Preservation versus resection of Denonvilliers' fascia in total mesorectal excision for male rectal cancer: follow-up analysis of the randomized PUF-01 trial.

Traditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers' fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.

Intradermal delivery of an angiotensin II receptor blocker using a personalized microneedle patch for treatment of hypertrophic scars.

High-quality postoperative rehabilitation is the focus of most patients currently, and hypertrophic scar (HS) greatly reduces the patient's quality of life due to the symptom of severe itching. Traditional HS therapies are associated with limitations, such as poor drug delivery efficiency for topical administration and severe pain for intralesional injection. In this study, we developed a personalized microneedle patch system for minimally invasive and effective treatment of HSs. The microneedle patches were personalized designed and fabricated with 3D printing in order to adapt to individual HS. The optimized microneedle patches were composed of dissolving gelatin and starch and loaded with losartan. Losartan, as a drug class of angiotensin II receptor blockers (ARBs), can effectively inhibit the proliferation and migration of hypertrophic scar fibroblasts (HSFs) and downregulate the gene expression related to scar formation in HSFs. The dissolving microneedle patches exhibited strong mechanical strength, effectively penetrated the stratum corneum of HSs and increased the losartan delivery into HSs upon dissolution of gelatin and starch. Together, the losartan-loaded microneedle patches effectively inhibited the formation of HSs in rabbit ears with reduced scar elevation index (SEI), and decreased fibrosis and collagen deposition in HSs. This personalized microneedle patch system increases the drug delivery efficiency into HSs with minimal invasion, and opens a new window for personalized management and treatment of skin diseases.

A novel nomogram for anastomotic leakage after surgery for rectal cancer: a retrospective study.

Background: Anastomotic leakage remains one of the most common serious complications after rectal cancer surgery. How to predict its occurrence and prevent it remains largely elusive. Objective: This study aimed to identify the risk factors of anastomotic leakage and construct a nomogram for predicting postoperative anastomotic leakage in patients with rectal cancer. Methods: The data of 406 patients with rectal cancer after gastrointestinal surgery in the Third Affiliated Hospital of Sun Yat-sen University from January 2011 to May 2020 were collected (243 in the training set and 163 in the testing set). Logistic regression was applied to determine the risk factors of postoperative anastomotic leakage of rectal cancer, and a nomogram prediction model was thus established. Predictive performance of the nomogram was evaluated by C-index and area under the receiver-operating characteristic (ROC) curve. Results: Logistic regression analysis showed that preoperative bowel obstruction (odds ratio [OR] = 12.846, 95% confidence interval CI [1.441-114.54], p = 0.022) and early first defecation after surgery (OR = 0.501, 95% CI [0.31-0.812], p = 0.005) were independent risk factors, which could be used to develop a nomogram to predict the occurrence of anastomotic leakage accurately. The evaluation of the prediction model shows that the C-index value of the model was 0.955, the area under the ROC curve (AUC) of the training set was 0.820, and the testing set was 0.747, whereas the optimal cut-off point based on the nomogram score was 174.6. Conclusion: This nomogram had a good prediction ability for postoperative anastomotic leakage in patients with rectal cancer. It can provide a reference for perioperative treatment and the selection of surgical methods to promote individualized and accurate treatment.

Abnormal Fibrinogen Level as a Prognostic Indicator in Coronavirus Disease Patients: A Retrospective Cohort Study.

Purpose: The coronavirus disease (COVID-19) pandemic poses a global threat, and identification of its prognostic biomarkers could prove invaluable. Fibrinogen (FIB) could be one such indicator as coagulation and fibrinolysis abnormalities are common among COVID-19 patients. We examined the role of FIB levels in the prognosis of COVID-19. Methods: This retrospective cohort study enrolled 1,643 COVID-19 patients from the Leishenshan Hospital in Wuhan, China. The follow-up was conducted from February 8, 2020 to April 15, 2020. The cohort was divided into three groups according to the FIB level on admission, and associations with mortality and disease severity were determined using Cox and logistic regression analyses, respectively. Further, Kaplan-Meier (K-M) analyses by log-rank tests were used to assess the survival of patients with varying FIB levels. Results: Patients with FIB < 2.2 g/L [hazard ratio (HR): 9.02, 95% confidence interval (CI): 1.91-42.59, P = 0.006] and >4.2 g/L (HR: 4.79, 95% CI: 1.14-20.20, P = 0.033) showed higher mortality risks compared to those with FIB between 2.2 and 4.2 g/L. The survival curves showed similar results in K-M analyses (P < 0.001). Additionally, an elevated FIB level was associated with a greater risk of developing critical disease (odds ratio: 2.16, 95% CI: 1.04-4.46, P = 0.038) than a FIB level within the normal range. Conclusion: Abnormal FIB levels may be associated with mortality risk among COVID-19 patients and could predict critical disease development. Thus, assessment of FIB levels may assist in determining the prognosis of COVID-19 patients.

A new proposed tumor-node-metastasis-age staging system for stage IV medullary thyroid carcinoma based on the SEER database.

Medullary thyroid carcinoma (MTC) is a rare and lethal cancer. There are currently controversies regarding its staging. This study aimed to verify the significance of the patient's age in the prognosis of MTC and propose its addition to the current staging system. Data on cancer-specific survival (CSS) from the Surveillance, Epidemiology, and End Results database between 2010 and 2015 were used. X-Tile, nomograms, Cox proportional hazards regression analysis, Kaplan-Meier curves, and log-rank tests were used to evaluate mortality rates to create a new staging system. A total of 849 patients were included. Patients were divided into three categories based on their ages at diagnosis: ≤41 years, n = 224 (26.4%); 42-71 years, n = 516 (60.8%); and ≥72 years, n = 109 (12.8%). Independent factors for survival in the multivariate analysis included age (42-71 years, hazard ratio [HR], 2.81, 95% confidence interval [CI], 1.07-7.42; ≥72 years, HR, 8.71, 95% CI, 2.88-26.34), T stage (T2, HR, 3.60, 95% CI, 1.31-9.88), and M stage (M1, HR, 8.43, 95% CI, 4.40-16.16), with P<0.05. The Harrell's concordance index for tumor node metastasis (TNM) nomogram and TNM-age nomogram was 0.904 and 0.908, respectively. The areas under the curve (AUCs) for a 3-year CSS were 0.88 and 0.873, respectively. The corresponding AUCs for a 5-year CSS were 0.892 and 0.888, respectively. A new TNM-age staging system based on cancer-specific mortality rate analysis is proposed. This system provides a more accurate risk stratification and ensures more rational treatment measures for patients with stage IV MTC.

Surgical Disparities of Parathyroid Carcinoma: Long-Term Outcomes and Deep Excavation Based on a Large Database.

PURPOSE: Parathyroid carcinoma (PC) is an uncommon endocrine disease, and surgery is considered the only potential cure. PC does not have a mature staging system because of the small number of PC patients. Our aim is to further investigate the prognostic factors associated with PC and explore the optimal extent of resection for PC patients. METHODS: Univariate and multivariate Cox regression analyses were conducted to explore the influence of relevant factors on cancer-specific survival (CSS) and overall survival (OS). Survival curves were generated using the Kaplan-Meier method and analyzed using the log-rank test. The mortality rates per 1,000 person-years were calculated to evaluate patients' follow-up data. We also performed subgroup analysis based on the extent of resection. RESULTS: The extent of resection was related to both CSS and OS, whereas race and extent of disease had a significant positive correlation with OS (all P < 0.05). Patients who underwent parathyroidectomy had remarkably better CSS and OS than patients who did not undergo definitive treatment. CONCLUSION: The extent of resection is related to CSS and OS in patients with PC. No significant difference in prognosis was observed between patients who underwent parathyroidectomy and those who underwent en bloc resection, which may provide useful parameters for the treatment of PC.

Comparing the Value of Cystatin C and Serum Creatinine for Evaluating the Renal Function and Predicting the Prognosis of COVID-19 Patients.

Background: Coronavirus disease- (COVID-19-) related renal function abnormality is associated with poor prognosis. However, the clinical significance of dynamic changes in renal function indicators has not been studied, and no studies have evaluated the renal function in COVID-19 patients by cystatin C. Objective: This study aimed to evaluate the effect of abnormal renal function on admission on prognosis of COVID-19 patients and the prognostic value of various renal function indicators. Methods: A total of 1,764 COVID-19 patients without a history of chronic kidney disease were categorized into two groups, an elevated cystatin C group and a normal cystatin C group, based on the results of renal function tests on admission. The clinical characteristics were compared between the two groups, and logistic or Cox regression analyses were performed to explore the associations between elevated cystatin C/serum creatinine levels and disease severity and survival. We also performed receiver operating characteristic (ROC) curve, Kaplan-Meier survival, and curve fitting analyses. Results: When adjusted for several significant clinical variables, elevated cystatin C levels on admission were independent predictors of disease severity (p < 0.001), and elevated creatinine levels were independent predictors of death (p = 0.020). Additionally, the ROC curve analysis shows that elevated cystatin C levels [area under the curve (AUC): 0.656] have a better predictive value for disease severity than elevated creatinine levels (AUC: 0.540). The survival curves of patients with elevated cystatin C/creatinine levels show a sharper decline than those of patients with normal cystatin C/creatinine levels (p < 0.001). The curve fitting analysis revealed that, compared to the flat curves of cystatin C and creatinine levels for patients who survived, the curves for patients who died kept rising, and cystatin C levels rose above the normal range earlier than creatinine. Conclusions: Elevated cystatin C, which occurs earlier than serum creatinine, is useful for the early detection of renal function abnormality and might have better predictive value for disease severity in COVID-19 patients, while elevated serum creatinine may have a better predictive value for risks of death.

Evaluation of gliomas peritumoral diffusion and prediction of IDH1 mutation by IVIM-DWI.

Glioma characterized by high morbidity and mortality, is one of the most common brain tumors. The application of intravoxel incoherent motion diffusion weighted imaging (IVIM-DWI) in differentiating glioma grading and IDH1 mutation status were poorly investigated. 78 glioma patients confirmed by pathological and imaging methods were enrolled. Glioma patients were measured using IVIM-DWI, then related parameters such as cerebral blood flow (CBF), perfusion fraction (f), pseudo diffusivity (D*), and true diffusivity (D), were derived. Receiver operating characteristic (ROC) curves were made to calculate specificity and sensitivity. The values of CBF1, CBF3, D*1, rCBF1-2, rCBF3-2, and age in group high-grade gliomas (HGG) were significantly higher than that of in group low-grade gliomas (LGG). The values of CBF1, CBF3, rCBF1-2, rCBF3-2, D*1, and age in group IDH1mut were significantly lower than that of in group IDH1wt. The levels of D1 and f1 were remarkably higher in the group IDH1mut than group IDH1wt. rCBF1-2 had a remarkably positive correlation with CBF1 (r=0.852, p<0.001). f1 showed a markedly negative correlation with CBF1 (r= -0.306, p=0.007). IVIM-DWI presented efficacy in differentiating glioma grading and IDH1 mutation status.

Effect of Denonvilliers' Fascia Preservation Versus Resection During Laparoscopic Total Mesorectal Excision on Postoperative Urogenital Function of Male Rectal Cancer Patients: Initial Results of Chinese PUF-01 Randomized Clinical Trial.

OBJECTIVE: To compare the outcomes of laparoscopic total mesorectal excision (L-TME) with Denonvilliers' fascia (DVF) preservation versus resection on urogenital function of male patients with rectal cancer. BACKGROUND: The protective effect of DVF during L-TME on pelvic autonomic nerves and postoperative urogenital function remains controversial. METHODS: Between August 26, 2015 and July 18, 2019, 253 male patients with cT1-4 (T1-2 for anterior wall) N0-2M0 rectal cancer from 11 institutions were enrolled, and randomly assigned to L-TME with DVF preservation (Exp-group, n = 123) or resection procedures (Con-group, n = 130). Urinary function was assessed by residual urine volume, maximal flow rate, and International Prostate Symptom Score; sexual function was assessed by 5-item version of the International Index of Erectile Function (IIEF-5) and ejaculation grading. RESULTS: The Exp-group patients showed a lower urinary dysfunction rate (6.8% vs 25.4%, P = 0.003), higher maximal flow rate (16.25 ±â€Š8.02 vs 12.40 ±â€Š7.05 mL/s, P = 0.007), and lower International Prostate Symptom Score (6.55 ±â€Š5.86 vs 8.57 ±â€Š5.85, P = 0.026) than the Con-group patients at 2 weeks after surgery. The incidence of erectile dysfunction (IIEF-5 ≤ 11) at 12 months after surgery was lower in the Exp-group than in the Con-group (12.5% vs 34.2%, P = 0.023); Exp-group manifested superior IIEF-5 (16.63 ±â€Š6.28 vs 12.26 ±â€Š6.83, P = 0.018). The incidence of ejaculation dysfunction was lower in the Exp-group than in the Con-group at 12 months after surgery (10.0% vs 29.4%, P = 0.034). CONCLUSIONS: DVF preservation during L-TME revealed protective effects on postoperative urogenital function, and could be a better choice for male rectal cancer patients with specific staging and location. TRIAL REGISTRATION NUMBER: NCT02435758.

Association of procalcitonin levels with the progression and prognosis of hospitalized patients with COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.

Dynamic Interleukin-6 Level Changes as a Prognostic Indicator in Patients With COVID-19.

BACKGROUND: Interleukin-6 (IL-6), a proinflammatory cytokine, has been reported to be associated with disease severity and mortality in patients with coronavirus disease 2019 (COVID-19). Yet, dynamic changes in IL-6 levels and their prognostic value as an indicator of lung injury in COVID-19 patients have not been fully elucidated. OBJECTIVE: To validate whether IL-6 levels are associated with disease severity and mortality and to investigate whether dynamic changes in IL-6 levels might be a predictive factor for lung injury in COVID-19 patients. METHODS: This retrospective, single-center study included 728 adult COVID-19 patients and used data extracted from electronic medical records for analyses. RESULTS: The mortality rate was higher in the elevated IL-6 group than in the normal IL-6 group (0.16 vs 5%). Cox proportional hazards and logistic regression analyses for survival (adjusted hazard ratio, 10.39; 95% confidence interval [CI], 1.09-99.23; p = 0.042) and disease severity (adjusted odds ratio, 3.56; 95% CI, 2.06-6.19; p < 0.001) revealed similar trends. Curve-fitting analyses indicated that patient computed tomography (CT) scores peaked on days 22 and 24. An initial decline in IL-6 levels on day 16 was followed by resurgence to a peak, nearly in tandem with the CT scores. CONCLUSION: Increased IL-6 level may be an independent risk factor for disease severity and in-hospital mortality and dynamic IL-6 changes may serve as a potential predictor for lung injury in Chinese COVID-19 patients. These findings may guide future treatment of COVID-19 patients.

Association Between Diabetes and COVID-19: A Retrospective Observational Study With a Large Sample of 1,880 Cases in Leishenshan Hospital, Wuhan.

Aims: This study aimed to investigate the clinical courses and outcomes of diabetes mellitus patients with coronavirus disease 2019 (COVID-19) in Wuhan. Methods: This study enrolled 1,880 consecutive patients with confirmed COVID-19 in Leishenshan Hospital. We collected and analyzed their data, including demographic data, history of comorbidity, clinical symptoms, laboratory tests, chest computed tomography (CT) images, treatment options, and survival. Results: The percentages of patients with diabetes among the severe and critical COVID-19 cases were higher than those among the mild or general cases (89.2%, 10.8 vs. 0%, p = 0.001). However, patients with and without diabetes showed no difference in the follow-up period (p = 0.993). The mortality rate in patients with or without diabetes was 2.9% (n = 4) and 1.1% (n = 9), respectively (p = 0.114). Univariate and multivariate Cox regression analyses and the Kaplan-Meier curves did not show any statistically significant differences between patients with and without diabetes (all p > 0.05). Conclusions: Our study results suggested that diabetes had no effect on the prognosis of COVID-19 patients but had a negative association with their clinical courses. These results may be useful for clinicians in the management of diabetic patients with COVID-19.

Is a simplified TNM staging system more clinically relevant than the American Joint Committee on Cancer system for the follicular variant of papillary thyroid cancer?

BACKGROUND: Despite the recent release of the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual, risk stratification for the follicular variant of papillary thyroid cancer (FVPTC), which is the second common variant of papillary thyroid carcinoma (PTC) after classical PTC, remains controversial. This study aimed to develop a more accurate and relevant staging system specifically for FVPTC. METHODS: Patients with FVPTC who were included in the Surveillance, Epidemiology, and End Results (SEER) open database between 2010 and 2015 were divided into 47 groups according to their TNM classifications and age. Subsequently, these 47 groups were categorized into appropriate stages based on Kaplan-Meier survival curves, mortality analyses, a Cox proportional hazards model, and clinical considerations. RESULTS: Our retrospective analysis of 17,628 cases yielded the following new staging classification: stage I, defined as age <55 years and any T/N/M or age ≥55 years and T1-3/any N/M0 (n=17,427, 98.85%); stage II, age ≥55 and T4/any N/M0 or age ≥55 and any T/N0/M1 (n=173, 0.99%); and stage III, age ≥55 and any T/N1/M1 (n=28, 0.16%). The overall mortality rates per 1,000-person-years were 4.135 [95% confidence interval (CI): 3.653-4.681], 71.193 (95% CI: 51.354-98.697), and 199.744 (95% CI: 115.983-343.997) for our new stages I, II, and III, respectively. The hazard ratios for the new stages II and III (reference: stage I) were 5.081 (95% CI: 3.110-8.301) and 21.690 (95% CI: 11.402-41.258), respectively. CONCLUSIONS: Compared to the 8th edition of the AJCC staging system, our newly proposed system provided more accurate risk stratification for patients with FVPTC, as demonstrated by actual survival and mortality outcomes. This new model may thus help guide more personalized treatment for these patients.

Identification of the surgical indication line for the Denonvilliers' fascia and its anatomy in patients with rectal cancer.

BACKGROUND: The high rate of urogenital dysfunction after traditional total mesorectal excision (TME) has caused doubts among scholars on the standard fashion of dissection. We have proposed the necessity to preserve the Denonvilliers' fascia in patients with rectal cancer. However, how to accurately locate the Denonvilliers' fascia is unclear. This study aimed to explore anatomical features of the Denonvilliers' fascia by comparing autopsy findings and observations of surgical videos so as to propose a dissection method for the preservation of pelvic autonomic nerves during rectal cancer surgery. METHODS: Five adult male cadaver specimens were dissected, and surgical videos of 135 patients who underwent TME for mid-low rectal cancer between January 2009 and February 2019 were reviewed to identify and compare the structure of the Denonvilliers' fascia. RESULTS: The monolayer structure of the Denonvilliers' fascia was observed in 5 male cadaver specimens, and it was located between the rectum, the bottom of the bladder, the seminal vesicles, the vas deferens, and the prostate. The Denonvilliers' fascia was originated from the rectovesical pouch (or rectum-uterus pouch), down to fuse caudally with the rectourethral muscle at the apex of the prostate, and fused to the lateral ligaments on both sides. The fascia was thinner on the midline with a thickness of 1.06 ± 0.10 mm. The crown shape of the Denonvilliers' fascia was slightly triangular, with a height of approximately 5.42 ± 0.16 cm at midline. Nerves were more densely distributed in front of the Denonvilliers' fascia than behind, especially on both sides of it. Under laparoscopic view, the Denonvilliers' fascia was originated at the lowest point of the rectovesical pouch (or rectum-uterus pouch), with a thickened white line which was a good mark for identifying the Denonvilliers' fascia. CONCLUSION: Identification of the surgical indication line for the Denonvilliers' fascia could help us identify the Denonvilliers' fascia, and it would improve our ability to protect the pelvic autonomic function of patients undergoing TME for rectal cancer.

Efficacy of Oxaliplatin/5-Fluorouracil/Capecitabine-Cetuximab Combination Therapy and Its Effects on K-Ras Mutations in Advanced Colorectal Cancer.

BACKGROUND The aim of this study was to perform an accurate exploration on the efficacy of oxaliplatin/5-fluorouracil/capecitabine-cetuximab combination therapy and its effects on K-Ras mutations in advanced colorectal cancer. MATERIAL AND METHODS Among 96 patients who suffered metastatic colorectal cancer without mutated K-Ras, 41 patients who were receiving treatment with oxaliplatin/5-fluorouracil/capecitabine and administered cetuximab as the initial treatment comprised the observation group; the remaining 55 patients receiving cetuximab as an alternative treatment comprised the control group. RESULTS The observation group experienced significantly higher objective response rates (ORRs), and disease control rates (DCRs), than the control group (P<0.05 for both). The median progression-free survival (PFS) rates of the observation group and the control groups were 11.2 months (95% confidence interval [CI]: 10.1-12.3 months) and 7.4 months (95% CI: 6.6-8.2 months). The median overall survival (OS) rates were 16.8 months (95% CI: 15.2-18.4 months) and 12.4 months (95% CI: 11.6-13.2 months), respectively. The observation group had significantly longer PFS and OS in comparison to the control group (P<0.05). The patients who underwent cetuximab treatment for ≥10 months had a slightly higher rate of K-Ras mutations than those treated with cetuximab for <10 months (9.1% versus 7.3%). CONCLUSIONS Oxaliplatin/5-fluorouracil/capecitabine plus cetuximab exhibited better efficacy as initial treatment than the alternative treatment; it was also highly safe. Unfortunately, some patients might develop K-Ras mutations after long duration of cetuximab treatment, suggesting that K-Ras mutations are correlated with tumor progression and depend on the duration or dose of cetuximab treatment.

Decreased CO2 Levels as Indicators of Possible Mechanical Ventilation-Induced Hyperventilation in COVID-19 Patients: A Retrospective Analysis.

Background: Six months since the outbreak of coronavirus disease (COVID-19), the pandemic continues to grow worldwide, although the outbreak in Wuhan, the worst-hit area, has been controlled. Thus, based on the clinical experience in Wuhan, we hypothesized that there is a relationship between the patient's CO2 levels and prognosis. Methods: COVID-19 patients' information was retrospectively collected from medical records at the Leishenshan Hospital, Wuhan. Logistic and Cox regression analyses were conducted to determine the correlation between decreased CO2 levels and disease severity or mortality risk. The Kaplan-Meier curve analysis was coupled with the log-rank test to understand COVID-19 progression in patients with decreased CO2 levels. Curve fitting was used to confirm the correlation between computed tomography scores and CO2 levels. Results: Cox regression analysis showed that the mortality risk of COVID-19 patients correlated with decreased CO2 levels. The adjusted hazard ratios for decreased CO2 levels in COVID-19 patients were 8.710 [95% confidence interval (CI): 2.773-27.365, P < 0.001], and 4.754 (95% CI: 1.380-16.370, P = 0.013). The adjusted odds ratio was 0.950 (95% CI: 0.431-2.094, P = 0.900). The Kaplan-Meier survival curves demonstrated that patients with decreased CO2 levels had a higher risk of mortality. Conclusions: Decreased CO2 levels increased the mortality risk of COVID-19 patients, which might be caused by hyperventilation during mechanical ventilation. This finding provides important insights for clinical treatment recommendations.

Rethinking the 8th AJCC System: Is It Suitable for Patients Aged <55 Years With Stage T4N1M0 Follicular Variant of Papillary Thyroid Carcinoma to Be Placed in Stage I?

PURPOSE: The newest (8th) edition of the TNM staging system published in 2017. In this edition, some significant changes happened from the previous edition. As a result, down-staging appeared in nearly one third of DTC patients. However, we don't know whether the new system predicts the survival of FVPTC patients accurately. Therefore, it is necessary to thoroughly evaluate the correlation between the new system and survival prediction in terms of FVPTC. METHODS: We enrolled 17,662 FVPTC patients from the Surveillance, Epidemiology, and End Results database. Factors associated with survival were identified by Cox regression analyses. The mortality rates per 1,000 person-years were calculated and compared. Cox proportional hazards regression quantified the risk of survival, and survival curves were produced by Kaplan-Meier analyses using log-rank tests. RESULTS: Age at diagnosis, race, T-stage at diagnosis, distant metastasis, radiation therapy, and surgery were independent factors associated with cancer-specific survival. Patients aged <55 years with stage T4N1M0 FVPTC had higher mortality rates per 1,000 person-years than patients in the same stage according to the 8th AJCC System. Cox proportional hazards regression reflected that patients aged <55 years with stage T1-3, any N, M0 or T4N0M0 disease (p=0.001) and patients aged ≥55 years with T1-2N0M0 disease (p=0.004) had significantly lower risks of cancer-specific survival (CSS) than those aged <55 years with stage T4N1M0 disease. The CSS curve of patients aged <55 years with stage T4N1M0 disease showed a decline on comparison with others belonging to stage I (p<0.001); and the curve was even not different from patients in stage II and stage III (p>0.05). CONCLUSION: Patients aged <55 years with stage T4N1M0 FVPTC had worse survival than patients in stage I; no difference was seen on comparison with stage II patients. We recommend this group of patients be upstaged in the 8th AJCC system.

Effect of breast cancer as the first or second primary cancer on the prognosis of women with thyroid cancer: a SEER database analysis.

BACKGROUND: Although many studies have evaluated the association between breast cancer (BC) and thyroid cancer (TC), this association has not been completely studied. In this study, we focused on the effect of BC as the first or second primary cancer on survival among women with TC. We present the following article in accordance with the STROBE reporting checklist. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we performed a retrospective cohort analysis of 134,785 women with BC and TC between 1974 and 2016. The patients were divided into three subgroups, namely, TC only (TC group, n=128,888), BC after TC (TC2BC group, n=3,000), and BC before TC (BC2TC group, n=2,897). The curves for overall survival (OS) and cancer-specific survival (CSS) were evaluated, and Cox regression analyses were performed to examine the effect of BC as the first and second primary cancer on the CSS and OS of TC patients. RESULTS: The CSS rates in the TC, TC2BC, and BC2TC groups were 96.96%, 98.70%, and 96.70%, respectively, and the OS rates were 91.17%, 77.13%, and 78.63%, respectively. Using the TC group as a reference, the hazard ratios (HRs) for the CSS of the TC2BC and BC2TC groups were 0.333 [95% confidence interval (CI): 0.243-0.456, P<0.001] and 1.299 (95% CI: 1.062-1.589, P=0.011), respectively. The corresponding HRs for the OS were 1.544 (95% CI: 1.428-1.668, P<0.001) and 3.429 (95% CI: 3.158-3.724, P<0.001), respectively. CONCLUSIONS: Among the female patients with TC, BC, as the second primary cancer, has a significant protective effect on the CSS of TC patients; however, when BC is the first primary cancer, it is a risk factor. Besides, BC is a risk factor for the OS of TC patients, especially for patients who develop TC after BC.

Oncogenic ADAM28 induces gemcitabine resistance and predicts a poor prognosis in pancreatic cancer.

BACKGROUND: Pancreatic cancer is a major cause of cancer-related death, with a 5-year overall survival rate being below 5%. The main causes of poor prognosis in pancreatic cancer include easy metastasis, high recurrence rate, and robust drug resistance. Gemcitabine is a first-line drug for patients with unresectable pancreatic cancer. However, due to drug resistance, the clinical effect is not satisfactory. ADAM28 is reported as a tumor promoter in some cancers, but its role in pancreatic cancer and gemcitabine chemoresistance in pancreatic cancer has not been elucidated. AIM: To identify if ADAM28 can act as an important target to reverse the gemcitabine drug resistance in pancreatic cancer. METHODS: RNA-sequence analysis was applied to explore the potential targets involved in the gemcitabine of pancreatic cancer. SW1990 pancreatic cancer cells were treated with an increased dose of gemcitabine, and the mRNA levels of ADAM28 were evaluated by RT-PCR. The protein and mRNA levels of ADAM28 were confirmed in the gemcitabine resistant and parallel SW1990 cells. The ADAM28 expression was also assessed in TCGA and GEO databases, and the results were confirmed in the collected tumor and adjacent normal tissues. The overall survival (OS) rate and relapse-free survival (RFS) rate of pancreatic cancer patients with high ADAM28 level and low ADAM28 level in TCGA were evaluated with Kaplan-Meier Plotter. Furthermore, the OS rate was calculated in pancreatic cancer patients with high tumor mutation burden (TMB) and low TMB. CCK-8 assay was used to examine the effect of ADAM28 on the viability of SW1990 cells. The ADAM28 and its co-expressed genes were analyzed in the cBioPortal for cancer genomics and subjected to GSEA pathway analysis. The correlations of ADAM28 with GSTP1, ABCC1, GSTM4, and BCL2 were analyzed based on TCGA data on pancreatic cancer. RESULTS: RNA-sequence analysis identified that ADAM28 was overexpressed in gemcitabine-resistant cells, and gemcitabine treatment could induce the expression of ADAM28. The mRNA and protein levels of ADAM28 were elevated in gemcitabine-resistant SW1990 cells compared with parallel cells. Also, the expression of ADAM28 was upregulated in pancreatic tumor tissues against normal pancreatic tissues. Notably, ADAM28 was highly expressed in the classical type than in the basal tumor type. Furthermore, the high expression of ADAM28 was associated with low OS and RFS rates. Interestingly, the high levels of ADAM28 was associated with a significantly lower OS rate in the high TMB patients, but not in the low TMB patients. Moreover, overexpression of ADAM28 could reduce the cell viability inhibition by gemcitabine, and knockdown of ADAM28 could enhance the proliferation inhibition by gemcitabine. The GSEA analysis showed that ADAM28 was related to the regulation of drug metabolism, and ADAM28 was significantly positively correlated with GSTP1, ABCC1, GSTM4, and BCL2. CONCLUSION: This study demonstrates that ADAM28 is overexpressed in pancreatic cancer, and closely involved in the regulation of gemcitabine resistance. Overexpression of ADAM28 is a novel prognostic biomarker in pancreatic cancer.

Long noncoding RNA LINC00511 promotes cell growth and invasion in triple-negative breast cancer by interacting with Snail.

Purpose: Aberrant long noncoding RNA expression has been frequently reported in cancer research, including in triple-negative breast cancer (TNBC). The aim of the present study was to investigate the involvement of LINC00511 in the progression and prognosis of TNBC. Materials and methods: The expression level of LINC00511 was examined by RT-PCR in TNBC tissues and in cell lines. MTT and colony formation assays were used to examine the cell growth ability. A Boyden assay was used to examine the cell invasion ability. RNA pull-down and RNA immunoprecipitation (RIP) assays were used to examine the proteins that interacted with LINC00511. Results: We demonstrated that the LINC00511 expression level was elevated in TNBC tissues when compared with that in normal breast tissues. The downregulation of LINC00511 decreased TNBC cell growth and invasion compared to those of the controls. To explore the molecular mechanisms underlying the biological activity of LINC00511, we identified proteins that bound to LINC00511 with RNA pull-down experiments. We showed that LINC00511 binds to the ß-transducin repeat containing (BTRC) E3 ubiquitin protein. Mechanistically, LINC00511 maintained the stability of Snail by impeding its ubiquitination and degradation by the BTRC E3 ubiquitin protein. Conclusion: Our data suggested that LINC00511 might serve as a novel molecular target for the treatment of TNBC.