Study on the preoperative value of serum SCC-Ag in predicting the stromal invasion of cervical squamous cell carcinoma.

To investigate the preoperative value of serum SCC-Ag in predicting the stromal invasion of cervical squamous cell carcinoma. This study retrospectively analyzed 78 patients with early cervical squamous cell carcinoma who underwent surgery as initial treatment at the Senior Department of Obstetrics and Gynecology, the Seventh Medical Center of PLA General Hospital from January 2018 to September 2022 was implemented. The clinicopathological characteristics were statistically compared. The ROC curve was drawn to determine the optimal critical level of  preoperative serum SCC-Ag value for predicting cervical stromal invasion. The depth of myometrial invasion was not related to the age of diagnosis and HPV infection (p > 0.05), while it was related to tumor size, staging, tissue differentiation, LVSI, lymph node metastasis (LNM) and preoperative serum SCC-Ag value (p < 0.05).The area under the curve (AUC) of serum SCC-Ag value was 0.894 (p = 0.000, 95% CI 0.824-0.964), and preoperative serum SCC-Ag value 1.65 ng/ml was the best cutoff for predicting cervical stromal invasion in cervical squamous cell carcinoma. The sensitivity and specificity of diagnosis were 92.3% and 78.8%, respectively. If the preoperative serum SCC-Ag leval more than 1.65 ng/ml in patients with cervical squamous cell carcinoma, the risk of cervical stromal invasion will increase, which can provide a reference for clinical treatment.

Qin L 《-》

Comparison of Two Modern Survival Prediction Tools, SORG-MLA and METSSS, in Patients With Symptomatic Long-bone Metastases Who Underwent Local Treatment With Surgery Followed by Radiotherapy and With Radiotherapy Alone.

Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. Level III, diagnostic study.

Lee CC ，Chen CW ，Yen HK ，Lin YP ，Lai CY ，Wang JL ，Groot OQ ，Janssen SJ ，Schwab JH ，Hsu FM ，Lin WH ... -  《-》

[Study on the difference and clinical value of serum amino acids in patients with laryngeal squamous cell carcinoma].

Objective:To detect the differences in types and levels of amino acids in the peripheral serum of patients with laryngeal squamous cell carcinoma and non-tumor patients, and explore their relationship with clinical parameters of laryngeal squamous cell carcinoma as well as their clinical value in diagnosis. Methods:High-performance liquid chromatography-tandem mass spectrometry（HPLC-MS） was employed to detect the serum amino acid contents and levels of 62 patients diagnosed with laryngeal carcinoma and 141 non-tumor patients at the First Affiliated Hospital of Jinzhou Medical University between September 2018 and February 2021. The study compared the differences in 22 non-essential and essential amino acids found in the serum between the experimental group and the control group. An ROC curve and risk scoring formula of multivariate linear logic regression model was utilized to evaluate the efficiency of serum amino acids in the early diagnosis of laryngeal carcinoma. Results:There were significant differences in the contents of fourteen types of amino acids between the experimental and control groups, with thirteen amino acids showing higher levels in the experimental group（P<0.05）. Seven of these amino acids were essential, including phenylalanine, threonine, leucine, valine, histidine, tyrosine, and citrulline. The other six amino acids were non-essential, including arginine, asparagine, cysteine, glycine, ornithine, and proline. Interestingly, the content of homocysteine in the experimental group was lower than that in the control group（P=0.024）. Further analysis showed that patients with laryngeal squamous cell carcinoma in TNM stage Ⅰ and Ⅱ had higher serum methionine levels compared to those in stages Ⅲ and Ⅳ（P=0.026）. In addition, the content of serum histidine was higher in patients with poorly differentiated squamous cell carcinoma compared to those with well-differentiated squamous cell carcinoma（P=0.041）. The level of asparagine in the serum of patients with laryngeal squamous cell carcinoma older than 64 years old was lower than that in patients younger than 64 years old（P=0.033）. The level of tryptophan in the serum of patients with a smoking history was lower than that in patients without a smoking history（P=0.033）. The level of citrulline in the serum of patients with a history of alcohol consumption was higher than that in patients with no history of alcohol consumption（P=0.003）. ROC curve analysis showed that out of the 14 different amino acids between the experimental and control groups, citrulline and cysteine were relatively effective as independent factors in the diagnosis of laryngeal squamous cell carcinoma, with an AUC of 0.856 and 0.850, respectively. Arginine was the most sensitive factor in the diagnosis of laryngeal squamous cell carcinoma（AUC=0.855）. However, citrulline alone had the highest specificity（0.830） in the diagnosis of laryngeal squamous cell carcinoma, and the combination of 12 amino acids significantly improved the diagnostic efficiency of laryngeal squamous cell carcinoma, with an AUC of 0.946, sensitivity of 0.887, and specificity of 0.894. A risk score formula for a multivariate logistic regression model was established based on the differential amino acid content in the serum. The risk score of laryngeal squamous cell carcinoma group was higher than that of the non-tumor group（P<0.001）. The AUC of risk score in the diagnosis of laryngeal squamous cell carcinoma was 0.953 with sensitivity and specificity of 0.957 and 0.855. Conclusion:This study found that there are differences in the contents of 14 amino acids among which 13 amino acids were increased in serum of patients with laryngeal squamous cell carcinoma, and were associated with age, clinical stage, pathological differentiation, smoking, and drinking. Combined detection of 12 amino acids can improve the diagnostic efficiency of laryngeal squamous cell carcinoma and serve as potential markers for the auxiliary diagnosis of laryngeal squamous cell carcinoma using peripheral blood samples. Additionally, the established risk score model was found to be more effective in the diagnosis of laryngeal squamous cell carcinoma, indicating its important potential value as an auxiliary diagnostic tool.

Sun Y ，Gan M ，Wu Y ，Gao W ，Lu Y ... -  《-》

Serum and urine nucleic acid screening tests for BK polyomavirus-associated nephropathy in kidney and kidney-pancreas transplant recipients.

BK polyomavirus-associated nephropathy (BKPyVAN) occurs when BK polyomavirus (BKPyV) affects a transplanted kidney, leading to an initial injury characterised by cytopathic damage, inflammation, and fibrosis. BKPyVAN may cause permanent loss of graft function and premature graft loss. Early detection gives clinicians an opportunity to intervene by timely reduction in immunosuppression to reduce adverse graft outcomes. Quantitative nucleic acid testing (QNAT) for detection of BKPyV DNA in blood and urine is increasingly used as a screening test as diagnosis of BKPyVAN by kidney biopsy is invasive and associated with procedural risks. In this review, we assessed the sensitivity and specificity of QNAT tests in patients with BKPyVAN. We assessed the diagnostic test accuracy of blood/plasma/serum BKPyV QNAT and urine BKPyV QNAT for the diagnosis of BKPyVAN after transplantation. We also investigated the following sources of heterogeneity: types and quality of studies, era of publication, various thresholds of BKPyV-DNAemia/BKPyV viruria and variability between assays as secondary objectives. We searched MEDLINE (OvidSP), EMBASE (OvidSP), and BIOSIS, and requested a search of the Cochrane Register of diagnostic test accuracy studies from inception to 13 June 2023. We also searched ClinicalTrials.com and the WHO International Clinical Trials Registry Platform for ongoing trials. We included cross-sectional or cohort studies assessing the diagnostic accuracy of two index tests (blood/plasma/serum BKPyV QNAT or urine BKPyV QNAT) for the diagnosis of BKPyVAN, as verified by the reference standard (histopathology). Both retrospective and prospective cohort studies were included. We did not include case reports and case control studies. Two authors independently carried out data extraction from each study. We assessed the methodological quality of the included studies by using Quality Assessment of Diagnostic-Accuracy Studies (QUADAS-2) assessment criteria. We used the bivariate random-effects model to obtain summary estimates of sensitivity and specificity for the QNAT test with one positivity threshold. In cases where meta-analyses were not possible due to the small number of studies available, we detailed the descriptive evidence and used a summative approach. We explored possible sources of heterogeneity by adding covariates to meta-regression models. We included 31 relevant studies with a total of 6559 participants in this review. Twenty-six studies included kidney transplant recipients, four studies included kidney and kidney-pancreas transplant recipients, and one study included kidney, kidney-pancreas and kidney-liver transplant recipients. Studies were carried out in South Asia and the Asia-Pacific region (12 studies), North America (9 studies), Europe (8 studies), and South America (2 studies). blood/serum/plasma BKPyV QNAT The diagnostic performance of blood BKPyV QNAT using a common viral load threshold of 10,000 copies/mL was reported in 18 studies (3434 participants). Summary estimates at 10,000 copies/mL as a cut-off indicated that the pooled sensitivity was 0.86 (95% confidence interval (CI) 0.78 to 0.93) while the pooled specificity was 0.95 (95% CI 0.91 to 0.97). A limited number of studies were available to analyse the summary estimates for individual viral load thresholds other than 10,000 copies/mL. Indirect comparison of thresholds of the three different cut-off values of 1000 copies/mL (9 studies), 5000 copies/mL (6 studies), and 10,000 copies/mL (18 studies), the higher cut-off value at 10,000 copies/mL corresponded to higher specificity with lower sensitivity. The summary estimates of indirect comparison of thresholds above 10,000 copies/mL were uncertain, primarily due to a limited number of studies with wide CIs contributed to the analysis. Nonetheless, these indirect comparisons should be interpreted cautiously since differences in study design, patient populations, and methodological variations among the included studies can introduce biases. Analysis of all blood BKPyV QNAT studies, including various blood viral load thresholds (30 studies, 5658 participants, 7 thresholds), indicated that test performance remains robust, pooled sensitivity 0.90 (95% CI 0.85 to 0.94) and specificity 0.93 (95% CI 0.91 to 0.95). In the multiple cut-off model, including the various thresholds generating a single curve, the optimal cut-off was around 2000 copies/mL, sensitivity of 0.89 (95% CI 0.66 to 0.97) and specificity of 0.88 (95% CI 0.80 to 0.93). However, as most of the included studies were retrospective, and not all participants underwent the reference standard tests, this may result in a high risk of selection and verification bias. urine BKPyV QNAT There was insufficient data to thoroughly investigate both accuracy and thresholds of urine BKPyV QNAT resulting in an imprecise estimation of its accuracy based on the available evidence. There is insufficient evidence to suggest the use of urine BKPyV QNAT as the primary screening tool for BKPyVAN. The summary estimates of the test sensitivity and specificity of blood/serum/plasma BKPyV QNAT test at a threshold of 10,000 copies/mL for BKPyVAN were 0.86 (95% CI 0.78 to 0.93) and 0.95 (95% CI 0.91 to 0.97), respectively. The multiple cut-off model showed that the optimal cut-off was around 2000 copies/mL, with test sensitivity of 0.89 (95% CI 0.66 to 0.97) and specificity of 0.88 (95% CI 0.80 to 0.93). While 10,000 copies/mL is the most commonly used cut-off, with good test performance characteristics and supports the current recommendations, it is important to interpret the results with caution because of low-certainty evidence.

Maung Myint T ，Chong CH ，von Huben A ，Attia J ，Webster AC ，Blosser CD ，Craig JC ，Teixeira-Pinto A ，Wong G ... -  《Cochrane Database of Systematic Reviews》

Accuracy of the Wound Healing Questionnaire in the diagnosis of surgical-site infection after abdominal surgery in low- and middle-income countries.

Telemedicine is being adopted for postoperative surveillance but requires evaluation for efficacy. This study tested a telephone Wound Healing Questionnaire (WHQ) to diagnose surgical site infection (SSI) after abdominal surgery in low- and middle-income countries. A multi-centre, international, prospective study was embedded in the FALCON trial; a factorial RCT testing measures to reduce SSI in seven low- and middle-income countries (NCT03700749). It was conducted according to a pre-registered protocol (SWAT126) and reported according to STARD guidelines. The reference test was in-person review by a trained clinician at 30 postoperative days according to US Centres for Disease Control criteria. The index test was telephone administration of an adapted WHQ at 27 to 30 postoperative days by a researcher blinded to the outcome of in-person review. The sum of item response scores generated an overall score between 0 and 29. The primary outcome was the diagnostic accuracy of the WHQ, defined as the proportion of SSI correctly identified by the telephone WHQ, and summarized using the area under the receiving operator characteristic curve (AUROC) and diagnostic test accuracy statistics. Patients were included from three upper-middle income (396 patients, 13 hospitals), three lower-middle income (746 patients, 19 hospitals), and one low-income country (54 patients, 4 hospitals). 90.3% (1088 of 1196) patients were successfully contacted. Those with non-midline incisions (adjusted odds ratio: 0.36, 95% c.i. 0.17 to 0.73, P=0.005) or a confirmed diagnosis of SSI on in-person assessment (odds ratio: 0.42, 95% c.i. 0.20 to 0.92, P=0.006) were harder to reach. The questionnaire correctly discriminated between most patients with and without SSI (AUROC 0.869, 95% c.i. 0.824 to 0.914), which was consistent across subgroups. A representative cut-off score of ≥4 displayed a sensitivity of 0.701 (0.610-0.792), specificity of 0.911 (0.878-0.943), positive predictive value of 0.723 (0.633-0.814) and negative predictive value of 0.901 (0.867-0.935). SSI can be diagnosed using a telephone questionnaire (obviating in-person assessment) in low resource settings.

NIHR Global Health Research Unit on Global Surgery 《-》