A therapeutic ERCP in an only 5.9 kg infant with obstruction jaundice using JF-260V duodenoscope.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has found extensive use in pediatric patients; however, challenges persist in the application of therapeutic ERCP in infants. CASE PRESENTATION: This case report details the presentation of a 5.9-kilogram infant with obstructive jaundice and suspected hemolytic anemia who underwent ERCP to alleviate biliary obstruction. The infant was admitted due to clay-colored stools, jaundice, and liver injury. Ultrasound and magnetic resonance cholangiopancreatography (MRCP) revealed dilation of the common bile duct (CBD) accompanied by the presence of stones. ERCP was conducted using a JF-260V duodenoscope under general anesthesia. Successful stone extraction and biliary drainage were achieved. CONCLUSIONS: In centers with considerable expertise in ERCP and pediatric anesthesia, the use of a conventional adult duodenoscope for therapeutic ERCP in infants can be considered safe and feasible, provided careful and stringent patient selection criteria are applied. In the future, clear guidelines and standardized protocols for the indications and procedures of pediatric ERCP should be established.

Association between trunk rotation and pelvic rotation in adolescents with idiopathic scoliosis.

BACKGROUND: Previous studies have suggested an association between pelvic rotation (PR) and scoliotic deformity in severe adolescent idiopathic scoliosis (AIS), but none have investigated this relationship in mild to moderate AIS. OBJECTIVE: To investigate the relationship between PR and trunk rotation in mild to moderate AIS. METHODS: This was a case-control study. The cases were 32 AIS patients with PR in the opposite direction to the thoracic curve, and the controls were 32 AIS patients with PR in the same direction as the thoracic curve. All patients were assessed with the Adams forwards bend test. Type II trunk rotation was selected as exposure. Logistic regression was used to estimate the association between PR direction and types of trunk rotation while accounting for confounders. Multiple linear regression was used to analyse the relationships between PR magnitude and the angle of trunk rotation (ATR). RESULTS: Logistic regression showed an unadjusted OR of 9.13 (95% CI 2.92-28.50, P< 0.001), and adjustment for sex and Cobb angle only slightly changed the OR (adjusted OR, 8.23; 95% CI, 2.51-27.01; P= 0.001). The concave/convex ratio was associated with ATR measurements in both cases (ß=-0.379; P= 0.030) and controls (ß=-0.468, P= 0.008). CONCLUSION: An association was found between PR and trunk rotation, which may help achieve more effective physiotherapy in mild to moderate AIS.

Heterogeneous Integration of Solid-State Quantum Systems with a Foundry Photonics Platform.

Diamond color centers are promising optically addressable solid-state spins that can be matter-qubits, mediate deterministic interaction between photons, and act as single photon emitters. Useful quantum computers will comprise millions of logical qubits. To become useful in constructing quantum computers, spin-photon interfaces must, therefore, become scalable and be compatible with mass-manufacturable photonics and electronics. Here, we demonstrate the heterogeneous integration of NV centers in nanodiamond with low-fluorescence silicon nitride photonics from a standard 180 nm CMOS foundry process. Nanodiamonds are positioned over predefined sites in a regular array on a waveguide in a single postprocessing step. Using an array of optical fibers, we excite NV centers selectively from an array of six integrated nanodiamond sites and collect the photoluminescence (PL) in each case into waveguide circuitry on-chip. We verify single photon emission by an on-chip Hanbury Brown and Twiss cross-correlation measurement, which is a key characterization experiment otherwise typically performed routinely with discrete optics. Our work opens up a simple and effective route to simultaneously address large arrays of individual optically active spins at scale, without requiring discrete bulk optical setups. This is enabled by the heterogeneous integration of NV center nanodiamonds with CMOS photonics.

Machine learning in predicting T-score in the Oxford classification system of IgA nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) is one of the leading causes of end-stage kidney disease (ESKD). Many studies have shown the significance of pathological manifestations in predicting the outcome of patients with IgAN, especially T-score of Oxford classification. Evaluating prognosis may be hampered in patients without renal biopsy. Methods: A baseline dataset of 690 patients with IgAN and an independent follow-up dataset of 1,168 patients were used as training and testing sets to develop the pathology T-score prediction (T pre) model based on the stacking algorithm, respectively. The 5-year ESKD prediction models using clinical variables (base model), clinical variables and real pathological T-score (base model plus T bio), and clinical variables and T pre (base model plus T pre) were developed separately in 1,168 patients with regular follow-up to evaluate whether T pre could assist in predicting ESKD. In addition, an external validation set consisting of 355 patients was used to evaluate the performance of the 5-year ESKD prediction model using T pre. Results: The features selected by AUCRF for the T pre model included age, systolic arterial pressure, diastolic arterial pressure, proteinuria, eGFR, serum IgA, and uric acid. The AUC of the T pre was 0.82 (95% CI: 0.80-0.85) in an independent testing set. For the 5-year ESKD prediction model, the AUC of the base model was 0.86 (95% CI: 0.75-0.97). When the T bio was added to the base model, there was an increase in AUC [from 0.86 (95% CI: 0.75-0.97) to 0.92 (95% CI: 0.85-0.98); P = 0.03]. There was no difference in AUC between the base model plus T pre and the base model plus T bio [0.90 (95% CI: 0.82-0.99) vs. 0.92 (95% CI: 0.85-0.98), P = 0.52]. The AUC of the 5-year ESKD prediction model using T pre was 0.93 (95% CI: 0.87-0.99) in the external validation set. Conclusion: A pathology T-score prediction (T pre) model using routine clinical characteristics was constructed, which could predict the pathological severity and assist clinicians to predict the prognosis of IgAN patients lacking kidney pathology scores.

Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography: A single-blind, multicenter, randomized controlled trial.

BACKGROUND: Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients' recovery. METHODS: This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group (n = 665) and fasting group (n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. RESULTS: The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t = 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26-0.71, P <0.001) and 0.76 (95% CI: 0.57-0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05-0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39-0.95, P = 0.028) in the multivariable models. CONCLUSION: Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery. TRAIL REGISTRATION: ClinicalTrials.gov, No. NCT03075280.

Unveiling the Effects of Carbon-Based Nanomaterials on Crop Growth: From Benefits to Detriments.

To systematically assess the impact of typical CNMs on the growth effects of cereal crops, we conducted a meta-analysis of 48 independent studies worldwide. The pooled results showed that shoot weight (13.39%) and antioxidant metabolite content (SOD: 106.32%, POD: 32.29%, CAT: 22.63%) of cereal crops exposed to the presence of CNMs were significantly increased, but phytohormones secretion (17.84%) was inhibited. The results of subgroup analysis showed that there were differences in the results of different CNM types with the same exposure concentration on growth effects. Short-term exposure adversely affected the root and photosynthetic capacity of the crop, but prolonged exposure instead showed a promoting effect. Multiple linear regression analysis showed that the concentration of CNMs and cereal variety variables were significantly associated with changes in multiple growth effect values. This work could offer references and fresh perspectives for investigating how nanoparticles and crops interact.

PD-L1 Enhanced by cis-Urocanic Acid on Langerhans Cells Inhibits Vγ4+ γδT17 Cells in Imiquimod-Induced Skin Inflammation.

Psoriasis is an IL-23/IL-17-mediated inflammatory autoimmune dermatosis, and UVB may contribute to immunosuppression and ameliorate associated symptoms. One of the pathophysiology underlying UVB therapy is the production of cis-urocanic acid (cis-UCA) by keratinocytes. However, the detailed mechanism is yet to be fully understood. In this study, we found FLG expression and serum cis-UCA levels were significantly lower in patients with psoriasis than in healthy controls. We also noted that cis-UCA application inhibited psoriasiform inflammation through the reduction of Vγ4+ γδT17 cells in murine skin and draining lymph nodes. Meanwhile, CCR6 was downregulated on γδT17 cells, which would suppress the inflammatory reaction at a distal skin site. We revealed that the 5-hydroxytryptamine receptor 2A, the known cis-UCA receptor, was highly expressed on Langerhans cells in the skin. cis-UCA also inhibited IL-23 expression and induced PD-L1 on Langerhans cells, leading to the attenuated proliferation and migration of γδT-cells. Compared to the isotype control, α-PD-L1 treatment in vivo could reverse the antipsoriatic effects of cis-UCA. PD-L1 expression on Langerhans cells was sustained through the cis-UCA-induced mitogen-activated protein kinase/extracellular signal-regulated kinase pathway. These findings uncover the cis-UCA-induced PD-L1-mediated immunosuppression on Langerhans cells, which facilitates the resolution of inflammatory dermatoses.

Preoperative pancreatic CT value is related to pancreatic fistula after pancreaticoduodenectomy: a retrospective study.

Background: Pancreatic fistula (PF) is the main complication in patients undergoing pancreaticoduodenectomy. Computed tomography (CT) value can reflect pancreatic tissue characteristics which is related to PF. This study was designed to study the relationship between the preoperative CT value and pancreatic fistula. Methods: We retrospectively reviewed the clinical and medical data of patients undergoing pancreaticoduodenectomy from 2017 to 2021. The pancreatic CT value and the CT value ratios of the pancreas and abdominal aorta (PCT/ACT) were measured and compared between the PF group and non-PF group. The values in different PF severity groups were compared using variance analysis. A cut-off value was selected by receiver operating characteristic (ROC) curve. Single-factor and multiple-factor analysis were performed to evaluate Correlation between PF and CT. Results: One hundred and twenty-seven cases were included in this study. The PCT/ACT in the PF group was significantly lower than that in the non-PF group (P<0.001), and the PCT/ACT value was correlatively lower in the severe PF group than in the mild PF group (P=0.008). A cutoff value of 0.99 was selected by ROC curves analysis. Further multifactor analysis identified PCT/ACT <0.99 to be an independent preoperative predictor [odds ratio (OR): 11.3, P<0.01]. Conclusions: The preoperative pancreatic CT value can indirectly reflect the histological condition of the pancreas and thus may related to postoperative PF after pancreaticoduodenectomy and provide useful information for surgeons in deciding upon the pancreaticojejunostomy method.

Potential factors affecting success rate and long term outcome in single balloon enteroscopy-assisted therapeutic endoscopic retrograde cholangiopancreatography in patients with pancreaticojejunal anastomotic stenosis: a retrospective study.

Background: Pancreaticojejunal anastomotic stenosis (PJS) after pancreaticoduodenectomy (PD) is difficult to treat. Single-balloon enteroscope-assisted endoscopic retrograde pancreatography (SBE-assisted ERP) is a safe way to treat PJS with the strength of minimally invasion and repeatability, but since its technical difficulty and few patient number, data on long-term outcomes remain limited. The optimal treatment is still unknown. We aim to study the safety, effectiveness, and long-term outcome of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERP in patients with PJS in this study. Methods: The clinical information of patients undergoing SBE-assisted therapeutic ERP from March 2016 to March 2021 were retrospectively analyzed. All patients were diagnosed as PJS and without any contraindication for therapeutic endoscopy. Treatment details, postoperative complications, factors influencing technical success rate were evaluated. Long-term outcomes results were obtained by clinical or telephone follow-up. Results: Sixteen patients with median age of 51 years were included in this study, surgical reconstruction methods including PD with Whipple reconstruction, PD with Child reconstruction, pylorus-preserving pancreaticoduodenectomy (PpPD) with Whipple reconstruction. Eight patients were successfully treated. No serious complications happened. Risk factors for the failure of pancreaticojejunal anastomotic site identification include the digestive tract reconstruction sequence, pancreaticojejunostomy method, pancreatic duct tube implantation, pancreatic duct width before surgery, and pancreatic fistula during perioperative period. The median follow-up time was 77.2 months, the mean indwelling time of the stent was 62.3 months [interquartile range (IQR), 6.8-153.7 months]. Two of eight patients developed recurrent PJS. The variation in body mass index (BMI) was +2.46 in the non-recurrence group compared to -1.09 in the recurrence group and -2.12 in the endoscopic retrograde cholangiopancreatography (ERCP) treatment failure group. Conclusions: ERP intervention should be carried out early once PJS occurs in order to increase success rate. BMI is a crucial indicator which can reflex PJS rehabilitation degree during follow-up. In order to reduce PJS recurrence rate, a wider pancreatic stent and a longer stent indwelling time are recommended.

Fibrinogen promotes gallbladder cancer cell metastasis and extravasation by inducing ICAM1 expression.

Fibrinogen plays an important role in tumor progression. Here, we explored the role of fibrinogen in gallbladder cancer (GBC) metastasis. The plasma fibrinogen level in M1 GBC patients was higher than in M0 GBC patients, indicating that fibrinogen may participate in GBC metastasis. Treatment of GBC cell lines with fibrinogen promoted metastasis and induced the expression of intercellular adhesion molecule 1 (ICAM1). ICAM1 overexpression promoted metastasis and knockdown inhibited it. The cell adhesion and transendothelial migration of GBC cells were enhanced by fibrinogen treatment and ICAM1 overexpression. In addition, the medium of fibrinogen-treated and overexpression-ICAM1 NOZ cells exhibited enhanced macrophages recruitment. This may work in concert to promote angiogenesis. Immunohistochemistry results on clinical specimens showed that higher fibrinogen levels, higher ICAM1 expression, higher blood vessel density, and higher macrophage levels were present simultaneously. Collectively, this study indicates fibrinogen promotes metastasis and extravasation by inducing ICAM1 expression to enhance tumor cell migration, cell adhesion, transendothelial migration and promote angiogenesis and increase vascular endothelial permeability.

Accumulation and Enrichment of Trace Elements by Yeast Cells and Their Applications: A Critical Review.

Maintaining the homeostasis balance of trace elements is crucial for the health of organisms. Human health is threatened by diseases caused by a lack of trace elements. Saccharomyces cerevisiae has a wide and close relationship with human daily life and industrial applications. It can not only be used as fermentation products and single-cell proteins, but also as a trace elements supplement that is widely used in food, feed, and medicine. Trace-element-enriched yeast, viz., chromium-, iron-, zinc-, and selenium-enriched yeast, as an impactful microelements supplement, is more efficient, more environmentally friendly, and safer than its inorganic and organic counterparts. Over the last few decades, genetic engineering has been developing large-scaled genetic re-design and reconstruction in yeast. It is hoped that engineered yeast will include a higher concentration of trace elements. In this review, we compare the common supplement forms of several key trace elements. The mechanisms of detoxification and transport of trace elements in yeast are also reviewed thoroughly. Moreover, genes involved in the transport and detoxification of trace elements are summarized. A feasible way of metabolic engineering transformation of S. cerevisiae to produce trace-element-enriched yeast is examined. In addition, the economy, safety, and environmental protection of the engineered yeast are explored, and the future research direction of yeast enriched in trace elements is discussed.

Druggable Targets and Compounds with Both Antinociceptive and Antipruritic Effects.

Pain and itch are both important manifestations of various disorders, such as herpes zoster, atopic dermatitis, and psoriasis. Growing evidence suggests that both sensations have shared mediators, overlapping neural circuitry, and similarities in sensitization processes. In fact, pain and itch coexist in some disorders. Determining pharmaceutical agents and targets for treating pain and itch concurrently is of scientific and clinical relevance. Here we review the neurobiology of pain and itch and discuss the pharmaceutical targets as well as novel compounds effective for the concurrent treatment of these sensations.

The Combination of a Novel GLUT1 Inhibitor and Cisplatin Synergistically Inhibits Breast Cancer Cell Growth By Enhancing the DNA Damaging Effect and Modulating the Akt/mTOR and MAPK Signaling Pathways.

Breast cancer is the most prevalent cancer and the second leading cause of cancer death in women. Cisplatin is a commonly used chemotherapeutic drug for breast cancer treatment. Owing to serious side effects, the combination of cisplatin with other drugs is an effective strategy to simultaneously reduce side effects and increase the anticancer efficacy. GLUT1 is an emerging target for cancer treatment since cancer cells usually consume more glucose, a phenomenon called the Warburg effect. In this study, we found that the combination of cisplatin and a novel GLUT1 inhibitor #43 identified from our previous high-throughput screening exerted a synergistic anticancer effect in MCF-7 and MDA-MB-231 breast cancer cells. Mechanism studies in MCF-7 cells revealed that combination of cisplatin and #43 significantly induced apoptosis, intracellular reactive oxygen species, and loss of mitochondrial membrane potential. Furthermore, #43 enhanced the DNA damaging effect of cisplatin. Akt/mTOR downstream signaling and the ERK signaling pathway usually involved in cell growth and survival were inhibited by the combination treatment. On the other hand, phosphorylation of p38 and JNK, which may be associated with apoptosis, was induced by the combination treatment. Altogether, our data indicate that oxidative stress, DNA damage, the Akt/mTOR and MAPK signaling pathways, and apoptosis may be involved in the synergism of cisplatin and #43 in breast cancer cells.

Precursor characteristics of mono-HAAs during chlorination and cytotoxicity of mono-HAAs on HEK-293T cells.

Monohaloacetic acids (mono-HAAs), a class of disinfection by-products widely occurred in drinking water, receives significant attention due to their extremely high toxicity. Many studies on the biological toxicity of mono-HAAs have been reported, yet the toxic effects of mono-HAAs on human renal cells (kidney is one of the target organs for disinfection by-products) has not been involved. Studies on organic precursors for mono-HAAs formation were also very limited due to their lower levels as compared to di-HAAs and tri-HAAs. Based on this, the formation of mono-HAAs after chlorination of some typical source water samples and their relationship with water quality parameters were investigated. Meanwhile, the cytotoxicity of monochloroacetic acid (MCAA), monobromoacetic acid (MBAA), and monoiodoacetic acid (MIAA) were tested using human embryonic kidney cells (HEK-293 T cells). The results showed that the levels of mono-HAAs formed during chlorination of source water samples were between 0.44 and 0.87 µg/L. Formation of MBAA positively (p < 0.05) correlated with bromide ion and dissolved organic carbon, but negatively (p < 0.01) correlated with SUVA254 (specific UV absorbance at 254 nm), while formation of MCAA was only positively (p < 0.05) related with SUVA254. These results suggested that although MCAA and MBAA both belong to the mono-HAAs, the characteristics of their organic precursors differ significantly. MCAA precursors have high aromaticity and are more hydrophobic, yet MBAA precursors have low aromaticity and are more hydrophilic. The half-lethal concentrations (LC50) of MCAA, MBAA, and MIAA on HEK293T cells were 1196-1211 µM, 16.07-18.96 µM, and 6.08-6.17 µM, respectively. An in-depth analysis showed that the cytotoxicity of mono-HAAs on HEK 293 T cells could not be explained by the parameters concerning cellular uptake (e.g., logP and pKa), but the SN2 reaction of C-X bond with cellular molecules (e.g., glyceraldehyde-3-phosphate dehydrogenase, etc) may be the relevant cause for the cytotoxicity of mono-HAAs on HEK 293 T cells.

Utility of endoscopic retrograde cholangiopancreatography in infant patients with conservational endoscopy.

BACKGROUND: The indications for endoscopic retrograde cholangiopancreatography (ERCP) in infant patients (age <1 year) differ from those in adults. A paucity of data and concerns about the potential lower effectiveness and more adverse effects limit its utility, even in tertiary care centres. In this study, we retrospectively analysed the indications, success rates, and adverse effects of ERCP in these groups. METHODS: From June 2014 to March 2018, 17 ERCPs were performed in 15 children [median age: 10.4 months (6-12 months); median weight: 6.6 kg (3.3-10.7 kg)]. A conventional duodenoscope was utilized in all procedures. All patients were followed up as inpatients. RESULTS: Fifteen therapeutic and two diagnostic procedures were managed by licensed paediatric endoscopist. Successful cannulation was obtained in all patients (100%). A high proportion (47.1%) of pancreaticobiliary maljunction (PBM) and therapeutic procedures (88.2%) were identified. Two cases of mild pancreatitis were recorded, accounting for 12.5% of the post-ERCP pancreatitis (PEP) rate. By multivariable analysis, recurrent acute pancreatitis and pancreatic duct (PD) cannulation/injection were identified as PEP-related risk factors. All complications were managed conservatively. CONCLUSIONS: ERCP in infant patients (0.5< age <1 year) could be safely completed by conservational endoscopy. A high proportion of PBM and therapeutic procedures were identified in our study cohort. The overall adverse-event rate was acceptable, and no serious complication occurred. The PEP-related independent risk factors included recurrent acute pancreatitis and PD cannulation/injection.

Development and Validation of a Prognostic Nomogram Based on the Systemic Immune-Inflammation Index for Resectable Gallbladder Cancer to Predict Survival and Chemotherapy Benefit.

OBJECTIVES: To investigate the prognostic significance of the systemic immune-inflammation index (SII) in patients after radical cholecystectomy for gallbladder cancer (GBC) using overall survival (OS) as the primary outcome measure. METHODS: Based on data from a multi-institutional registry of patients with GBC, significant prognostic factors after radical cholecystectomy were identified by multivariate Cox proportional hazards model. A novel staging system was established, visualized as a nomogram. The response to adjuvant chemotherapy was compared between patients in different subgroups according to the novel staging system. RESULTS: Of the 1072 GBC patients enrolled, 691 was randomly selected in the discovery cohort and 381 in the validation cohort. SII>510 was found to be an independent predictor of OS (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.42-2.54). Carbohydrate antigen 199(CA19-9), tumor differentiation, T stage, N stage, margin status and SII were involved in the nomogram. The nomogram showed a superior prediction compared with models without SII (1-, 3-, 5-year integrated discrimination improvement (IDI):2.4%, 4.1%, 5.4%, P<0.001), and compared to TNM staging system (1-, 3-, 5-year integrated discrimination improvement (IDI):5.9%, 10.4%, 12.2%, P<0.001). The C-index of the nomogram in predicting OS was 0.735 (95% CI 0.683-0.766). The novel staging system based on the nomogram showed good discriminative ability for patients with T2 or T3 staging and with negative lymph nodes after R0 resection. Adjuvant chemotherapy offered significant survival benefits to these patients with poor prognosis. CONCLUSIONS: SII was an independent predictor of OS in patients after radical cholecystectomy for GBC. The new staging system identified subgroups of patients with T2 or T3 GBC with negative lymph nodes who benefited from adjuvant chemotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier (NCT04140552).

Efficacy and safety of ciprofol for the sedation/anesthesia in patients undergoing colonoscopy: Phase IIa and IIb multi-center clinical trials.

OBJECTIVE: Ciprofol is a new intravenous anesthetic agent similar to propofol that has the pharmacodynamic characteristics of a rapid rate of onset and recovery in pre-clinical experiments. The aims of the present clinical trials were to compare the efficacy and safety of ciprofol emulsion for sedation or general anesthesia during colonoscopy and to define optimal doses for a subsequent phase III clinical trial. METHODS: A phase IIa multi-center, open-label, non-randomized, positive control, dose-escalating study was performed to determine a recommended phase IIb dose (RP2D) of ciprofol to induce sedation or anesthesia in patients undergoing colonoscopy. Phase IIb was also a multi-center clinical trial, but the patients were randomized into 3 groups at a ratio of 1:1:1. It was a double-blinded, propofol controlled study that administered ciprofol 0.4 mg/kg (n = 31) and 0.5 mg/kg (n = 32) or propofol at 2.0 mg/kg (n = 31), with the aim of establishing the optimal dose of ciprofol. The primary endpoint was the colonoscopy success rate. Secondary endpoints were the duration of colonoscope insertion, recovery time, number of top-up doses needed, and the total dose of ciprofol or propofol required to maintain adequate sedation or anesthesia. In addition, we evaluated the satisfaction of sedation/anesthesia from the endoscopists, anesthetists and patients' points of view. Safety was assessed according to the incidence of AEs including serious AEs and drug related AEs and the assessment of vital signs, a 12-lead ECG and laboratory tests. RESULTS: In the phase IIa trial, the colonoscopy success rates in the 0.2-0.5 mg/kg ciprofol and propofol 2.0 mg/kg groups were 100% and all doses were safe and well tolerated. Ciprofol doses of 0.4 mg/kg and 0.5 mg/kg are recommended for subsequent IIb phases. In the phase IIb trial, a 100% success rate was reconfirmed in all the dosage groups. The mean time of colonoscope insertion in the ciprofol 0.4 mg/kg, ciprofol 0.5 mg/kg and propofol 2.0 mg/kg groups were 1.9, 1.5 and 1.5 min, the mean recovery times from colonoscope withdrawal were 6.1, 5.1, and 4.3 min, and the times to discharge were 11.8, 11.2 and 10.6 min, respectively. The satisfaction ratings of anesthetists in the ciprofol 0.5 mg/kg group (9.5 ± 0.8) were higher than in the ciprofol 0.4 mg/kg (9.2 ± 1.0) and propofol 2.0 mg/kg (9.2 ± 0.9) groups. The incidence of sedation and anesthesia-related AEs was highest in the propofol 2.0 mg/kg group (25.8%), followed by the ciprofol 0.5 mg/kg group (21.9%), and was least in the ciprofol 0.4 mg/kg group (16.1%) (P = 0.750). CONCLUSIONS: Ciprofol was safe and well tolerated at doses ranging from 0.1 mg/kg to 0.5 mg/kg. Ciprofol 0.4-0.5 mg/kg induced equivalent sedation/anesthesia and had a similar safety profile to propofol 2.0 mg/kg during colonoscopy without producing serious AEs.

Clinical validation and utility of Chinese Eppendorf Itch Questionnaire in adults with chronic pruritus symptoms.

BACKGROUND: Pruritus, or itch, is a prevalent symptom causing profound health burden in many dermatological and non-dermatological disorders. Several itch questionnaires have been created to assess itch. Particularly, Eppendorf Itch Questionnaire (EIQ) is widely accepted since it encompasses various aspects of itch, including intensity, affects, coping behavior, and motivation to scratch. METHODS: In a cross-sectional survey, we examined the validity, reliability and clinical utility of Traditional Chinese EIQ. RESULTS: We administered the consensus version to 128 adults (median: 48.5 years, interquartile range [IQR]: 39-63) with active itch for more than 6 weeks at the Outpatient Clinics of three medical centers in Taiwan. Clinical diagnoses included psoriasis (N = 82), xerosis (N = 34), or other dermatitis (N = 12). Cronbach's alpha for each EIQ scale ranged 0.82-0.98, suggesting good to excellent internal consistency and reliability. Three EIQ scales significantly correlated with visual analogue scale (VAS) for itch intensity (P ≤ 0.001 for median test), supporting for its concurrent validity. None of EIQ scale was statistically correlated with Psoriasis Area Severity Index (PASI) scores in psoriasis patients, confirming its discriminant validity. Moreover, patients of different diagnoses had distinct responses to the multi-scale EIQ index, affording it a better clinical test (area-under-the-ROC curve [AUC]: 0.76, 95% CI: 0.63-0.90) than VAS alone (AUC: 0.42, 95%CI: 0.24-0.59) in distinguishing dermatitis/eczema-related itch from psoriasis or xerosis-related itch. CONCLUSION: We demonstrated the reliability and validity of Chinese EIQ in adult patients with chronic itch at the outpatient setting. The study also revealed the diversified aspects of itch across patients with various dermatoses.