Endovascular thrombectomy (EVT) access in remote areas is limited. Preliminary data suggest that long distance transfers for EVT may be beneficial; however, the magnitude and best imaging strategy at ...the referring center remains uncertain. We hypothesized that patients transferred >300 miles would benefit from EVT, achieving rates of functional independence (modified Rankin Scale mRS score of 0-2) at 3 months similar to those patients treated at the comprehensive stroke center in the randomized EVT extended window trials and that the selection of patients with computed tomography perfusion (CTP) at the referring site would be associated with ordinal shift toward better outcomes on the mRS.
This is a retrospective analysis of patients transferred from 31 referring hospitals >300 miles (measured by the most direct road distance) to 9 comprehensive stroke centers in Australia and New Zealand for EVT consideration (April 2016 through May 2021).
There were 131 patients; the median age was 64 53-74 years and the median baseline National Institutes of Health Stroke Scale score was 16 12-22. At baseline, 79 patients (60.3%) had noncontrast CT+CT angiography, 52 (39.7%) also had CTP. At the comprehensive stroke center, 114 (87%) patients underwent cerebral angiography, and 96 (73.3%) proceeded to EVT. At 3 months, 62 patients (48.4%) had an mRS score of 0 to 2 and 81 (63.3%) mRS score of 0 to 3. CTP selection at the referring site was not associated with better ordinal scores on the mRS at 3 months (mRS median of 2 1-3 versus 3 1-6 in the patients selected with noncontrast CT+CT angiography,
=0.1). Nevertheless, patients selected with CTP were less likely to have an mRS score of 5 to 6 (odds ratio 0.03 0.01-0.19;
<0.01).
In selected patients transferred >300 miles, there was a benefit for EVT, with outcomes similar to those treated in the comprehensive stroke center in the EVT extended window trials. Remote hospital CTP selection was not associated with ordinal mRS improvement, but was associated with fewer very poor 3-month outcomes.
Few studies have documented the viability of
-derived recombinant human bone morphogenetic protein-2 (rhBMP-2) in transforaminal lumbar interbody fusion (TLIF). This study aimed to assess the safety ...and fusion rate of rhBMP-2 in TLIF.
The study was conducted as a prospective, multicenter, single-arm trial, and 30 patients needing one- or two-level TLIF were enrolled. Fusion rate was assessed using the 12-month interbody fusion rate on CT. Postoperative problems, including seroma, radiculitis, and ectopic bone formation, which have been documented as risks associated with rhBMP-2 in prior studies, were recorded.
The study demonstrated fusion outcomes in all instances at 52 and 104 weeks post-surgery. Significant improvements were observed in clinical outcomes, with ODI, SF-36, and VAS scores, all achieving statistical significance (
< 0.0001). No perioperative adverse events requiring reoperation were reported, and there were no incidences of seroma, radiculitis, cage migration, grafted bone extrusion, postoperative neurologic deficit, or deep wound infection.
The study demonstrates the high safety and efficacy in inducing bone fusion of
-derived rhBMP-2 in TLIF, with a notable absence of adverse postoperative complications. Trial registration: This study protocol was registered at Korea Clinical Research Information Service (number identifier: KCT0004738) on July 2020.
To compare the diagnostic accuracy of aspiration biopsy and dilatation and curettage (D&C) in patients diagnosed with endometrial hyperplasia prior to hysterectomy.
We retrospectively reviewed ...medical records of 250 patients diagnosed with endometrial hyperplasia by endometrial sampling between July 2003 and March 2020. Endometrial sampling was performed by aspiration biopsy (n = 150) or D&C (n = 100), followed by hysterectomy within 6 months. Pathological findings of hysterectomy specimens of the two groups were compared to preoperative findings.
The overall diagnostic concordance between endometrial sampling specimen including D&C and aspiration biopsy, and hysterectomy specimen was 51.0% (51/100) and 41.3% (62/150), respectively. Patients whose preoperative specimen was obtained by D&C were upgraded less significantly than those who underwent aspiration biopsy (21.0% vs 36.7%; P = 0.008). In particular, significantly fewer patients were upgraded after D&C than after aspiration biopsy in hyperplasia without atypia (12.5% vs 29.0%; P = 0.028). In addition, when the final pathological upgrade rate to endometrial carcinoma was evaluated between the two methods of endometrial sampling, significantly fewer cases were noted after D&C than after aspiration biopsy (15.0% vs 27.3%; P = 0.022).
In our study, D&C more accurately reflected the final diagnosis in patients with endometrial hyperplasia than aspiration biopsy based on the histological examination of hysterectomy specimens. When considering the management strategy for women with an endometrial hyperplasia diagnosis obtained by aspiration biopsy, physicians should consider the significant rate of upgraded diseases with this method of endometrial sampling.
Renal cell carcinoma (RCC) is the most common type of kidney malignancy worldwide with Pembrolizumab and axitinib treatment (Pembro/Axi) amongst the most effective first-line immunotherapies for ...advanced RCC. However, it remains difficult to predict treatment response and early resistance. Therefore, we evaluated whether baseline serum interleukin-6 (IL-6) could be a predictive biomarker. Between November 2019 and December 2021, 58 patients with advanced RCC were enrolled, administered first-line Pembro/Axi, and baseline blood samples were analyzed using flow cytometry. The mean baseline serum IL-6 concentration was 8.6 pg/mL in responders and 84.1 pg/mL in patients with progressive disease. The IL-6 cut-off value was set at 6.5 pg/mL using time-dependent receiver operating characteristic curves, with 37.9% of patients having high baseline serum IL-6 levels and 62.1% having low levels. Objective response rates were 58.3% and 36.4% in low and high IL-6 groups, respectively. Overall survival and progression-free survival were longer in patients with low IL-6 levels than in those with high levels. High IL-6 levels were related to reduced interferon-γ and tumor necrosis factor-α production from CD8+ T cells. Overall, high baseline serum IL-6 levels were associated with worse survival outcomes and reduced T-cell responses in Pembro/Axi-treated advanced RCC patients.
We aimed to discover cell line‐specific overexpressed HOX genes responsible for chemoresistance and to identify the mechanisms behind HOX‐induced cell line‐specific chemoresistance in EOC. Ten HOX ...genes and eight EOC cell lines were tested for any cell line‐specific overexpression that presents a mutually exclusive pattern. Cell viability was evaluated after treatment with cisplatin and/or siRNA for cell line‐specific overexpressed HOX genes. Immunohistochemical (IHC) staining for HOXB9 was performed in 84 human EOC tissues. HOXA10 and HOXB9 were identified as cell line‐specific overexpressed HOX genes for SKOV‐3 and RMUG‐S, respectively. Inhibiting the expression of cell line‐specific HOX genes, but not of other HOX genes, significantly decreased cell viability. In SKOV‐3 cells, cell viability decreased to 46.5% after initial 10 µM cisplatin treatment; however, there was no further decrease upon additional treatment with HOXA10 siRNA. In contrast, cell viability did not significantly decrease upon cisplatin treatment in RMUG‐S cells, but decreased to 65.5% after additional treatment with HOXB9 siRNA. In both cell lines, inhibiting cell line‐specific HOX expression enhanced apoptosis but suppressed the expression of epithelial‐mesenchymal transition (EMT) markers such as vimentin, MMP9, and Oct4. IHC analysis showed that platinum‐resistant cancer tissues more frequently had high HOXB9 expression than platinum‐sensitive cancer tissues. HOXB9, which is overexpressed in RMUG‐S but not in SKOV‐3 cells, appeared to be associated with cell line‐specific platinum resistance in RMUG‐S. Inhibiting HOXB9 overexpression in RMUG‐S cells may effectively eliminate platinum‐resistant ovarian cancer cells by facilitating apoptosis and inhibiting EMT.
This study aimed to determine the factors influencing patients' choice of physician at the first visit through database analysis of a tertiary hospital in South Korea. We collected data on the first ...treatments performed by physicians who had treated patients for at least 3 consecutive years over 10 years (from 2003 to 2012) from the database of Seoul National University's affiliated tertiary hospital. Ultimately, we obtained data on 524,012 first treatments of 319,004 patients performed by 115 physicians. Variables including physicians' age and medical school and patients' age were evaluated as influencing factors for the number of first treatments performed by each physician in each year using a Poisson regression through generalized estimating equations with a log link. The number of first treatments decreased over the study period. Notably, the relative risk for first treatments was lower among older physicians than among younger physicians (relative risk 0.96; 95% confidence interval 0.95 to 0.98). Physicians graduating from Seoul National University (SNU) also had a higher risk for performing first treatments than did those not from SNU (relative risk 1.58; 95% confidence interval 1.18 to 2.10). Finally, relative risk was also higher among older patients than among younger patients (relative risk 1.03; 95% confidence interval 1.01 to 1.04). This study systematically demonstrated that physicians' age, whether the physician graduated from the highest-quality university, and patients' age all related to patients' choice of physician at the first visit in a tertiary university hospital. These findings might be due to Korean cultural factors.
This is a retrospective study which aims to identify major determinants of successful laparoscopic radical hysterectomy (LRH) versus abdominal radical hysterectomy (ARH) performed by inexperienced ...surgeons for stage IA2-IIA cervical cancer. A total of 161 consecutive patients with stage IA2-IIA cervical cancer who underwent RH were grouped into 2 groups according to the surgeons' experience with LRH: experienced surgeon versus inexperienced surgeon. After matching for age and risk factors, surgical and survival outcomes were compared. Experienced surgeon selected patients with earlier-stage and fewer risk factors for LRH than ARH, but inexperience surgeons did not. After matching, the vaginal tumor-free margin of LRH was shorter than that of ARH in experienced surgeon group (1.3 versus 1.7 cm, p=0.007); however, the vaginal tumor-free margin was longer than that of ARH in the inexperienced surgeon group (1.8 versus 1.3 cm, p=0.035). The postoperative hospital stay of LRH was shorter than that of ARH in experienced surgeon group (5.5 versus 7.7 days, p<0.001), but not different from that of ARH in the inexperienced surgeon group. Vaginal tumor-free margin >1.8 cm (OR 7.33, 95% CI 1.22-40.42), stage >IB1 (OR 8.83, 95% CI 1.51-51.73), and estimated blood loss >575 mL (OR 33.95, 95% CI 4.87-236.79) were independent risk factors for longer postoperative hospital stay in the inexperienced surgeon group. There was no difference of 5-year-profression-free survival of LRH patients between experienced surgeon and inexperienced surgeon groups after matching (55.1 versus 33.3%, p=0.391). Selection of earlier-stage disease and moderate vaginal tumor-free margin might be important for an inexperienced surgeon to successfully perform LRH with minimal complications in stage IA2-IIA cervical cancer.
The need to perform genetic sequencing to diagnose the polymerase epsilon exonuclease (
) subtype of endometrial cancer (EC) hinders the adoption of molecular classification. We investigated ...clinicopathologic and protein markers that distinguish the
from the copy number (CN)-low subtype in EC.
Ninety-one samples (15
, 76 CN-low) were selected from The Cancer Genome Atlas EC dataset. Clinicopathologic and normalized reverse phase protein array expression data were analyzed for associations with the subtypes. A logistic model including selected markers was constructed by stepwise selection using area under the curve (AUC) from 5-fold cross-validation (CV). The selected markers were validated using immunohistochemistry (IHC) in a separate cohort.
Body mass index (BMI) and tumor grade were significantly associated with the
subtype. With BMI and tumor grade as covariates, 5 proteins were associated with the EC subtypes. The stepwise selection method identified BMI, cyclin B1, caspase 8, and X-box binding protein 1 (XBP1) as markers distinguishing the
from the CN-low subtype. The mean of CV AUC, sensitivity, specificity, and balanced accuracy of the selected model were 0.97, 0.91, 0.87, and 0.89, respectively. IHC validation showed that cyclin B1 expression was significantly higher in the
than in the CN-low subtype and receiver operating characteristic curve of cyclin B1 expression in IHC revealed AUC of 0.683.
BMI and expression of cyclin B1, caspase 8, and XBP1 are candidate markers distinguishing the
from the CN-low subtype. Cyclin B1 IHC may replace
sequencing in molecular classification of EC.
We purposed to develop machine learning models predicting survival outcomes according to the surgical approach for radical hysterectomy (RH) in early cervical cancer. In total, 1056 patients with ...2009 FIGO stage IB cervical cancer who underwent primary type C RH by either open or laparoscopic surgery were included in this multicenter retrospective study. The whole dataset consisting of patients’ clinicopathologic data was split into training and test sets with a 4:1 ratio. Using the training set, we developed models predicting the probability of 5-year progression-free survival (PFS) and overall survival (OS) with tenfold cross validation. The developed models were validated in the test set. In terms of predictive performance, we measured the area under the receiver operating characteristic curve (AUC) values. The logistic regression models comprised of preoperative variables yielded AUCs of 0.679 and 0.715 for predicting 5-year PFS and OS rates, respectively. Combining both logistic regression and multiple machine learning models, we constructed hybrid ensemble models, and these models showed much improved predictive performance, with 0.741 and 0.759 AUCs for predicting 5-year PFS and OS rates, respectively. We successfully developed models predicting disease recurrence and mortality after primary RH in patients with early cervical cancer. As the predicted value is calculated based on the preoperative factors, such as the surgical approach, these ensemble models would be useful for making decisions when choosing between open or laparoscopic RH.
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