI 1.04 to 2.34, P = 0.0332) increased risk of recurrence when treating D-TGCT of the knee with an arthroscopic approach. When evaluating only the subset of studies that had data for both arthroscopic and open approaches, the incidence rate per year for arthroscopic procedures was 0.17 (95% CI 0.11 to 0.27, P < 0.0001) and for open procedures was 0.11 (95% CI 0.06 to 0.19, P < 0.0001). The rate of overall complications was 0.04 (95% CI 0.01 to 0.08, P < 0.0001). CONCLUSION: Arthroscopic surgical management of D-TGCT of the knee in our study resulted in a 1.56 times risk of recurrence as compared with the open approach. The percent of overall complications was minimal.
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Tumor de Células Gigantes de Bainha Tendinosa , Sinovite Pigmentada Vilonodular , Artroscopia , Tumor de Células Gigantes de Bainha Tendinosa/epidemiologia , Tumor de Células Gigantes de Bainha Tendinosa/cirurgia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Estudos RetrospectivosRESUMO
Chordomas are rare, slow-growing neoplasms thought to arise from the foetal notochord remnant. A limited number of studies that examined the mutational profiles in chordomas identified potential driver mutations, including duplication in the TBXT gene (encoding brachyury), mutations in the PI3K/AKT signaling pathway, and loss of the CDKN2A gene. Most chordomas remain without clear driver mutations, and no fusion genes have been identified thus far. We discovered a novel TERT in-frame fusion involving RPH3AL (exon 5) and TERT (exon 2) in the index chordoma case. We screened a discovery cohort of 18 additional chordoma cases for TERT gene rearrangement by FISH, in which TERT rearrangement was identified in one additional case. In our independent, validation cohort of 36 chordomas, no TERT rearrangement was observed by FISH. Immunohistochemistry optimized for nuclear TERT expression showed at least focal TERT expression in 40/55 (72.7%) chordomas. Selected cases underwent molecular genetic profiling, which showed low tumor mutational burdens (TMBs) without obvious driver oncogenic mutations. We next examined a cohort of 1,913 solid tumor patients for TERT rearrangements, and TERT fusions involving exon 2 were observed in 7/1,913 (0.4%) cases. The seven tumors comprised five glial tumors, and two poorly differentiated carcinomas. In contrast to chordomas, the other TERT-rearranged tumors were notable for higher TMBs, frequent TP53 mutations (6/7) and presence of other driver oncogenic mutations, including a concurrent fusion (TRIM24-MET). In conclusion, TERT gene rearrangements are seen in a small subset (2/55, 3.6%) of chordomas. In contrast to other TERT-rearranged tumors, where the TERT rearrangements are likely passenger events, the possibility that TERT protein overexpression representing a key event in chordoma tumorigenesis is left open.
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Cordoma/patologia , Rearranjo Gênico , Neoplasias/patologia , Telomerase/genética , Cordoma/genética , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias/genética , PrognósticoRESUMO
Extraskeletal myxoid chondrosarcoma (EMC) is a rare sarcoma of uncertain differentiation, characterized by recurrent chromosomal translocation involving NR4A3 (9q22.33) in more than 90% of cases. Five fusion partners for NR4A3 have been described including: EWSR1 (22q12.2), TAF15 (17q12), FUS (16p11.2), TCF12 (15q21), and TFG (3q12.2). This report describes a patient with an EMC at the dorsum of the right foot. The tumor showed a cord-like and reticular pattern in a background of myxoid matrix. The tumor cells demonstrated an epithelioid morphology with prominent nucleoli. The tumor cells were positive for synaptophysin, GFAP, with focal positivity for CD117, S100, Cam5.2, and NSE, and negative for AE1/3, desmin, and SMA. An RNA next-generation sequencing test showed a SMARCA2-NR4A3 gene fusion which has not been previously reported. The exon 3 of SMARCA2 was fused to exon 3 of NR4A3. This fusion was confirmed by NR4A3 break-apart FISH, although both SMARCA2 (9p24.3) and NR4A3 (9q22.33) are located on chromosome 9. The tumor cells showed retained expression of INI1 and SMARCA2 by immunohistochemistry.
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Condrossarcoma/patologia , Proteínas de Ligação a DNA/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/patologia , Proteínas de Fusão Oncogênica/genética , Receptores de Esteroides/genética , Receptores dos Hormônios Tireóideos/genética , Fatores de Transcrição/genética , Condrossarcoma/genética , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo e de Tecidos Moles/genética , PrognósticoRESUMO
Barrett's esophagus (BE) is a precursor to esophageal adenocarcinoma (EAC). Recently, long noncoding RNAs (lncRNAs) have been identified as key regulators of biological pathways. However, involvement of lncRNAs in the development of BE and EAC has not been well-studied. The aims of the current study were: (1) to study involvement of the lncRNA, miR205HG, in the development of BE and EAC; (2) to clarify the role of miR205HG in in vitro and in vivo experiments; and (3) to investigate the mechanism of miR205HG involving the Hedgehog (Hh) signaling pathway. These experiments revealed that miR205HG was downregulated in EAC vs. normal esophageal epithelia (NE) as well as in EAC cell lines, and its forced overexpression inhibited EAC cell proliferation and cell cycle progression in vitro. Similarly, overexpression of miR205HG inhibited xenograft tumor growth in mice In vivo. Finally, we show that one mechanism of action of miR205HG involves the Hh signaling pathway: miR205HG and Hh expression levels were inversely correlated in both EAC (r = -0.73) and BE (r = -0.83) tissues, and in vitro studies revealed details of Hh signaling inhibition induced by miR205HG. In conclusion, these findings establish that lncRNA miR205HG functions as a tumor suppressor in the development of BE and EAC, at least in part through its effect on the Hh signaling pathway.
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OBJECTIVE: To assess the economic burden of tenosynovial giant cell tumor (TGCT) among US employed workforce. METHODS: Patients with TGCT medical claims (Nâ=â1395) and matched controls (1:10) without TGCT claims (Nâ=â13,950) were identified from the OptumHealth Care Solutions, Inc. database (January 1, 1999 to March 31, 2017). Adjusted regression models were used to compare healthcare resource utilization, time lost from work, and associated costs between cohorts. RESULTS: In patients with TGCT, the rates of inpatient admissions, emergency room visits, outpatient visits, and work loss days were 2.8, 1.5, 2.2, and 2.6 times those of matched controls, respectively (all Pâ<â0.001). Total annual all-cause healthcare costs and work loss-related costs were $9368 and $2708 higher for TGCT patients than for matched controls, respectively (all Pâ<â0.001). CONCLUSIONS: TGCT was associated with a significant healthcare and work loss burden on US employers.
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Efeitos Psicossociais da Doença , Tumor de Células Gigantes de Bainha Tendinosa , Custos de Cuidados de Saúde , Humanos , Estudos Retrospectivos , Estados Unidos/epidemiologia , Recursos HumanosRESUMO
INTRODUCTION: Patients with amoebic liver abscess (ALA) may require percutaneous catheter drainage (PCD). Once the PCD output is substantially reduced or has ceased along with clinical recovery, residual collections on radiological evaluation may concern the treating physicians. The prevalence and significance of such collections is unknown, and the subsequent approach how to tackle them is unclear. METHODS: Consecutive patients with one or more uncomplicated ALAs requiring drainage were prospectively enrolled from 3 hospitals and managed based on a standard approach. Catheter removal was attempted after the patients fulfilled all 4 of the following criteria: disappearance of abdominal pain, absence of fever for at least 48 h, an improving trend of TLC (documented on 2 consecutive reports), and catheter drain output of < 10 ml/day for at least 2 consecutive days. RESULTS: A total of 110 patients (mean age 46.6 ± 10.5 years, 93.6% males, 89.1% alcoholics) underwent PCD placement; 69 patients (69/110; 62.7%) met all 4 criteria within 5 days of PCD placement (optimal response) and had an uncomplicated course. Patients with suboptimal responses (41/110; 37.3%) were evaluated for local and systemic complications; the appearance of fresh collections (5/110; 4.5%), abscess rupture (2/110; 1.8%), bile leakage (3/110; 2.7%), cholangitis (2/110; 1.8%), thrombophlebitis (2/110; 1.8%) and hospital-acquired infections (2/110; 1.8%) were diagnosed and treated accordingly. Ultimately, PCD removal (based on the fulfilment of all 4 criteria) was universally successful after a median of 5 days (IQR, 4-9 days). None of the patients had symptom recurrence after PCD removal, although residual collections were still seen in 97.3% of patients at the time of PCD removal and in 92.1% and 84.9% of patients available for follow-up at 1 and 3 months, respectively. CONCLUSION: Based on our clinical protocol, PCD removal in ALA can be successfully expedited even in the presence of residual collections. An inability to fulfill all 4 criteria within 5 days of PCD placement warrants further evaluations for local and systemic complications that require additional therapeutic measures.
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Abscesso Hepático Amebiano , Adulto , Catéteres , Protocolos Clínicos , Drenagem , Feminino , Humanos , Abscesso Hepático Amebiano/diagnóstico por imagem , Abscesso Hepático Amebiano/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
Ischemic necrosis of surgical flaps after reconstruction is a major clinical problem. Hypoxia-inducible factor-1α (HIF-1α) is considered the master regulator of the adaptive response to hypoxia. Among its many properties, it regulates the expression of genes encoding angiogenic growth factors, which have a short half-life in vivo. To achieve a continuous application of the therapeutic, we utilized DNA plasmid delivery. Transcription of the DNA plasmid confirmed by qRT-PCR showed significantly increased mRNA for HIF-1α in the transfected tissue compared to saline control tissue. Rats were preconditioned by injecting with either HIF-1α DNA plasmid or saline intradermally in the designated flap region on each flank. Seven days after preconditioning, each rat had two isolated pedicle flaps raised with a sterile silicone sheet implanted between the skin flap and muscle layer. The flaps preconditioned with HIF-1α DNA plasmid had significantly less necrotic area. Angiogenesis measured by CD31 staining showed a significant increase in the number of vessels per high powered field in the HIF-1α group (p < 0.05). Our findings offer a potential therapeutic strategy for significantly promoting the viability of surgical pedicle flaps by ischemic preconditioning with HIF-1α DNA plasmid.
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Subunidade alfa do Fator 1 Induzível por Hipóxia , Retalhos Cirúrgicos , Animais , DNA , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Plasmídeos/genética , Ratos , Ratos Sprague-Dawley , Sobrevivência de TecidosRESUMO
Chondrosarcoma is the second most common primary bone malignancy, representing one fourth of all primary bone sarcomas. It is typically resistant to radiation and chemotherapy treatments. However, the molecular mechanisms that contribute to cancer aggressiveness in chondrosarcomas remain poorly characterized. Here, we studied the role of mitochondrial transporters in chondrosarcoma aggressiveness including chemotherapy resistance. Histological grade along with stage are the most important prognostic biomarkers in chondrosarcoma. We found that high-grade human chondrosarcoma tumors have higher expression of the mitochondrial protein, translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20), compared to low-grade tumors. TOMM20 overexpression in human chondrosarcoma cells induces chondrosarcoma tumor growth in vivo. TOMM20 drives proliferation, resistance to apoptosis and chemotherapy resistance. Also, TOMM20 induces markers of epithelial to mesenchymal transition (EMT) and metabolic reprogramming in these mesenchymal tumors. In conclusion, TOMM20 drives chondrosarcoma aggressiveness and resistance to chemotherapy.
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Neoplasias Ósseas/metabolismo , Condrossarcoma/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Proliferação de Células/efeitos dos fármacos , Condrossarcoma/tratamento farmacológico , Condrossarcoma/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , Membranas Mitocondriais/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Células Tumorais CultivadasRESUMO
Proximal tibial metaphyseal bone loss compromises the alignment and fixation of components during revision total knee arthroplasty. In massive, segmental defects with loss of collateral ligamentous support and lack of bone to support the use of prosthetic augments or metaphyseal cones or sleeves, a hinged proximal tibial replacement or a so-called "megaprosthesis" should be available. While proximal tibial replacement is the reconstructive method of choice in the setting of bone tumor resection, applications in non-oncologic joint arthroplasty are rare and may offer an opportunity for limb salvage in dire clinical scenarios with massive proximal tibial bone loss. This report reviews 6 cases of proximal tibial replacement.
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Extra-articular synovial chondromatosis is a rare entity in the foot and ankle. We present a case of a 49-year-old female who presented for evaluation of a palpable concern following trauma; which was found to represent synovial chondromatosis. This case demonstrates the multimodality imaging findings, including ultrasound and MRI, with histopathologic correlation.