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BACKGROUND AND PURPOSE: Radiomics offers little explainability. This study aims to develop a radiomics model (Rad-Score) using diffusion-weighted imaging (DWI) to predict high-risk patients for nodal metastasis or recurrence in endometrial cancer (EC) and corroborate with choline metabolism. MATERIALS AND METHODS: From August 2015 to July 2018, 356 EC patients were enrolled. Rad-Score was developed using LASSO regression in a training cohort (n = 287) and validated in an independent test cohort (n = 69). MR spectroscopy (MRS) was also used in 230 patients. Nuclear MRS measured choline metabolites in 70 tissue samples. The performance was compared against European Society for Medical Oncology (ESMO) risk groups. A P < .05 denoted statistical significance. RESULTS: Rad-Score achieved 71.1% accuracy in the training and 71.0% in the testing cohorts. Incorporating clinical parameters of age, tumor type, size, and grade, Rad-Signature reached accuracies of 73.2% in training and 75.4% in testing cohorts, closely matching the performance to the post-operatively based ESMO's 70.7% and 78.3%. Rad-Score was significantly associated with increased total choline levels on MRS (P = .034) and tissue levels (P = .019). CONCLUSIONS: Development of a preoperative radiomics risk score, comparable to ESMO clinical standard and associated with altered choline metabolism, shows translational relevance for radiomics in high-risk EC patients. TRIAL REGISTRATION: This study was registered in ClinicalTrials.gov on 2015-08-01 with Identifier NCT02528864.
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Colina , Neoplasias do Endométrio , Humanos , Feminino , Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/metabolismo , Colina/metabolismo , Pessoa de Meia-Idade , Idoso , Medição de Risco/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/metabolismo , Adulto , Espectroscopia de Ressonância Magnética/métodos , Metástase Linfática/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , RadiômicaRESUMO
We aimed to investigate human papillomavirus (HPV) prevalence and genotype distribution and prognostic factors in vaginal cancer (VC). VC patients who received treatment between 1989 and 2020 were retrospectively reviewed. L1 general polymerase chain reaction (PCR) followed by HPV Blot (King Car, I-Lan, Taiwan) and E6 type-specific-PCR were performed for genotyping firstly. P16 and p53 immunohistochemistry staining was performed. Univariate and multivariate analyses identified predictors of clinical outcomes.79 VC patients were eligible for analysis. 73 patients (92.4%) were squamous cell carcinoma (SCC) and 6 (7.6%) as non-SCC. The median follow-up time was 134.3 months (range 0.9-273.4). Among nine initially HPV-negative cases, seven were identified as being positive through HPV16/18/45/52/58 whole-genome amplification followed by Sanger sequencing (WGASS). HPV DNA sequences were detected in 98.6% of SCC and 83.3% of non-SCC, respectively, with HPV16 (49.4%), HPV52 (15.2%) and HPV58 (8.9%) being predominant. Patients with paraaortic lymph node (LN) metastasis had a 5-year cancer-specific survival (CSS) rate of 0%. Multivariate analysis revealed that only p16 and stage were significantly correlated with prognosis. Variables with strong correlations (p16- and HPV-positivity, LN metastasis and stage), were included in models 2-5 alternatively. Stage III/IV (hazard ratio [HR] = 3.64-4.56) and LN metastasis (HR = 2.81-3.44) were significant negative predictors of CSS, whereas p16-positivity (HR = 0.29-0.32) and HPV-positivity (HR = 0.14) were related to better prognosis. In conclusion, 97.5% of VCs were HPV-positive with WGASS. Stage III/IV and LN metastasis were significant negative predictors, whereas p16- and HPV-positivity were significantly associated with better prognosis.
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BACKGROUND: Immune checkpoint inhibitors (ICIs) that against programmed cell death protein-1 (PD-1) and its ligand PD-L1 have been approved as a promising treatment of many human cancers. However, the responses to these ICIs were limited in patients with ovarian cancer. Studies have indicated that the response to PD-1/PD-L1 blockade might be correlated with the PD-L1 expression level in cancer cells. Nucleophosmin (NPM/B23) was found to be a potential target for immunotherapy. Whether NPM/B23 plays a role in cancer-associated immunity, such as PD-1/PD-L1 axis, and its underlying mechanisms remain largely unknown in ovarian cancer. METHODS: We applied ovarian cancer cell lines as research models. The effect of modulating PD-L1 by NPM/B23 was subsequently confirmed via Western blot, flow cytometry, qRT-PCR, luciferase reporter assays, and immunoprecipitation. Protein stability and ubiquitin assay assays were used to analyze the interplay between NPM/B23 and NF-ĸB/p65 in PD-L1 regulation. The MOSEC/Luc xenograft mouse model was used to validate the role of NPM/B23-PD-L1 through tumor growth in vivo. RESULTS: Our results revealed that NPM/B23 negatively regulates PD-L1 expression via a protein complex with NF-κB/p65 and through an IFN-γ pathway. Moreover, NPM/B23 inhibitor/modulator sensitized ovarian cancer cells to the anti-PD-1 antibody by regulating PD-L1 expression in the immunocompetent mouse model. Compared to anti-PD-1 antibody alone, a combination of anti-PD-1 antibody and NPM/B23 inhibitor/modulator showed reduced tumorigenesis and increased CD8+ T-cell expansion, thus contributing to prolonged survival on MOSEC/Luc-bearing mouse model. CONCLUSION: Targeting NPM/B23 is a novel and potential therapeutic approach to sensitize ovarian cancer cells to immunotherapy.
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RATIONALE: Early neurological deterioration (END) within 72 h of stroke onset is associated with poor prognosis. Optimizing hydration might reduce the risk of END. AIMS: This study aimed to determine in acute ischemic stroke patients if enhanced hydration versus standard hydration reduced the incidence of major (primary) and minor (secondary) END, as well as whether it increased the incidence of early neurological improvement (secondary), at 72 h after admission. SAMPLE SIZE ESTIMATE: A total of 244 participants per arm. METHODS AND DESIGN: A prospective, double-blinded, multicenter, parallel-group, randomized controlled trial conducted at four hospitals from April 2014 to July 2020, with data analyzed in August 2020. The sample size estimated was 488 participants (244 per arm). Ischemic stroke patients with measurable neurological deficits of onset within 12 h of emergency department presentation and blood urea nitrogen/creatinine (BUN/Cr) ratio ⩾ 15 at point of admission were enrolled and randomized to 0.9% sodium chloride infusions of varying rates-enhanced hydration (20 mL/kg body weight, one-third given via bolus and remainder over 8 h) versus standard hydration (60 mL/h for 8 h), followed by maintenance infusion of 40-80 mL/h for the subsequent 64 h. The primary outcome measure was the incidence of major END at 72 h after admission, defined as an increase in National Institutes of Health Stroke Scale of ⩾ 4 points from baseline. RESULTS: Overall, 487 participants were randomized (median age 67 years; 287 females). At 72 h, 7 (2.9%) in the enhanced hydration arm and 5 (2.0%) in the standard hydration developed major END (p = 0.54). The incidence of minor END and early neurological improvement did not differ between treatment arms. CONCLUSION AND RELEVANCE: Enhanced hydration did not reduce END or improve short-term outcomes in acute ischemic stroke. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02099383, https://clinicaltrials.gov/study/NCT02099383).
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Significance: Monitoring blood glucose levels is crucial for individuals with diabetes. Noninvasive methods for measuring serum glucose levels have been explored to aid in blood glucose control for diabetes management. Aim: We introduced a noncontact optical glucometer (NCGM) for measuring glucose levels in the aqueous humor of the human eye. We also investigated the correlation between glucose levels in the NCGM and the aqueous humor, blood samples, and self-monitoring blood glucose devices. Approach: The optical system used in this study measured both the near-infrared absorption and polarized rotatory distribution of glucose molecules in the human aqueous humor. This prospective study's outcomes were eye aqueous glucose level, preoperative blood glucose level, intraoperative blood glucose level, and NCGM reading of patients in a single center in Taiwan. Results: The NCGM's measurements showed a strong correlation with blood glucose levels (intra-class correlation [ICC]: 0.95 to 0.98) and aqueous humor glucose levels (ICC: 0.76), indicating its ability to noninvasively measure blood glucose levels in human subjects. Conclusions: This NCGM may offer a convenient, pain-free, and rapid tool for measuring blood glucose levels in diabetic patients. The device could represent a significant advancement in noncontact hybrid optical glucose measurement systems.
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Diabetes Mellitus , Dispositivos Ópticos , Humanos , Glicemia , Humor Aquoso , Estudos Prospectivos , GlucoseRESUMO
OBJECTIVE: This study compared the outcomes of laparotomic radical hysterectomy (LRH) and minimally invasive radical hysterectomy (MISRH) in patients with early-stage cervical cancer. METHODS: The clinical data of patients with early-stage cervical cancer who underwent LRH or MISRH (laparoscopic/robotic) at Chang Gung Memorial Hospital, Linkou Branch, from 2002 to 2017 were retrospectively reviewed. The surgical safety (operation time, blood loss, blood transfusion rate, length of postoperative stay, and perioperative complications), overall survival (OS), disease-free survival (DFS), and recurrence pattern were analyzed. Propensity score matching (PSM) at a 3:1 ratio was performed to balance prognostic variables. RESULTS: Of the 760 patients (entire cohort), 614 underwent LRH and 146 underwent MISRH. After PSM, 394 and 140 patients were included in the LRH and MISRH groups, respectively. The 5-year OS rate was significantly lower in the MISRH group than in the LRH group (85.6% vs. 93.2%, p=0.043), and the 5-year DFS rate (p=0.21) did not differ significantly. After PSM, the 5-year OS rates did not differ significantly between the MISRH and LRH groups (87.1% vs. 92.1%, p=0.393). The MISRH group had a significantly shorter operation time (p<0.001), lower intraoperative blood loss (p<0.001), lower blood transfusion rate (p<0.001), and shorter postoperative stay (p<0.001) but a significantly higher rate of intraoperative bladder injury (p<0.001) than the LRH group. CONCLUSION: After PSM, MISRH is associated with nonsignificantly lower OS but a significantly higher risk of intraoperative urological complications than LRH.
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With the rising need for accessible cervical cancer screening, self-sampling methods offer a promising alternative to traditional physician-led sampling. This study aims to evaluate the efficacy of the HygeiaTouch Self Sampling Kit for Women in detecting human papillomavirus (HPV) types and predicting cervical lesions. We studied the concordance in identifying high-risk HPV (hrHPV) types between samples collected by physicians and those self-collected by women using a self-sampling kit for validation. Women aged 21-65, fitting into specific categories based on their cervical health history were eligible. Cohen's kappa coefficient to gauge concordance between the two specimen types and relative accuracy metrics in identifying cervical intraepithelial neoplasia (CIN) were also calculated, with physician-sampled specimens serving as a reference. A total of 1210 participants from three institutes were involved. The self-sampling kit closely matched the physician-led method in terms of collecting valid specimens (100% vs. 100%), identifying hrHPV types (kappa: 0.75, 95% confidence interval [95% CI]: 0.72-0.79; agreement: 87.7%, 95% CI: 85.8-89.6) and predicting CIN grade 2 or worse (CIN2+) (relative sensitivity: 0.949, relative accuracy: 0.959). Kappa values varied between 0.71 and 0.83 for different hrHPV types and combinations, with an overall value 0.75 (95% CI: 0.72-0.79) signifying robust compatibility between the two methods. Our study underscores the potential of the HygeiaTouch Self Sampling Kit as a reliable, efficient, and user-friendly alternative to traditional sampling methods. This suggests that self-sampling could be pivotal in expanding cervical cancer screening accessibility and enhancing detection rates.
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Infecções por Papillomavirus , Médicos , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Papillomavirus Humano , Detecção Precoce de Câncer/métodos , Papillomaviridae/genética , Manejo de Espécimes/métodos , Esfregaço Vaginal/métodos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Concurrent chemoradiotherapy (CCRT) is the standard of care for locally advanced cervical cancer. In this study, we analyzed the pretreatment clinical and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) characteristics of patients with locally advanced cervical squamous cell carcinoma (SCC) to develop a scoring prototype for risk stratification. METHODS: Two cohorts were constructed in this study. Cohort 1 comprised patients with cervical SCC with 2009 FIGO stage III-IVA or stage I-II with positive pelvic or para-aortic lymph node (PALN) on PET/CT from AGOG09-001 trial. Cohort 2 comprised patients with similar characteristics who had received adequate therapy in our hospital between 2016 and 2021. Pretreatment patient characteristics and PET/CT parameters including maximum standardized uptake value (SUVmax) and metabolic tumor volume (MTV) of primary tumor and nodal SUVmax were assessed for cancer-specific survival (CSS) using multivariate Cox regression. RESULTS: Analysis of combined data from cohorts 1 (n = 55) and 2 (n = 128) indicated age ≥ 66 years, primary tumor MTV ≥87 mL, and positive PALN on PET/CT to be independently significant adverse predictors for CSS (p < 0.001, p = 0.014, and p = 0.026, respectively) with a median follow-up duration of 51 months. Assigning a score of 1 to each adverse predictor, patients with cumulative risk scores of 0, 1, 2, and 3 were discovered to have a 5-year CSS of 86.9%, 71.0%, 32.2%, and 0%, respectively (p < 0.001). CONCLUSION: Age, primary tumor MTV, and positive PALN on PET/CT may serve as independent predictors of poor survival in patients with locally advanced cervical SCC. Our findings indicate that patients without any adverse factors can receive standard CCRT, whereas those with at least one adverse factor can consider novel combination therapies or clinical trials.
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Carcinoma de Células Escamosas , Quimiorradioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/diagnóstico por imagem , Pessoa de Meia-Idade , Idoso , Medição de Risco , Estadiamento de Neoplasias , Fluordesoxiglucose F18 , Medicina de Precisão/métodos , Adulto , Carga TumoralRESUMO
OBJECTIVE: Lynch syndrome (LS) is a hereditary cancer predisposition syndrome with a significantly increased risk of colorectal and endometrial cancers. Current standard practice involves universal screening for LS in patients with newly diagnosed colorectal or endometrial cancer using a multi-step screening protocol (MSP). However, MSP may not always accurately identify LS cases. To address this limitation, we compared the diagnostic performance of immediate germline sequencing (IGS) with MSP in a high-risk group. METHODS: A total of 31 Taiwanese women with synchronous or metachronous endometrial and colorectal malignancies underwent MSP which included immunohistochemical staining of DNA mismatch repair (MMR) proteins, MLH1 promoter hypermethylation analysis, and germline sequencing to identify pathogenic variants. All patients who were excluded during MSP received germline sequencing for MMR genes to simulate IGS for the detection of LS. RESULTS: Our findings indicate that IGS surpassed MSP in terms of diagnostic yield (29.0% vs. 19.4%, respectively) and sensitivity (90% vs. 60%, respectively). Specifically, IGS successfully identified nine LS cases, which is 50% more than the number detected through MSP. Additionally, germline methylation analysis revealed one more LS case with constitutional MLH1 promoter hypermethylation, bringing the total LS cases to ten (32.3%). Intriguingly, we observed no significant differences in clinical characteristics or overall survival between patients with and without LS in our cohort. CONCLUSION: Our study suggests that IGS may potentially offer a more effective approach compared to MSP in identifying LS among high-risk patients. This advantage is evident when patients have been pre-selected utilizing specific clinical criteria.
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Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias do Endométrio , Humanos , Feminino , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Biomarcadores Tumorais/análise , Detecção Precoce de Câncer/métodos , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Células Germinativas/química , Células Germinativas/metabolismo , Células Germinativas/patologia , Reparo de Erro de Pareamento de DNA/genética , Proteína 1 Homóloga a MutL/genética , Metilação de DNARESUMO
BACKGROUND: We aimed to develop and validate a preoperative CT-based radiomics signature for differentiating lymphoma versus benign splenomegaly. METHODS: We retrospectively analyzed CT studies from 139 patients (age range 26-93 years, 43% female) between 2011 and 2019 with histopathological diagnosis of the spleen (19 lymphoma, 120 benign) and divided them into developing (n = 79) and testing (n = 60) datasets. The volumetric radiomic features were extracted from manual segmentation of the whole spleen on venous-phase CT imaging using PyRadiomics package. LASSO regression was applied for feature selection and development of the radiomic signature, which was interrogated with the complete blood cell count and differential count. All p values < 0.05 were considered to be significant. RESULTS: Seven features were selected for constructing the radiomic signature after feature selection, including first-order statistics (10th percentile and Robust Mean Absolute Deviation), shape-based (Surface Area), and texture features (Correlation, MCC, Small Area Low Gray-level Emphasis and Low Gray-level Zone Emphasis). The radiomic signature achieved an excellent diagnostic accuracy of 97%, sensitivity of 89%, and specificity of 98%, distinguishing lymphoma versus benign splenomegaly in the testing dataset. The radiomic signature significantly correlated with the platelet and segmented neutrophil percentage. CONCLUSIONS: CT-based radiomics signature can be useful in distinguishing lymphoma versus benign splenomegaly and can reflect the changes in underlying blood profiles.
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BACKGROUND: The International Society of Urological Pathology (ISUP) grade and positive surgical margins (PSMs) after radical prostatectomy (RP) may reflect the prognosis of prostate cancer (PCa) patients. This study aimed to investigate whether DCE-MRI parameters (i.e., Ktrans, kep, and IAUC) could predict ISUP grade and PSMs after RP. METHOD: Forty-five PCa patients underwent preoperative DCE-MRI. The clinical characteristics and DCE-MRI parameters of the 45 patients were compared between the low- and high-risk (i.e., ISUP grades III-V) groups and between patients with or without PSMs after RP. Multivariate logistic regression analysis was used to identify the significant predictors of placement in the high-risk group and PSMs. RESULTS: The DCE parameter Ktrans-max was significantly higher in the high-risk group than in the low-risk group (p = 0.028) and was also a significant predictor of placement in the high-risk group (odds ratio [OR] = 1.032, 95% confidence interval [CI] = 1.005-1.060, p = 0.021). Patients with PSMs had significantly higher prostate-specific antigen (PSA) titers, positive biopsy core percentages, Ktrans-max, kep-median, and kep-max than others (all p < 0.05). Of these, positive biopsy core percentage (OR = 1.035, 95% CI = 1.003-1.068, p = 0.032) and kep-max (OR = 1.078, 95% CI = 1.012-1.148, p = 0.020) were significant predictors of PSMs. CONCLUSION: Preoperative DCE-MRI parameters, specifically Ktrans-max and kep-max, could potentially serve as preoperative imaging biomarkers for postoperative PCa prognosis based on their predictability of PCa risk group and PSM on RP, respectively.
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Background: Few studies have compared robotic-arm-assisted unisurgeon uniportal surgeries with conventional human-assisted uniportal video-assisted thoracoscopic surgeries (VATSs) in terms of surgical efficacy and patient safety. In the present study, we compared the aforementioned surgeries. Methods: We explored two robotic endoscope holders-a passive robotic platform (ENDOFIXexo, EA group) and a pedal-controlled active robotic platform (MTG-100, MA group)-for unisurgeon uniportal surgeries and compared the surgical outcomes with those of human-assisted uniportal surgeries (HA group) in 228 patients with a lung lesion (size, <5 cm). The primary parameters for this comparison were surgical efficacy, patient safety, and short-term patient outcomes. Results: No significant differences were observed among the EA, MA, and HA groups. The success rate of robotic-arm-assisted unisurgeon uniportal wedge resection was 100%, regardless of the group. No major differences were noted in preparation time between the EA and MA groups. Segmentectomy was more favorable in the EA group than in the MA group. The rates of surgical conversion were 5% and 60% in the EA and MA groups, respectively. The EA and MA groups did not differ considerably from the HA group in terms of postoperative complications. Conclusions: Unisurgeon uniportal wedge resection may be effectively performed using a robotic endoscope holder, without the need for any human assistants with an expert hand. However, the rate of surgical conversion increases with the complexity of uniportal anatomic resections. The passive platform appears to be more suitable for unisurgeon uniportal surgery than the active pedal-controlled platform given the equipment in contemporary operating rooms.
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Importance: Randomized clinical trials (RCTs) and meta-analyses have reported inconsistent conclusions regarding optimal distal radius fracture (DRF) treatment in older adults and are limited due to the inclusion of cohort studies with small sample sizes. A network meta-analysis (NMA) addresses these limitations by only synthesizing direct and indirect evidence from RCTs and may clarify optimal DRF treatment in older adults. Objective: To examine DRF treatment results in optimal short-term and intermediate-term patient-reported outcomes. Data Sources: Searches of MEDLINE, Embase, Scopus, and Cochrane Central Register of Controlled Trials were conducted for RCTs that investigated DRF treatment outcomes in older adults between January 1, 2000, and January 1, 2022. Study Selection: Randomized clinical trials including patients with a mean age of 50 years or older that compared the following DRF treatments were eligible for inclusion: casting, open reduction and internal fixation with volar lock plating (ORIF), external fixation, percutaneous pinning, and nail fixation. Data Extraction and Synthesis: Two reviewers independently completed all data extraction. An NMA aggregated all direct and indirect evidence among DRF treatments. Treatments were ranked by surface under the cumulative ranking curve score. Data are reported as standard mean differences (SMDs) and 95% CIs. Main Outcomes and Measures: The primary outcome was short-term (≤3 months) and intermediate-term (>3 months to 1 year) Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire scores. Secondary outcomes included Patient-Rated Wrist Evaluation (PRWE) scores and 1-year complication rates. Results: In this NMA, 23 RCTs consisting of 3054 participants (2495 women [81.7%]) with a mean (SD) age of 66 (7.8) years were included. At 3 months, DASH scores were significantly lower for nail fixation (SMD, -18.28; 95% CI, -29.93 to -6.63) and ORIF (SMD, -9.28; 95% CI, -13.90 to -4.66) compared with casting. The PRWE scores were also significantly lower for ORIF (SMD, -9.55; 95% CI, -15.31 to -3.79) at 3 months. In the intermediate term, ORIF was associated with lowered DASH (SMD, -3.35; 95% CI, -5.90 to -0.80) and PRWE (SMD, -2.90; 95% CI, -4.86 to -0.94) scores. One-year complication rates were comparable among all treatments. Conclusions and Relevance: The findings of this NMA suggest that ORIF may be associated with clinically significant improvements in short-term recovery compared with casting for multiple patient-reported outcomes measures with no increase in 1-year complication rates. Shared decision-making with patients may be useful to identify patient preferences regarding recovery to determine optimal treatment.
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Fraturas do Rádio , Fraturas do Punho , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Fixação de Fratura/métodos , Fixação Interna de Fraturas/métodos , Metanálise em Rede , Fraturas do Rádio/cirurgia , MasculinoRESUMO
OBJECTIVE: To report obstetric outcomes in pregnant women with previous pelvic ring injury (PRI) and investigate the correlation between residual pelvic deformity and the mode of delivery. DESIGN: Retrospective cohort study. SETTING: Single medical centre in Taiwan. POPULATION: Forty-one women with PRI histories from 2000 to 2021 who subsequently underwent pregnancy and delivery. METHODS: All patients had complete PRI treatment and radiological follow up for at least 1 year. The demographic data, radiological outcomes after PRI and obstetric outcomes were collected to investigate the potential factors of delivery modes using non-parametric approaches and logistic regression. Caesarean section (CS) rates among different subgroups were reported. MAIN OUTCOME MEASURES: Comparisons of demographic data and radiological outcomes (Matta/Tornetta criteria and Lefaivre criteria) after PRI among patients who had subsequent pregnancy and underwent vaginal deliveries (VD) or CS. RESULTS: There were 14 VD and 27 CS in 41 patients. Nine patients underwent CS because of their PRI history, 12 patients underwent CS for other obstetric indications and 20 underwent trial of labour. Based on the logistic regression model, retained trans-iliosacral implants did not significantly increase the risk of CS (odds ratio [OR] 1.20; 95% CI 0.17-8.38). Higher pelvic asymmetry value by Lefaivre criteria was a potential risk factor for CS after previous PRI (OR 1.52; 95% CI 1.043-2.213). CONCLUSIONS: VD is possible after PRI. Retained trans-iliosacral implants do not affect the delivery outcome. Residual pelvic asymmetry after PRI by Lefaivre criteria is a potential risk factor for CS.
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Cesárea , Parto Obstétrico , Feminino , Gravidez , Humanos , Cesárea/efeitos adversos , Estudos Retrospectivos , Parto Obstétrico/efeitos adversos , Fatores de Risco , Taiwan/epidemiologiaRESUMO
BACKGROUND: We investigated whether mutations in plasma circulating tumor DNA (ctDNA) can provide prognostic insight in patients with different histological types of ovarian carcinoma. We also examined the concordance of mutations detected in ctDNA samples with those identified in the corresponding formalin-fixed paraffin-embedded (FFPE) tumor specimens. METHODS: Between July 2016 and December 2017, 29 patients with ovarian carcinoma were prospectively enrolled. FFPE tumor specimens were obtained from all participants. A total of 187 blood samples for ctDNA analysis were collected before surgery (C0), immediate after surgery before adjuvant chemotherapy (C1), and at six-month intervals. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. RESULTS: The study cohort consisted of 13 (44.8%) patients with high-grade serous carcinomas (HGSC), 9 (31.0%) with clear cell carcinoma, 2 (6.9%) with mucinous carcinomas, 4 (13.8%) with low-grade serous carcinomas, and 1 (3.4%) with endometrioid carcinoma. Twenty-four (82.8%) patients had at least one detectable ctDNA variant. The concordance rate between mutations identified in pretreatment ctDNA and corresponding FFPE tumor specimens was 92.3% for patients with HGSC and 58.6% for the entire cohort. The median follow-up time was 33.15 months (range: 0.79-46.13 months). Patients with an advanced stage disease more likely had detectable ctDNA mutations before surgery (C0) and after surgery at C1, while those with HGSC more likely had ctDNA mutations detected before surgery. The presence of ctDNA mutations at C1 was an independent predictor of worse OS with a hazard ratio of 6.56 (95% confidence interval, (1.07-40.17) for detectable versus undetectable C1 ctDNA variants, p = 0.042). CONCLUSIONS: ctDNA mutations are common in patients with ovarian carcinoma. The presence of ctDNA mutations after surgery was an independent predictor of less favorable PFS and OS.
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Carcinoma , DNA Tumoral Circulante , Neoplasias Ovarianas , Humanos , Feminino , DNA Tumoral Circulante/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/cirurgia , Mutação/genética , Prognóstico , Período Pós-Operatório , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genéticaRESUMO
Uterine carcinosarcoma (UCS) is a highly aggressive gynecologic malignancy. Recurrent or persistent/progressive disease is usually fatal. We aimed to investigate the management and prognosis of these patients. Clinical records of UCS patients from June 1987 to April 2020 were retrospectively reviewed. The stage was re-assigned with the FIGO 2009 staging system. Univariate and multivariate analyses were used to identify the independent predictors of survival after recurrence (SAR) and cancer-specific survival (CSS). Of the 168 patients, 98 experienced treatment failure. The median time to treatment failure (TTF) was 8.1 months (range: 0.0-89.1). The median follow-up time of censored patients was 32.0 months (range: 16.8-170.7). The 5-year SAR rates of those with recurrent or persistent/progressive disease were 7.6%. On multivariate analysis, salvage therapy mainly using radiotherapy (HR 0.27, 95% CI: 0.10-0.71) or chemotherapy (HR 0.41, 95% CI: 0.24-0.72) or chemoradiotherapy (CRT) (HR 0.33, 95% CI: 0.15-0.75) were associated with improved SAR, whereas disseminated recurrence was associated with significantly worse SAR (HR 3.94, 95% CI: 1.67-9.31, p = 0.002). Salvage therapy using radiotherapy or chemotherapy or CRT significantly improved SAR. Surgery significantly improved CSS but not SAR, adjusting for confounding factors.
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Carcinossarcoma , Neoplasias Uterinas , Humanos , Feminino , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/patologia , PrognósticoRESUMO
Heterologous prime-boost COVID-19 vaccine strategy may facilitate mass COVID-19 immunization. We reported early immunogenicity and safety outcomes of heterologous immunization with a viral vector vaccine (ChAdOx1) and a spike-2P subunit vaccine (MVC-COV1901) in a participant-blinded, randomized, non-inferiority trial (NCT05054621). A total of 100 healthy adults aged 20-70 years having the first dose of ChAdOx1 were 1:1 randomly assigned to receive a booster dose either with ChAdOx1 (n = 50) or MVC-COV1901 (n = 50) at an interval of 4-6 or 8-10 weeks. At day 28 post-boosting, the neutralizing antibody geometric mean titer against wild-type SARS-CoV-2 in MVC-COV1901 recipients (236 IU/mL) was superior to that in ChAdOx1 recipients (115 IU/mL), with a GMT ratio of 2.1 (95% CI, 1.4 to 2.9). Superiority in the neutralizing antibody titer against Delta variant was also found for heterologous MVC-COV1901 immunization with a GMT ratio of 2.6 (95% CI, 1.8 to 3.8). Both spike-specific antibody-secreting B and T cell responses were substantially enhanced by the heterologous schedule. Heterologous boosting was particularly prominent at a short prime-boost interval. No serious adverse events occurred across all groups. The findings support the use of heterologous prime-boost with ChAdOx1 and protein-based subunit vaccines.
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COVID-19 , Vacinas Virais , Adulto , Anticorpos Neutralizantes , COVID-19/prevenção & controle , Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Humanos , SARS-CoV-2 , Vacinas de Subunidades Antigênicas , Vacinas SintéticasRESUMO
BACKGROUND: The study aimed to assess the clinical characteristics of patients with nocardiosis, to evaluate the in vitro susceptibility of antimicrobial agents against Nocardia species, and to explore changes in antimicrobial susceptibilities in this era of multidrug resistance. METHODS: Nocardia isolates were identified to the species level using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S rRNA, hsp65, and secA1 gene sequencing, and minimum inhibitory concentrations (MICs) of 15 antimicrobial agents were assessed with the broth microdilution method. RESULTS: Eighty-nine isolates from 68 patients were identified to species level. The most common species were Nocardia brasiliensis (n = 28, 31.5%), followed by N. farcinica (n = 24, 27%) and N. cyriacigeorgica (n = 16, 18%). Skin and soft tissue were the most common sites of nocardiosis. In multivariate analysis, cutaneous infection (OR, 0.052; p = 0.009), immunosuppressant use (OR, 16.006; p = 0.013) and Charlson combidity index (OR, 1.522; p = 0.029) were significant predictors for death. In total, 98.9% isolates were susceptible to trimethoprim-sulfamethoxazole and linezolid. Further, the MIC range and resistance rate of all Nocardia species to ceftriaxone, imipenem, and amoxicillin-clavulanic acid were found to generally increase over time. CONCLUSION: Considering that trimethoprim-sulfamethoxazole is effective against most Nocardia species, it is the antibiotic of choice in Taiwan. Besides, amikacin, tigecycline, and linezolid showed high activity against Nocardia species and are thus good alternatives or additional therapies to treat nocardiosis, depending on patient's underlying conditions and site of infection.
Assuntos
Anti-Infecciosos , Nocardiose , Nocardia , Amicacina/farmacologia , Amicacina/uso terapêutico , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Humanos , Imipenem/farmacologia , Imipenem/uso terapêutico , Imunossupressores/uso terapêutico , Linezolida , Testes de Sensibilidade Microbiana , Nocardia/genética , Nocardiose/tratamento farmacológico , RNA Ribossômico 16S/genética , Taiwan , Centros de Atenção Terciária , Tigeciclina/farmacologia , Tigeciclina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/farmacologia , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
BACKGROUND: Lateral epicondylitis is a common enthesopathy, possibly caused by overuse and repetitive activity. Although nonoperative management is the primary approach for treating lateral epicondylitis, clinical guidelines and the literature fail to identify the most effective nonoperative treatment. Therefore, the authors conducted a network meta-analysis to compare the effectiveness of physical therapy and electrophysiotherapy treatments for the treatment of lateral epicondylitis. METHODS: The authors searched MEDLINE, EMBASE, Web of Science, and Scopus for peer-reviewed randomized controlled trials evaluating the effectiveness of physical therapy and electrophysiotherapy treatments. Data related to article characteristics and outcomes (grip strength and pain visual analog scale score) were collected. RESULTS: Twenty-three clinical trials including 1363 participants (mean age ± SD, 47.4 ± 7.5 years; 53.1 percent women) were included in this study. Pain visual analog scale demonstrated significant reductions in scores after treatment with magnetic field [mean difference (95 percent CI), -1.88 (-2.66 to -1.11)], exercise [-0.90 (-1.69 to -0.1)], and acoustic waves [-0.83 (-1.37 to -0.29)] compared with placebo. For grip strength, no treatment modality was found to be significantly effective. A sensitivity analysis that excluded studies with high publication bias and high degrees of heterogeneity produced similar results to the main analysis with the exception of statistically improved grip strength after light therapy [mean difference (95 percent CI), 5.38 (1.71 to 9.04)] and acoustic wave therapy [7.79 (2.44 to 13.15)]. CONCLUSIONS: Electrophysiotherapy treatments should be prioritized over physical therapy. Magnetic field therapy was associated with pain reduction, whereas acoustic wave and light therapy were associated with increased grip strength. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.
Assuntos
Cotovelo de Tenista , Feminino , Humanos , Metanálise em Rede , Dor , Medição da Dor , Modalidades de Fisioterapia , Cotovelo de Tenista/terapiaRESUMO
OBJECTIVE: This study (Asian Gynecologic Oncology Group [AGOG]13-001/Taiwanese Gynecologic Oncology Group [TGOG]1006) was to validate human papillomavirus (HPV)16 as an independent good prognostic factor and investigate the impact of treatment modalities to cervical adenocarcinoma and adenosquamous carcinoma (AD/ASC). MATERIALS AND METHODS: Patients receiving primary treatment at AGOG and TGOG member hospitals for cervical AD/ASC were retrospectively (1993-2014) and prospectively (since 2014) enrolled. DNA extraction from paraffin-embedded tissue (FFPE) specimens was used for HPV genotyping. Those with suspected endometrial origin were excluded for analysis. RESULTS: A total of 354 patients with valid HPV results were enrolled, 287 (81.1%) of which had HPV-positive tumors. The top-3 types were HPV 18 (50.8%), HPV16 (22.9%) and HPV45 (4.0%). The HPV16-negativity rates varied widely across hospitals. 322 patients were eligible for prognostic analyses. By multivariate analysis, advanced stage (HR5.8, 95% confidence interval [CI] 2.1-15.8; HR5.8, 95% CI 1.6-20.5), lymph node metastasis (HR4.6, 95% CI 2.7-7.9; HR7.3, 95% CI 3.8-14.0), and HPV16-positivity (HR0.3, 95% CI 0.1-0.6; HR0.3, 95% CI 0.1-0.9) were independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Stage I patients with primary surgery had better 5-year PFS (82.8% vs 50.0% p = 0.020) and OS (89.3% vs 57.1%, p = 0.017) than those with non-primary surgery, while the propensity scores distribution were similar among the treatment groups. CONCLUSION: This study confirmed that HPV16-positivity was a good prognostic factor for PFS and OS in AD/ASC, and patients seemed to have better outcome with primary surgery than non-primary surgery.