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1.
Ann Oncol ; 35(9): 792-804, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38908482

RESUMO

BACKGROUND: Hormone receptor expression is a known positive prognostic and predictive factor in breast cancer; however, limited evidence exists on its prognostic impact on prognosis of young patients harboring a pathogenic variant (PV) in the BRCA1 and/or BRCA2 genes. PATIENTS AND METHODS: This international, multicenter, retrospective cohort study included young patients (aged ≤40 years) diagnosed with invasive breast cancer and harboring germline PVs in BRCA genes. We investigated the impact of hormone receptor status on clinical behavior and outcomes of breast cancer. Outcomes of interest [disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS)] were first investigated according to hormone receptor expression (positive versus negative), and then according to breast cancer subtype [luminal A-like versus luminal B-like versus triple-negative versus human epidermal growth factor receptor 2 (HER2)-positive breast cancer]. RESULTS: From 78 centers worldwide, 4709 BRCA carriers were included, of whom 2143 (45.5%) had hormone receptor-positive and 2566 (54.5%) hormone receptor-negative breast cancer. Median follow-up was 7.9 years. The rate of distant recurrences was higher in patients with hormone receptor-positive disease (13.1% versus 9.6%, P < 0.001), while the rate of second primary breast cancer was lower (9.1% versus 14.7%, P < 0.001) compared to patients with hormone receptor-negative disease. The 8-year DFS was 65.8% and 63.4% in patients with hormone receptor-positive and negative disease, respectively. The hazard ratio of hormone receptor-positive versus negative disease changed over time for DFS, BCSS, and OS (P < 0.05 for interaction of hormone receptor status and survival time). Patients with luminal A-like breast cancer had the worst long-term prognosis in terms of DFS compared to all the other subgroups (8-year DFS: 60.8% in luminal A-like versus 63.5% in triple-negative versus 65.5% in HER2-positive and 69.7% in luminal B-like subtype). CONCLUSIONS: In young BRCA carriers, differences in recurrence pattern and second primary breast cancer among hormone receptor-positive versus negative disease warrant consideration in counseling patients on treatment, follow-up, and risk-reducing surgery.


Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Receptor ErbB-2 , Receptores de Estrogênio , Receptores de Progesterona , Humanos , Feminino , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/metabolismo , Estudos Retrospectivos , Proteína BRCA1/genética , Proteína BRCA2/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Prognóstico , Intervalo Livre de Doença , Adulto Jovem , Mutação em Linhagem Germinativa , Heterozigoto , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
2.
Anaesthesia ; 79(6): 603-610, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38114306

RESUMO

Hyperangulated videolaryngoscopes are known to increase the success rate of tracheal intubation in the setting of difficult airway management when used with a stylet or bougie. However, there is controversy over which adjunct is more useful. This randomised study aimed to compare first attempt tracheal intubation success rate between a stylet and bougie when using a hyperangulated videolaryngoscope. We recruited patients aged > 20 years who were scheduled for elective surgery under general anaesthesia and required tracheal intubation. We only included patients with factors predicting difficult tracheal intubation based on pre-anaesthesia airway evaluation. Tracheal intubation was attempted using a Glidescope® with either a stylet or bougie as an adjunct according to group assignment. Primary outcome was the success rate of the first tracheal intubation attempt, and secondary outcomes were success of second and third attempts; tracheal intubation time; and occurrence of sore throat, dysphagia or hoarseness. A total of 166 patients were included. The success rate of the first tracheal intubation attempt was significantly higher in patients allocated to the bougie group compared with those allocated to the stylet group (81/83 (98%) vs. 73/83 (88%), respectively; p = 0.032). The number of patients who needed two attempts was significantly lower in those allocated to the bougie group compared with those allocated to the stylet group (1/83 (1%) vs. 9/83 (11%), respectively; p = 0.018). Each group had one patient (1%) where tracheal intubation was achieved after a third attempt. There was no significant difference in the occurrence of sore throat, dysphagia and hoarseness between the two groups. When difficult tracheal intubation is anticipated and a hyperangulated videolaryngoscope is used, the success rate of the first attempt is higher when a bougie is used compared with a stylet.


Assuntos
Intubação Intratraqueal , Laringoscópios , Laringoscopia , Humanos , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Laringoscopia/métodos , Laringoscopia/instrumentação , Gravação em Vídeo , Adulto , Faringite/etiologia , Faringite/epidemiologia , Desenho de Equipamento , Anestesia Geral/métodos , Resultado do Tratamento , Rouquidão/etiologia
3.
Phys Rev Lett ; 131(20): 201802, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38039466

RESUMO

We search for energetic electron recoil signals induced by boosted dark matter (BDM) from the galactic center using the COSINE-100 array of NaI(Tl) crystal detectors at the Yangyang Underground Laboratory. The signal would be an excess of events with energies above 4 MeV over the well-understood background. Because no excess of events are observed in a 97.7 kg·yr exposure, we set limits on BDM interactions under a variety of hypotheses. Notably, we explored the dark photon parameter space, leading to competitive limits compared to direct dark photon search experiments, particularly for dark photon masses below 4 MeV and considering the invisible decay mode. Furthermore, by comparing our results with a previous BDM search conducted by the Super-Kamionkande experiment, we found that the COSINE-100 detector has advantages in searching for low-mass dark matter. This analysis demonstrates the potential of the COSINE-100 detector to search for MeV electron recoil signals produced by the dark sector particle interactions.

4.
J Dairy Sci ; 106(12): 9576-9586, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37678766

RESUMO

We investigated the effects of road transportation and administration of the vitamin E and selenium (ESe) on circulating cortisol, haptoglobin, blood metabolites, oxidative biomarkers, white blood cell profiles, and behaviors in pregnant dairy heifers. Forty pregnant Holstein heifers were randomly assigned to one of 4 treatments: no transportation and no ESe administration, no transportation and ESe administration, transportation and no administration, and transportation and ESe administration. The ESe (70 IU/kg dry matter feed of dl-α-tocopheryl acetate and 0.3 mg/kg dry matter feed of sodium selenite) was orally delivered once a day from 7 d before transportation to 3 d after transportation. The heifers were transported in trucks designed for cattle transportation. Blood was collected 1 h before transportation, immediately after transportation (IAT), and at 6, 24, and 48 h after transportation. Behaviors were recorded using a video camera for 2 consecutive days after transportation. Transported/non-ESe-administered heifers had greater cortisol at IAT, haptoglobin at 6 and 24 h after transportation, total oxidative status at 6 h after transportation, and nonesterified fatty acid levels, white blood cell numbers, and neutrophil percentages at IAT and 6 h after transportation in the blood than nontransported heifers. Transported/non-ESe-administered heifers had lower total antioxidative status levels at 48 h after transportation and lymphocyte percentages at IAT and 6 h after transportation than nontransported heifers. Lying time was shorter in transported heifers than nontransported/non-ESe-administered heifers. Transported/ESe-administered heifers had lower cortisol, total oxidative status, nonesterified fatty acid levels at IAT, and haptoglobin concentrations at 6 and 24 h after transportation than transported/non-ESe-administered heifers. Transported/ESe-administered heifers had greater total antioxidative status levels at 48 h after transportation than transported/non-ESe-administered heifers. No ESe administration effects were observed for white blood cell number and neutrophil and lymphocyte percentages and lying time. In conclusion, road transportation caused temporary oxidative stress. Administrating ESe partially alleviated the stress, suggesting that ESe administration could be a viable strategy to reduce stress in transported pregnant heifers, providing a novel role of vitamin E and selenium for improving animal welfare.


Assuntos
Selênio , Gravidez , Animais , Bovinos , Feminino , Selênio/farmacologia , Hidrocortisona , Haptoglobinas , Vitamina E/farmacologia , Antioxidantes/farmacologia , Meios de Transporte , Ácidos Graxos
5.
Tech Coloproctol ; 27(11): 1119-1122, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37368080

RESUMO

PURPOSE: The aim of the present report wasto describe a novel technique of robotic abdominoperineal resection (APR) for the treatment of T4b low rectal cancer using the da Vinci® Single-Port (SP) system (Intuitive Surgical, Sunnyvale, CA, USA). METHODS: A 3-cm transverse incision was made in the left lower quadrant of the abdomen, in the area designated for permanent colostomy. A Uniport® (Dalim Medical, Seoul, Korea) was introduced and a 25 mm multichannel SP trocar was inserted into the Uniport. A 5-mm laparoscopic assistant port was introduced on the upper midline. A video showing each step of the technique is attached. RESULTS: Two consecutive female patients (70 and 74 years old) underwent SP robotic APR with partial resection of the vagina 8 weeks after preoperative chemoradiotherapy. In both cases, rectal cancer was located 1 cm above the anal verge and invaded the vagina (initial stage and ymrT stage T4b). Operative time was 150 and 180 min, respectively. Estimated blood loss was 10 and 25 ml, respectively. No postoperative complications occurred. The length of postoperative hospital stay was 5 days in both cases. The final pathological stage was ypT4bN0 and ypT3N0 respectively. CONCLUSIONS: In this first experience, SP robotic APR appears to be a safe and feasible procedure for locally advanced low rectal cancer. In addition, the invasiveness of the procedure is reduced by means of the SP system, which only requires a single incision in the area designated for colostomy. Prospective studies on a larger number of patients are necessary to confirm the outcomes of this technique compared to other minimally invasive approaches.

6.
Osteoarthritis Cartilage ; 30(9): 1210-1221, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35513246

RESUMO

OBJECTIVE: This study was performed to characterize selected rhodanine derivatives as potential preclinical disease-modifying drugs for experimental osteoarthritis (OA) in mice. METHODS: Three rhodanine derivatives, designated rhodanine (R)-501, R-502, and R-503, were selected as candidate OA disease-modifying drugs. Their effects were evaluated by intra-articular (IA) injection in OA mouse models induced by DMM (destabilization of the medial meniscus) or adenoviral overexpression in joint tissues of hypoxia-inducible factor (HIF)-2α or zinc importer ZIP8. The regulatory mechanisms impacted by the rhodanine derivatives were examined in primary-culture chondrocytes and fibroblast-like synoviocytes (FLS). RESULTS: All three rhodanine derivatives inhibited OA development caused by DMM or overexpression of HIF-2α or ZIP8. Compared to vehicle-treated group, for example, IA injection of R-501 in DMM-operated mice reduced median OARSI grade from 3.78 (IQR 3.00-5.00) to 1.89 (IQR 0.94-2.00, P = 0.0001). R-502 and R-503 also reduced from 3.67 (IQR 2.11-4.56) to 2.00 (IQR 1.00-2.00, P = 0.0030) and 2.00 (IQR 1.83-2.67, P = 0.0378), respectively. Mechanistically, the rhodanine derivatives inhibited the nuclear localization and transcriptional activity of HIF-2α in chondrocytes and FLS. They did not bind to Zn2+ or modulate Zn2+ homeostasis in chondrocytes or FLS; instead, they inhibited the nuclear localization and transcriptional activity of the Zn2+-dependent transcription factor, MTF1. HIF-2α, ZIP8, and interleukin-1ß could upregulate matrix-degrading enzymes in chondrocytes and FLS, and the rhodanine derivatives inhibited these effects. CONCLUSION: IA administration of rhodanine derivatives significantly reduced OA pathogenesis in various mouse models, demonstrating that these derivatives have disease-modifying therapeutic potential against OA pathogenesis.


Assuntos
Cartilagem Articular , Osteoartrite , Rodanina , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Cartilagem Articular/patologia , Condrócitos/metabolismo , Modelos Animais de Doenças , Camundongos , Osteoartrite/metabolismo , Preparações Farmacêuticas/metabolismo , Rodanina/metabolismo , Rodanina/farmacologia
7.
Clin Exp Immunol ; 205(1): 75-88, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33759187

RESUMO

Follicular T helper (Tfh) and regulatory (Tfr) cells are distinct subsets of CD4+ T lymphocytes, regulating humoral immune responses in the germinal center. It is widely accepted that dysregulated Tfh and Tfr cells are associated with autoimmunity. In this study, we evaluated the frequencies of circulating chemokine receptor (CXCR)5+ programmed cell death 1 (PD-1+ ) Tfh (cTfh) and CXCR5+ PD-1+ forkhead box protein 3 (FoxP3+ ) CD25+ Tfr (cTfr) cells, and their corresponding cytokines from the peripheral blood mononuclear cells of 28 patients with relapsing-remitting multiple sclerosis (MS) and 16 age- and sex-matched healthy controls (HC). Subsets of cTfh cells by Th1- and Th17-related surface markers (CXCR3 and CCR6) were also evaluated. We found that the frequency of cTfh cells was significantly higher in MS patients compared to that of HC. Conversely, the frequency of cTfr cells was lower in MS patients than that of HC. Interleukin (IL)-21-producing cTfh cells were significantly increased in MS patients, while IL-10-secreting cTfr cells were lower in MS patients compared to levels in HC. Among cTfh cells, cTfh17.1 cells were the major subtypes that were significantly increased in MS patients compared to HC, with the frequency of IL-21-secreting cells being the highest. These results suggest that an imbalanced distribution of cTfh and cTfr exist in MS patients, which contributes to the reciprocally altered IL-21 and IL-10 production.


Assuntos
Citocinas/imunologia , Esclerose Múltipla Recidivante-Remitente/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Biomarcadores/metabolismo , Feminino , Fatores de Transcrição Forkhead/imunologia , Humanos , Interleucina-10/imunologia , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucinas/imunologia , Leucócitos Mononucleares/imunologia , Masculino , Receptores CXCR5/imunologia , Células Th1/imunologia , Células Th17/imunologia
8.
BJOG ; 128(12): 1938-1948, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34028167

RESUMO

OBJECTIVE: To quantify familial risk of endometriosis among full siblings and examine interactions between family history and smoking, age at menarche or body mass index (BMI). DESIGN, SETTING AND POPULATION: Population-based nationwide cohort study. METHODS: Using data from the Korean National Health Insurance and Screening Programme databases on kinship, healthcare utilisation, lifestyle and anthropometrics, we identified 2 109 288 women with full siblings and their environmental risk factors from 2002 to 2018. Familial risks were estimated using Cox proportional-hazards models, represented as incidence risk ratios (IRR) with 95% CI. Interaction between family history and smoking, age at menarche or BMI were assessed on an additive scale. MAIN OUTCOME MEASURES: IRR of endometriosis among women with and without affected siblings. RESULTS: From 19 195 women with affected siblings, 1126 developed endometriosis with an incidence of 35.45/10 000 person-years. Familial risk of endometriosis with versus without affected siblings was increased to IRR 2.75 (95% CI 2.25-3.36), and the highest risk was with affected twins (IRR 6.98; 95% CI 4.19-11.62). Women with both a family history and either smoking, early menarche or low BMI had a significantly higher risk of endometriosis compared with the general population and can be regarded as a high-risk group, the IRRs were 4.28 (95% CI 2.43-7.55), 3.47 (95% CI 2.82-4.26) and 3.09 (95% CI 2.68-3.56), respectively. Substantial effect modification of the associations was noted by smoking and early menarche, as their combined risk with family history exceeded the sum of their individual risks, which was also statistically significant. CONCLUSION: Genetic factors are the primary contributor to the familial aggregation of endometriosis. Significant gene-environment interaction exists between family history and smoking or early menarche. TWEETABLE ABSTRACT: Significant gene-environment interaction exists between family history of endometriosis and smoking or early menarche.


Assuntos
Suscetibilidade a Doenças/epidemiologia , Suscetibilidade a Doenças/etiologia , Endometriose/epidemiologia , Endometriose/etiologia , Irmãos , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Feminino , Interação Gene-Ambiente , Humanos , Incidência , Menarca , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , República da Coreia/epidemiologia , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Adulto Jovem
9.
Clin Exp Dermatol ; 46(8): 1504-1510, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34081799

RESUMO

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, various adverse skin reactions to long-term mask wearing have been reported. AIM: To assess the clinical features of mask-induced dermatoses and to recommend prevention and treatment options. METHODS: From April to August 2020, questionnaires including topics such as demographic information, pre-existing skin disorders, reported mask-related symptoms, daily mask-wearing duration and frequency, types of masks used and whether the participant was a healthcare worker, were distributed to patients in 12 hospitals. Dermatologists assessed skin lesions, confirmed diagnosis and recorded treatments. RESULTS: Itchiness was the most frequent symptom, mostly affecting the cheeks. The most common skin disease was new-onset contact dermatitis (33.94%), followed by new-onset acne (16.97%) and worsening of pre-existing acne (16.97%). Daily wearing of masks was significantly (P = 0.02) associated with new-onset contact dermatitis. More than half of patients with pre-existing skin problems experienced disease worsening while wearing masks. Longer duration of wearing (> 6 h/day, P = 0.04) and use of cotton masks (P < 0.001) significantly increased acne flare-up. Healthcare workers had a higher incidence of skin disease. Skin lesions were generally mild and well tolerated with topical treatment. The study had some limitations: the effect of seasonal characteristics and other risk factors were not assessed, and the patients were visiting dermatological clinics and had interest in their skin status, thus, there may have been selection bias. CONCLUSION: Mask-induced/-triggered dermatoses contribute to increase the dermatological burden during the pandemic.


Assuntos
Dermatite Ocupacional/etiologia , Dermatoses Faciais/etiologia , Máscaras/efeitos adversos , Recursos Humanos em Hospital , Acne Vulgar/etiologia , Adulto , COVID-19/prevenção & controle , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias/prevenção & controle , Prurido/etiologia , República da Coreia , SARS-CoV-2 , Centros de Atenção Terciária
10.
Tech Coloproctol ; 25(9): 1065-1071, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34156568

RESUMO

BACKGROUND: We developed a novel suprapubic single-port robotic right hemicolectomy (spRHC) procedure for patients with right colon cancer using a da Vinci SP Surgical System. The aim of this study was to determine the safety and feasibility of this technique. METHODS: We performed the spRHC procedure on five patients with right colon cancers between July and September 2020. All procedures including colon mobilization, D3 lymphadenectomy, and intracorporeal anastomosis were completed using the single-port robotic platform through a mini-transverse suprapubic incision and an additional assistant port. Data regarding patient characteristics, perioperative outcomes and pathologic results were analyzed. RESULTS: Four of the five patients were males. The median age was 69 years (range, 58-77 years).Two patients received preoperative chemotherapy for advanced colon cancer. The median total operative time was 160 min (range, 150-240 min). The median docking time was 4 min 40 s (range, 2 min 10 s-5 min 10 s). The median console time was 105 min (range, 100-120 min). There were no conversions to multiport or open surgeries. The median hospital stay was 7 days (range, 5-12 days). One patient experienced a wound infection. The median number of harvested lymph nodes was 41 (range, 39-50 lymph nodes). CONCLUSIONS: SpRHC is safe and feasible. However, further comparative studies are needed to assess whether this procedure can provide patients with significant benefits compared with multiport robotic surgery.


Assuntos
Neoplasias do Colo , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Idoso , Colectomia , Neoplasias do Colo/cirurgia , Humanos , Excisão de Linfonodo , Masculino , Duração da Cirurgia
11.
Tech Coloproctol ; 25(7): 857-864, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34052901

RESUMO

BACKGROUND: The da Vinci single-port (SP) system is designed to facilitate single-incision robotic surgery in a narrow space. We developed a new procedure of rectal resection using this system. The aim of the present study was to evaluate the technical feasibility and safety of SP robotic rectal resection for rectal cancer patients based on our initial experience. METHODS: A study was conducted on consecutive patients with mid or low rectal cancer who had SP robotic resection at our institution between July and September 2020. The demographic characteristics, perioperative data, and pathology results of the patients were retrospectively analyzed. RESULTS: There were 5 patients (3 males, 2 females, median age 57 years (range 36-73 years). The median tumor height from the anal verge was 4 cm (range 3-5 cm). Two patients received preoperative chemoradiotherapy for advanced rectal cancer. A single docking was conducted, and the median docking time was 4 min 20 s (range 3 min 30 s to 5 min). The median total operation time was 195 min (range 155-240 min), and the median time of pelvic dissection was 45 min (range 36-62 min). All patients had circumferential and distal tumor-free resection margins. One patient experienced an anastomosis-related complication. The median duration of hospital stay was 7 days (range 7-8 days). CONCLUSIONS: Our initial experience suggests that SP robotic rectal resection is safe and feasible. Further clinical trials comparing SP and multiport robotic rectal resection should be conducted to verify the superior aspects of this new system.


Assuntos
Laparoscopia , Protectomia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Robótica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
12.
Tech Coloproctol ; 25(4): 413-423, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33594627

RESUMO

BACKGROUND: The long-term outcomes of minimally invasive lateral pelvic lymph node dissection (LPND) are not completely known. The aim of this study was to compare long-term outcomes between robotic and laparoscopic LPND in low rectal cancer patients with suspected lymph node metastasis in the pelvic sidewall. METHODS: We retrospectively reviewed the records of all rectal cancer patients who had laparoscopic or robotic total mesorectal excision (TME) with LPND between March 2006 and June 2016. Stage IV patients were excluded. The outcomes of patients who had laparoscopic and robotic TME with LPND were compared. RESULTS: Twenty-nine patients had laparoscopic LPND and 70 had robotic LPND. No significant differences in patient characteristics were observed between the two groups. The urinary retention rate was lower in the robotic group than in the laparoscopic group (7.1% vs. 24.1%; p = 0.043). During a median follow-up of 44.3 months, the overall recurrence rates were 48.3% and 31.4% in the laparoscopic and robotic groups, respectively (p = 0.175). The 5-year disease-free survival rates were 50.4% and 67.0% in the laparoscopic and robotic groups, respectively (p = 0.227). The 5-year overall survival rates were 65.0% and 92.2% in the laparoscopic and robotic groups, respectively (p = 0.017). CONCLUSIONS: Robotic TME with LPND is safe and feasible. In particular, it is associated with lower urinary retention. Robotic TME with LPND might yield a similar local recurrence rate and 5-year disease-free survival, but favorable long-term overall survival as compared to the laparoscopic approach. However, considering the retrospective nature and both major variables of TME and LPND involved together, this should be cautiously interpreted.


Assuntos
Laparoscopia , Neoplasias Retais , Procedimentos Cirúrgicos Robóticos , Humanos , Excisão de Linfonodo , Linfonodos , Recidiva Local de Neoplasia , Neoplasias Retais/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
13.
Insect Mol Biol ; 29(1): 56-65, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31290213

RESUMO

Fused in sarcoma (FUS) is a DNA/RNA-binding protein associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. The exact molecular mechanisms by which FUS results in neurotoxicity have not yet been fully elucidated. Here, we found that parkin is a genetic suppressor of defective phenotypes induced by exogenous human wild type FUS in Drosophila. Although parkin overexpression did not modulate the FUS protein expression level, the locomotive defects in FUS-expressing larvae and adult flies were rescued by parkin expression. We found that FUS expression in muscle tissues resulted in a reduction of the levels and assembly of mitochondrial complex I and III subunits, as well as decreased ATP. Remarkably, expression of parkin suppressed these mitochondrial dysfunctions. Our results indicate parkin as a neuroprotective regulator of FUS-induced proteinopathy by recovering the protein levels of mitochondrial complexes I and III. Our findings on parkin-mediated neuroprotection may expand our understanding of FUS-induced ALS pathogenesis.


Assuntos
Esclerose Lateral Amiotrófica/genética , Drosophila/metabolismo , Proteína FUS de Ligação a RNA/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Trifosfato de Adenosina/metabolismo , Esclerose Lateral Amiotrófica/patologia , Animais , Animais Geneticamente Modificados , Modelos Animais de Doenças , Drosophila/genética , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Larva , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Músculos/metabolismo , Músculos/patologia , Proteína FUS de Ligação a RNA/genética , Ubiquitina-Proteína Ligases/genética
14.
Osteoporos Int ; 31(10): 2017-2024, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32483682

RESUMO

Benign paroxysmal positional vertigo (BPPV) was related to a 1.28 times higher risk of osteoporosis. In addition, osteoporosis was associated with a 1.34 times higher risk of BPPV. This bidirectional relation was maintained after adjusting past medical histories and lifestyle factors, including obesity, smoking, and alcohol consumption. To our knowledge, this is the first study to explore the reciprocal association between BPPV and osteoporosis. In subgroup analyses, only women showed a reciprocal association between BPPV and osteoporosis. INTRODUCTION: A previous population cohort study suggested an association between osteoporosis and benign paroxysmal positional vertigo (BPPV). This study aimed to investigate the bidirectional association between BPPV and osteoporosis. METHODS: The Korean National Health Insurance Service-Health Screening Cohort data from 2002 to 2013 were used. In study I, the 50,897 osteoporosis patients were 1:1 matched with control I participants for age, sex, income, and region of residence. The previous histories of BPPV were analyzed in both groups using conditional logistic regression analysis. In study II, 9621 BPPV patients were 1:4 matched with control II participants. The previous histories of osteoporosis were analyzed in both groups using conditional logistic regression analysis. According to age and sex, subgroup analyses were achieved in both studies I and II. RESULTS: A total of 1.6% (822/50,897) of osteoporosis patients and 1.3% (644/50,897) of control I participants had BPPV. The osteoporosis patients demonstrated a 1.28 times higher chance of developing BPPV (95% confidence intervals [95% CI] = 1.16-1.42, P < 0.001). In study II, 21.2% (2040/9621) of BPPV patients and 17.6% (6790/38,484) of control II participants had osteoporosis. The BPPV patients showed 1.34 times higher chance of having osteoporosis (95% CI = 1.26-1.43, P < 0.001). In the analysis of the women subgroup, these relations were reliable. CONCLUSION: Osteoporosis patients had increased odds of having BPPV. On the other hand, BPPV patients had increased odds of having osteoporosis. This bidirectional relation was consistent only in the women subgroup.


Assuntos
Vertigem Posicional Paroxística Benigna , Osteoporose , Vertigem Posicional Paroxística Benigna/complicações , Vertigem Posicional Paroxística Benigna/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Incidência , Osteoporose/complicações , Osteoporose/epidemiologia
15.
Osteoporos Int ; 31(4): 647-654, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31919536

RESUMO

This study aims to investigate lumbar spine (LS) volumetric bone density (vBMD) as a risk factor for complications (pseudoarthrosis, instrumentation failure, adjacent fractures), re-operation, and time to complication after fusion. INTRODUCTION: Lumbar spine (LS) fusion surgery is increasingly performed worldwide. Complications after fusion result in significant morbidity and healthcare costs. Multiple factors, including osteoporosis, have been suggested to contribute to risk of complications and re-operation. However, most studies have used DXA, which is subject to artifact in patients with spine pathology, and none have investigated the relationship between BMD and timing of post-operative complications. This study aims to investigate LS volumetric bone density (vBMD) as a risk factor for complications (pseudoarthrosis, instrumentation failure, adjacent fractures), re-operation, and time to complication after fusion. METHODS: We evaluated a cohort of 359 patients who had initial LS fusion surgery at our institution, had pre-operative LS CTs and post-operative imaging available for review. Demographic factors, smoking status, vBMD, and details of surgical procedure were related to likelihood and timing of post-operative complications. RESULTS: Mean age was 60 ± 14 years, vBMD 122 ± 37 g/cm3. Median follow-up was 11 months. Skeletal complications occurred in 47 patients (13%); 34 patients (10%) required re-operation. Low vBMD (directly measured and estimated using HU) and smoking were associated with increased risk of skeletal complications. Each increase in baseline vBMD of 10 g/cm3 decreased the complication hazard and increased the complication-free duration in time-to-event analysis (hazard ratio 0.91, 95% CI 0.83-0.98, p < 0.02). CONCLUSIONS: Low vBMD was a significant risk factor for early post-operative complications in patients undergoing LS fusion. Prospective studies are needed to confirm these findings and to elucidate the optimal timing for follow-up and strategies for prevention of post-operative complications in this population.


Assuntos
Densidade Óssea , Osteoporose , Idoso , Criança , Humanos , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoporose/epidemiologia , Osteoporose/etiologia , Estudos Prospectivos , Fatores de Risco
16.
Br J Dermatol ; 182(2): 427-433, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31077333

RESUMO

BACKGROUND: Sentinel lymph node biopsy (SLNB) is usually performed using a triple technique that includes lymphoscintigraphy (LSG), which involves the injection of a radiolabelled tracer, blue dye injection, and detection of the radioisotope with a gamma probe. However, blue dye injection may cause pathological misinterpretation and obscure clinical margins, especially when combined with Mohs micrographic surgery (MMS) for cutaneous melanoma. OBJECTIVES: To assess the efficacy of SLNB without blue dye injection in patients who subsequently underwent MMS for melanomas of the lower extremities. METHODS: We evaluated patients who underwent MMS with or without SLNB using preoperative localization of the primary melanoma via LSG and intraoperative confirmation using a gamma probe between 2010 and 2016. RESULTS: Seventy-two patients with melanoma of mean Breslow thickness 3·03 ± 1·44 mm were evaluated. Sixty-five of the 72 patients underwent SLNB, the success rate of which was 98%. The 5-year overall and disease-free survival rates were 78% and 76%, respectively. CONCLUSIONS: Blue dye injection can be omitted without compromising the accuracy of standard SLNB. Omitting blue dye injection also has marked advantages in MMS for melanoma. What's already known about this topic? Sentinel lymph node biopsy (SLNB) is usually performed using a triple technique including lymphoscintigraphy, which involves the injection of a radiolabelled tracer, blue dye injection, and radioisotope detection using a gamma probe. Blue dye injection may cause pathological misinterpretation and obscure clinical margins. What does this study add? Omitting the dye does not decrease diagnostic accuracy and is particularly advantageous for Mohs micrographic surgery (MMS) in melanomas with clinically indistinct tumour borders. SLNB without blue dye injection is feasible in MMS for melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Extremidade Inferior , Linfonodos , Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Cirurgia de Mohs , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia
17.
Br J Dermatol ; 182(4): 907-915, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31233609

RESUMO

BACKGROUND: While studies report a lower incidence of skin cancer in white patients with vitiligo compared with controls, the skin cancer incidence in Asian patients with vitiligo is unknown. OBJECTIVES: To quantify the incidence of melanoma and nonmelanoma skin cancer (NMSC) in Korean patients with vitiligo and compare it with matched nonvitiligo controls. METHODS: A retrospective matched cohort study was performed with 131 245 incident vitiligo cases and 2 624 900 age- and sex-matched (1 : 20) controls at index date, who were selected from the Korean National Health Insurance database between January 2005 and December 2017. Stratified Cox proportional hazards regression (stratified by sex, birth year and index year) was used to calculate the hazard ratio (HR) of skin cancer in patients with vitiligo. RESULTS: Patients with vitiligo were followed up for a mean duration of 6·34 years compared with a follow-up period of 6·27 years for matched controls. Ultraviolet (UV) treatment-adjusted HR for melanoma in patients with vitiligo was 3·32 [95% confidence interval (CI) 2·29-4·81] and 1·29 (95% CI 1·06-1·56) for NMSC. The HRs for melanoma and NMSC in the vitiligo population without a history of UV treatment were 3·37 (95% CI 2·32-4·90) and 1·35 (95% CI 1·11-1·64), respectively. CONCLUSIONS: In contrast to white patients with vitiligo, the risk of skin cancer was increased in the Korean vitiligo population. However, it is noteworthy that the skin cancer incidence in Korean patients with vitiligo was lower than that of their white counterparts. Owing to possible ethnic differences in the susceptibility to skin cancer, skin cancer surveillance in the vitiligo population may be adjusted for race. What's already known about this topic? Prior studies have reported a lower incidence of melanoma and nonmelanoma skin cancer (NMSC) in white patients with vitiligo compared with nonvitiligo controls. The skin cancer incidence in Asian patients with vitiligo is unknown. What does this study add? In contrast to white patients, the risk of both melanoma and NMSC was increased in Korean patients with vitiligo compared with controls. Owing to possible ethnic differences in susceptibility to skin cancer, skin cancer surveillance in the vitiligo population should be adjusted for race.


Assuntos
Melanoma , Neoplasias Cutâneas , Vitiligo , Estudos de Coortes , Humanos , Incidência , Melanoma/epidemiologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/epidemiologia , Vitiligo/epidemiologia
18.
Eur J Neurol ; 27(8): 1546-1555, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32320109

RESUMO

BACKGROUND AND PURPOSE: Data on the pregnancy outcome of neuromyelitis optica spectrum disorder (NMOSD) remain limited, especially for woman who had received immunosuppressive treatment before becoming pregnant. The aim was to evaluate the outcome of pregnancy amongst patients with NMOSD who attempted to become pregnant after NMOSD onset and to identify risk factors that predict pregnancy-related attack. METHODS: Medical records from 29 patients who attempted to become pregnant after NMOSD onset were retrospectively evaluated and the patients were interviewed for pregnancy outcomes. Pregnancy-related attack was defined as an attack that occurred during pregnancy or within 1 year of delivery. RESULTS: Amongst the 29 patients, 26 had 33 pregnancies after NMOSD symptom onset. The 33 pregnancies after NMOSD onset resulted in 24 live births (healthy neonates except one with low birth weight), six miscarriages and three elective abortions. Pregnancy-related attack occurred in nine (75%) of 12 pregnancies before initiation of immunosuppressive therapy, but in only five (24%) of 21 pregnancies after initiation of immunosuppressive therapy (P = 0.009). Multivariable analysis indicated that pregnancy-related attack was negatively associated with pregnancy after initiation of rituximab (odds ratio 0.048, 95% confidence interval 0.004-0.546). CONCLUSION: Successful pregnancy without maternal and neonatal complications may be feasible in patients with NMOSD. Rituximab treatment before pregnancy might help to prevent pregnancy-related attack in patients with NMOSD.


Assuntos
Neuromielite Óptica , Complicações na Gravidez , Feminino , Humanos , Imunossupressores/uso terapêutico , Recém-Nascido , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/epidemiologia , Gravidez , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Rituximab/uso terapêutico
19.
Eur J Neurol ; 27(6): 1003-1009, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32125747

RESUMO

BACKGROUND AND PURPOSE: Hearing loss (HL) is one of the most influential risk factors of dementia in older adults. However, its potential association with neurodegeneration is not well established. The association between HL and cortical thickness in cognitively normal older adults was evaluated. METHODS: In all, 982 cognitively normal older adults (age ≥65 years) were identified from the Health Promotion Center at the Samsung Medical Center from September 2008 to December 2014. The participants underwent pure-tone audiometry and brain magnetic resonance imaging. HL was evaluated according to a four-frequency (0.5, 1, 2, 4 kHz) pure-tone average. Participants were divided into three groups according to pure-tone average (normal hearing ≤15 dB, minimal HL 16-25 dB, mild-to-severe HL >25 dB). Cortical thickness in the HL groups was compared with that of the normal hearing group. RESULTS: In women, right ear HL was associated with cortical thinning: the minimal HL group showed cortical thinning in the left frontal and bilateral occipital areas and the mild-to-severe HL group showed cortical thinning in the bilateral frontal, right temporal and bilateral occipital areas compared to the normal hearing group. In men, there was no significant association between HL on either side and cortical thickness. CONCLUSION: In older women, right ear HL is associated with neurodegeneration even in a cognitively normal state. Therefore, managing HL especially in older women may be an effective strategy for dementia prevention.


Assuntos
Afinamento Cortical Cerebral , Perda Auditiva , Idoso , Audiometria de Tons Puros , Encéfalo , Feminino , Perda Auditiva/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino
20.
Scand J Rheumatol ; 49(4): 323-331, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32286141

RESUMO

OBJECTIVE: Epidemiological studies on inflammatory myopathies (IMs) show widely variable results, and studies on Asians are lacking. Despite emerging interest in the cardiovascular disease (CVD) risk associated with IMs, the prevalence of CVD in IM patients and its impact on mortality remain unclear. We conducted a nationwide, population-based study on the incidence, mortality, and associated major CVD events of IMs in the Republic of Korea over 11 years. METHOD: Using the nationwide, population-based National Health Insurance claims database and the Rare Intractable Disease registration programme, we estimated incidence, mortality, and CVD occurrence. Survival was examined using the Kaplan-Meier method. Mortality rate in IMs with CVD was analysed by Cox proportional hazards regression. RESULTS: There were 3014 incident cases, 640 of whom died during the study period. The mean annual incidence was 7.16/106. Dermatomyositis (DM) and polymyositis (PM) had 5 year survival rates of 76.8% and 79.3%, respectively. Cardiovascular events occurred in 155 patients and 40.6% of IM patients with CVD died. Acute myocardial infarction in men had the highest risk of any CVD event in both DM [standardized incidence ratio (SIR) 4.2, 95% confidence interval (95% CI) 2.4-7.2] and PM (SIR 3.5, 95% CI 1.8-7.0). Haemorrhagic stroke had the highest hazard ratio (HR) in both DM (HR 2.31, 95% CI 1.13-4.70) and PM patients (HR 2.10, 95% CI 1.03-4.27) compared with the general population with CVD. CONCLUSION: We found persistently low incidence, poor survival, and high major CVD incidence in IMs, and increased mortality in IMs with CVD.


Assuntos
Doenças Cardiovasculares/mortalidade , Miosite/complicações , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Adulto Jovem
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