Establishment of a swine model of delayed bleeding after endoscopic procedure.

Objectives: Although delayed bleeding after endoscopic procedures has become a problem, currently, there are no appropriate animal models to validate methods for preventing it. This study aimed to establish an animal model of delayed bleeding after endoscopic procedures of the gastrointestinal tract. Methods: Activated coagulation time (ACT) was measured using blood samples drawn from a catheter inserted into the external jugular vein of swine (n = 7; age, 6 months; mean weight, 13.8 kg) under general anesthesia using the cut-down method. An upper gastrointestinal endoscope was inserted orally, and 12 mucosal defects were created in the stomach by endoscopic mucosal resection using a ligating device. Hemostasis was confirmed at this time point. The heparin group (n = 4) received 50 units/kg of unfractionated heparin via a catheter; after confirming that the ACT was ≥200 s 10 min later, continuous heparin administration (50 units/kg/h) was started. After 24 h, an endoscope was inserted under general anesthesia to evaluate the blood volume in the stomach and the degree of blood adherence at the site of the mucosal defect. Results: Delayed bleeding was observed in three swine (75%) in the heparin-treated group, who had a maximum ACT of >220 s before the start of continuous heparin administration. In the non-treated group (n = 3), no prolonged ACT or delayed bleeding was observed at 24 h. Conclusion: An animal model of delayed bleeding after an endoscopic procedure in the gastrointestinal tract was established using a single dose of heparin and continuous heparin administration after confirming an ACT of 220 s.

Judges and lawyers' beliefs in repression and dissociative amnesia may imperil justice: further guidance required.

This article examines continuing misunderstanding about memory function especially for trauma, across three UK samples (N = 717). Delayed allegations of child sexual and physical abuse are prevalent in Western legal systems and often rely upon uncorroborated memory testimony to prove guilt. U.K. legal professionals and jurors typically assess the reliability of such memory recall via common sense, yet decades of scientific research show common sense beliefs often conflict with science. Recent international surveys show controversial notions of repression and accurate memory recovery remain strongly endorsed. In historical cases, these notions may lead to wrongful convictions. The current study surveyed the U.K. public, lawyers, and mental health professionals' beliefs about repression, dissociative amnesia and false memories. Study findings give unique data on judges' and barristers' beliefs. Overall, the study findings reinforce international scientists' concerns of a science - knowledge-gap. Repression was strongly endorsed by lay, legal and clinical participants (> 78%) as was dissociative amnesia (> 87%). Moreover, suboptimal professional legal education and juror guidance may increase misunderstanding. Correcting beliefs about memory function, and extending the contribution of memory science in the courtroom remains an important quest for cognitive scientists.

Different characteristics between acute and delayed proximal junctional failure in elderly patients undergoing corrective surgery for adult spinal deformity: Comparative analysis of risk factor, failure mode, and clinical consequences.

BACKGROUND CONTEXT: While numerous studies have been conducted on proximal junctional failure (PJF), the clinical significance of acute and delayed PJF remains poorly understood. PURPOSE: The primary object of this study is to investigate the risk factors separately for acute and delayed PJF. Secondly, we aim to assess the incidence of each failure mode and their clinical consequences in relation to acute and delayed PJF. STUDY DESIGN/SETTING: Retrospective comparative study. PATIENT SAMPLE: Patients aged ≥60 years who underwent deformity correction with ≥5-level fusion to sacrum. OUTCOME MEASURES: Risk factor, failure modes, and patient-reported outcome measure (PROM) METHODS: Acute PJF is defined as PJF occurring within 6 months, while delayed PJF occurring after 6 months. Risk factors were analyzed by comparing various clinical and radiographic parameters among three groups: no, acute, and delayed PJF groups. The failure modes, including soft tissue failure, vertebral fracture, fixation failure, and myelopathy, were compared among these groups. The clinical subsequences after PJF development were evaluated by assessing the change in proximal junctional angle (PJA), revision rate, and patient-reported outcome measure (PROM). RESULTS: A study cohort of 363 patients was included in the analysis. Among them, 156 patients experienced PJF, with 87 patients (55.8%) in the acute PJF group and 69 patients (44.2%) in the delayed PJF group. Multivariate analyses showed that older age (Odds ratio [OR] = 1.057, 95% confidence interval [CI] = 1.002 - 1.118), osteoporosis (OR=2.149, 95% CI = 1.074 - 4.300), high American Society of Anesthesiology ASA score (OR=2.150, 95% CI = 1.089 - 4.245), and overcorrection relative to the age-adjusted pelvic incidence - lumbar lordosis target (OR=4.031, 95% CI = 1.962 - 8.280) were identified as risk factors for the development of acute PJF. On the other hand, a high body mass index (OR=1.150, 95% CI = 1.049 - 1.251) and an uppermost instrumented vertebra located at ≤ T10 (OR=2.267, 95% CI = 1.205 - 4.268) were found to be associated with delayed occurrence of PJF. No radiographic parameters were found to be related to the development of delayed PJF. In terms of failure modes, vertebral fracture and fixation failure were more commonly observed in acute PJF, while soft tissue failure and myelopathy were more predominant in delayed PJF. The clinical course was more aggressive in the acute PJF group compared to the delayed PJF group, as evidenced by a greater increase in PJA, a higher revision rate, and worse PROM. CONCLUSIONS: This study demonstrated different risk factors between the acute and delayed PJF. It was found that overcorrection relative to the age-adjusted PI-LL target increased the risk of acute PJF, but had no impact on the development of delayed PJF. Therefore, a different surgical strategy needs to be established to mitigate both acute and delayed PJF.

The influence of working memory mechanisms on false memories in immediate and delayed tests.

There is growing evidence that false memories can occur in working memory (WM) tasks with only a few semantically related words and seconds between study and test. Abadie and Camos (2019) proposed a new model to explain the formation of false memories by describing the role of articulatory rehearsal and attentional refreshing, the two main mechanisms for actively maintaining information in WM. However, this model has only been tested in recognition tasks. In the present study, we report four experiments testing the model in recall tasks in which the active maintenance of information in WM plays a more important role for retrieval. Short lists of semantically related items were held for a short retention interval filled with a concurrent task that either impaired or not the use of each of the WM maintenance mechanisms. Participants were asked to recall the items immediately after the concurrent task (immediate test) or later, at the end of a block of several trials (delayed test). In the immediate test, semantic errors were more frequent when WM maintenance was impaired. Specifically, rehearsal prevented the occurrence of semantic errors in the immediate test, while refreshing had no effect on their occurrence in this test, but increased semantic errors produced only in the delayed test. These results support Abadie and Camos (2019) model and go further by demonstrating the role of active information maintenance in WM in the emergence of false memories. The implications of these findings for understanding WM-LTM relationships are discussed.

Factors Affecting Length of Stays in the Emergency Department of a Teaching Hospital: A Retrospective Study From Najran, Saudi Arabia.

BACKGROUND:  Reducing the frequency of emergency department (ED) patient visits for treatment, particularly in urgent instances, is a global healthcare objective. Additionally, a more extended stay in the ED can harm a patient's prognosis during later hospitalization. This study aims to investigate the factors affecting the length of stay in the ED in a teaching hospital. METHODS: A retrospective chart review study was done between January 1, 2021, and February 31, 2021, involving 122 adult patients who had delayed ED visits to King Khalid Hospital in Najran, Saudi Arabia. Data on the patient's characteristics, visit time, and the causes for the delay based on the Canadian Triage and Acuity Scale (CTAS) were gathered and analyzed. Factors associated with more than six hours of delay were investigated in a univariate analysis. RESULT: The mean age was 52.3 ±13.5 years, and 42 (34.4%) were more than 65 years of age. More than half of the study population were female (n=66; 54.1%). Most delays occurred among CTAS 4 and 5 cases (47.5%), and 22 (18.0%) occurred during holidays. The mean delay time was 6.1 ±1.8 hours. The leading delay causes were multiple consultations with further investigations (37.7%) and conflict between the teams (36.1%). In univariate analysis, ED visiting at holiday time (OR: 0.14; 95% CI: 0.04-0.40, p <0.001) and CTAS 4 and 5 (OR: 2.22; 95% CI: 0.95-5.30, p = 0.003) significantly had more delay. Factors associated with delay in univariate analysis were multiple consultations with further investigations (OR: 2.82; 95% CI: 1.32-6.26, p = 0.013), various assessments in different ED areas with a late arrival of the specialist (OR: 0.43; 95% CI: 0.20-0.91, p = 0.042), and conflict between the teams (OR: 2.50; 95% CI: 1.17-5.54, p = 0.031). CONCLUSION: In this study, multiple assessments in different ED areas and conflict between the teams were the main factors that caused delays in ED. Implementing a timeframe monitoring system for consultations while emphasizing accelerated decision-making and disposition for patients and understanding teamwork collaboration may reduce patients' length of stay in the ED. Implementing these strategies and evaluating their impact on the length of stay in the ED requires further investigation.

Optimizing outcomes: A retrospective analysis of discharge safety for elderly mTBI patients on anticoagulation therapy.

BACKGROUND: Mild traumatic brain injuries (mTBIs) pose a significant risk, particularly in the elderly population on anticoagulation therapy. The safety of discharging these patients from the emergency department (ED) with a negative initial computed tomography (CT) scan has been debated due to the risk of delayed intracranial hemorrhage (d-ICH). OBJECTIVE: To compare outcomes, including d-ICH, between elderly patients on anticoagulation therapy presenting with mTBI who were admitted versus discharged from the ED after an initial negative head CT scan. METHODS: We conducted a retrospective observational study at the Chaim Sheba Medical Center, assessing outcomes of 1598 elderly patients on anticoagulation therapy who presented with mTBI and an initial negative head CT scan. Patients were either admitted for 24-h observation (Group A, n = 829) or discharged immediately from the ED (Group B, n = 769). The primary outcome was incidence of d-ICH within 14 days. RESULTS: Among the 1598 patients included in the study, 46 admitted patients and 1 discharged patient returned within 14 days for repeat CT, identifying one asymptomatic hemorrhage in the discharged patient. Mortality at 30 days was significantly higher in admitted patients compared to discharged patients (4.8% vs. 1.8%, p = 0.001), though cause of death was unrelated to head injury in both groups. CONCLUSION: In elderly patients on anticoagulation with mTBI and a negative initial CT, admission was associated with a higher risk of d-ICH compared to discharge. These findings have implications for clinical decision-making in this high-risk population.

Prenatal heavy metal exposure and pediatric asthma, allergic rhinitis, atopic dermatitis: a systematic review and meta-analysis.

OBJECTIVE: We review the prevalence of allergic diseases in children across prenatal exposures to heavy metals. METHODS: This systematic review and meta-analysis is registered in the PROSPERO database (CRD42023478471). A comprehensive search of PubMed, Web of Science, Medline and Cochrane library was conducted from the database inception until 31 October 2023. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the quality of included studies. We used a random-effects model to summarize the effects from the studies. RESULTS: A total of 16 studies were included, 120,065 mother-child pairs enrolled. The NOS scores indicated that the quality of the literature included in the study was of a high standard. CONCLUSION: The final results indicate that prenatal exposure to Pb increased the incidence of wheeze and Eczema in infants, and exposure to Ni and CD increased the incidence of AD in infants.

A study on factors influencing delayed sputum conversion in newly diagnosed pulmonary tuberculosis based on bacteriology and genomics.

Conversion of sputum from positive to negative is one of the indicators to evaluate the efficacy of anti-tuberculosis treatment (ATT). We investigate the factors associated with delayed sputum conversion after 2 or 5 months of ATT from the perspectives of bacteriology and genomics. A retrospective study of sputum conversion in sputum positive 1782 pulmonary tuberculosis (PTB) was conducted from 2021 to 2022 in Beijing, China. We also designed a case-matched study including 24 pairs of delayed-sputum-conversion patients (DSCPs) and timely-sputum-conversion patients (TSCPs), and collect clinical isolates from DSCPs before and after ATT and initial isolates of TSCPs who successfully achieved sputum conversion to negative after 2 months of ATT. A total of 75 strains were conducted drug sensitivity testing (DST) of 13 anti-TB drugs and whole-genome sequencing (WGS) to analyze the risk factors of delayed conversion and the dynamics changes of drug resistance and genomics of Mycobacterium tuberculosis (MTB) during ATT. We found TSCPs have better treatment outcomes and whose initial isolates show lower levels of drug resistance. Clinical isolates of DSCPs showed dynamically changing of resistance phenotypes and intra-host heterogeneity. Single nucleotide polymorphism (SNP) profiles showed large differences between groups. The study provided insight into the bacteriological and genomic variation of delayed sputum conversion. It would be helpful for early indication of sputum conversion and guidance on ATT.

Primary decompressive craniectomy in patients with large intracerebral hematomas due to aneurysmal subarachnoid hemorrhage.

BACKGROUND: Decompressive craniectomy (DC) can alleviate increased intracranial pressure in aneurysmal subarachnoid hemorrhage patients with concomitant space-occupying intracerebral hemorrhage, but also carries a high risk for complications. We studied outcomes and complications of DC at time of ruptured aneurysm repair. METHODS: Of 47 patients treated between 2010 and 2020, 30 underwent DC during aneurysm repair and hematoma evacuation and 17 did not. We calculated odds ratios (OR) for delayed cerebral ischemia (DCI), angiographic vasospasm, DCI-related infarction, and unfavorable functional outcome (extended Glasgow Outcome Scale 1-5) at three months. Complication rates after DC and cranioplasty in the aneurysmal subarachnoid hemorrhage patients were compared to those of all 107 patients undergoing DC for malignant cerebral infarction during the same period. RESULTS: In DC versus no DC patients, proportions were for clinical DCI 37% versus 53% (OR = 0.5;95%CI:0.2-1.8), angiographic vasospasm 37% versus 47% (OR = 0.7;95%CI:0.2-2.2), DCI-related infarctions 17% versus 47% (OR = 0.2;95%CI:0.1-0.7) and unfavorable outcome 80% versus 88% (OR = 0.5;95%CI:0.1-3.0). ORs were similar after adjustment for baseline predictors for outcome. Complications related to DC and cranioplasty occurred in 18 (51%) of subarachnoid hemorrhage patients and 41 (38%) of cerebral infarction patients (OR = 1.7;95%CI:0.8-3.7). CONCLUSIONS: In patients with aneurysmal subarachnoid hemorrhage and concomitant space-occupying intracerebral hemorrhage, early DC was not associated with improved functional outcomes, but with a reduced rate of DCI-related infarctions. This potential benefit has to be weighed against high complication rates of DC in subarachnoid hemorrhage patients.

Recovery from sport-induced muscle damage in relation to match-intervals in major events.

Muscle damage could affect the next match performance in sports when the time to recover from a previous match is shorter. We examined the interval between matches in nine team sports (e.g., soccer, rugby, field hockey, basketball, volleyball, baseball) and two racket sports (badminton, tennis) in World Cups held in 2022-2023, 2020 Tokyo Olympic Games and Gland Slam in 2023. We then performed narrative review using three electronic databases (PubMed, Scopus, Google Scholar) to get information about muscle damage and recovery in the 11 sports, and discussed whether the intervals in the events would be enough for athletes. We found that the match intervals varied among sports and events ranging from 0 to 17 days. The interval was the shortest for softball (0-2 days) and the longest (5-17 days) for rugby. Regarding muscle damage, changes in muscle function and/or performance measures after a match were not reported for cricket, volleyball and softball, but some information was available for other sports, although the studies did not necessarily use athletes who participated in the major events. It was found that recovery was longer for soccer and rugby than other sports. Importantly, the match-intervals in the events did not appear to accommodate the recovery time required from the previous match in many sports. This could increase a risk of injury and affect players' conditions and health. Changing the match-intervals may be difficult, since it affects the budget of sporting events, but an adequate interval between matches should be considered for each sport from the player's and coach's point of view.

Decreased Positive Fecal Occult Blood Tests and Delayed Medical Presentation for Colorectal Cancer during the Initial COVID-19 Pandemic Period: A Single-center Experience.

Objectives: This study aimed to investigate the impact of the COVID-19 pandemic on the examination and treatment of colorectal cancer (CRC) and on the behaviors of patients and practitioners. Methods: This is a retrospective analysis of the CRC patients who presented to our department between April 2019 and March 2021 and underwent surgery. Clinical presentation of CRC and time from symptom onset to medical presentation were compared between the control (April 2019 to March 2020, n=124) and COVID-19 pandemic periods (April 2020 to March 2021, n=111). Results: Two hundred and thirty-five patients were reviewed. The rate of positive fecal occult blood tests was significantly lower during the COVID-19 pandemic period (13.5 vs. 25.0%, P = 0.027). Among the symptomatic patients who had melena and abdominal symptoms, the time from symptom onset to medical presentation was significantly longer during the COVID-19 period (115 vs. 31 days, P < 0.001). In addition, the interval between presenting to a practitioner and being referred to our department was similar between the two periods (19 vs. 13 days, P = 0.092). There were no significant differences in the stage of cancer between the two periods. The rate of preoperative sub-obstruction was significantly higher during the COVID-19 period (41.4 vs 23.4%, P = 0.003). There was no significant difference in overall survival and recurrence-free survival between two periods. Conclusions: Hesitation to seek examination and treatment for CRC was observed in patients but not in practitioners during the COVID-19 pandemic period. The prognosis did not change.

Colorectal Post-polypectomy Bleeding in Outpatient versus Inpatient Treatment: Propensity Score Matching Analysis.

Objectives: Delayed bleeding is the most frequent adverse event associated with endoscopic mucosal resection (EMR) and hot snare polypectomy (HSP) of colorectal polyps. However, whether the incidence of delayed bleeding differs between outpatient and inpatient treatment is unknown. Therefore, in this study, we aimed to evaluate delayed bleeding rates between outpatient and inpatient endoscopic treatments and clarify the safety of outpatient treatment. Methods: We enrolled 469 patients (1077 polyps) and 420 patients (1080 polyps) in the outpatient and inpatient groups, respectively, who underwent EMR or HSP for colorectal polyps at our institution between April 2020 and May 2023. Using propensity score matching, we evaluated the delayed bleeding rates between the two groups. Delayed bleeding was defined as a hemorrhage requiring endoscopic hemostasis occurring within 14 days of the procedure. Results: Propensity score matching created 376 (954 polyps) matched patient pairs. The median maximum diameter of polyps removed was 10 mm in both groups. Delayed bleeding rates per patients were 1.3% (5/376) in the outpatient group and 2.9% (11/376) in the inpatient group (P=0.21). In term of per polyp, early delayed bleeding (occurring within 24 hours) rates were higher in the inpatient group than outpatient group (0.2% [2/954] vs. 1.1% [10/954], respectively; P=0.04). No severe bleeding requiring a transfusion occurred in either group. Conclusions: Outpatient endoscopic treatment did not increase delayed bleeding compared with inpatient treatment. Outpatient treatment would be safe and common for the removal of colorectal polyps.

Stroke-Like Migraine Attacks After Radiation Therapy (SMART) Syndrome: A Case Report.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare and delayed complication of brain irradiation involving impaired cerebrovascular autoregulation, and diagnosis is based on distinct clinic-radiographic findings and exclusion of differentials. We report a 38-year-old man, who received cranial irradiation 28 years before and developed episodes of headache and visual aura, followed by left hemianopia, aphasia, behavioral disturbances, and focal seizures. An MRI of the brain revealed gyral swelling with restricted diffusion and mild contrast enhancement over the right temporoparietal and occipital region, and fludeoxyglucose-FDG PET scan showed hyperperfusion in the corresponding brain region. He improved completely with pulse steroids and antiseizure medications. The recognition of this syndrome is important as we can reassure patients and their families and help avoid unnecessary and invasive diagnostic tests.

The Immediate and Delayed Maximal Non-Irritating Skin Testing Concentrations of ß-lactam Antibiotics.

BACKGROUND: Maximal skin testing (ST) nonirritant concentrations (NICs) are consistent for penicillin and aminopenicillin amongst guidelines. However, there is variability amongst guidelines for maximal ST NICs of cephalosporins. OBJECTIVE: To determine maximal immediate and delayed ST NICs of 15 ß-lactams in ß-lactam-tolerant and ß-lactam-naïve participants. METHODS: We performed a single-center, nonrandomized prospective study between September 2019 and January 2022 in adult participants. Participants received skin prick testing (SPT) and intradermal test (IDT) injections at six increasing concentrations of 1 or more ß-lactams. A concentration was considered irritant when more than 5% of participants had a positive test. A positive test was defined as a wheal ≥3 mm than negative control accompanied by a ≥5 mm flare for SPT/IDT and induration ≥5 mm with associated erythema at 48 hours for delayed readings (dIDT). Sensitivity analyses using 3 alternative IDT positive criteria were conducted. RESULTS: A total of 747 participants with a median age of 64 (IQR 54-72), 52% males, 85% White, and 92% Non-Hispanic underwent 20,858 skin tests. All undiluted SPT concentrations were nonirritant. We found the following maximal IDT/dIDT NICs (mg/ml): ampicillin (41.6/125), ampicillin-sulbactam (93.8/187.5), aztreonam (6.3/25), cefazolin (55/165), cefepime (35/140), cefoxitin (45/90), ceftaroline (7.5/15), ceftriaxone (58.3/175), cefuroxime (55/110), ertapenem (16.6/50), imipenem-cilastin (6.3/25), meropenem (8.3/25), nafcillin (31.3/62.5), oxacillin (20.9/83.5), and piperacillin-tazobactam (112.5/225). dIDTs were almost all completely non-irritant close or at undiluted concentrations. There were no differences when we applied 3 IDT positivity criteria to our raw data. CONCLUSION: Our results suggest that SPTs with undiluted stock ß-lactam antibiotic concentrations are nonirritant. Compared to previously published nonirritant concentrations, we propose a 2 to 50-fold increase to the maximal IDT and dIDT NICs of 15 ß-lactam antibiotics. When performing dIDTs, a higher concentration should be used rather than the same IDT concentration.

Pharmacobezoar Associated Prolonged Clinical Course in a Patient with Immediate Release Quetiapine Overdose.

INTRODUCTION: Quetiapine is available in both immediate-release (IR) and extended-release (XR) formulations. Quetiapine XR overdose is known to cause delayed increase in serum quetiapine concentrations. However, it is not certain whether quetiapine IR overdose would similarly cause a delayed increase in serum quetiapine concentrations. CASE REPORT: A 57-year-old woman with depression who was taking half a tablet of 25 mg quetiapine IR daily was transported to our emergency department with a complaint of disturbance of consciousness 12 h after a quetiapine IR overdose. On arrival, her initial vital signs were heart rate of 116 beats per minute, blood pressure of 77/43 mm Hg, and oxygen saturation of 91% under 10 L oxygen administration. Whole body plain computed tomography showed a large amount of gastric hyperdense content suggesting pharmacobezoar with a volume of 71.2 ml. After treatment with respiratory and circulatory support, gastric lavage was performed. Her disturbance of consciousness persisted until day 5, and she was extubated on day 7. The serum concentrations of quetiapine were 2690 ng/mL at 12 h after overdose, 5940 ng/mL at 40 h, and 350 ng/mL at 124 h after overdose. Serum concentrations of other co-ingestions were all below lethal levels. CONCLUSION: A massive quetiapine IR overdose with pharmacobezoars can cause a delayed increase in serum quetiapine concentrations.

Eccentric exercise-induced delayed onset trunk muscle soreness alters high-density surface EMG-torque relationships and lumbar kinematics.

We aimed to assess high-density surface electromyography (HDsEMG)-torque relationships in the presence of delayed onset trunk muscle soreness (DOMS) and the effect of these relationships on torque steadiness (TS) and lumbar movement during concentric/eccentric submaximal trunk extension contractions. Twenty healthy individuals attended three laboratory sessions (24 h apart). HDsEMG signals were recorded unilaterally from the thoracolumbar erector spinae with two 64-electrode grids. HDsEMG-torque signal relationships were explored via coherence (0-5 Hz) and cross-correlation analyses. Principal component analysis was used for HDsEMG-data dimensionality reduction and improvement of HDsEMG-torque-based estimations. DOMS did not reduce either concentric or eccentric trunk extensor muscle strength. However, in the presence of DOMS, improved TS, alongside an altered HDsEMG-torque relationship and kinematic changes were observed, in a contraction-dependent manner. For eccentric trunk extension, improved TS was observed, with greater lumbar flexion movement and a reduction in δ-band HDsEMG-torque coherence and cross-correlation. For concentric trunk extensions, TS improvements were observed alongside reduced thoracolumbar sagittal movement. DOMS does not seem to impair the ability to control trunk muscle force, however, perceived soreness induced changes in lumbar movement and muscle recruitment strategies, which could alter motor performance if the exposure to pain is maintained in the long term.

The Effect of Immune Checkpoint Inhibitor Therapy on Pre-Existing Gastroparesis and New Onset of Symptoms of Delayed Gastric Emptying.

Immune checkpoint inhibitors (ICIs) can cause myenteric plexopathy, which could result in delayed gastric emptying (GE) and possibly gastroparesis. We assessed the clinical outcomes of patients who had pre-existing gastroparesis or who developed symptoms of delayed GE following ICI therapy. We retrospectively identified adults with ICD-9 and ICD-10 codes for gastroparesis who received ICI therapy between 1 January 2020 and 31 December 2022 at a tertiary cancer center. Of 76 eligible patients, 37 had pre-existing gastroparesis; 39 (0.2% of the more than 18,000 screened) developed symptoms of delayed GE after ICI therapy, of which 27 (69%) patients had an alternative etiology for delayed GE. Four patients (11%) with pre-existing gastroparesis had a flare-up after ICI, and the median time to flare-up was 10.2 months (IQR, 0.7-28.6 months); for patients with new onset of suspected delayed GE after ICI, the median time to symptom onset was 12.8 months (IQR, 4.4-35.5 months). The clinical symptom duration of patients without an alternative etiology (74.5 days (IQR, 21.5-690 days)) and those with an alternative etiology (290 days (IQR, 147-387 days)) did not differ significantly (p = 1.00). Delayed GE after ICI therapy is a rare presentation but has a late onset and a prolonged symptom duration.

The pentatricopeptide repeat protein DG1 promotes the transition to bilateral symmetry during Arabidopsis embryogenesis through GUN1-mediated plastid signals.

During Arabidopsis embryogenesis, the transition of the embryo's symmetry from radial to bilateral between the globular and heart stage is a crucial event, involving the formation of cotyledon primordia and concurrently the establishment of a shoot apical meristem (SAM). However, a coherent framework of how this transition is achieved remains to be elucidated. In this study, we investigated the function of DELAYED GREENING 1 (DG1) in Arabidopsis embryogenesis using a newly identified dg1-3 mutant. The absence of chloroplast-localized DG1 in the mutants led to embryos being arrested at the globular or heart stage, accompanied by an expansion of WUSCHEL (WUS) and SHOOT MERISTEMLESS (STM) expression. This finding pinpoints the essential role of DG1 in regulating the transition to bilateral symmetry. Furthermore, we showed that this regulation of DG1 may not depend on its role in plastid RNA editing. Nevertheless, we demonstrated that the DG1 function in establishing bilateral symmetry is genetically mediated by GENOMES UNCOUPLED 1 (GUN1), which represses the transition process in dg1-3 embryos. Collectively, our results reveal that DG1 functionally antagonizes GUN1 to promote the transition of the Arabidopsis embryo's symmetry from radial to bilateral and highlight the role of plastid signals in regulating pattern formation during plant embryogenesis.