Enteric duplication cysts in paediatric population along with literature review / Quistes de duplicación entérica en población pediátrica y revisión de la literatura

The clinical presentation of enteric duplication cysts is dependent on the location of the cyst with symptoms varying from nausea and vomiting to abdominal distension, pain and perforation. Four patients were identified who were diagnosed with enteric duplication cysts within the period from 2019 to 2023. Three of the patients presented with signs of intestinal obstruction-abdominal distension and pain, while one had an antenatally detected abdominal mass. There were three boys and one girl with ages ranging from 4 months to 14 years. Three cases of ileal and one case of caecal duplication cyst were reported. Most of the cases showed ileal/caecal mucosa while one case demonstrated ectopic gastric mucosa. The treatment of these cysts includes surgical excision. Although radiological investigations help in arriving at a provisional diagnosis, the final diagnosis can be confirmed only after histopathological examination. Early treatment prevents complications and results in a good prognosis for the patient. (AU)

La presentación clínica de los quistes de duplicación entérica depende de la ubicación del quiste, y los síntomas varían desde náuseas y vómitos hasta distensión abdominal, dolor y perforación. Se identificaron cuatro pacientes que fueron diagnosticados con quistes de duplicación entérica en el período de 2019 a 2023. Tres de los pacientes presentaron signos de obstrucción intestinal (distensión abdominal y dolor), mientras que uno tenía una masa abdominal detectada prenatalmente. Eran tres niños y una niña con edades comprendidas entre 4 meses y 14 años. Se notificaron tres casos de quiste de duplicación ileal y un caso de quiste de duplicación cecal. La mayoría de los casos mostraron mucosa ileal/cecal, mientras que un caso mostró mucosa gástrica ectópica. El tratamiento de estos quistes incluye la escisión quirúrgica. Aunque las investigaciones radiológicas ayudan a llegar a un diagnóstico provisional, el diagnóstico final solo puede confirmarse después del examen histopatológico. El tratamiento precoz previene complicaciones y redunda en un buen pronóstico para el paciente. (AU)

The clinical effect of an electric massage chair on chemotherapy-induced nausea and vomiting in cancer patients: randomized phase II cross-over trial.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse events in cancer patients and can negatively affect their quality of life (QoL). This study aimed to evaluate the clinical efficacy of an electric massage chair (EMC) for the treatment of CINV. METHODS: A randomized phase II cross-over trial was conducted on solid cancer patients who received moderate (MEC) to high emetogenic chemotherapy (HEC). The participants were randomly assigned to receive their first chemotherapy either on a standard bed (Group A) or in an EMC (Group B) during the infusion. The patients were then crossed over to the next cycle. CINV and QoL questionnaires were collected from the participants. RESULTS: A total of 59 patients completed the trial protocol and were included in the analysis, with 29 and 30 patients in Groups A and B, respectively. The mean INVR (Index of Nausea, Vomiting, and Retching) score in the 2nd day of the first cycle was higher in Group B (3.63 ± 5.35) than Group A (2.76 ± 4.78), but the difference was not statistically significant (p = 0.5367). The complete response rate showed little difference between the groups. Among the high-emetic risk subgroups, patients who received HEC (p = 0.04595), younger patients (p = 0.0108), and non-colorectal cancer patients (p = 0.0495) presented significantly lower CINV scores when EMC was applied. CONCLUSION: Overall, there was no significant difference in INVR scores between standard care and EMC. Applying EMC at the first chemotherapy infusion may help preserve QoL and reduce CINV in high-risk patients. TRIAL REGISTRATION: KCT0008200, 17/02/2023, Retrospectively registered.

Gastro-Intestinal Symptoms in Palliative Care Patients.

This review of the palliation of various gastro-intestinal (GI) symptoms encountered in cancer patients is by no means exhaustive. Frequent symptoms such as constipation, nausea and vomiting, bowel obstructions, ascites and bleeds will be discussed, focusing on their assessment and most importantly, how to control the associated symptoms. All of these symptoms and GI complications can significantly impact patients' quality of life (QOL) and should be treated as quickly and aggressively as possible.

Formulation of Metoclopramide Hydrochloride-Loaded Lipid Carriers by QbD Approach for Combating Nausea: Safety and Bioavailability Evaluation in New Zealand Rabbit.

The focus of the research was to overcome the limitations of metoclopramide (MTC) when administered intranasally. The aim was to improve its bioavailability, increase patient compliance, and prolong its residence time in the nasal cavity. MTC-loaded liposomes were prepared by applying the film hydration method. A study was conducted to determine how formulation variables affected encapsulation efficiency (EE %), mean particle size (MPS), and zeta potential (ZP). The MTC-liposomes were further loaded into the in situ gel (gellan gum) for longer residence times following intranasal administration. pH, gelling time, and in vitro release tests were conducted on the formulations produced. In vivo performance of the MTC-loaded in situ gels was appraised based on disparate parameters such as plasma peak concentration, plasma peak time, and elimination coefficient compared to intravenous administration. When the optimal liposome formulation contained 1.98% of SPC, 0.081% of cholesterol, 97.84% of chloroform, and 0.1% of MTC, the EE of MTC was 83.21%, PS was 107.3 nm. After 5 h, more than 80% of the drug was released from MTC-loaded liposome incorporated into gellan gum in situ gel formulation (Lip-GG), which exhibited improved absorption and higher bioavailability compared to MTC loaded into gellan gum in situ gel (MTC-GG). Acceptable cell viability was also achieved. It was found out that MTC-loaded liposomal in situ gel formulations administered through the nasal route could be a better choice than other options due to its ease of administration, accurate dosing, and higher bioavailability in comparison with MTC-GG.

The emerging emetogenicity of trifluridine/tipiracil (TAS­102) from patient self-reporting: a multicenter, prospective, observational study.

BACKGROUND: Trifluridine/tipiracil (TAS-102) is an oral anticancer drug with adequate efficacy in unresectable colorectal cancer, but frequently also induces chemotherapy-induced nausea and vomiting (CINV). To investigate the occurrence of CINV and antiemetic therapy in patients with colorectal cancer treated with TAS-102 (JASCC-CINV 2001). METHODS: We conducted a multicenter, prospective, observational study in patients with colorectal cancer who received TAS-102 without dose reduction for the first time. Primary endpoint was the incidence of vomiting during the overall period. Secondary endpoints were the incidence of nausea, significant nausea, anorexia, other adverse events (constipation, diarrhea, insomnia, fatigue, dysgeusia) and patient satisfaction. Patient diaries were used for primary and secondary endpoints. All adverse events were subjectively assessed using PRO-CTCAE ver 1.0. and CTCAE ver 5.0. RESULTS: Data from 100 of the 119 enrolled patients were analyzed. The incidence of vomiting, nausea, and significant nausea was 13%, 67%, and 36%, respectively. The incidence of vomiting in patients with and without prophylactic antiemetic therapy were 20.8% and 10.5%, respectively. Prophylactic antiemetics were given to 24% of patients, of whom 70% received D2 antagonists. Multivariate Cox proportional hazards analysis showed that experience of CINV in previous treatment tended to be associated with vomiting (hazard ratio [HR]: 7.13, 95% confidence interval [CI]: 0.87-58.5, P = 0.07), whereas prophylactic antiemetic administration was not (HR: 1.61, 95 CI: 0.50-5.21, P = 0.43). With regard to patient satisfaction, the proportion of patients who were "very satisfied," "satisfied," "slightly satisfied" or "somewhat satisfied" was 81.8%. CONCLUSIONS: The low incidence of vomiting and high patient satisfaction suggest that TAS-102 does not require the use of uniform prophylactic antiemetic treatments. However, patients with the experience of CINV in previous treatment might require prophylactic antiemetic treatment.

Bilateral Bow Hunter Syndrome Associated with Loss of Cervical Physiological Curvature.

BACKGROUND Bow hunter syndrome is a rare disease that is often overlooked. It presents with complex and variable clinical symptoms and causes, making diagnosis and treatment challenging. This case report focuses on a young patient with bilateral bow hunter syndrome, possibly caused by the loss of cervical physiological curvature. The aim is to enhance understanding and awareness of the disease. It is important to consider the possibility of bow hunter syndrome in young patients with long-term poor neck posture and symptoms such as dizziness, nausea, vomiting, and neck rotation-related symptoms. In such cases, thorough examination of posterior circulation hemodynamics and vascular morphology is recommended. CASE REPORT A 25-year-old woman was admitted to the hospital mainly because of "dizziness for 10 hours." The dizziness was aggravated when the right side of the neck was turned and the body position changed. This was accompanied by visual rotation, nausea, and vomiting. Bow hunter syndrome was diagnosed based on the clinical symptoms and hemodynamic examination of the posterior circulation. The patient was given a cervical collar to limit excessive twisting of the neck and instructed to avoid large-angle deflection of the neck after discharge. During the 3-month follow-up, no characteristic symptoms (such as dizziness) reappeared. CONCLUSIONS Bow hunter syndrome is a rare clinical posterior circulation compression syndrome with complex etiology. This case suggests that the simple disappearance of cervical curvature may be related to the occurrence of bow hunter syndrome. The dynamic monitoring of blood flow by color Doppler ultrasound and transcranial Doppler in different head positions provides clear clues to suspected bow hunter syndrome. With the help of computed tomography angiography, the diagnosis of bow hunter syndrome may be obtained by noninvasive examination.

Evaluation of chemotherapy-induced nausea and vomiting in pediatric patients with high-grade glioma treated with lomustine-a case series.

PURPOSE: Although lomustine has been used as a chemotherapeutic agent for decades, no recommendation on appropriate chemotherapy-induced nausea and vomiting (CINV) prophylaxis is available. As CINV is considered one of the most bothersome side effects of chemotherapy, adequate prophylaxis is of relevance to improve quality of life during cancer treatment. The aim of this retrospective case series was to report the incidence and severity of CINV in pediatric patients with high-grade glioma treated with lomustine and to formulate recommendations for appropriate CINV prophylaxis. METHODS: Pediatric patients treated with lomustine for high-grade glioma according to the ACNS 0423 protocol were identified retrospectively. Two researchers independently reviewed and classified complaints of CINV and administered CINV prophylaxis. Treatment details, tumor localization, and response to therapy were systematically extracted from the patients' files. RESULTS: Seventeen children aged 8-18 years received a median of four cycles of lomustine. CINV complaints and administered prophylaxis were evaluable in all patients. Moderate or severe CINV was observed in 13/17 (76%) patients. Administered prophylactic CINV regimens varied from no prophylaxis to triple-agent combinations. CONCLUSION: In this case series, we identified lomustine as a highly emetogenic chemotherapeutic agent. According to the current guidelines, CINV prophylaxis with a 5-HT3 receptor antagonist in combination with dexamethasone and (fos)aprepitant is recommended.

Clinical presentation and management of methanol poisoning outbreaks in Riyadh, Saudi Arabia: a retrospective analysis.

BACKGROUND: Acute methanol intoxication, whether unintentional or deliberate, necessitates prompt intervention to prevent severe morbidity and mortality. Homemade alcoholic beverages are a frequent source of such poisoning. This retrospective analysis examined two outbreaks of methanol intoxication in Saudi Arabia. It investigated the clinical presentation, implemented management strategies, and any lasting complications (sequelae) associated with these cases. The aim was to assess the potential impact of different treatment modalities and the timeliness of their initiation on patient outcomes. METHODS: This was a retrospective case series of methanol poisoning cases which presented to the adult emergency department (ED) at King Abdulaziz Medical City (KAMC) in Riyadh, Saudi Arabia. There were two separate outbreaks in the city, the first one was from September 1 to September 10, 2020 and the second one was from May 14 to May 20, 2021. Electronic charts were reviewed, and data were extracted to previously prepared data extraction sheets. RESULT: From the 22 patients who arrived in the ED alive, the most common complaints were nausea or vomiting followed by altered level of consciousness. About 9% from the patient were hypotensive, 36% were tachycardic, 41% were tachypneic and 4% were having SpO2 < 94%. Brain CT was abnormal in 6 patients. Vision impairment was the most common sequalae of methanol poisoning (7 out of 12 patients who were assessed by ophthalmologist, 58%). When the patients were divided based on severity (mild, moderate, severe), nausea or vomiting and loss of consciousness were the most common complaints among the moderate group while loss of consciousness predominated in the severe group. Two patients presented with low blood pressure and were in the sever group. The severe group had a mean Glasgow Coma Scale (GCS) of 8. Most of the patients in the severity groups underwent the same management apart from those who died or deposited. Eight patients in the severe group had to be intubated. CONCLUSION: This study demonstrates the multifaceted clinical presentation of methanol poisoning, culminating in a 17.4% mortality rate. Notably, our findings emphasize the critical role of prompt diagnosis and swift initiation of combined fomepizole therapy and hemodialysis in mitigating mortality and minimizing the potential for chronic visual sequelae associated with methanol poisoning.

Comparison of Remimazolam and Propofol on Postoperative Delirium in Elderly Patients Undergoing Radical Resection of Colon Cancer: A Single-Center Prospective Randomized Controlled Study.

BACKGROUND We compared the effect of remimazolam and propofol intravenous anesthesia on postoperative delirium in elderly patients undergoing laparoscopic radical resection of colon cancer. MATERIAL AND METHODS One hundred patients undergoing elective radical operation of colon cancer under general anesthesia were divided into a remimazolam group (group R) and propofol group (group P) by a random number table method. During anesthesia induction and maintenance, group R was intravenously injected with remimazolam to exert sedation; however, in group P, propofol was injected instead of remimazolam. The occurrence of postoperative delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit scale and postoperative pain was assessed with the visual analogue score (VAS). The primary outcome measures were the incidence and duration of delirium within 7 days following surgery. Secondary outcome measures included postoperative VAS scores, intraoperative anesthetic drug dosage, and adverse reactions, including nausea and vomiting, hypoxemia, and respiratory depression. RESULTS There was no significant difference in baseline data between the 2 groups (P>0.05). There was no statistically significant difference in the incidence and duration of postoperative delirium between the 2 groups (P>0.05). There were no significant differences in VAS scores, remifentanil consumption, and adverse reactions, including nausea and vomiting, hypoxemia, and respiratory depression between the 2 groups (P>0.05). CONCLUSIONS In elderly patients undergoing radical colon cancer surgery, remimazolam administration did not improve or aggravate the incidence and duration of delirium, compared with propofol.

[Comparison of the early analgesic efficacy of three different drugs after anterior cruciate ligament reconstruction].

OBJECTIVE: The pain-relieving effect and safety of compound aminopyrine phenacetin tablets, tramcontin (tramadol hydrochloride sustained-release tablets) and dolantin in the early stage of autologous tendon reconstruction of the anterior cruciate ligament (ACL) of the knee joint were compared. METHODS: Retrospective analysis of postoperative pain and drug analgesia in 45 patients performed by the same group from November 2018 to February 2019. The random area group design was divided into two groups according to whether ACL rupture was combined with meniscal injury, group A was 24 patients with ACL reconstruction of knee joint and group B was 21 patients with ACL fracture combined with meniscus injury. The two groups were divided into three subgroups respectively according to the actual treatment of postoperative analgesic drugs received by the patients, including 4 cases of compound aminopyrine phenacetin tablets, 11 cases of oral tramcontin, 9 cases of intramuscular dolantin combined with phenergan in group A; 3 cases of compound aminopyrine phenacetin tablets, 10 cases of oral tramcontin, and 8 cases of intramuscular dolantin combined with phenergan in group B. When the early postoperative patients complain about pain and actively ask for analgesia. When the patients complained about pain after the operation and actively asked for analgesia, they were randomly given painkillers, tramcontin or dolantin combined with phenergan to relieve pain. Pain visual analogue scale (VAS) was used to evaluate pain relief and observe the occurrence of adverse reactions. RESULTS: There were no significant dif-ferences in gender, age, body mass index, and time of hospital stay between the two groups of patients (P > 0.05). In the patients who used tramcontin and dolantin combined with phenergan to relieve pain judging by VAS score before and 1 h after taking the drug, it was found that the pain situation of the patient was significantly relieved, and the difference before and after taking the drug had statistical significance (P < 0.05). Pairwise comparisons of the three drugs applied in the two groups showed significantly greater pain relief in the dolantin combined with phenergan group than in the remaining two drugs. There was no significant difference (P > 0.05). Dolantin was prone to nausea and vomiting, but the application of phenergan was also used to reduce side effects. In terms of adverse reactions, only 1 case of nausea occurred in the tramcontin group for simple ACL reconstruction, and none of the patients in the other groups showed serious complications and allergic reactions. CONCLUSION: Whether in cruciate ligament reconstruction alone or combined with meniscus molding or suture, compound aminopyrine phenacetin tablets, tramcontin, dolantin combined with phenergan can effectively relieve pain. Among the three drugs, dolantin caused the largest pain relief. At the same time, the combination of phenergan effectively reduced the adverse reactions, such as vomiting and nausea, and increased the drug safety.

2020 ASCO, 2023 NCCN, 2023 MASCC/ESMO, and 2019 CCO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in cancer patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common toxicity that may impair the quality of life of patients with various malignancies ranging from early to end stages. In light of frequent changes to the guidelines for optimal management of CINV, we undertook this narrative review to compare the most recent guidelines published by ASCO (2020), NCCN (2023), MASCC/ESMO (2023), and CCO (2019). The processes undertaken by each organization to evaluate existing literature were also described. Although ASCO, NCCN, MASCC/ESMO, and CCO guidelines for the treatment and prevention of CINV share many fundamental similarities, the literature surrounding low and minimal emetic risk regimens is lacking. Current data regarding adherence to these guidelines is poor and warrants further investigation to improve care.

The timing, duration, and severity of nausea and vomiting of pregnancy and adverse birth outcomes among controls without birth defects in the National Birth Defects Prevention Study.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) occurs in approximately 70% of pregnant people, with varying severity and duration. Treatments include pharmacologic and herbal/natural medications. The associations between NVP and birth outcomes, including preterm birth, small for gestational age (SGA), and low birth weight are inconclusive. OBJECTIVE: To determine whether NVP and reported medications are associated with adverse birth outcomes. METHODS: We used data from the population-based, multisite National Birth Defects Prevention Study (1997-2011) to evaluate whether self-reported NVP according to timing, duration, and severity or its specific treatments were associated with preterm birth, SGA, and low birth weight among controls without birth defects. Odds ratios (aOR) and 95% confidence intervals (CI) were adjusted for sociodemographic, reproductive, and medical factors. For any NVP, duration, treatment use, and severity score analyses, the comparison group was participants with no reported NVP. For timing analyses, the comparison group was women with no reported NVP in the same trimester of pregnancy. RESULTS: Among 6018 participants, 4339 (72.1%) reported any NVP. Among those with NVP, moderate or severe symptoms were more common than mild symptoms. Any versus no NVP was not associated with any of the outcomes of interest. NVP in months 4-6 (aOR 1.21, 95% CI: 1.00, 1.47) and 7-9 (aOR 1.57, 95% CI: 1.22, 2.01) of pregnancy were associated with an increase in the risk of preterm birth. NVP lasting one trimester in duration was associated with decrease in risk of SGA (aOR: 0.74, 95% CI: 0.58, 0.95), and NVP present in every trimester of pregnancy had a 50% increase in risk of preterm birth (aOR: 1.50, 95% CI: 1.11, 2.05). For NVP in months 7-9 and preterm birth, ORs were elevated for moderate (aOR: 1.82, 95% CI: 1.26, 2.63), and severe (aOR: 1.53, 95% CI: 1.06, 2.19) symptoms. NVP was not significantly associated with low birth weight. Our analyses of medications were limited by small numbers, but none suggested increased risk of adverse outcomes associated with use of the medication. CONCLUSION: Mild NVP and NVP limited to early pregnancy appear to have no effect or a small protective effect on birth outcomes. Long-lasting NVP, severe NVP, and NVP later in pregnancy may increase risk of preterm birth and SGA.

Deletion of concurrent chemotherapy on the basis of sequential chemoradiotherapy for non-metastatic stage T4 nasopharyngeal carcinoma in IMRT era.

PURPOSE: Intensity-modulated radiotherapy (IMRT) combined with concurrent chemotherapy is deemed as the mainstay treatment in locoregionally advanced nasopharyngeal carcinoma (NPC). Nevertheless, the tolerance of severe acute toxicity of concurrent chemotherapy was unsatisfied. In addition, T4 is the predicting factor of poor prognosis for NPC patients. In this retrospective analysis, the long-term outcomes IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy for T4 non-metastatic NPC were analyzed. MATERIALS AND METHODS: From January 2005 to November 2016, a total of 145 biopsy-proven non-metastatic T4 NPC was treated with IMRT combined by induction chemotherapy with or without adjuvant chemotherapy. The survival and side effects of the patients were analyzed. RESULTS: Median follow-up time was 74 months (ranges, 8-186 months). 10.0%, 61.3%, 27.3%, and 1.3% developed grade 1, 2, 3, and 4 mucositis during IMRT, respectively. 5.5% and 2.0% patients experienced grade 1 and 2 nausea and vomiting; no patients developed grade 3 or 4 nausea and vomiting. Of 145 patients enrolled, 5-year and 10-year overall survival(OS) rates were 73.7% and 53.9%, local progression-free survival(LPFS) rates were 86.1% and 71.6%, regional progression-free survival(RPFS) rates were 96.7% and 92.8%, distant metastasis-free survival (DMFS) rates were 86.7%, 78.2%, respectively. At the last follow-up, five patients developed cranial nerve injury, one patient developed mandibular bone necrosis, four patients developed temporal lobe injury, four patients developed nasopharyngeal massive hemorrhage (three cases after recurrence and one case without recurrence), and five patients developed second primary tumor. CONCLUSION: The survival outcomes of treating T4 NPC IMRT combined by induction chemotherapy deleting concurrent chemotherapy with or without adjuvant chemotherapy are encouraging. Moreover, mucosal reaction, nausea, and vomiting reaction were reduced during IMRT.

Effect of ginger and P6 acupressure on chemotherapy-induced nausea and vomiting: a randomized controlled study.

OBJECTIVE: To evaluate the effect of ginger with P6 acupressure in preventing and treating chemotherapy-induced nausea and vomiting (CINV) in cancer patients. METHOD: A total of 172 participants were randomly divided into the control, ginger, acupressure, and joint groups, who were hospitalized in the Affiliated Hospital of Xuzhou Medical University from February and September 2022. The baseline characteristics, nausea, vomiting, and retching, benefit finding, functional living index-emesis, treatment satisfaction, and adverse reaction, were used in data collection. RESULTS: No significant difference was found in benefit finding and adverse reactions among the four groups (P > 0.05). Ginger significantly improved delayed CINV and function living index-nausea (P < 0.05) but had no significant effect on acute CINV, retching, and delayed vomiting, functional living index-emesis, and treatment satisfaction (P>0.05). Acute nausea and retching, delayed nausea, vomiting, and retching, functional living index-emesis, and treatment satisfaction were effectively improved in the acupressure and joint groups (P < 0.05). CONCLUSION: Ginger with P6 acupressure may contribute to improving CINV in patients undergoing chemotherapy.

Safety and tolerability of atogepant for the preventive treatment of migraine: a post hoc analysis of pooled data from four clinical trials.

BACKGROUND: Conventional, non-specific preventive migraine treatments often demonstrate low rates of treatment persistence due to poor efficacy or tolerability. Effective, well-tolerated preventive treatments are needed to reduce migraine symptoms, improve function, and enhance quality of life. Atogepant is a migraine-specific oral calcitonin gene-related peptide receptor antagonist that is indicated for the preventive treatment of migraine in adults. This analysis evaluated the safety and tolerability profile of atogepant for the preventive treatment of migraine, including adverse events (AEs) of interest, such as constipation, nausea, hepatic safety, weight changes, and cardiac disorders. METHODS: This post hoc analysis was performed using data pooled from 2 (12-week) randomized, double-blind, placebo-controlled trials (RCTs) and 2 (40- and 52-week) open-label long-term safety (LTS) trials of oral atogepant for episodic migraine (EM). RESULTS: The safety population included 1550 participants from the pooled RCTs (atogepant, n = 1142; placebo, n = 408) and 1424 participants from the pooled LTS trials (atogepant, n = 1228; standard care [SC], n = 196). In total, 643/1142 (56.3%) atogepant participants and 218/408 (53.4%) placebo participants experienced ≥ 1 treatment-emergent AEs (TEAEs) in the RCTs. In the LTS trials, 792/1228 (64.5%) of atogepant participants and 154/196 (78.6%) of SC participants experienced ≥ 1 TEAEs. The most commonly reported TEAEs (≥ 5%) in participants who received atogepant once daily were upper respiratory tract infection (5.3% in RCTs, 7.7% in LTS trials), constipation (6.1% in RCTs, 5.0% in LTS trials), nausea (6.6% in RCTs, 4.6% in LTS trials), and urinary tract infection (3.4% in RCTs, 5.2% in LTS trials). Additionally, weight loss appeared to be dose- and duration-dependent. Most TEAEs were considered unrelated to study drug and few led to discontinuation. CONCLUSIONS: Overall, atogepant is safe and well tolerated in pooled RCTs and LTS trials for the preventive treatment of EM in adults. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02848326 (MD-01), NCT03777059 (ADVANCE), NCT03700320 (study 302), NCT03939312 (study 309).

Activation of GFRAL+ neurons induces hypothermia and glucoregulatory responses associated with nausea and torpor.

GFRAL-expressing neurons actuate aversion and nausea, are targets for obesity treatment, and may mediate metformin effects by long-term GDF15-GFRAL agonism. Whether GFRAL+ neurons acutely regulate glucose and energy homeostasis is, however, underexplored. Here, we report that cell-specific activation of GFRAL+ neurons using a variety of techniques causes a torpor-like state, including hypothermia, the release of stress hormones, a shift from glucose to lipid oxidation, and impaired insulin sensitivity, glucose tolerance, and skeletal muscle glucose uptake but augmented glucose uptake in visceral fat. Metabolomic analysis of blood and transcriptomics of muscle and fat indicate alterations in ketogenesis, insulin signaling, adipose tissue differentiation and mitogenesis, and energy fluxes. Our findings indicate that acute GFRAL+ neuron activation induces endocrine and gluco- and thermoregulatory responses associated with nausea and torpor. While chronic activation of GFRAL signaling promotes weight loss in obesity, these results show that acute activation of GFRAL+ neurons causes hypothermia and hyperglycemia.

Nausea-induced suppression of feeding is mediated by central amygdala Dlk1-expressing neurons.

The motivation to eat is suppressed by satiety and aversive stimuli such as nausea. The neural circuit mechanisms of appetite suppression by nausea are not well understood. Pkcδ neurons in the lateral subdivision of the central amygdala (CeA) suppress feeding in response to satiety signals and nausea. Here, we characterized neurons enriched in the medial subdivision (CeM) of the CeA marked by expression of Dlk1. CeADlk1 neurons are activated by nausea, but not satiety, and specifically suppress feeding induced by nausea. Artificial activation of CeADlk1 neurons suppresses drinking and social interactions, suggesting a broader function in attenuating motivational behavior. CeADlk1 neurons form projections to many brain regions and exert their anorexigenic activity by inhibition of neurons of the parabrachial nucleus. CeADlk1 neurons are inhibited by appetitive CeA neurons, but also receive long-range monosynaptic inputs from multiple brain regions. Our results illustrate a CeA circuit that regulates nausea-induced feeding suppression.