Prevalence of Polypharmacy in Elderly Population Worldwide: A Systematic Review and Meta-Analysis.

BACKGROUND: Polypharmacy (PP) is common in elderly population and associated with some adverse clinical outcomes and increases healthcare burdens. We performed this systemic review and meta-analysis to estimate worldwide prevalence of PP and explore associated factors in the elderly. METHODS: The PubMed, Web of Science, Cochrane Library, and Ovid EMBASE databases were searched for studies published until May 30, 2022. We included observational studies representative of general patients aged ≥60 in which PP was defined as multiple drugs ≥5. Studies were excluded if only a particular group of the elderly population (e.g., with diabetes) were included. The primary outcome was the prevalence of PP. Random-effect models were employed to estimate the overall or variable-specific pooled estimates of PP. Secondary outcomes were hyperpolypharmacy (HPP, defined as multiple drugs ≥10) and PP prevalence based on different study years, genders, locations, populations, and so forth. RESULTS: We included 122 original observational studies with an overall population of 57 328 043 individuals in the meta-analysis. The overall prevalence of PP and HPP in the elderly population worldwide was 39.1% (95% confidence interval [CI], 35.5%-42.7%) and 13.3% (95% CI, 10.4%-16.5%), respectively. The prevalence of PP in Europe, Oceania, North America, Asia, and South America was 45.8% (95% CI, 41.5%-50.2%), 45.5% (95% CI, 26.7%-64.3%), 40.8% (95% CI, 29.8%-51.6%), 29.0% (95% CI, 20.0%-38.0%), and 28.4% (95% CI, 24.0%-32.8%), respectively (p < 0.01). Multivariate meta-regressions showed geographical regions of Europe or North America, age ≥70, and residence from nursing homes were independently associated with higher PP prevalence. CONCLUSIONS: Nearly 40% of the elderly population is exposed to PP. The prevalence of PP is significantly higher in elderly individuals aged 70 or older, in developed regions and in nursing homes. It is important to focus on avoiding inappropriate PP in this population to address the growing burden of PP.

Causal relationships between psychological disorders and functional gastrointestinal disorders: a bidirectional two-sample Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies have shown bidirectional associations between psychological disorders (e.g. depression and anxiety) and functional gastrointestinal disorders. However, whether the relationships are causal is uncertain. Here, we used a bidirectional two-sample Mendelian randomization method to investigate the association between psychological disorders and functional gastrointestinal disorders (FGIDs). METHODS: We obtained genome-wide association study summary statistics for two common psychological disorders: depression (170 756 cases) and anxiety (31 977 cases), as well as for three common FGIDs: functional dyspepsia with 6666 cases, constipation with 26 919 cases, and irritable bowel syndrome (IBS) with 7053 cases. These summary statistics were retrieved from several publicly available genome-wide association study databases. The inverse variance weighted method was used as the main Mendelian randomization method. RESULTS: Inverse variance weighted Mendelian randomization analyses showed statistically significant associations between genetically predicted depression and risk of functional dyspepsia [odds ratio (OR): 1.40, 95% confidence interval (CI): 1.08-1.82], constipation (OR: 1.28, 95% CI: 1.13-1.44), and IBS (OR: 1.51, 95% CI: 1.37-1.67). Genetically predicted anxiety was associated with a higher risk of IBS (OR: 1.13, 95% CI: 1.10-1.17) instead of functional dyspepsia and constipation. In addition, genetically predicted IBS instead of functional dyspepsia and constipation was associated with a higher risk of depression (OR: 1.33, 95% CI: 1.12-1.57) and anxiety (OR: 2.05, 95% CI: 1.05-4.03). CONCLUSION: Depression is a causal risk factor for three common FGIDs. A bidirectional causal relationship between IBS and anxiety or depression was also identified.

Horizontal duodenal papilla is associated with a special spectrum of pancreaticobiliary diseases: a retrospective magnetic resonance cholangiopancreatography-based study.

Background: Horizontal duodenal papilla (HDP) is not an uncommon ectopic major papilla. The impact of HDP on the occurrence of pancreaticobiliary diseases remains unclear. Here, we explored the associations in patients who underwent magnetic resonance cholangiopancreatography (MRCP). Methods: Consecutive patients who underwent MRCP at Xijing Hospital (Xi'an, China) between January 2020 and December 2021 were eligible. Patients were divided into HDP and regular papilla (RP) according to the position of the major papilla. The primary outcome was the proportion of congenital pancreaticobiliary diseases. Results: A total of 2,194 patients were included, of whom 72 (3.3%) had HDP. Compared with the RP group (n = 2,122), the HDP group had a higher proportion of congenital pancreaticobiliary diseases, especially choledochal cyst (CC) or anomalous pancreaticobiliary junction (APBJ) (6.9% vs 1.4%, P = 0.001). More gallbladder cancer (6.9% vs 1.2%, P < 0.001) and pancreatic cysts (27.8% vs 16.3%, P = 0.01) were also identified in the HDP group. Morphologically, the HDP group had a longer extrahepatic bile duct (8.4 [7.6-9.3] cm vs 7.2 [6.5-8.1] cm, P < 0.001), and larger angles between the common bile duct-duodenum and pancreatic duct-duodenum. Multivariate analysis showed that the presence of HDP was an independent risk factor for gallbladder cancer. Conclusions: This study confirmed that HDP was not rare in patients underwent MRCP. A higher prevalence of congenital pancreaticobiliary malformations (especially CC or APBJ), gallbladder cancer and pancreatic cysts was observed in patients with HDP, as well as distinctive morphologic features.

Inter-cell type interactions that control JNK signaling in the Drosophila intestine.

JNK signaling is a critical regulator of inflammation and regeneration, but how it is controlled in specific tissue contexts remains unclear. Here we show that, in the Drosophila intestine, the TNF-type ligand, Eiger (Egr), is expressed exclusively by intestinal stem cells (ISCs) and enteroblasts (EBs), where it is induced by stress and during aging. Egr preferentially activates JNK signaling in a paracrine fashion in differentiated enterocytes (ECs) via its receptor, Grindelwald (Grnd). N-glycosylation genes (Alg3, Alg9) restrain this activation, and stress-induced downregulation of Alg3 and Alg9 correlates with JNK activation, suggesting a regulatory switch. JNK activity in ECs induces expression of the intermembrane protease Rhomboid (Rho), driving secretion of EGFR ligands Keren (Krn) and Spitz (Spi), which in turn activate EGFR signaling in progenitor cells (ISCs and EBs) to stimulate their growth and division, as well as to produce more Egr. This study uncovers an N-glycosylation-controlled, paracrine JNK-EGFR-JNK feedforward loop that sustains ISC proliferation during stress-induced gut regeneration.

The Influencing Factors of Frailty and Quality of Life in Elderly Patients After Spinal Surgery.

Background: To study the related factors of frailty and quality of life in elderly patients after spinal surgery. Methods: The anxiety, depression, frailty, and quality of life of all patients were assessed by the Anxiety screening scale (GAD-7), Depression screening scale (PHQ-9), Frailty screening scale (FRAIL), and European five-dimensional health scale (EQ-5D-5L) 1 day before surgery (DAY-0). A numeric rating scale (NRS) was used to evaluate patients' pain during activities on the 1st day (POD-1), 3rd day (POD-3), and 30th day (POD-30) after operation. FRAIL scale and EQ-5D-5L were used to evaluate patients' frailty and quality of life on POD-30 and 90th day (POD-90) after the operation. Results: There were significant differences in age, body mass index (BMI), preoperative serum albumin level (ALB), and NRS score on POD-1 between the two groups (P<0.05). Age and PHQ-9 score were positively correlated with EQ-5D-5L score (P<0.05, r Age=0.245, rPHQ-9=0.217), and preoperative ALB level was negatively correlated with EQ-5D-5L score (P<0.05, r ALB=-0.274). Conclusion: The older the age, the larger the BMI and the higher the NRS score on the first day after surgery, the more prone to frailty in elderly patients after spinal surgery; The older age and the lower the preoperative ALB level, the worse the quality of life in elderly patients after spinal surgery.

The associations between functional dyspepsia and potential risk factors: A comprehensive Mendelian randomization study.

BACKGROUND: Previous cross-sectional studies have identified multiple potential risk factors for functional dyspepsia (FD). However, the causal associations between these factors and FD remain elusive. Here we aimed to fully examine the causal relationships between these factors and FD utilizing a two-sample MR framework. METHODS: A total of 53 potential FD-related modifiable factors, including those associated with hormones, metabolism, disease, medication, sociology, psychology, lifestyle and others were obtained through a comprehensive literature review. Independent genetic variants closely linked to these factors were screened as instrumental variables from genome-wide association studies (GWASs). A total of 8875 FD cases and 320387 controls were available for the analysis. The inverse variance weighted (IVW) method was employed as the primary analytical approach to assess the relationship between genetic variants of risk factors and the FD risk. Sensitivity analyses were performed to evaluate the consistency of the findings using the weighted median model, MR-Egger and MR-PRESSO methods. RESULTS: Genetically predicted depression (OR 1.515, 95% confidence interval (CI) 1.231 to 1.865, p = 0.000088), gastroesophageal reflux disease (OR 1.320, 95%CI 1.153 to 1.511, p = 0.000057) and years of education (OR 0.926, 95%CI 0.894 to 0.958, p = 0.00001) were associated with risk for FD in univariate MR analyses. Multiple medications, alcohol consumption, poultry intake, bipolar disorder, mood swings, type 1 diabetes, elevated systolic blood pressure and lower overall health rating showed to be suggestive risk factors for FD (all p<0.05 while ≥0.00167). The positive causal relationship between depression, years of education and FD was still significant in multivariate MR analyses. CONCLUSIONS: Our comprehensive MR study demonstrated that depression and lower educational attainment were causal factors for FD at the genetic level.

L-DOPA ameliorates hippocampus-based mitochondria respiratory dysfunction caused by GCI/R injury.

Mitochondrial dysmorphology/dysfunction follow global cerebral ischemia-reperfusion (GCI/R) injury, leading to neuronal death. Our previous researches demonstrated that Levodopa (L-DOPA) improves learning and memory impairment in GCI/R rats by increasing synaptic plasticity of hippocampal neurons. This study investigates if L-DOPA, used in Parkinson's disease treatment, alleviates GCI/R-induced cell death by enhancing mitochondrial quality. Metabolomics and transcriptomic results showed that GCI/R damage affected the Tricarboxylic acid (TCA) cycle in the hippocampus. The results of this study show that L-DOPA stabilized mitochondrial membrane potential and ultrastructure in hippocampus of GCI/R rats, increased dopamine level in hippocampus, decreased succinic acid level, and stabilized Ca2+ level in CA1 subregion of hippocampus. As a precursor of dopamine, L-DOPA is presumed to improves mitochondrial function in hippocampus of GCI/R rats. However, dopamine cannot cross the blood-brain barrier, so L-DOPA is used in clinical therapy to supplement dopamine. In this investigation, OGD/R models were established in isolated mouse hippocampal neurons (HT22) and primary rat hippocampal neurons. Notably, dopamine exhibited a multifaceted impact, demonstrating inhibition of mitochondrial reactive oxygen species (mitoROS) production, stabilization of mitochondrial membrane potential and Ca2+ level, facilitation of TCA circulation, promotion of aerobic respiratory metabolism, and downregulation of succinic acid-related gene expression. Consistency between in vitro and in vivo results underscores dopamine's significant neuroprotective role in mitigating mitochondrial dysfunction following global cerebral hypoxia and ischemia injury. Supplement dopamine may represent a promising therapy to the cognitive impairment caused by GCI/R injury.

A multi-omics analysis-based model to predict the prognosis of low-grade gliomas.

Lower-grade gliomas (LGGs) exhibit highly variable clinical behaviors, while classic histology characteristics cannot accurately reflect the authentic biological behaviors, clinical outcomes, and prognosis of LGGs. In this study, we carried out analyses of whole exome sequencing, RNA sequencing and DNA methylation in primary vs. recurrent LGG samples, and also combined the multi-omics data to construct a prognostic prediction model. TCGA-LGG dataset was searched for LGG samples. 523 samples were used for whole exome sequencing analysis, 532 for transcriptional analysis, and 529 for DNA methylation analysis. LASSO regression was used to screen genes with significant association with LGG survival from the frequently mutated genes, differentially expressed genes, and differentially methylated genes, whereby a prediction model for prognosis of LGG was further constructed and validated. The most frequently mutated diver genes in LGGs were IDH1 (77%), TP53 (48%), ATRX (37%), etc. Top significantly up-regulated genes were C6orf15, DAO, MEOX2, etc., and top significantly down-regulated genes were DMBX1, GPR50, HMX2, etc. 2077 genes were more and 299 were less methylated in recurrent vs. primary LGG samples. Thirty-nine genes from the above analysis were included to establish a prediction model of survival, which showed that the high-score group had a very significantly shorter survival than the low-score group in both training and testing sets. ROC analysis showed that AUC was 0.817 for the training set and 0.819 for the testing set. This study will be beneficial to accurately predict the survival of LGGs to identify patients with poor prognosis to take specific treatment as early, which will help improve the treatment outcomes and prognosis of LGG.

Assessing watershed-scale impacts of best management practices and elevated atmospheric carbon dioxide concentrations on water yield.

Changes in water yield are influenced by many intersecting biophysical elements, including climate, on-land best management practices, and landcover. Large-scale reductions in water yield may present a significant threat to water supplies globally. Many of these intersecting factors are intercorrelated and confounded, making it challenging to separate the factors' individual contributions to shaping local streamflow dynamics. Comprehensive hydrological models constructed based on a well-established understanding of biophysical processes are often employed to address these matters. However, these models rarely incorporate all relevant factors influencing local hydrological processes, due to the reliance of these models on the latest, albeit limited, state-of-the-art research. For instance, complexities inherent in watershed hydrology, which involve multilayered interactions among potentially many biophysical factors, leave the direct analysis of subtle impacts on water yields measured in-situ largely intractable. Therefore, we propose an innovative approach to assess impacts of elevated atmospheric CO2 concentrations and flow diversion terraces (FDTs) on stream discharge rates at the watershed scale. Initially, we use a comprehensive hydrological model to account for the impacts of major climatic and landuse/landcover factors on changes in field-acquired measurements of water yield. Next, we employ conventional and advanced statistical methods to decompose the residuals of model predictions to facilitate the identification of subtle influences promoted by increases in atmospheric CO2 concentrations and the application of FDTs in an agriculture-dominated watershed. Through this innovative approach, we find that FDTs contributed to a watershed-wide, net water-yield reduction of 188.0 mm (or 28.9 %) from 1992 to 2014. Ongoing increases in ambient CO2 concentrations, which are responsible for an overall reduction in a watershed-level assessment of stomatal conductance, have led to a minor increase in stream discharge rates during the same 23-year period, i.e., 0.45 mm of water yield per year, or 1.6 % overall. Streamflow reductions explicitly caused by regional warming in the area alone, on account of increased evapotranspiration, may be overestimated due to the opposing, synergistic effects on water yield associated with CO2-enrichment of the lower atmosphere and the annual application of FDTs.

Individualized intervention based on a preparation-related prediction model improves adequacy of bowel preparation: A prospective, multi-center, randomized, controlled study.

AIMS: An easy-to-use preparation-related model (PRM) predicting inadequate bowel preparation (BP) was developed and proved superior to traditional models in our previous study. Here we aimed to investigate whether PRM-based individualized intervention can improve BP adequacy. METHODS: Patients undergoing morning colonoscopy were prospectively enrolled in 5 endoscopic centers in China. After standard BP of split-dose polyethylene glycol (PEG) was completed, patients were randomized (1:1) to the individualized group or standard group. High-risk patients predicted by PRM score ≥3 were instructed to drink an additional 1.5 L PEG in the individualized group while not in standard group. The primary endpoint was the rate of adequate BP, defined by segmental Boston bowel preparation scale ≥2. Secondary outcomes included adenoma detection rate (ADR) and adverse events. RESULTS: 900 patients were randomly allocated to the individualized group (n = 449) and the control (n = 451). Baseline characteristics were similar between the two groups. The rates of high-risk patients were 19.6 % in individualized group and 19.7 % in standard group. In intention-to-treat analysis, adequate BP was 91.8 % in individualized group and 84.7 % in the standard group (p = 0.001). Among high-risk patients, adequate BP rate was 94.3 % in individualized group and 49.3 % in standard group (p < 0.001), and ADR were 40.9 % vs 16.9 %, respectively (p < 0.001). No significant differences were found regarding the adverse events and willingness to repeat BP (all p >0.05). CONCLUSIONS: The individualized intervention using an additional dose of PEG to high-risk patients predicted by PRM, significantly improved BP quality. The intervention significantly improved ADR in high-risk patients. (ClinicalTrials.gov number: NCT04434625).

Transcutaneous Auricular Vagal Nerve Stimulation Is Effective for the Treatment of Functional Dyspepsia: A Multicenter, Randomized Controlled Study.

INTRODUCTION: Vagal nerve stimulation (VNS) can be used to modulate gastrointestinal motility, inflammation, and nociception. However, it remains unclear whether VNS is effective in adult patients with functional dyspepsia (FD). We investigated the effectiveness of transcutaneous auricular VNS (taVNS) in patients with FD. METHODS: Consecutive patients with FD meeting Rome IV criteria with modified FD Symptom Diary score ≥10 were enrolled. Patients were randomly allocated to 10-Hz taVNS (V10 group), 25-Hz taVNS (V25 group), or sham group, with 30 minutes of treatment twice a day for 4 weeks. The primary outcome was the response rate at week 4, defined as the proportion of patients whose modified FD Symptom Diary score was reduced ≥5 when compared with the baseline. Secondary outcomes included adequate relief rate and adverse events. RESULTS: A total of 300 patients were randomized to V10 (n = 101), V25 (n = 99), and sham groups (n = 100). After 4 weeks of treatment, V10 and V25 groups had a higher response rate (81.2% vs 75.9% vs 47%, both P < 0.001) and adequate relief rate (85.1% vs 80.8% vs 67%, both P < 0.05) compared with the sham group. There was no significant difference between V10 and V25 in response rate and adequate relief rate (both P > 0.05). The efficacy of taVNS (both 10 and 25 Hz) lasted at week 8 and week 12 during follow-up period. Adverse events were all mild and comparable among the 3 groups (1%-3%). DISCUSSION: Our study firstly showed that 4-week taVNS (both 10 and 25 Hz) was effective and safe for the treatment of adult FD ( clinicaltrials.gov number: NCT04668534).

DNMT1 expression partially dictates 5-Azacytidine sensitivity and correlates with RAS/MEK/ERK activity in gastric cancer cells.

Though DNMTs inhibitors were widely used in myelodysplastic syndrome and leukaemia, their application in solid tumours has been limited by low response rate and lack of optimal combination strategies. In gastric cancer (GC), the therapeutic implication of KRAS mutation or MEK/ERK activation for combinational use of DNMTs inhibitors with MEK/ERK inhibitors remains elusive. In this study, stable knockdown of DNMT1 expression by lentiviral transfection led to decreased sensitivity of GC cells to 5-Azacytidine. KRAS knockdown in KRAS mutant GC cells or the MEK/ERK activation by EGF stimulation in GC cells increased DNMT1 expression, while inhibition of MEK/ERK activity by Selumetinib led to decreased DNMT1 expression. 5-Azacytidine treatment, which led to dramatic decline of DNMTs protein levels and increased activity of MEK/ERK pathway, altered the activity of MEK/ERK inhibitor Selumetinib on GC cells. Both RAS-dependent gene expression signature and expression levels of multiple MEK/ERK-dependent genes were correlated with DNMT1 expression in TCGA stomach cancer samples. In conclusion, DNMT1 expression partially dictates 5-Azacytidine sensitivity and correlates with RAS/MEK/ERK activity in GC cells. Combining DNMTs inhibitor with MEK/ERK inhibitor might be a promising strategy for patients with GC.[Figure: see text].

Clinical and virological features of asymptomatic and mild symptomatic patients with SARS-CoV-2 Omicron infection at Shanghai Fangcang shelter hospital.

OBJECTIVE: The objective of this study is to evaluate and compare clinical and virological characteristics of asymptomatic and mild symptomatic patients of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2.2 variant infection and identify risk factors associated with the prolonged viral negative conversion duration. METHODS: We conducted a retrospective observational study in a Shanghai (China) Fangcang shelter hospital from April 9 to May 17, 2022. The patient-related demographic or clinical data were retrospectively recorded. Comparisons of demographic and clinical characteristics between asymptomatic and mild-symptomatic patients were performed. Cox regression was performed to identify the risk factors of prolonged viral negative conversion duration. RESULTS: A total of 551 patients confirmed with SARS-CoV-2 Omicron variant infection were enrolled in the study. Of these, 297 patients (53.9%) were asymptomatic and 254 patients (46.1%) had mild symptoms. When comparing the clinical and virological characteristics between the asymptomatic and mild symptomatic groups, several clinical parameters, including age, gender, time to viral clearance from the first positive swab, chronic comorbidities, and vaccination dose did not show statistically significant differences. In mild symptomatic patients, the median viral negative conversion duration (NCD) was 7 days (interquartile range [IQR]: 5-9), which was comparable to the median of 7 days (IQR: 5-10) in asymptomatic patients (p = .943). Multivariate Cox analysis revealed that patients age ≥ 60 years had a significantly higher hazard ratio (HR) for prolonged viral NCD (HR: 1.313; 95% confidence interval: 1.014-1.701, p = .039). CONCLUSION: Asymptomatic and symptomatic patients with non-severe SARS-CoV-2 Omicron BA.2.2 variant infection have similar clinical features and virological courses. Old age was an independent risk factor for prolonged SARS-CoV-2 conversion time.

Effects of different doses of dopamine receptor agonist pramipexole on neurobehaviors and changes of mitochondrial membrane potentials in rats with global cerebral ischemia-reperfusion injury.

OBJECTIVE: To explore the effects of different doses of dopamine receptor agonist pramipexole on neurobehaviors and changes of mitochondrial membrane potential in rats with global cerebral ischemia-reperfusion injury. METHODS: A total of 75 SPF Sprague-Dawley male rats were randomly divided into sham group (n=20), model group (n=20), pramipexole administration group (n=35). The rat model of global cerebral ischemia-reperfusion injury was prepared by the modified Pulsinelli's four-vessel occlusion method. Pramipexole administration group was administered intraperitoneally in rats with global cerebral ischemia-reperfusion injury at different doses of pramipexole 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, 2 mg/kg, once a day for 14 consecutive days. Based on the results of modified neurological severity scores, open field test and morphology by Nissl's staining to determine the optimal dose of pramipexole. Mitochondrial membrane potential in the optimal dose of pramipexole administration group were measured by the JC-1 fluorescent probe staining method. RESULTS: 1. Different doses of pramipexole 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, and 2 mg/kg, were used as drug administration in rats with global cerebral ischemia-reperfusion injury for 14 consecutive days, and we found that all four doses of pramipexole could improve the modified neurological severity scores of rats with global cerebral ischemia-reperfusion injury to varying degrees, but only 0.5 mg/kg pramipexole at 1, 3, 7 and 14 days consistently reduced modified neurological severity scores and improved neurological function in rats with global cerebral ischemia-reperfusion injury. In the open-field test, only 0.5 mg/kg pramipexole increased the number of entries into the central zone, duration spent in the central zone, total distance travelled in the open field and average velocity, which improved the spontaneous activities and reduced anxiety and depression of rats with global cerebral ischemia-reperfusion injury. 2. Different doses of pramipexole 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg, and 2 mg/kg for 14 consecutive days significantly increased the number of surviving neurons in the hippocampal CA1 subfield in rats with global cerebral ischemia-reperfusion injury to varying degrees. Based on these results, we tentatively found that 0.5 mg/kg pramipexole may be the optimal dose in all of the above. 3. We found that 0.5 mg/kg pramipexole significantly increased the mitochondrial membrane potential in rats after global cerebral ischemia-reperfusion injury. CONCLUSION: Different doses of dopamine receptor agonist pramipexole improved neurological function of rats with global cerebral ischemia-reperfusion injury to varying degrees, and 0.5 mg/kg pramipexole may be the optimal dose in all of the above. Pramipexole may produce neuroprotective effects by protecting neurons in the hippocampus and improving the mitochondrial membrane potential after global cerebral ischemia-reperfusion injury.

Prolonged cannulation time is an independent risk factor for moderate-to-severe post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis: a large cohort study.

Background: Moderate-to-severe post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis contributes to most of the poor outcomes of patients with post-ERCP pancreatitis (PEP). However, it remains unclear which part of the patient is more vulnerable to moderate-to-severe PEP (MS PEP). In this study, we aimed to identify the risk factors independently associated with MS PEP. Methods: Consecutive patients with native papilla who had undergone ERCP were included in this study. The patient-related and procedure-related variables were retrieved from a prospectively maintained ERCP database. The primary outcome was the incidence of PEP. MS PEP was defined as a prolonged hospital stay of ≥4 days (as per the Cotton criteria) or the presence of organ failure (as per the revised Atlanta criteria). A logistic regression analysis was conducted to identify the risk factors. Results: A total of 6,944 patients with native papilla who had undergone elective ERCP from January 2010 to February 2022 were included in this study. Among these 6,944 patients, 362 (5.2%) patients developed PEP. Among these 362 patients, 76 (1.1%) or 17 (0.2%) had MS PEP as per the Cotton criteria and the revised Atlanta criteria, respectively. The logistic analysis revealed that the independent risk factors for overall and mild PEP were similar, and included being female and inadvertent pancreatic duct (PD) cannulation. A total cannulation time >15 min was also found to be an independent risk factor for MS PEP as defined by both the Cotton criteria and the revised Atlanta criteria. Conclusions: This study found that female patients and those who had inadvertent PD cannulation were at risk of mild PEP. A total cannulation time >15 min was also found to be a risk factor for developing MS PEP.

Analysis of clinical diagnosis and treatment of intestinal volvulus.

BACKGROUND: The aim of this study is to investigate the clinical characteristics and treatment experience of intestinal volvulus, and to analyze the incidence of adverse events and related risk factors of intestinal volvulus. METHODS: Thirty patients with intestinal volvulus admitted to the Digestive Emergency Department of Xijing Hospital from January 2015 to December 2020 were selected. The clinical manifestations, laboratory tests, treatment and prognosis were retrospectively analyzed. RESULTS: A total of 30 patients with volvulus were enrolled in this study, including 23 males (76.7%), with a median age of 52 years (33-66 years). The main clinical manifestations were abdominal pain in 30 cases (100%), nausea and vomiting in 20 cases (67.7%), cessation of exhaust and defecation in 24 cases (80%), and fever in 11 cases (36.7%). The positions of intestinal volvulus were jejunum in 11 cases (36.7%), ileum and ileocecal in 10 cases (33.3%), sigmoid colon in 9 cases (30%). All 30 patients received surgical treatment. Among the 30 patients underwent surgery, 11 patients developed intestinal necrosis. We found that the longer the disease duration (> 24 h), the higher the incidence of intestinal necrosis, and the higher the incidence of ascites, white blood cell count and neutrophil ratio in the intestinal necrosis group were significantly higher than those in the non-intestinal necrosis group (p < 0.05). After treatment, 1 patient died of septic shock after operation, and 2 patients with recurrent volvulus were followed up within 1 year. The overall cure rate was 90%, the mortality rate was 3.3%, and the recurrence rate was 6.6%. CONCLUSION: Laboratory examination, abdominal CT and dual-source CT are very important for the diagnosis of volvulus in patients with abdominal pain as the main symptom. Increased white blood cell count, neutrophil ratio, ascites and long course of disease are important for predicting intestinal volvulus accompanied by intestinal necrosis. Early diagnosis and timely intervention can save lives and prevent serious complications.

Low-dose of magnesium sulfate solution was not inferior to standard regime of polyethylene glycol for bowel preparation in elderly patients: a randomized, controlled study.

BACKGROUND: Large polyethylene glycol (PEG) is a standard regimen for bowel preparation. However, elderly patients suffered from adverse events. This study was to compare the efficacy and safety of oral magnesium sulfate solution (MSS) vs standard PEG in elderly patients undergoing colonoscopy. METHODS: Elderly patients aged 60-90 years, from two endoscopic centers, were enrolled in China. Patients were randomized to take a low dose of MSS or a standard PEG regime in a split-dose regime. The primary endpoint was the proportion of patients with adequate bowel preparation, which was defined as the total Boston Bowel Preparation Scale (BBPS) ≥6 and each segmental BBPS was ≥2. Secondary outcomes included adenoma detection rate (ADR), safety, adverse events, cecal intubation rate, willingness to repeat BP, and so on. RESULTS: 1174 elderly patients were randomly allocated to the MSS group (n = 588) or the standard group (n = 586). Adequate BP was achieved in 94.0% of patients in the MSS group and 92.5% in the control (p = .287). ADR was also comparable between the two groups (43.0% and 39.9%, p = .282). Compared with the standard group, MSS group reported less abdominal discomfort (1.7% vs 6.0%), less nausea (13.6% vs 21.0%) and vomiting (1.2% vs 4.2%). The change in serum potassium levels after preparation in the standard group was significantly lower than that in the MSS group (-0.19 ± 0.08 vs -0.41 ± 0.11, p = .037). CONCLUSIONS: Low dose of MSS was not inferior to the standard PEG regime in terms of bowel preparation quality for elderly patients. Low-dose MSS offered fewer adverse events and better tolerability. It is a preferable choice for the elderly to undergo bowel preparation for colonoscopy. CLINICAL TRIAL REGISTRATION NUMBER: NCT04948567.

Temporal heterogeneity in photosystem II photochemistry in Artemisia ordosica under a fluctuating desert environment.

Acclimation strategies in xerophytic plants to stressed environmental conditions vary with temporal scales. Our understanding of environmentally-induced variation in photosystem II (PSII) processes as a function of temporal scales is limited, as most studies have thus far been based on short-term, laboratory-controlled experiments. In a study of PSII processes, we acquired near-continuous, field-based measurements of PSII-energy partitioning in a dominant desert-shrub species, namely Artemisia ordosica, over a six-year period from 2012-2017. Continuous-wavelet transformation (CWT) and wavelet coherence analyses (WTC) were employed to examine the role of environmental variables in controlling the variation in the three main PSII-energy allocation pathways, i.e., photochemical efficiency and regulated and non-regulated thermal dissipation, i.e., Φ PSII, Φ NPQ, and Φ NO, respectively, across a time-frequency domain from hours to years. Convergent cross mapping (CCM) was subsequently used to isolate cause-and-effect interactions in PSII-energy partitioning response. The CWT method revealed that the three PSII-energy allocation pathways all had distinct daily periodicities, oscillating abruptly at intermediate timescales from days to weeks. On a diurnal scale, WTC revealed that all three pathways were influenced by photosynthetically active radiation (PAR), air temperature (T a), and vapor pressure deficit (VPD). By comparing associated time lags for the three forms of energy partitioning at diurnal scales, revealed that the sensitivity of response was more acutely influenced by PAR, declining thereafter with the other environmental variables, such that the order of influence was greatest for T a, followed by VPD, and then soil water content (SWC). PSII-energy partitioning on a seasonal scale, in contrast, displayed greater variability among the different environmental variables, e.g., Φ PSII and Φ NO being more predisposed to changes in T a, and Φ NPQ to changes in VPD. CCM confirmed the causal relationship between pairings of PSII-energy allocation pathways, according to shrub phenology. A. ordosica is shown to have an innate ability to (i) repair damaged PSII-photochemical apparatus (maximum quantum yield of PSII photochemistry, with F v/F m > 0.78), and (ii) acclimatize to excessive PAR, dry-air conditions, and prolonged drought. A. ordosica is relatively sensitive to extreme temperature and exhibits photoinhibition.

Superiority of a preparation-related model for predicting inadequate bowel preparation in patients undergoing colonoscopy: A multicenter prospective study.

BACKGROUND AND AIM: Three models based on patient-related factors have been developed to predict inadequate bowel preparation (BP). However, the performance of the models seems suboptimal. This study aimed to develop a novel preparation-related model and compare it with the available patient-related models. METHODS: Patients receiving standard BP were prospectively enrolled from five endoscopic centers. Patient-related and preparation-related factors for inadequate BP (defined by segmental Boston Bowel Preparation Scale score < 2) were identified by logistic regression. A preparation-related model was derived and internally validated in 906 patients. The comparisons of models were assessed by discrimination and calibration. The preparation-related model was also externally validated. RESULTS: Several patient-related factors (male and American Society of Anesthesiologists Physical Status Classification System score ≥ 3) and preparation-related factors (drinking-to-stool interval ≥ 3 h, preparation-to-colonoscopy interval ≥ 6 h, and poor rectal effluent) were found to be independently associated with inadequate BP (all P < 0.05). C-statistics was 0.81 for the preparation-related model in the training cohort (n = 604), significantly higher than three available patient-based models (0.58-0.61). Similar results were observed in the validation cohort (n = 302). Calibration curves showed close agreement in the preparation-related model (R2  = 0.315 in the training cohort and 0.279 in the validation cohort). The preparation-related model was externally validated in another 606 patients with C-index of 0.80. CONCLUSIONS: A new preparation-related model (consisting of drinking-to-stool interval ≥ 3 h, preparation-to-colonoscopy interval ≥ 6 h, and poor last rectal effluent) was developed and performed better than three available patient-related models. This easy-to-use model may be a useful decision-support tool on individualized plans in patients undergoing BP.

The Incidence and Severity of Post-ERCP Pancreatitis in Patients Receiving Standard Administration of NSAIDs: a Systematic Review and Meta-analysis.

BACKGROUND: Routine rectal administration of 100 mg of diclofenac or indomethacin was demonstrated to be an effective prevention method to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. The systematic review and meta-analysis aimed to estimate the incidence and severity of post-ERCP pancreatitis (PEP) and explore the discrepancies of PEP incidences among different subgroups. METHODS: The PubMed, Web of Science, and Ovid EMBASE databases were searched for studies published until December 2020. Only randomized controlled trials (RCTs) reported rectal administration of 100 mg or higher doses of diclofenac or indomethacin, with PEP as the primary outcomes were eligible for inclusion. The overall and severity of PEP were estimated. Subgroup analysis was performed based on geographic regions, risk level, study beginning time, type of NSAIDs, administration time, and sample size. RESULTS: There were 26 randomized controlled trials (RCTs) with 7954 patients in 31 NSAIDs arms. The pooled incidences were 7.2% for overall PEP (95% confidence interval (CI) 5.9-8.5%), 5.0% for mild PEP (95% CI, 4.0-6.0%), and 1.5% for moderate and severe PEP (0.8-2.3%). PEP rate were higher in patients receiving rectal indomethacin than that of patients receiving rectal diclofenac (7.8% (95% CI, 6.4-9.3%) vs 3.8% (95% CI, 2.2-5.3%), p = 0.009). The PEP rates of high-risk patients and average-risk patients were 8.9% (95% CI, 5.6-12.2%) and 6.4% (95% CI, 5.1-7.6%), respectively (p = 0.160). CONCLUSIONS: The incidence of PEP was higher in patients receiving 100 mg rectal indomethacin than patients receiving 100 mg diclofenac. The effect of 100 mg diclofenac versus indomethacin on preventing PEP requires further study.