A repeated gonadotropin-releasing hormone agonist trigger improves pregnancy outcomes of frozen-thawed embryo transfer in GnRH antagonist cycles: a retrospective propensity-matched score analysis.

PURPOSE: To evaluate whether co-treatment of repeated GnRHa triggers with GnRH antagonist protocols can improve the clinical outcomes in in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) procedures. METHODS: In this retrospective study, 712 Chinese Han women aged 20-42 undergoing autologous IVF/ICSI-ET with a flexible GnRH antagonist protocol were analyzed. The 735 cycles were split into the single (n = 238) and the repeated (n = 497) GnRHa groups. In the single GnRHa group, 0.2 mg of triptorelin was given for oocyte maturation, whereas in the repeated GnRHa group, two doses of 0.2 mg were administered 12 h apart. PSM design was used for a fair comparison. The main study outcomes included the clinical pregnancy rate (CPR), live birth rate (LBR), good-quality embryo rate, and fertilization rate. Multivariate logistic regression analyses were used to identify all potential factors affecting clinical outcomes. RESULTS: Post-PSM, analysis of 159 cycles per group showed the repeated GnRHa group outperforming the single GnRHa group in IVF fertilization rates (71.5% vs. 67.7%, P < 0.05) and good-quality embryo rate (47.1% vs. 43.7%, P < 0.05). Furthermore, the repeated GnRHa group achieved higher CPR (72.6% vs. 53.4%, P < 0.05) and LBR (59.7% vs. 43.8%, P < 0.05) in FET cycles. Multivariate logistic regression indicated a significant negative correlation between the use of a single GnRHa trigger and both clinical pregnancy (OR = 0.382, P < 0.05) and live birth (OR = 0.518, P < 0.05). CONCLUSION: Our study reported that individuals who received a repeated GnRHa trigger exhibited higher CPR and LBR during FET cycles compared to those who received a single dose GnRHa trigger.

Immune triggers preceding neuralgic amyotrophy.

BACKGROUND AND PURPOSE: Infections and vaccinations have been identified as potential immunological triggers of neuralgic amyotrophy (NA), but the exact type and frequency of the preceding agents is unknown. METHODS: This was a multicentre, prospective, observational, matched case-control study. NA was diagnosed by neuromuscular experts according to validated clinical criteria and electrodiagnostic studies. Clinical data and biological samples of NA patients were collected within 90 days from disease onset between June 2018 and December 2023. All NA patients were asked about prior infection and vaccination in the month before disease onset. Serological tests for hepatitis E virus, human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, Epstein-Barr virus, cytomegalovirus, parvovirus B19, varicella-zoster virus, Borrelia burgdorferi, Mycoplasma pneumoniae and Bartonella henselae were performed in a central laboratory. Each case was matched with a healthy control for age, sex, place of residence and time of blood collection. RESULTS: Fifty-seven patients and corresponding controls were included. The mean age was 45 years for both groups. NA onset was preceded by a symptomatic infectious trigger confirmed by microbiological tests in 15/57 (26.3%) patients. Coronavirus disease 2019 vaccination was considered a potential trigger in 7/57 (12.3%) subjects. An acute viral infection was associated with a bilateral involvement of the brachial plexus (p = 0.003, Cramèr's V = 0.43). CONCLUSIONS: Confirmed immune triggers (infection or vaccination) preceded disease onset in 22/57 (38.6%) NA cases. We suggest to test NA patients in the acute phase for intracellular antigens, especially in the case of concomitant bilateral involvement and hepatitis.

Neck Reflex Points: A New Clinical Test? Prevalence in Two Cohorts and Its Covariates.

Background: Neck reflex points (NRPs) are 2 × 6 potentially tender areas of the neck, denominated NRP-C0 to NRP-C7. They are different from muscular trigger points and become tender in response to chronic trigeminal irritation. NRP examination has a high inter-rater reproducibility. We investigated the prevalence of NRPs in two populations to investigate their usefulness as a clinical test for trigeminal irritation. Methods: In total, 165 patients with chronic pain and 431 students were examined for NRP tenderness using a three-level pain scale: absent pain (PI = 0), mild tenderness (PI = 1), or marked tenderness (PI = 2). Results: In patients, we found more tender NRPs than in the student group (p < 0.001), and on the left side, more tender NRPs were found in NRP-C0-C4. Left and right NRPs appeared independently (kappa 0.1-0.4), except for NRP-C7 (kappa 0.55). Females had more tender NRPs (p < 0.001). Tenderness was independent of age, BMI, and pre-existing diseases. Conclusions: NRP tenderness occurs more frequently in patients than in students, independent from potential covariates. Our results, together with previous findings, support the use of NRP examination as a clinical test for chronic silent inflammation of the trigeminal region. These data provide a base for further studies investigating correlations of NRPs with clinical findings.

Higher-order epistasis within Pol II trigger loop haplotypes.

RNA polymerase II (Pol II) has a highly conserved domain, the trigger loop (TL), that controls transcription fidelity and speed. We previously probed pairwise genetic interactions between residues within and surrounding the TL for the purpose of understand functional interactions between residues and to understand how individual mutants might alter TL function. We identified widespread incompatibility between TLs of different species when placed in the Saccharomyces cerevisiae Pol II context, indicating species-specific interactions between otherwise highly conserved TLs and its surroundings. These interactions represent epistasis between TL residues and the rest of Pol II. We sought to understand why certain TL sequences are incompatible with S. cerevisiae Pol II and to dissect the nature of genetic interactions within multiply substituted TLs as a window on higher order epistasis in this system. We identified both positive and negative higher-order residue interactions within example TL haplotypes. Intricate higher-order epistasis formed by TL residues was sometimes only apparent from analysis of intermediate genotypes, emphasizing complexity of epistatic interactions. Furthermore, we distinguished TL substitutions with distinct classes of epistatic patterns, suggesting specific TL residues that potentially influence TL evolution. Our examples of complex residue interactions suggest possible pathways for epistasis to facilitate Pol II evolution.

Does hCG-trigger in the mild stimulation protocol for endometrial preparation have any effect on pregnancy outcome in frozen-thawed embryo transfer?

BACKGROUND: Recent literature has explored the role of human chorionic gonadotropin (hCG) triggering in frozen embryo transfer (FET) cycles with natural endometrial preparation. Despite this, the impact of hCG triggering on pregnancy outcomes following endometrial preparation with mild stimulation (mST) using Letrozole and Gonadotropins remains inadequately characterized. This study aimed to elucidate the effects of hCG-trigger on pregnancy outcomes in mST-FET cycles. METHODS: In the present retrospective cohort study, the pregnancy outcomes of 409 eligible patients who underwent FET cycles with endometrial preparation using a mild ovarian stimulation protocol by letrozole plus low dose gonadotropins at the Royan Institute between 2020 and 2022, were investigated. The study population were segregated into two distinct groups according to type of ovulation: the spontaneous ovulation group (n = 138) and the hCG-trigger group (n = 271). The pregnancy outcomes including implantation and clinical pregnancy rates (CPR) and live birth rates (LBR) were compared between two groups. The multivariable logistic regression was performed to detect the most significant variables related to the LBR in the mST-FET cycles. RESULTS: Demographic and baseline characteristics were comparable between groups. No significant difference was found in terms of implantation rate (0.65 ± 0.32 vs. 0.60 ± 0.30, P-value: 0.31), CPR (37% vs. 39.7%, P-value: 0.53), and LBR (35.5% vs. 37.3%, P-value: 0.74) in the spontaneous ovulation and hCG-trigger groups, respectively. The logistic regression analysis revealed that only the stage of the transferred embryo exhibited a significant relationship with LBR (blastocyst vs. cleavage: odds ratio (OR); 2.33, 95% confidence interval (CI):1.41-3.86, P-value = 0.001). CONCLUSION: Pregnancy outcomes in the mST-FET cycles, including implantation rate, CPR, and LBR are comparable in cycles with or without hCG triggering. Based on the findings from multivariate regression analysis, the sole significant predictive factor for the LBR was the transfer of blastocyst embryos. It is recommended that these results be examined and discussed in future prospective studies with a larger sample size, considering the lack of comparable research in this field.

[Comparison of the clinical efficacy on chronic abdominal wall pain between trigger-point electroacupuncture and transversus abdominis plane block]. / æ¿€ç—›ç‚¹ç”µé’ˆç–—æ³•ä¸Žè ¹æ¨ªè‚Œå¹³é¢é˜»æ»žæ²»ç–—æ ¢æ€§è ¹å£ç–¼ç—›çš„ç–—æ•ˆå¯¹æ¯”.

OBJECTIVES: To compare the clinical efficacy between trigger-point (TrP) electroacupuncture and transversus abdominis plane (TAP) block in treatment of chronic abdominal wall pain (CAWP). METHODS: A total of 62 CAWP patients were randomly divided into a TrP electroacupuncture group (31 cases, 1 case dropped off) and a TAP block group (31 cases, 1 case dropped off). Electroacupuncture at trigger points was delivered in the TrP electroacupuncture group, and TAP block was administered under ultrasonic guidance in the TAP block group. Separately, the score of the numerical pain rating scale (NRS) was observed before treatment and in 1 week, 1 month and 3 months after treatment；the scores of the self-rating anxiety scale (SAS) and the self-rating depressive scale (SDS) observed before treatment and in 1 week and 3 months after treatment；and the score of the short form 36 questionnaire (SF-36) was observed before treatment and in 3 months after treatment. The utilization rate of remedial drugs was recorded during follow-up visit. The clinical efficacy was compared. RESULTS: At each time point after treatment, NRS score decreased in comparison with that before treatment (P<0.05), the scores of SAS and SDS 1 week and 3 months after treatment were reduced (P<0.05) and the each item score of SF-36 increased (P<0.05) 3 months after treatment of each group. Compared with the outcomes in the TAP block group, NRS scores were reduced 1 month and 3 months after treatment respectively (P<0.05), the scores of SAS and SDS decreased (P<0.05) and SF-36 score was elevated (P<0.05) 3 months after treatment in the TrP electroacupuncture group. There was no significant difference in the utilization rate of remedial drugs between the two groups. The clinical efficacy of the TrP electroacupuncture group (96.7%) was superior to that of the TAP block group (83.3%, P<0.05). CONCLUSIONS: Both TrP electroacupuncture and TAP block can markedly relieve pain, attenuate the emotional symptoms of anxiety and depression and improve the quality of life in the patients with chronic abdominal wall pain. The clinical efficacy of TrP electroacupuncture is better than that of TAP block 3 months after treatment.

Dual trigger or hCG alone: A retrospective analysis on patients with diminished ovarian reserve under in vitro fertilization and embryo transfer (IVF-ET) treatment.

OBJECTIVE: With remarkable deficiency in both oocyte stock and competence, the prognosis of IVF-ET in diminished ovarian reserve (DOR) is obstinately poor, underscoring warranted optimization to current procedures. We compared the efficacy of dual-trigger (hCG plus GnRH-a) and hCG alone on the outcomes for DOR patients. STUDY DESIGN: A total of 381 couples and 857 controlled ovarian stimulation (COS) cycles, and 222 couples and 366 frozen embryo transfer (FET) ones were included. The intermediate outcomes during oocyte retrieval and in vitro culture were compared based on COS dataset, while outcomes after embryo transfer analyzed based on FET dataset. The marginal effect of all study factors and covariates were evaluated with a cluster-weighted GEE model. RESULTS AND CONCLUSION: Neither the intermediate nor implantation outcomes were improved by dual-trigger. The OR values were 1.08 (95 % CI: 0.41-2.78) for retrieval cancellation, 1.33 (95 % CI: 0.89-2.00) for oocyte harvest, 1.04(95 %CI: 0.94-1.15) for viable embryo and 1.03(95 %CI: 0.88-1.19) for top-quality embryo. Similarly, the ORs were 0.90 (95 %CI: 0.62-1.30) for implantation and 0.97 (95 %CI: 0.56-1.69) for clinical pregnancy. This equivalence remained unchanged after adjusting for the covariates such as age, BMI, controlled ovarian stimulation protocols, etc. Thus, dual-trigger cannot provide significant advantage over hCG in related to immediate or clinical outcomes of IVF-ET treatments in DOR patients.

Trigger Point Injections for Myofascial Pain in Terminal Cancer: A Randomized Trial.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a single trigger point injection (TPI) of a local anesthetic for the treatment of myofascial pain syndrome (MPS) in patients with incurable cancer. METHODS: This multicenter, exploratory, open-label, randomized comparative trial was conducted in five specialized palliative care departments. Hospitalized patients with incurable cancer who had been experiencing pain related to MPS were randomized to receive either a TPI of 1% lidocaine plus conventional care (TPI group) or conventional care alone (control group). The short-term efficacy and occurrence of adverse events were compared between groups. The primary endpoint was the percentage of patients who experienced a reduction in pain scores of ≥ 50%, assessed using an 11-point Numerical Rating Scale, at 3 days post-intervention. Adverse events were assessed using the Common Terminology Criteria for Adverse Events v5.0. RESULTS: Fifty patients were enrolled, and the trial completion rate was 100%. The proportion of patients who experienced an improvement in Numerical Rating Scale pain scores of ≥ 50% was 70.8% (95% confidence interval, 52.4% to 89.2%) in the TPI group and 0.0% in the control group; the difference was statistically significant (p < 0.001). In the TPI group, one case (4.2%) of Grade 1 nausea and one case (4.2%) of Grade 1 somnolence were reported. CONCLUSION: A single TPI of a local anesthetic is safe and efficacious in inducing an immediate reduction in MPS-related pain in patients with incurable cancer.

Trigger finger - Poor outcome of surgery associated with younger age, pain, psoriatic arthritis and atopic disease.

Background: Trigger finger, or stenosing tendovaginitis, is one of the most common causes of hand disability, where a finger or thumb painfully snaps and locks due to a tendon-sheath size mismatch at the A1 pulley. The exact aetiology of trigger finger is unknown, though it is associated with factors like diabetes, rheumatic disease and carpal tunnel syndrome. The main purpose of this prospective study was to explore clinical characteristics and comorbidities in a cohort of 139 patients who underwent surgery for trigger finger and find factors of importance for the outcome 1 year postoperatively. Methods: Pain, range of motion, hand function evaluated by the Disabilities of the Arm Shoulder and Hand questionnaire as well as Quinnell grade of triggering were examined preoperatively. Symptom duration, working status, medical history and comorbidities at baseline were also noted. Further, range of motion was evaluated 3 months after surgery, pain and hand function were evaluated 3 and 12 months after surgery. An outcome scale with three levels was defined. The development of any new comorbidities was monitored during an extended postoperative observation period, with a mean duration of 70 months (range: 56-88 months). Results: Poor outcome was strongly associated with younger age (P = 0.0009), a high level of preoperative pain in the operated hand (P = 0.0027), psoriatic arthritis (P = 0.021) and atopic disease (P = 0.028; odds ratio [OR]: 3.87, 95% confidence interval [CI]: 1.15-13.04). A low range of motion preoperatively did not affect the outcome. Carpal tunnel syndrome was the most common comorbidity but did not affect the outcome. A good preoperative range of motion, good hand function and less pain were associated with better outcomes. Conclusion: Younger age, a high level of preoperative pain, psoriatic arthritis and atopic disease were factors associated with a worse outcome of trigger finger surgery. Pain and disability decreased 3 months postoperatively and continued to decrease between 3 and 12 months.

Events preceding death after high-risk surgery analyzed by Global Trigger Tool and reflective-thematic approach.

BACKGROUND: Postoperative mortality might be influenced by postoperative care, vigilance, and competence to rescue. This study aims to describe the course of events preceding death in a high-risk surgical cohort. METHODS: We analyzed hospital records of patients who died within 30 days after surgery in 4 high volume hospitals using (1) reflective narrative thematic approach to identify recurring themes reflecting issues with conduct of care and (2) Global Trigger Tool to describe incidence, timing, and types of adverse events (AEs) leading to harm. RESULTS: Preoperative predicted median risk of death in the studied group was 9%/13% according to SORT/P-POSSUM, respectively. Nine recurring themes were identified. Prominent themes were "consensus concerning aim and/or risk with planned surgery," "level of (intraoperative) competence and monitoring," and in the postoperative period "level of care and vigilance" on signs of deterioration. We found a total of 303 AEs, with only three patients (5%) having no adverse events. Most common severity category was "I," that is "contributed to patient's death" (n = 110, 36% of all AEs). Of these, 60% were classified as preventable or probably preventable. The peak incidence of AEs was seen on the day of index surgery. Most common types of AEs were "failure of vital functions" (n = 79, 26%), followed by infections (n = 45, 15%). CONCLUSIONS: A high predicted risk of death and a peak of adverse events on the day of index surgery were detected. Identified themes reflect lack of documented multi-professional consensus on how to handle prevalent perioperative risk, vigilance, and postoperative level of care.

Comparing the performance of multiple trigger tools in identifying medication-related hospital readmissions.

BACKGROUND: Multiple trigger tools have been developed to identify medication-related hospital (re)admissions (MRRs); however, the accuracy of these tools in real-world clinical practice is uncertain. The objective of this study was to compare the accuracy of four different trigger tools (OPERAM, STOPP/START criteria, ADR-tool, and QUADRAT) to identify MRRs compared with clinical adjudication. METHODS: We conducted a secondary analysis of patients readmitted within 30 days to seven departments of a teaching hospital. In the primary study, which involved a retrospective chart review of 1111 readmissions, MRRs and their potential preventability were clinically adjudicated by physicians and pharmacists. In the current study, four trigger tools were applied by a different physician and pharmacist panel. Patients of all ages were included. Trigger tools included both explicit items specifying the event and the associated medication and implicit items requiring clinical knowledge. The accuracy of each trigger tool was assessed by calculating the proportion of clinically adjudicated MRRs each tool identified overall as well as according to explicit and implicit triggers separately. The accuracy of each tool to identify potentially preventable MRRs was also calculated. RESULTS: Of 1111 readmissions, 181 were adjudicated as medication-related (mean age 69 years, 56% male); 72 (40%) MRRs were potentially preventable. The original OPERAM tool identified 166 (92%) MRRs (62% through explicit triggers). The STOPP/START criteria identified 23 (13%, 7% through explicit triggers), the ADR tool identified 51 (28%, all explicit triggers), and the QUADRAT tool identified 76 (42%; all explicit triggers) MRRs. Of the 72 potentially preventable MRRs, OPERAM identified 59 (82%), STOPP/START identified 18 (25%), ADR identified 20 (28%), and QUADRAT identified 21 (29%). CONCLUSION: The original OPERAM tool identified the highest proportion of (preventable) MRRs. However, this tool includes many implicit triggers requiring expert clinical knowledge. Future studies should assess the practicality of implementing this tool in daily practice.

Risk Factors for Requiring Ulnar Superficialis Slip Resection During Trigger Finger Release.

PURPOSE: Ulnar superficialis slip resection (USSR) has been described to address persistent postoperative triggering following trigger finger release (TFR). The primary purpose of our study was to evaluate the results of simultaneous TFR and USSR under wide-awake local anesthesia no tourniquet (WALANT). The secondary purpose was to identify patient characteristics and risk factors associated with persistent triggering following A1 pulley release requiring USSR. METHOD: We retrospectively identified 1,005 patients who underwent TFR at one institution by a single fellowship-trained, hand surgeon under WALANT from 2015 to 2023. Nine hundred ninety-two patients were treated with TFR alone. Twelve patients (1.2%) underwent USSR because of persistent triggering that was identified in the operating room after release of the A1 pulley. An age-, sex-, and body mass index-matched cohort of 28 patients who underwent TFR alone was created. Medical records were reviewed for demographics and complications. RESULTS: A total of 12 patients (14 digits) underwent TFR with USSR. The long finger was the most commonly affected finger (6, 42%). Patients in the USSR group had more average lifetime trigger fingers compared with the control group (4 vs 1). Additionally, the percentage of patients who had previously undergone TFRs for other fingers was higher in the USSR group (100%) compared with the control group (36%). After surgery, 6 patients (4 USSR and 2 control) underwent formal hand therapy for postoperative stiffness with USSR patients receiving therapy more often than controls. CONCLUSIONS: Although uncommon, some patients (1.2%) who undergo TFR require USSR for persistent triggering following A1 pulley release. Patients who have had more lifetime trigger fingers and/or who have previously undergone TFR for other fingers are more likely to need USSR. No serious complications were incurred by patients who underwent USSR, but these patients may benefit from hand therapy compared to those undergoing isolated TFR. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Origin of ventricular fibrillation triggers in a model of localized repolarization heterogeneity.

BACKGROUND: Heterogeneities in ventricular repolarization contribute significantly to the genesis of ventricular fibrillation (VF). Although clinical arrhythmias are spontaneously triggered by premature ventricular complexes, these triggers are difficult to document and little is known about their site of origin. OBJECTIVES: The purpose of this study was to characterize spontaneous VF initiation in an experimental model of repolarization heterogeneity and to identify the origin of triggers in relation to the spatial dispersion of repolarization. METHODS: Spatially limited repolarization heterogeneity was created in isolated perfused porcine right ventricles (N = 16) by local administration of pinacidil (20 µM) in a terminal branch of the right coronary artery. High-resolution optical mapping and pseudo-electrocardiography were performed in control conditions and after pinacidil perfusion. RESULTS: No arrhythmia occurred at baseline, but 74 VF episodes were observed in 13 hearts (82%) after pinacidil perfusion and were most often initiated by a ventricular trigger with a short coupling interval (297 ± 66 ms). Sixteen VF initiations were optically mapped in 4 hearts. Mapping showed triggers originating in all cases from the border zone between altered and normal repolarization areas where local action potential duration and repolarization time gradients were steep (15.9 and 15.8 ms/mm vs 1.5 and 3.0 ms/mm in nontrigger sites). Optical action potential traces were compatible with a phase 2 reexcitation mechanism. The subsequent VF cycles were driven by activities located in the same region. CONCLUSION: This model of localized repolarization heterogeneity is able to produce spontaneous VF initiation. Our study demonstrates that VF triggers originate consistently from the border zone of repolarization dispersion.

Effect of progesterone concentration on hCG trigger day on clinical outcomes after high-quality single blastocyst transfer in GnRH antagonist cycles.

Objective: To investigate whether progesterone levels on the human chorionic gonadotropin (hCG) trigger day are associated with clinical outcomes in fresh cycles and the first frozen-thawed cycles (the freeze-all strategy) following the transfer of a high-quality single blastocyst. Methods: This single-center retrospective analysis was conducted on patients undergoing in vitro fertilization with the gonadotropin-releasing hormone (GnRH) antagonist protocol from January 2017 to December 2023. The study included the first and second oocyte retrieval cycles with progesterone levels ≤2 ng/ml on hCG trigger day. Clinical pregnancy rates and early miscarriage rates were compared among groups using curve fitting, threshold effect analysis, and multivariable regression. Results: When progesterone levels were between 1 and 2 ng/ml, the pregnancy rate in fresh cycles was only 51% of that in cycles with progesterone levels ≤1 ng/ml (95% CI: 0.33, 0.79, p = 0.0028). And the pregnancy rate decreased by 25% (95% CI: 0.51, 1.09) for frozen cycles, although there was no statistically significant (p = 0.1273). When cycle types were used as a binary variable in multivariate regression analysis, it was found that the clinical pregnancy rate in frozen cycles was 1.84 times higher than in fresh cycles (OR = 1.84, 95% CI: 1.38-2.47). For progesterone levels between 1 and 2 ng/ml, the clinical pregnancy rate in frozen cycles was 2.90 times that of fresh cycles (OR = 2.90, 95% CI: 1.59, 5.29, p = 0.0015). Progesterone levels on hCG day had no impact on the clinical pregnancy rate in thaw cycles, nor did they affect miscarriage rates in fresh or thaw cycles (p > 0.05). Conclusion: When progesterone levels on hCG trigger day were between 1 and 2 ng/ml, the clinical pregnancy rate for frozen-thawed cycles of high-quality single blastocyst transfer using an GnRH antagonist protocol significantly surpasses that of fresh cycles, thus elective frozen embryo transfer after the freeze-all strategy is recommended.

A reactive oxygen species-triggerable theranostic prodrug system.

Abnormally elevated levels of reactive oxygen species (ROS) are considered one of the characteristics of tumors and have been extensively employed in the construction of tumor-activated prodrugs. However, ideal ROS-activated molecular triggers that possess high sensitivity and easy functionalization for tailoring specific prodrugs, remain scarce. In this work, we developed a highly reactive oxygen species (hROS, such as •OH, ONOO- and HOCl)-responsive molecular trigger (namely FDROS-4) through the conjunction of methylene blue (MB) and 2, 6-bis (hydroxymethyl) aniline via urea bond, integrating imaging and therapeutic functions. FDROS-4 could be readily modified as multifunctional prodrugs and efficiently activated by hROS, leading to the release of near-infrared emissive MB and parent drugs. By using chlorambucil as a model drug and incorporating varying numbers of galactose as liver-targeting ligands, we designed and synthesized a series of prodrugs named FDROS-6, FDROS-7, and FDROS-8. The optimal prodrug, FDROS-7, could self-assemble into monocomponent nanoparticles, exhibiting enhanced biocompatibility and therapeutic efficacy compared to the parent drug. This hROS-activated molecular trigger holds promise for the development of stimulus-responsive prodrugs in chemotherapy.

A rapid and robust organ repair polyacrylamide/alginate adhesive hydrogel mediated via interfacial adhesion-trigger molecules.

Adhesive hydrogels have been widely explored as tissue adhesives for wound sealing and repair. However, developing adhesive hydrogels with simple preparation techniques and strong adhesion to internal organs in a short time remains a challenge. In this study, we developed a strategy for robust and rapid tissue adhesion of internal organ sealing and repair by an interfacial adhesion-molecule triggered hydrogel system. In this system, polyphenol molecules act as adhesion-trigger reagents to achieve fast and strong adhesion of polyacrylamide/alginate hydrogels on the surface of wound tissue by rapidly forming abundant hydrogen bonds at the interface. The adhesion energy is significantly enhanced by 45 times under the mediation of polyphenol adhesion-trigger molecules, resulting in a robust (> 600 J m-2) tissue adhesion in just 30 s. This interfacial adhesion system demonstrates good biocompatibility, strong sealing performance on multiple organs (porcine heart, lung, stomach, and intestine), and excellent repair properties in gastric perforation wounds of rabbits in vivo. Moreover, immunocytochemical and transcriptomic analyses reveal that this interfacial adhesion system significantly promotes vascular regeneration and inhibits inflammatory responses during wound repairing. The proposed hydrogel provides a facile strategy for rapid and robust tissue adhesion, and shows potential applications in organ sealing and repair.

Revision A1 Pulley Release: An Analysis of Risk Factors Using a National Database.

PURPOSE: Trigger finger release (TFR) is a commonly performed procedure in hand surgery. Trigger finger release has a high success rate, but recurrence can occur. Data on revision TFR (rTFR) are sparse, with little known regarding factors associated with the need for revision surgery. Our purpose was to analyze risk factors associated with rTFR procedures. METHODS: Using a national database (PearlDiver Research Program), patients who underwent TFR between 2015 and 2022 were identified using Current Procedural Terminology and International Classification of Diseases (ICD)-10 codes. Patients were included if they received an ICD-10 diagnosis of trigger finger on the same day as their release or within 2 weeks of their procedure. Patients who underwent rTFR were determined through identification of a secondary procedure completed in the same digit on the ipsilateral hand performed after the index procedure. Revision rates at 1, 3, and 5 years were recorded. Demographics and comorbidities were categorically examined via univariate and multivariable logistic regression analyses. RESULTS: A total of 46,613 patients meeting inclusion criteria were identified after TFR with 1,793 (3.85%) undergoing revision release. Multivariable analysis demonstrated that diabetes, ischemic heart disease, and male sex were associated with statistically significantly increased odds of revision procedures at 1, 3, and 5 years from the initial operation. Age >65 years and hypertension were associated with an increased odds of revision surgery at 3 and 5 years, and carpal tunnel syndrome as a risk factor at 1 and 3 years only. Hypothyroidism was associated with a decreased revision rate at all time points and tobacco use at 5 years only. CONCLUSIONS: These data demonstrate that male sex, diabetes, and heart disease are risk factors for requiring revision TFR in the short and medium terms. This information can add to preoperative counseling with patients undergoing surgical treatment of trigger digits. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Transdermal iontophoresis versus high power pain threshold ultrasound in Mechanical Neck Pain: a randomized controlled trial.

BACKGROUND: The investigation aimed to assess the impacts of magnesium sulphate (MgSO4) iontophoresis and high-power pain-threshold ultrasound (HPPT-US) on pain, range of motion (ROM), and functional activity in physical therapy students suffering from mechanical cervical pain. METHODS: Typically, 75 males aged 19 to 30 years suffering from mechanical neck pain were enrolled in this investigation. Participants were divided at random into three groups. Group A received iontophoresis plus conventional physical therapy program, Group B received HPPTUS along with conventional therapy, and Group C received conventional therapy only. The outcomes were pain evaluated by visual analog scale (VAS) and Digital Electronic Pressure Algometer, cervical range of motion measured by Myrin gravity reference goniometer, and Arabic Neck disability index (ANDI) evaluate neck function. RESULTS: The differences within and between groups were detected utilizing a mixed-design multivariate analysis of variance (MANOVA). The within- and between-group analysis of all outcome measures revealed that there were statistically significant differences at post-intervention between high-power ultrasound and conventional group at all variables and also between iontophoresis and conventional group, but there was no statistically significant variation between high-power ultrasound and iontophoresis. CONCLUSION: MgSO4 iontophoresis and HPPT-US are effective in decreasing pain, improving neck function, and improving neck ROM in subjects with mechanical neck pain who have active myofascial trigger points (MTrPs) on the upper fibers of the trapezius with no superiority of one over the other. TRAIL REGISTRATION: The study was registered in the Clinical Trials Registry (registration no: NCT05474898) 26/7/2022.

Embryological Classification of Arrhythmogenic Triggers Initiating Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a prevalent multifactorial arrhythmia associated with specific single-nucleotide polymorphisms (SNPs). Pulmonary vein (PV) isolation is an established treatment for AF; however, recurrence risk remains caused by AF triggers beyond the PVs. Understanding the embryological origins of these triggers could improve treatment outcomes. OBJECTIVES: This study aimed to investigate the association between embryologically categorized AF triggers, clinical and genetic backgrounds, and postablation prognosis. METHODS: In cohort 1, comprising 3,067 patients with AF undergoing PV isolation, the clinical characteristics and outcomes were analyzed. Among them, 815 patients underwent genetic analysis using AF-associated SNPs (cohort 2). Patients were delineated based on the developmental origin of the AF triggers: common PV, sinus venosus (SV), and primitive atrium (PA). RESULTS: SV-origin extra-PV AF triggers occurred in 20.3% (n = 622) of patients, whereas PA-origin triggers occurred in 11.9% (n = 365) of patients in cohort 1. Multivariate analysis of cohort 2 revealed that female sex, lower body mass index, absence of hypertension, rs2634073 near PITX2, and rs6584555 in NEURL1 were associated with SV-AF, whereas nonparoxysmal AF and rs2634073 near PITX2 were predictors of PA-AF. The PA group had a significantly higher arrhythmia recurrence rate after repeated procedures than the common PV (HR: 1.75; 95% CI: 1.34-2.29; P < 0.001) and SV-AF (HR: 1.31; 95% CI: 1.19-1.45; P < 0.001) groups with more de novo AF triggers. However, the incidence of adverse events did not differ significantly among the 3 groups. CONCLUSIONS: SV-derived AF triggers may have hereditary factors with a favorable postablation prognosis, whereas PA-derived triggers are linked to AF persistence and poor ablation response. Variants near PITX2 may play a pivotal role in extra-PV triggers.