Diagnostic value of CRP for predicting the severity of acute pancreatitis: a systematic review and meta-analysis.

BACKGROUND: C-reactive protein (CRP) is a pentameric protein commonly used as a biomarker of inflammation or stress response which can be obtained during routine blood tests. Therefore, we conducted a systematic review and meta-analysis to explore its ability to predict the severity of acute pancreatitis (AP). This meta-analysis was registered in the PROSPERO system (registration number: CRD42022353769). METHODS: 41 studies with 6156 cases of acute pancreatitis, retrieved from PubMed, Cochrane Library, Springer, and Embase databases, were incorporated. We calculated the pooled estimates for predicting the severity of acute pancreatitis based on CRP levels. We also calculated the combined negative likelihood ratio (NLR), combined positive likelihood ratio (PLR) and combined diagnostic odds ratio (DOR) using a bivariate mixed model. Sensitivity analysis was used to examine the robustness of the results. Factors associated with heterogeneity were identified by meta-regression analysis. A summary operating characteristic (SROC) curve was generated to assess the diagnostic value of CRP in predicting severe acute pancreatitis. Fagan's test was used to calculate likelihood ratios and post-test probabilities, and publication bias was gauged by asymmetry tests. RESULTS: SROC analysis yielded an AUC of 0.85 (95%CI: 0.81-0.88) with a sensitivity of 0.76 (95%CI: 0.69-0.83) and specificity of 0.79 (95%CI: 0.74-0.83). The combined NLR, PLR and DOR were 0.30 (0.23-0.40), 3.66 (2.94-4.55) and 12.19 (8.05-18.44) respectively. Sensitivity analysis demonstrated the stability of our results after omitting any study. Finally, meta-regression analysis indicated that the description of the reference test, prospective design, blinding method and spectrum of the disease could account for heterogeneity in this meta-analysis. CONCLUSION: CRP has significant value as a biomarker for assessing AP severity. Besides, other parameters such as patient history, physical signs, and imaging should be considered to determine disease severity.

Retraction notice to "A nomogram for predicting in-hospital overall survival of hypertriglyceridemia-induced severe acute pancreatitis: A single center, cross-sectional study" [HLY 10 (2023) e23454].

[This retracts the article DOI: 10.1016/j.heliyon.2023.e23454.].

Comparison of Gout Flares With the Initiation of Treat-to-Target Allopurinol and Febuxostat: A Post-Hoc Analysis of a Randomized Multicenter Trial.

OBJECTIVE: Initiating urate-lowering therapy (ULT) in gout can precipitate arthritis flares. There have been limited comparisons of flare risk during the initiation and escalation of allopurinol and febuxostat, administered as a treat-to-target strategy with optimal anti-inflammatory prophylaxis. METHODS: This was a post-hoc analysis of a 72-week randomized, double-blind, placebo-controlled, noninferiority trial comparing the efficacy of allopurinol and febuxostat. For this analysis, the occurrence of flares was examined during weeks 0 to 24 when ULT was initiated and titrated to a serum urate (sUA) goal of less than 6 mg/dl (<5 mg/dl if tophi). Flares were assessed at regular intervals through structured participant interviews. Predictors of flare, including treatment assignment, were examined using multivariable Cox proportional hazards regression. RESULTS: Study participants (n = 940) were predominantly male (98.4%) and had a mean age of 62.1 years with approximately equal proportions receiving allopurinol or febuxostat. Mean baseline sUA was 8.5 mg/dl and all participants received anti-inflammatory prophylaxis (90% colchicine). In a multivariable model, there were no significant associations of ULT treatment (hazard ratio [HR] 1.17; febuxostat vs allopurinol), ULT-dose escalation (HR 1.18 vs no escalation), prophylaxis type, or individual comorbidity with flare and no evidence of ULT-dose escalation interaction. Factors independently associated with flare risk during ULT initiation/escalation included younger age, higher baseline sUA, and absence of tophi. CONCLUSION: These results demonstrate that gout flare risk during the initiation and titration of allopurinol is similar to febuxostat when these agents are administered according to a treat-to-target strategy using gradual ULT-dose titration and best practice gout flare prophylaxis.

Efficacy and Safety of Allopurinol and Febuxostat in Patients With Gout and CKD: Subgroup Analysis of the STOP Gout Trial.

RATIONALE & OBJECTIVE: We conducted a prespecified examination of the efficacy and safety of allopurinol and febuxostat administered using a treat-to-target strategy in trial participants with chronic kidney disease (CKD). STUDY DESIGN: Prespecified subcohort analysis of a randomized controlled trial. SETTING & PARTICIPANTS: A substudy of the STOP Gout Trial in participants with CKD. CKD was defined as an estimated glomerular filtration rate (eGFR) 30-59mL/min/1.73m2 at baseline. EXPOSURE: Trial participants with CKD and gout and serum urate (SUA) concentration of≥6.8mg/dL were randomized 1:1 to receive allopurinol or febuxostat. Urate-lowering therapy (ULT) was titrated during weeks 0-24 to achieve a goal SUA of<6.0mg/dL (<5.0mg/dL with tophi) (phase 1) and maintained during weeks 25-48 (phase 2). Gout flare was assessed between weeks 49-72 (phase 3). OUTCOME: Gout flare between weeks 49-72 (phase 3) was the primary outcome. Secondary outcomes included SUA goal achievement and ULT dosing at end of phase 2, and serious adverse events. ANALYTICAL APPROACH: Outcomes between treatment groups were compared using logistic regression models for binary outcomes, and Poisson regression for flare rates. Multivariable models were subsequently used, adjusting for factors identified to be imbalanced by treatment arm. RESULTS: CKD was present in 351 of 940 participants; 277 were assessed for the primary outcome. Fewer patients randomized to allopurinol had a flare during phase 3 (32% vs 45%; P=0.02) despite similar attainment of the SUA goal (79% vs 81%; P=0.6) by the end of phase 2. Acute kidney injury was more common in participants with stage 3 CKD randomized to allopurinol compared with febuxostat. LIMITATIONS: Limited power to assess infrequent safety events, largely male, older population. CONCLUSIONS: Allopurinol and febuxostat are similarly efficacious and well-tolerated in the treatment of gout in people with CKD when used in a treat-to-target regimen with lower incidence of gout flares in participants randomized to allopurinol. PLAIN-LANGUAGE SUMMARY: The STOP Gout Trial was a multicenter, randomized, double-blind, noninferiority, comparative effectiveness trial, which found that allopurinol was noninferior to febuxostat in gout flare prevention and that both medications were similarly efficacious in reaching a serum urate goal when used as part of a treat-to-target approach. A significant proportion of patients with chronic kidney disease (CKD) are afflicted by gout, yet there is a lack of high-quality comparative effectiveness data comparing allopurinol and febuxostat in these patients. We evaluated the efficacy and safety of allopurinol and febuxostat in the subgroup of STOP Gout Trial participants with stage 3 CKD and found that allopurinol and febuxostat are similarly efficacious and well-tolerated in the treatment of gout in people with CKD when used in a treat-to-target regimen, with lower incidence of gout flares in participants randomized to allopurinol.

Establishment of a mortality risk nomogram for predicting in-hospital mortality of sepsis: cohort study from a Chinese single center.

Objective: To establish a mortality risk nomogram for predicting in-hospital mortality of sepsis patients in the Chinese population. Methods: Data were obtained from the medical records of sepsis patients enrolled at the Affiliated Huadu Hospital, Southern Medical University, between 2019 and 2021. A total of 696 sepsis patients were initially included in our research, and 582 cases were finally enrolled after screening and divided into the survival group (n = 400) and the non-survival group (n = 182) according to the incidence of mortality during hospitalization. Twenty-eight potential sepsis-related risk factors for mortality were identified. Least absolute shrinkage and selection operator (LASSO) regression was used to optimize variable selection by running cyclic coordinate descent with k-fold (tenfold in this case) cross-validation. We used binary logistic regression to build a model for predicting mortality from the variables based on LASSO regression selection. Binary logistic regression was used to establish a nomogram based on independent mortality risk factors. To validate the prediction accuracy of the nomogram, receiver operating characteristic curve (ROC) analysis, decision curve analysis (DCA) and restricted cubic spline (RCS) analysis were employed. Eventually, the Hosmer-Lemeshow test and calibration curve were used for nomogram calibration. Results: LASSO regression identified a total of ten factors, namely, chronic heart disease (CHD), lymphocyte count (LYMP), neutrophil-lymphocyte ratio (NLR), red blood cell distribution width (RDW), C reactive protein (CRP), Procalcitonin (PCT), lactic acid, prothrombin time (PT), alanine aminotransferase (ALT), total bilirubin (Tbil), interleukin-6 (IL6), that were incorporated into the multivariable analysis. Finally, a nomogram including CHD, LYMP, NLR, RDW, lactic acid, PT, CRP, PCT, Tbil, ALT, and IL6 was established by multivariable logistic regression. The ROC curves of the nomogram in the training and validation sets were 0.9836 and 0.9502, respectively. DCA showed that the nomogram could be applied clinically if the risk threshold was between 29.52 and 99.61% in the training set and between 31.32 and 98.49% in the testing set. RCS showed that when the value of independent risk factors from the predicted model exceeded the median, the mortality hazard ratio increased sharply. The results of the Hosmer-Lemeshow test (χ2 = 0.1901, df = 2, p = 0.9091) and the calibration curves of the training and validation sets showed good agreement with the actual results, which indicated good stability of the model. Conclusion: Our nomogram, including CHD, LYMP, NLR, RDW, lactic acid, PT, CRP, PCT, Tbil, ALT, and IL6, exhibits good performance for predicting mortality risk in adult sepsis patients.

Predictive value of the neutrophil-to-lymphocyte ratio in the prognosis and risk of death for adult sepsis patients: a meta-analysis.

Background: The neutrophil-to-lymphocyte ratio (NLR) is a commonly used biomarker for acute inflammation that often rises during sepsis, making it a valuable diagnostic indicator for clinical practice. However, no consensus has been reached on the prognostic value of NLR for predicting the prognosis and mortality risk in adult sepsis patients. In light of this controversy, we conducted a meta-analysis to clarify the prognostic significance of NLR in adult sepsis patients. The meta-analysis was registered in the PROSPERO database (registration number CRD42023433143). Methods: We performed a comprehensive literature search in PubMed, Cochrane Library, Ovid, and Springer databases, using retrieval terms "sepsis" or "septic shock" and "prognosis" or "mortality" for studies published between January 1, 2000, and May 31, 2023. Children and neonates with sepsis were excluded from our research. Two independent researchers conducted the literature search and data extraction. Consensus was reached when discrepancies occurred, and in case of persistent discrepancies, the final decision was made by the research supervisor. The hazard ratio (HR) and its corresponding 95% confidence interval (95% CI) were extracted from each study included in the analysis. A random-effects model was used to synthesize all HRs and their 95% CIs. Sensitivity analysis was performed to investigate heterogeneity. Sensitivity analysis was conducted to identify studies that had a significant impact on the overall results of the meta-analysis. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. Egger's test was also used to investigate publication bias in this meta-analysis. Results: After a comprehensive literature search and screening, we included 12 studies comprising 10,811 patients for the meta-analysis. The pooled results indicated that patients with a higher NLR level were associated with a poor prognosis (Random-effects model, HR: 1.6273, 95% CI: 1.3951-1.8981). Heterogeneity testing showed significant heterogeneity (I2 = 87.2%, 95% CI: 79.5-92, p<0.0001). Sensitivity analysis was performed to investigate the sources of heterogeneity, which revealed that the omission of one highly sensitive study significantly reduced the I2 value. After removing this study, a strong association was found between a higher NLR level and poor prognosis and risk of death in adult sepsis patients (Random-effects model, HR: 1.6884, 95% CI: 1.4338-1.9882). Both subgroup analysis and meta-regression indicated that the study design and testing time of NLR were sources of heterogeneity. Egger's test showed no obvious publication bias in this meta-analysis. Conclusion: NLR is a reliable and valuable biomarker for predicting prognosis and the risk of death in adult sepsis patients. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023433143] PROSPERO, identifier [CRD42023433143].

Peroxidase like Zn doped Prussian blue facilitates salinity tolerance in winter wheat through seed dressing.

Salt stress severely limits the growth and yield of wheat in saline-alkali soil. While nanozymes have shown promise in mitigating abiotic stress by scavenging reactive oxygen species (ROS) in plants, their application in alleviating salt stress for wheat is still limited. This study synthesized a highly active nanozyme catalyst known as ZnPB (Zn-modified Prussian blue) to improve the yield and quality of wheat in saline soil. According to the Michaelis-Menten equation, ZnPB demonstrates exceptional peroxidase-like enzymatic activity, thereby mitigating oxidative damage caused by salt stress. Additionally, studies have shown that the ZnPB nanozyme is capable of regulating intracellular Na+ efflux and K+ retention in wheat, resulting in a decrease in proline and soluble protein levels while maintaining the integrity of macromolecules within the cell. Consequently, field experiments demonstrated that the ZnPB nanozyme increased winter wheat yield by 12.15 %, while also significantly enhancing its nutritional quality. This research offers a promising approach to improving the salinity tolerance of wheat, while also providing insights into its practical application.

Safety testing of Ovaprene: An investigational nonhormonal monthly vaginal contraceptive.

OBJECTIVES: Evaluate the safety of Ovaprene, an investigational nonhormonal vaginal contraceptive designed for monthly use. STUDY DESIGN: Open-label, multicenter study enrolling heterosexually-active women with previous permanent contraception who underwent assessments during five menstrual cycles: baseline postcoital test cycle, diaphragm postcoital test cycle, Ovaprene safety cycle, and two Ovaprene postcoital test cycles. Safety outcomes included treatment-emergent adverse events, systemic laboratory findings, pelvic examinations, colposcopies, Nugent scores, determination of community state types of vaginal microbiota, and anti-Escherichia coli activity and inflammatory markers in cervicovaginal fluids. RESULTS: We enrolled 38 participants. Of these, 33 used Ovaprene and completed 77 Ovaprene cycles. The most common product-related urogenital treatment-emergent adverse events were bacterial vaginosis and vaginal odor. The frequency of transitioning from Lactobacillus-dominated community state type to community state type IV (not Lactobacillus-dominated) was similar before Ovaprene use and afterwards. Mean Nugent scores were <4 at each visit without a discernible upward trend. Inflammatory markers showed wide variation but no upward trend, and E. coli inhibitory activity of cervical secretions did not change. We found no Staphylococcus aureus, the causative agent in toxic shock syndrome, on used Ovaprenes or in vaginal samples. No clinically important changes in systemic laboratory findings, pelvic examinations, or colposcopies occurred during Ovaprene use. CONCLUSIONS: Ovaprene use did not result in cervicovaginal irritation or adverse effects on resident vaginal microbiota and did not impact transitions from a Lactobacillus-dominated community state type to community state type IV. IMPLICATIONS: The finding that the use of Ovaprene, an investigational monthly user-controlled nonhormonal vaginal contraceptive, does not appear to result in adverse changes in vaginal health during short-term use supports further evaluation of the contraceptive potential of the device.

Immune effector dysfunction signatures predict outcomes in patients with colorectal cancer.

BACKGROUND: Immune effector dysfunction (IED) is mainly manifested as immune exhaustion and senescence, which are the primary obstacles to the success of cancer immunotherapy. In the current study, we characterized the prognostic relevance of IED signatures in patients with colorectal cancer (CRC). METHODS: Immunohistochemistry (IHC) data of CRC tissue samples from 41 newly diagnosed patients in our clinical center (HDPH cohort) were used to investigate the prognostic importance of IED signatures. The results were validated by the RNA sequencing data of 372 CRC patients from the Cancer Genome Atlas (TCGA) database. RESULTS: In the HDPH cohorts, high Natural Killer (NK) and CD8+ tumor-infiltrating lymphocytes (TILs) were associated with poor overall survival (OS) and relapse-free survival (RFS) in CRC patients. Optimal IED signatures, including high expression of CCR9, ISG20, and low expression of ICOS, and CACNA2D2, predicted poor OS and RFS. Moreover, high-risk scores estimated by a weighted combination of these four IED genes were associated with poor OS and RFS. Notably, risk stratification was constructed by combining risk score and tumor node metastasis (TNM) stage better than TNM stage alone in predicting OS and RFS for CRC patients. The above results were confirmed in the TCGA cohort. CONCLUSION: CCR9, ISG20, ICOS, and CACNA2D2 were optimal IED signatures for predicting the outcomes of CRC patients, which might be a potential biomarker for prognostic stratification and designing novel CRC therapy.

Menstrual cup use and intrauterine device expulsion in a copper intrauterine device randomized trial.

OBJECTIVE: To evaluate menstrual cup use and intrauterine device (IUD) expulsion. STUDY DESIGN: We performed a secondary analysis of a 3-year contraceptive efficacy trial comparing two copper 380 mm2 IUDs. Investigators randomized participants approximately 1:4 to the TCu380A or NTCu380-Mini IUD. Approximately 12 months after enrollment began, we advised participants against menstrual cup use due to observed IUD expulsions in cup users. We evaluated IUD expulsion (including spontaneous partial and complete expulsion and accidental self-removal) at 12 and 36 months. We used multivariable logistic regression to evaluate IUD expulsion by age, baseline menstrual volume, body mass index, IUD type, menstrual cup use, parity, and uterine length. RESULTS: This analysis included 1046 participants (203 TCu380A and 843 NTCu380-Mini), with 879 (84.0%) nulliparas. Through 12 and 36 months, expulsion occurred in 74 (7.1%, 95% CI 5.5-8.6%) and 133 (12.7%, 95% CI 10.7-14.7%) participants, respectively. Overall, 250 (23.9%) reported menstrual cup use. More menstrual cup users than non-users experienced expulsion through 12 months (32/203 [15.8%] vs. 42/843 [5.0%]) and 36 months (58/250 [23.2%] vs. 75/796 [9.4%]). Through 36 months, NTCu380-Mini menstrual cup users had higher expulsion odds, while TCu380A cup users did not. Menstrual cup users more frequently experienced accidental self-removal than non-users in participants using the TCu380A (3/53 [5.7%] vs. 0/150 [0.0%]) and the NTCu380-Mini (20/197 [10.2%] vs. 7/646 [1.1%]). In multivariable regression, we found increased odds of expulsion through 36 months in participants using menstrual cups with the NTCu380-Mini (aOR 3.13, 95% CI 1.16-8.46) and <25 years (aOR 1.59, 95% CI 1.07-2.34). CONCLUSIONS: We found higher odds of IUD expulsion with menstrual cup and concurrent NTCu380-Mini IUD use over 36 months of use, but not with concurrent TCu380A IUD use. Menstrual cup users experienced higher likelihood of accidental self-removal regardless of IUD type. IMPLICATIONS: Menstrual cup and NTCu380-Mini use may increase IUD expulsion risk and may increase accidental self-removal risk with TCu380A and NTCu380-Mini use. Clinicians should advise patients of these risks and consider warning patients using an IUD shaped like the NTCu380-Mini (Nova-T frames) of expulsion risk with menstrual cup use.

Successful postcoital testing of Ovaprene: An investigational non-hormonal monthly vaginal contraceptive.

OBJECTIVE: Evaluate reduction in progressively motile sperm per high power field (HPF) in midcycle cervical mucus after intercourse with Ovaprene: an investigational monthly non-hormonal vaginal contraceptive consisting of a vaginal ring and mechanical barrier, releasing spermiostatic ferrous gluconate. STUDY DESIGN: Open-label, multicenter study enrolling heterosexually-active women with previous permanent contraception. Participants underwent a baseline postcoital test cycle with no device to confirm the presence of sperm, followed by one diaphragm postcoital test cycle, one Ovaprene safety cycle, and two Ovaprene postcoital test cycles. In each postcoital test cycle, participants underwent a midcycle cervical mucus evaluation to confirm an Insler score ≥10 and absence of sperm, and then returned two to four hours after vaginal intercourse for repeat cervical mucus evaluation. We considered <5 progressively motile sperm/HPF indicative of preliminary contraceptive effectiveness. RESULTS: We enrolled 38 participants; 23 completed the study. All participants had ≥5 progressively motile sperm/HPF in the baseline cycle and <5 progressively motile sperm/HPF in all 49 Ovaprene cycles and all 35 diaphragm cycles, meeting the definition of a successful postcoital test. This was true regardless of examiner blinding, prior vaginal delivery or vaginal ring use, body mass index, or dislodgements noted by the participant or investigator. The mean of 27.2 (±17.9) progressively motile sperm/HPF in baseline postcoital test cycles was reduced to 0.5 (±1.1) and 0.5 (±1.3) progressively motile sperm/HPF in the first and second Ovaprene cycles, respectively. Ovaprene fit all participants and all could insert, position, and remove it. CONCLUSION: Use of Ovaprene resulted in meeting the prespecified criterion for contraceptive effect by all participants during all postcoital test cycles. IMPLICATIONS: The finding that use of Ovaprene, an investigational monthly non-hormonal vaginal contraceptive, resulted in postcoital testing of cervical mucus that met the pre-specified definition of success (<5 progressively motile sperm/HPF) supports further evaluation of contraceptive efficacy of the device in users at risk for pregnancy.

A nomogram for predicting in-hospital overall survival of hypertriglyceridemia-induced severe acute pancreatitis: A single center, cross-sectional study.

Background: Hypertriglyceridemia-induced severe acute pancreatitis (HTG-SAP) is a type of pancreatitis characterized by an abnormal elevation of plasma triglyceride. HTG-SAP has been associated with various complications and a high mortality rate. In this study, we established a nomogram for predicting the overall survival (OS) of HTG-SAP patients during hospitalization. Methods: 128 HTG-SAP cases hospitalized at the Affiliated Huadu Hospital, Southern Medical University, from 2019 to 2022 were analyzed retrospectively. A nomogram including prognostic factors correlated with OS during hospitalization was established by multivariate Cox regression analysis. We internally validated the nomogram using time-dependent (at 1-, 2-, and 3- months) survival receiver operating characteristic (SROC) and calibration curve with 500 iterations of bootstrap resampling. Time-dependent decision curve analysis (DCA) was employed to validate the clinical value of the nomogram. Results: Multivariate Cox regression indicated that serum triglyceride, red blood cell distribution width (RDW), lactic acid, and interleukin-6 (IL6) were independent prognostic factors for OS of HTG-SAP patients during hospitalization and were used to construct a nomogram. The time-dependent area under the curve (AUC) values at 1-, 2-, and 3- months were 0.946, 0.913, and 0.929, respectively, and the Concordance index (C-index) of the nomogram was 0.916 (95%CI 0.871-0.961). The time-dependent calibration curves indicated good consistency between the observed and predicted outcomes. The time-dependent DCAs also revealed that the nomogram yielded a high clinical net benefit. After stratifying the included cases into two risk groups based on the risk score obtained from the nomogram, the high-risk group exhibited a significantly inferior overall survival (OS) compared to the low-risk group (p < 0.0001). Conclusions: Our nomogram exhibited good performance in predicting the overall survival of HTG-SAP patients during hospitalization.

Determinants of Achieving Serum Urate Goal with Treat-to-Target Urate-Lowering Therapy in Gout.

OBJECTIVE: Using trial data comparing treat-to-target allopurinol and febuxostat in gout, we examined participant characteristics associated with serum urate (SU) goal achievement. METHODS: Participants with gout and SU ≥6.8 mg/dL were randomized to allopurinol or febuxostat, titrated during weeks 0 to 24, and maintained weeks 25 to 48. Participants were considered to achieve SU goal if the mean SU from weeks 36, 42, and 48 was <6.0 mg/dL or <5 mg/dL if tophi were present. Possible determinants of treatment response were preselected and included sociodemographics, comorbidities, diuretic use, health-related quality of life (HRQoL), body mass index, and gout measures. Determinants of SU response were assessed using multivariable logistic regression with additional analyses to account for treatment adherence. RESULTS: Of 764 study participants completing week 48, 618 (81%) achieved SU goal. After multivariable adjustment, factors associated with a greater likelihood of SU goal achievement included older age (adjusted odds ratio [aOR] 1.40 per 10 years), higher education (aOR 2.02), and better HRQoL (aOR 1.17 per 0.1 unit). Factors associated with a lower odds of SU goal achievement included non-White race (aORs 0.32-0.47), higher baseline SU (aOR 0.83 per 1 mg/dL), presence of tophi (aOR 0.29), and the use of diuretics (aOR 0.52). Comorbidities including chronic kidney disease, hypertension, diabetes, and cardiovascular disease were not associated with SU goal achievement. Results were not meaningfully changed in analyses accounting for adherence. CONCLUSIONS: Several patient-level factors were predictive of SU goal achievement among patients with gout who received treat-to-target urate-lowering therapy (ULT). Approaches that accurately predict individual responses to treat-to-target ULT hold promise in facilitating personalized management and improving outcomes in patients with gout.

Comparison of the safety profile, conversion rate and hospitalization duration between early and delayed laparoscopic cholecystectomy for acute cholecystitis: a systematic review and meta-analysis.

Background: Although the past decade has witnessed unprecedented medical progress, no consensus has been reached on the optimal approach for patients with acute cholecystitis. Herein, we conducted a systematic review and meta-analysis to assess the differences in patient outcomes between Early Laparoscopic Cholecystectomy (ELC) and Delayed Laparoscopic Cholecystectomy (DLC) in the treatment of acute cholecystitis. Our protocol was registered in the PROSPERO database (registration number: CRD42023389238). Objectives: We sought to investigate the differences in efficacy, safety, and potential benefits between ELC and DLC in acute cholecystitis patients by conducting a systematic review and meta-analysis. Methods: The online databases PubMed, Springer, and the Cochrane Library were searched for randomized controlled trials (RCTs) and retrospective studies published between Jan 1, 1999 and Jan 1, 2022. Results: 21 RCTs and 13 retrospective studies with a total of 7,601 cases were included in this research. After a fixed-effects model was applied, the pooled analysis showed that DLC was associated with a significantly high conversion rate (OR: 0.6247; 95%CI: 0.5115-0.7630; z = -4.61, p < 0.0001) and incidence of postoperative complications (OR: 0.7548; 95%CI: 0.6197-0.9192; z = -2.80, p = 0.0051). However, after applying a random-effects model, ELC was associated with significantly shorter total hospitalization duration than DLC (MD: -4.0657; 95%CI: -5.0747 to -3.0566; z = -7.90, p < 0.0001). Conclusion: ELC represents a safe and feasible approach for acute cholecystitis patients since it shortens hospitalization duration and decreases the incidence of postoperative complications of laparoscopic cholecystectomy. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=389238, identifier (CRD42023389238).

Impact of Elexacaftor/Tezacaftor/Ivacaftor on Healthcare Resource Utilization and Associated Costs Among People With Cystic Fibrosis in the US: A Retrospective Claims Analysis.

INTRODUCTION: Cystic fibrosis (CF) is a life-limiting genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a CFTR modulator (CFTRm) that targets the underlying cause of CF. Based on safety and efficacy demonstrated in clinical trials, ELX/TEZ/IVA is approved in the US for the treatment of CF in people aged ≥ 2 years who have ≥ 1 F508del-CFTR mutation or a CFTR mutation that is responsive to ELX/TEZ/IVA based on in vitro data. While ELX/TEZ/IVA demonstrated unprecedented improvements in lung function and dramatic reductions in pulmonary exacerbations (PEx) and associated hospitalizations in clinical trials, a limited number of studies have examined the impact of ELX/TEZ/IVA on healthcare resource utilization (HCRU) and associated costs in a real-world setting. The aim of this retrospective study was to evaluate changes in PEx, HCRU, and associated non-CFTRm healthcare costs following initiation of ELX/TEZ/IVA among people with CF aged ≥ 12 years in the US. METHODS: We evaluated the rates of PEx, HCRU, and associated costs before and after initiation of ELX/TEZ/IVA in people with CF aged ≥ 12 years using data from the Merative MarketScan® Commercial Claims and Encounters Database and the Merative Multi-State Medicaid Database from April 21, 2019 to December 31, 2020. Because the study period included time following the onset of the COVID-19 pandemic, we limited our primary analysis to the period prior to the pandemic (October 21, 2019 to March 12, 2020). Outcomes following the onset of the pandemic (March 13 to December 31, 2020) were examined in an exploratory analysis. RESULTS: In both commercially insured and Medicaid-insured people with CF, ELX/TEZ/IVA was associated with reductions in PEx, hospitalizations, and associated costs prior to the COVID-19 pandemic, and these reductions were maintained following the onset of the pandemic. CONCLUSIONS: These findings suggest that ELX/TEZ/IVA reduces the burden and costs associated with PEx and hospitalizations in people with CF.

Establishment of a 7-gene prognostic signature based on oxidative stress genes for predicting chemotherapy resistance in pancreatic cancer.

Background: Oxidative stress is involved in regulating various biological processes in human cancers. However, the effect of oxidative stress on pancreatic adenocarcinoma (PAAD) remained unclear. Methods: Pancreatic cancer expression profiles from TCGA were downloaded. Consensus ClusterPlus helped classify molecular subtypes based on PAAD prognosis-associated oxidative stress genes. Limma package filtered differentially expressed genes (DEGs) between subtypes. A multi-gene risk model was developed using Lease absolute shrinkage and selection operator (Lasso)-Cox analysis. A nomogram was built based on risk score and distinct clinical features. Results: Consistent clustering identified 3 stable molecular subtypes (C1, C2, C3) based on oxidative stress-associated genes. Particularly, C3 had the optimal prognosis with the greatest mutation frequency, activate cell cycle pathway in an immunosuppressed status. Lasso and univariate cox regression analysis selected 7 oxidative stress phenotype-associated key genes, based on which we constructed a robust prognostic risk model independent of clinicopathological features with stable predictive performance in independent datasets. High-risk group was found to be more sensitive to small molecule chemotherapeutic drugs including Gemcitabine, Cisplatin, Erlotinib and Dasatinib. The 6 of 7 genes expressions were significantly associated with methylation. Survival prediction and prognostic model was further improved through a decision tree model by combining clinicopathological features with RiskScore. Conclusion: The risk model containing seven oxidative stress-related genes may have a greater potential to assist clinical treatment decision-making and prognosis determination.

Acceptability of Single-dose Clindamycin Gel for Bacterial Vaginosis: A Randomized Controlled Trial.

PURPOSE: The goal of this study was to assess the acceptability of a single-dose bioadhesive 2% clindamycin vaginal gel for bacterial vaginosis (BV). METHODS: This double-blind, placebo-controlled, randomized study compared a new clindamycin gel with placebo gel (2:1 ratio). The primary objective was efficacy; secondary objectives were safety and acceptability. Subjects were evaluated at screening, days 7 to 14 (Day 7-14), and days 21 to 30 (test-of-cure [TOC]). An acceptability questionnaire with 9 questions was administered at the Day 7-14 visit, and a subset of questions (#7-#9) was asked again at the TOC visit. At Visit 1, subjects were provided with a daily electronic diary (e-Diary) to collect information regarding study drug administration, vaginal discharge, odor, itching, and any other treatments used. Study site staff reviewed e-Diaries at the Day 7-14 and TOC visits. FINDINGS: A total of 307 women with BV were randomized to treatment (204 to the clindamycin gel group and 103 to the placebo gel group). Most (88.3%) reported at least one previously diagnosed BV episode, and more than one half (55.4%) had experience with other vaginal treatments for BV. At the TOC visit, almost all (91.1%) of the clindamycin gel subjects described their overall experience with the study drug as "satisfied" or "very satisfied," 95.8% indicated that they would be "likely" or "very likely" to use the product again if it became available after the study and they had BV again, and 93.7% would be "likely" or "very likely" to recommend their treatment to a friend who had BV. Almost all (90.2%) clindamycin-treated subjects responded that application was "clean" or "fairly clean," as opposed to "neither clean nor messy," "fairly messy," or "messy." Although 55.4% experienced leakage in the days after application, only 26.9% of those indicated that it was bothersome. Subjects receiving clindamycin gel also reported improvement in both odor and discharge, commencing shortly after dosing and continuing through the assessment period, regardless of whether they met the critical cure criteria. IMPLICATIONS: A single dose of a new bioadhesive 2% clindamycin vaginal gel showed rapid resolution of symptoms and was highly acceptable as a treatment for bacterial vaginosis. CLINICALTRIALS: gov identifier: NCT04370548.

Bioinformatics-based construction of prognosis-related methylation prediction model for pancreatic cancer patients and its application value.

Objective: Pancreatic adenocarcinoma (PAAD) is a highly malignant gastrointestinal tumor with almost similar morbidity and mortality. In this study, based on bioinformatics, we investigated the role of gene methylation in PAAD, evaluated relevant factors affecting patient prognosis, screened potential anti-cancer small molecule drugs, and constructed a prediction model to assess the prognosis of PAAD. Methods: Clinical and genomic data of PAAD were collected from the Tumor Genome Atlas Project (TCGA) database and gene expression profiles were obtained from the GTEX database. Analysis of differentially methylated genes (DMGs) and significantly differentially expressed genes (DEGs) was performed on tumorous samples with KRAS wild-type and normal samples using the "limma" package and combined analysis. We selected factors significantly associated with survival from the significantly differentially methylated and expressed genes (DMEGs), and their fitting into a relatively streamlined prognostic model was validated separately from the internal training and test sets and the external ICGC database to show the robustness of the model. Results: In the TCGA database, 2,630 DMGs were identified, with the largest gap between DMGs in the gene body and TSS200 region. 318 DEGs were screened, and the enrichment analysis of DMGs and DEGs was taken to intersect DMEGs, showing that the DMEGs were mainly related to Olfactory transduction, natural killer cell mediated cytotoxicity pathway, and Cytokine -cytokine receptor interaction. DMEGs were able to distinguish well between PAAD and paraneoplastic tissues. Through techniques such as drug database and molecular docking, we screened a total of 10 potential oncogenic small molecule compounds, among which felbamate was the most likely target drug for PAAD. We constructed a risk model through combining three DMEGs (S100P, LY6D, and WFDC13) with clinical factors significantly associated with prognosis, and confirmed the model robustness using external and internal validation. Conclusion: The classification model based on DMEGs was able to accurately separate normal samples from tumor samples and find potential anti-PAAD drugs by performing gene-drug interactions on DrugBank.

Partnering for Integrated Care: A Learning Collaborative for Primary Care and Oral Health Teams.

PURPOSE: The Teaming and Integrating for Smiles and Health (TISH) Learning Collaborative was developed to help health care organizations accelerate progress in integrating delivery of oral and primary care. By providing expert support and a structure for testing change, the project aimed to improve the early detection of hypertension in the dental setting and of gingivitis in the primary care setting, and to increase the rate of bidirectional referrals between oral and primary care partners. We report its outcomes. METHODS: A total of 17 primary and oral health care teams were recruited to participate in biweekly virtual calls over 3 months. Participants tested changes to their models of care through Plan-Do-Study-Act cycles between calls. Sites tracked the percentages of patients screened and referred, completed the TeamSTEPPS (Team Strategies and Tools to Enhance Performance and Patient Safety) and Interprofessional Assessment questionnaires, and provided qualitative feedback and updates in storyboard presentations. RESULTS: On average, with implementation of the TISH Learning Collaborative, sites displayed a nonrandom improvement in the percentages of patients screened for hypertension, referred for hypertension, referred to primary care, and referred for gingivitis. Gingivitis screening and referral to oral health care were not markedly improved. Qualitative responses indicated that teams made progress in screening and referral workflows, improved communication between medical and dental partners, and furthered understanding of the connection between primary care and oral care among staff and patients. CONCLUSIONS: The TISH project is evidence that a virtual Learning Collaborative is an accessible and productive avenue to improve interprofessional education, further primary care and oral partnerships, and achieve practical progress in integrated care.