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Objective: We report a case of biopsy-proven giant cell arteritis after an initial presentation of area postrema syndrome., Methods: A 65-year-old man was evaluated using MRI, temporal artery biopsy, and ultrasound., Results: The patient presented with refractory nausea, vomiting, and hiccups that caused weight loss without any other neurologic or clinical symptoms. His MRI scan 15 days later revealed a hyperintense sign on the area postrema with no abnormal diffusion or contrast enhancement, compatible with isolated area postrema syndrome. An extensive workup for inflammation and other etiologies including neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody disorder, and multiple sclerosis (MS) showed negative results. The patient responded to treatment with methylprednisolone. Two months after the initial clinical manifestation, the patient developed fatigue, headache, and scalp tenderness. He was diagnosed with giant cell arteritis after ultrasonography and biopsy were performed. He responded well to oral glucocorticoids and had only 1 relapse during tapering. He has not had arteritic ischemic optic neuropathy or any new episodes of area postrema syndrome., Discussion: This case demonstrates the importance of expanding the differential diagnosis in patients with area postrema syndrome and no other signs of NMOSD., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: The objective of this study was to report and discuss clinical analysis, including the diagnosis and treatment of 4 cases of neuromyelitis optica spectrum disease (NMOSD) with area postrema syndrome (APS) as the first symptom., Methods: Four patients with intractable nausea, vomiting, and confirmed NMOSD were included in the final analysis. All of these patients were initially misdiagnosed and mismanaged., Results: Among the 4 patients, 3 were admitted to the department of gastroenterology at the onset of the disease, and 2 were not correctly diagnosed and treated promptly due to misdiagnosis. Therefore, their symptoms worsened, and they were transferred to Intensive Care Unit (ICU) for life support. No obvious early medulla lesions were found in one patient. One patient was treated with intravenous immunoglobulin, methylprednisolone, and plasma exchange, but there was no significant clinical improvement, after which the disease relapsed during the treatment with low-dose rituximab., Conclusion: The clinical manifestations of NMOSD are complex and diverse, and the initial symptoms, onset age of the patient, and magnetic resonance imaging (MRI) findings can influence the final diagnosis. Early identification of the APS and timely therapy can prevent visual and physical disabilities, even respiratory failure, coma, and cardiac arrest. Therefore, it is necessary to identify specific and sensitive serum and imaging markers for predicting the prognosis and recurrence of the disease., (© 2022. The Author(s).)

Objectives: To study the clinical and gastroscopic features of children with cyclic vomiting syndrome., Methods: A retrospective analysis was performed on the medical data of 63 children with cyclic vomiting syndrome who were hospitalized and followed up in Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University from August 2019 to March 2022., Results: Among the 63 children, there were 30 boys and 33 girls, with a mean age of 6.11 years, a mean course of disease of 2.57 years, and a mean vomiting period of 4.04 days. The most common accompanying symptom was listlessness or somnolence (55/63, 87%), followed by anorexia (45/63, 71%), abdominal pain or abdominal discomfort (40/63, 63%), constipation (19/63, 30%), salivation (12/63, 19%), nausea (11/63, 17%), headache (11/63, 17%), fever (6/63, 10%), and rash (1/63, 2%). All 63 children underwent gastroscopy, among whom 3 had no marked abnormalities, 22 (35%) had chronic superficial gastritis or chronic non-atrophic gastritis alone, and 38 (60%) had other abnormal changes aside from chronic gastritis (16 children with reflux esophagitis, 12 with bile reflux gastritis, 13 with duodenitis, 10 with erosive gastritis, and 5 with gastric or duodenal ulcer). Among the 63 children, 42 underwent pathological examinations of gastric mucosa, among whom 5 had no marked abnormalities, 34 had mild chronic gastritis, 2 had moderate chronic gastritis, and 1 had severe chronic gastritis. Among the 63 children, 15 received 24-hour dynamic esophageal pH monitoring during the interictal period, among whom 9 children were found to have pathological acid reflux., Conclusions: In addition to recurrent vomiting, most children with cyclic vomiting syndrome also have the symptoms such as somnolence or listlessness, anorexia, and abdominal pain. The main manifestation on gastroscopy is chronic gastritis, and most children may also have reflux esophagitis, bile reflux gastritis, and erosive gastritis. Mild chronic gastritis is the main pathological change of gastric mucosa.

Objective: A case-control study was adopted to investigate the efficacy and side effects of irinotecan combined with nedaplatin (NP) versus paclitaxel combined with cisplatin for locally advanced cervical cancer (CC) neoadjuvant chemotherapy (NACT) and to analyze the changes in tumor marker levels., Methods: A total of 96 patients with locally advanced CC who were treated from October 2019 to October 2021 were enrolled in our hospital as the research subjects, and their clinical data were collected for retrospective analysis and grouped according to their treatment regimens. Among them, 53 patients received paclitaxel combined with cisplatin as the control group, and the other 43 patients received irinotecan combined with NP as the observation group. The clinical effectiveness of neoadjuvant chemotherapy and alterations in tumor markers (CEA, AFP, CA125, and SCCA) were compared between the two groups. The incidence of common chemotherapy side effects was observed and compared between the two groups, including nausea and vomiting, abdominal pain and diarrhea, liver function impairment, bone marrow suppression, transient hyperglycemia, rash, ECG abnormalities, peripheral neurotoxicity, and muscle aches and pains., Results: The clinical efficiency of neoadjuvant chemotherapy was 97.67% in the observation group and 81.13% in the control group, with no statistically significant difference between the groups ( P > 0.05). There was no significant difference in CEA, AFP, and CA125 between the two groups before and after chemotherapy, but the decrease of SCCA before and after chemotherapy was statistically significant. There was no significant difference in the incidence of liver function damage, myelosuppression, abnormal ECG, and rash between the two groups ( P > 0.05). There are statistically significant differences in the incidence of nausea and vomiting, transient hyperglycemia, peripheral neurotoxicity, and muscle aches between the observation and control groups ( P < 0.05). The incidence of nausea and vomiting, transient hyperglycemia, peripheral neurotoxicity, and muscle aches was higher in the control group than in the observation group, with statistically significant differences ( P < 0.05). The difference in the incidence of diarrhea and abdominal pain between the observation group and the control group was statistically significant ( P < 0.05), and the incidence of diarrhea and abdominal pain in the observation group was higher than that in the control group., Conclusion: Irinotecan in combination with nedaplatin can be an effective neoadjuvant chemotherapy regimen for advanced localized cervical cancer, particularly in patients with combined diabetes., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yu Jiang et al.)

Background: Severe acute malnutrition (SAM) is defined as a weight-for-height < -3z scores of the median WHO growth standards, or visible severe wasting or the presence of nutritional edema. SAM related mortality rates in under-five children are well documented in Ethiopia but data on their predictors are limited. We aimed to document factors associated with SAM related mortality to inform better inpatient management., Methods: A facility-based retrospective cohort study was conducted among children admitted due to SAM at Pawe General Hospital, Northwest Ethiopia, from the 1st of January 2015 to the 31st of December 2019. Data from the records of SAM children were extracted using a standardized checklist. Epi-Data version 3.2 was used for data entry, and Stata version 14 was used for analysis. Bi-variable and multivariable Cox regression analyses were conducted to identify predictors of mortality. Variables with P<0.05 were considered significant predictors of mortality., Results: Five-hundred sixty-eight SAM cases were identified of mean age was 27.4 (SD± 16.5) months. The crude death rate was 91/568 (16.02%) and the mean time to death was determined as 13 (±8) days. Independent risk factors for death were: (i) vomiting AHR = 5.1 (1.35-21.1, p = 0.026), (ii) diarrhea AHR = 2.79 (1.46-5.4, p = 0.002), (iii) needing nasogastric therapy AHR = 3.22 (1.65-6.26, p = 0.001), (iv) anemia AHR = 1.89 (1.15-3.2, p = 0.012), and (v) being readmitted with SAM AHR = 1.7 (1.12-2.8, p = 0.037)., Conclusion: SAM mortality was high in under-five children in our setting. The identified risk factors should inform treatment and prevention strategies. Improved community health education should focus on healthy nutrition and seeking early treatment. Inpatient mortality may be reduced by stricter adherence to treatment guidelines and recognizing early the key risk factors for death., Competing Interests: The authors declare that there are no competing interests.

Introduction: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently described steroid-responsive meningoencephalomyelitis positive for cerebrospinal fluid (CSF) anti-GFAP antibody. Area postrema syndrome (APS) involves intractable hiccups, nausea, and vomiting, which is caused by medulla oblongata (MO) impairment. APS is a characteristic symptom of aquaporin-4 (AQP4) autoimmunity, and it helps to differentiate between AQP4 and GFAP autoimmunity. Conversely, although 6 cases of autoimmune GFAP astrocytopathy with APS and MO lesions have been reported, the association between GFAP autoimmunity and APS is unclear. We report the case of a patient with autoimmune GFAP astrocytopathy presenting with APS-like symptoms without MO lesions and discuss the mechanisms underlying the symptoms., Methods: CSF anti-GFAP antibody was detected using cell-based assays and immunohistochemical assays., Results: A 54-year-old Japanese man developed persistent hiccups, intermittent vomiting, fever, anorexia, and inattention. Brain magnetic resonance imaging (MRI) showed periventricular lesions with radial linear periventricular enhancement, suggesting autoimmune GFAP astrocytopathy. However, no obvious MO lesions were identified on thin-slice images. Spinal cord MRI revealed hazy lesions with patchy enhancement along the cervical and thoracic cord. CSF analysis demonstrated inflammation, with positive results for anti-GFAP antibodies. Anti-AQP4 antibodies in the serum and CSF were negative. Esophagogastroduodenoscopy revealed gastroparesis and gastroesophageal reflux disease, and vonoprazan, mosapride, and rikkunshito were effective only against persistent hiccups. Steroid therapy was initiated, allowing clinical and radiological improvements. Repeated MRIs demonstrated no obvious MO lesions., Conclusion: This report suggests that autoimmune GFAP astrocytopathy presents with APS-like symptoms without obvious MO lesions. The possible causes of hiccups were gastroparesis and cervical cord lesions. Gastroesophageal reflux disease was not considered a major cause of the hiccups. Intermittent vomiting appeared to be associated with gastroparesis, cervical cord lesions, and viral-like symptoms. Testing for anti-GFAP antibodies should be considered in patients with APS-like symptoms in the context of typical clinical-MRI features of autoimmune GFAP astrocytopathy., (© 2022 S. Karger AG, Basel.)

Purpose: Nausea and vomiting are the most painful and feared side effects for patients during chemotherapy. Currently, most studies focus on the occurrence of CINV during the risk phase. We initiated this real-world study to understand the actual occurrence of CINV throughout all phases, to provide a basis to prevent CINV in patients during chemotherapy and improve their quality of life., Methods: This prospective real-world study was conducted at 17 major cancer centers in Sichuan, China. Cancer patients who were about to receive moderately/highly emetogenic chemotherapy were included in the study. Occurrences of nausea and vomiting were recorded using patient diaries, and physicians are responsible for recording patient clinical data., Results: A total of 1,139 patients were included in this study between August 2018 and April 2019. In this study, the incidence of acute CINV was 55.3%, delayed CINV was 62.3%, and CINV beyond the risk period was 36%. All phases overall, the overall complete control (CC) rate of CINV was 30.1 and 32.1% for highly and moderately emetogenic chemotherapy regimens, respectively. The median CC time for CINV was 7 days, but only 21.5% of these patients used antiemetic regimens according to the NCCN guideline., Conclusion: In the real world, the incidence of CINV is high in patients receiving chemotherapy, and nausea and vomiting may occur beyond the risk period; the low level of standardized antiemetic treatment in compliance with the guideline might have been the main reason for unsatisfactory prevention and control of CINV in this study., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Coronavirus disease 2019 (COVID-19), which is caused by infection with SARS-CoV-2, presents with a broad constellation of both respiratory and nonrespiratory symptoms, although it is primarily considered a respiratory disease. Gastrointestinal symptoms-including nausea, abdominal pain, vomiting, and diarrhea-rank chief among these. When coupled with the presence of viral RNA in fecal samples, the presence of gastrointestinal symptoms raises relevant questions regarding whether SARS-CoV-2 can productively infect the upper or lower gastrointestinal tract. Despite the well-documented prevalence of gastrointestinal symptoms and the high rate of SARS-CoV-2 fecal RNA shedding, the biological, clinical, and epidemiological relevance of these findings is unclear. Furthermore, the isolation of replication-competent virus from fecal samples has not been reproducibly and rigorously demonstrated. Although SARS-CoV-2 shedding likely occurs in a high proportion of patients, gastrointestinal symptoms affect only a subset of individuals. Herein, we summarize what is known about gastrointestinal symptoms and fecal viral shedding in COVID-19, explore the role of the gut microbiome in other respiratory diseases, speculate on the role of the gut microbiota in COVID-19, and discuss potential future directions. Taking these concepts together, we propose that studying gut microbiota perturbations in COVID-19 will enhance our understanding of the symptomology and pathophysiology of this novel devastating disease., (© 2021 Brooks and Bhatt; Published by Cold Spring Harbor Laboratory Press.)

Aldosterone synthase deficiency (ASD) is a rare potentially life-threatening genetic disorder that usually presents during infancy due to pathogenic variants in the CYP11B2 gene. Knowledge about CYP11B2 variants in the Arab population is scarce. Here, we present and analyze five Palestinian patients and their different novel pathogenic variants. Data on clinical presentation, electrolytes, plasma renin activity, and steroid hormone levels of five patients diagnosed with ASD were summarized. Sequencing of the CYP11B2 gene exons was followed by evolutionary conservation analysis and structural modeling of the variants. All patients were from highly consanguineous Palestinian families. The patients presented at 1-4 months of age with recurrent vomiting, poor weight gain, hyponatremia, hyperkalemia, and low aldosterone levels. Genetic analysis of the CYP11B2 gene revealed three homozygous pathogenic variants: p.Ser344Profs*9, p.G452W in two patients from an extended family, and p.Q338stop. A previously described pathogenic variant was found in one patient: p.G288S. We described four different CYP11B2 gene pathogenic variants in a relatively small population. Our findings may contribute to the future early diagnosis and therapy for patients with ASD among Arab patients who present with failure to thrive and compatible electrolyte disturbances., (© 2021 Wiley Periodicals LLC.)

A systematic review was undertaken to describe dexamethasone doses studied for chemotherapy-induced vomiting (CIV) prophylaxis in pediatric patients and their effects on achieving complete acute CIV control. No dose-finding studies were identified. However, 16 studies assessing pediatric patients who received dexamethasone were included and classified according to the emetogenicity of chemotherapy administered. Eight different total daily dexamethasone doses were administered to patients on day 1 of highly emetogenic chemotherapy: three in conjunction with aprepitant/fosaprepitant plus a 5HT 3 antagonist and five in conjunction with a 5HT 3 antagonist. Five different total daily dexamethasone doses were administered in conjunction with a 5HT 3 antagonist to patients on day 1 of moderately emetogenic chemotherapy. Due to the heterogeneity of studies identified, meta-analysis was not possible. The optimal dexamethasone dose to control acute CIV and to minimize harms in pediatric patients remains uncertain. This is a key area for future research., (© 2020 Wiley Periodicals LLC.)

Although cannabinoid hyperemesis syndrome (CHS) was first reported more than 15 years ago, it still remains an unfamiliar clinical entity among physicians worldwide. CHS is categorized by Rome IV classification as a functional gastroduodenal disorder. It is characterized by stereotypical episodic vomiting in the setting of chronic, daily cannabis use, with cycles decreasing by the cessation of cannabis. CHS is also associated with abdominal pain reduced by hot baths and showers with comparative well-being between attacks. Thus, its clinical presentation resembles 'classic' cyclic vomiting syndrome, but eliciting a cannabis history is crucial in diagnosing this entity. In acute attacks, parenteral benzodiazepines are very effective. For prevention and long-term management, tricyclic antidepressants such as amitriptyline are the mainstay of therapy requiring doses in the range of 50-200 mg/d to achieve symptom control. In addition, counseling to achieve marijuana cessation, accompanied by antianxiety medications, is necessary for sustaining clinical outcomes. Once the patient is in remission and off marijuana for a period of 6-12 months, then tapering the dose of amitriptyline can be implemented, with the goal of no therapy being achieved in the majority of patients over time. With the legalization of marijuana in many states, CHS will become an increasingly prevalent clinical entity, so educating about CHS is an important goal, particularly for emergency department physicians who generally first encounter these patients., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Breakthrough chemotherapy-induced vomiting (CIV) is defined as CIV occurring after adequate antiemetic prophylaxis. Olanzapine and metoclopramide are two drugs recommended for the treatment of breakthrough CIV in children, without adequate evidence. We conducted an open-label, single-center, phase 3 randomized controlled trial comparing the safety and efficacy of olanzapine and metoclopramide for treating breakthrough CIV., Procedure: Children aged 5-18 years who developed breakthrough CIV after receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy were randomly assigned to the metoclopramide or olanzapine arm. The primary objective of the study was to compare the complete response (CR) rates between patients receiving olanzapine or metoclopramide for treating breakthrough CIV during 72 hours after the administration of the study drug. Secondary objectives were to compare CR rates for nausea and toxicities between the two arms., Results: Eighty patients were analyzed (39 in the olanzapine arm and 41 in the metoclopramide arm). CR rates were significantly higher in the olanzapine arm compared with the metoclopramide arm for vomiting (72% vs 39%, P = 0.003) and nausea (59% vs 34%, P = 0.026). Seven patients in the metoclopramide arm crossed over to the olanzapine arm and none crossed over in the olanzapine arm (P < 0.001). The mean nausea score in the olanzapine arm was significantly lower than the metoclopramide arm after the initiation of the rescue antiemetic (P = 0.01). Hyperglycemia and drowsiness were more commonly seen in the olanzapine arm., Conclusion: Olanzapine is superior to metoclopramide for the treatment of breakthrough CIV in children. Drowsiness and hyperglycemia need to be monitored closely in children receiving olanzapine for breakthrough CIV., (© 2020 Wiley Periodicals LLC.)

An increasing fraction of patients with metastatic cancer develop leptomeningeal dissemination of disease (LMD), and survival is dismal 1-3 . We conducted a single-arm, phase 2 study of pembrolizumab in patients with solid tumor malignancies and LMD (NCT02886585). Patients received 200 mg of pembrolizumab intravenously every 3 weeks until definitive progression or unacceptable toxicity. The primary endpoint was rate of overall survival at 3 months (OS3). Secondary objectives included toxicity, response rate and time to intracranial or extracranial disease progression. A Simon two-stage design was used to compare a null hypothesis OS3 of 18% against an alternative of 43%. Twenty patients-17 with breast cancer, two with lung cancer and one with ovarian cancer-were enrolled into the pre-specified evaluation group having received at least one dose of pembrolizumab. The median follow-up of surviving patients was 6.3 months (range, 2.2-12.5 months). The percentage of patients who experienced one (or more) grade 3 or higher adverse events at least possibly related to treatment was 40%, the most frequent being hyperglycemia (n = 6), nausea (n = 7) and vomiting (n = 7). The study met the primary endpoint, as 12 of 20 (OS3, 0.60; 90% confidence interval, 0.39-0.78) patients were alive at 3 months after enrollment. Pembrolizumab is safe and feasible and displays promising activity in patients with LMD. Further investigations are needed to identify which patients with LMD can benefit from pembrolizumab.

Purpose: To identify factors associated with chemotherapy-induced vomiting (CIV) control in pediatric patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC)., Materials and Methods: An individual, patient-level, pooled analysis was performed using data from five clinical trials of aprepitant or fosaprepitant in pediatric patients receiving HEC or MEC. The proportion of individuals who experienced no vomiting (complete CIV control) during the phase of interest was the primary study end point. The association of acute-phase complete CIV control (from first chemotherapy dose to 24 hours after the last chemotherapy dose of the chemotherapy block) with age, sex, race, cancer type, acute-phase duration, and antiemetic regimen was examined. Association of the same factors and acute-phase complete CIV control with complete CIV control in the delayed phase (end of acute phase until ≤ 96 hours later) was examined., Results: A total of 735 patients (mean age, 8.9 years; range, 0.3 to 17.9 years) were included in the acute-phase analysis. Acute-phase complete CIV control was less likely in older patients (relative risk [RR], 0.97 per year; 95% CI, 0.96 to 0.98 per year) and longer acute-phase duration (RR, 0.89 per day; 95% CI, 0.84 to 0.94 per day). Receipt of ondansetron plus aprepitant or fosaprepitant was associated with a higher likelihood of acute-phase complete CIV control versus ondansetron alone (RR, 1.28; 95% CI, 1.09 to 1.50). Delayed-phase complete CIV control was more likely in patients with acute-phase complete CIV control (RR, 1.19; 95% CI, 1.06 to 1.34) and in those who received aprepitant or fosaprepitant., Conclusion: Younger age, shorter acute-phase duration, and antiemetic regimen were associated with acute-phase complete CIV control in pediatric patients receiving HEC or MEC. Acute-phase complete CIV control and antiemetic regimen were associated with delayed-phase complete CIV control.

Purpose: The purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)-induced nausea and vomiting., Materials and Methods: Patients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by sex, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6., Results: A total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], -7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, -2.3%; 95% CI, -13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, -7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups., Conclusion: In all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

The functional abnormality of brain areas accounting for the migraine remains to be elucidated. Most related studies have used functional magnetic resonance imaging to investigate brain areas involved in migraine. However, the results are heterogeneous. In this study, we used a convenient tool to explore the brain regions involved in migraine. In this study, 40 children with migraine and 40 sex- and age-matched health controls were enrolled, and electroencephalogram was used to explore the functional abnormal areas of migraine through electroencephalogram bands and low-resolution electromagnetic tomography analysis. The results revealed that spectrum edge frequency 50 in all electroencephalogram channels in patients with migraine were lower than those in controls. Significant differences were discovered over frontal areas. In addition, significantly higher current density over the frontopolar prefrontal cortex and orbitofrontal cortex and higher connectivity over the left prefrontal cortex were observed in patients with migraine. We suggest that functional disturbance of the prefrontal cortex may play a potential role in children with migraine, and that low-resolution electromagnetic tomography is a reliable and convenient tool for studying the functional disturbance of migraine., (© 2020 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.)

Introduction: Chemotherapy-induced nausea and vomiting (CINV) is one of the scariest chemotherapy-induced adverse effects. We evaluated the adherence to the 2017 American Society of Clinical Oncology (ASCO), the latest guideline recommendations, for the management of acute CINV at our institute., Methods: During a 6-months cross-sectional study on outpatient's cancer patients, we collected data from the prescription documents during temporary hospitalization and compared the results with ASCO guideline recommendations., Results: The most prescribed prophylactic regimens for the management of CINV were combination of aprepitant, granisetron, and dexamethasone and metoclopramide (51.8%). Regarding prescription compatibility in our center with ASCO guideline recommnedations, selection of different regimens for prophylaxis of acute CINV in our institute was compliant in 0 %, 22%, 4%, and 40% of high, moderate, low, and minimal emetogenic potential of chemotherapy regimen groupss, respectively., Conclusion: Although our hospital is a referral and university-affiliated center, adherence to the ASCO guideline recommendations for prophylaxis of CINV was poor.

Nausea and vomiting are common symptoms in the hospital setting, with numerous causes. Common precipitants leading to or complicating inpatient hospital admissions include nausea and vomiting secondary to drugs, gastrointestinal disturbances, metabolic aberrancies, and vestibular pathologies. Appropriate selection and prescribing of antiemetic drugs is therefore important for healthcare professionals. There are numerous antiemetics available to physicians, ranging from muscarinic, dopaminergic and serotoninergic drugs, each acting on a different part of the nausea-vomiting cascade. This review describes the main pathophysiological processes involved in the development of symptomatic nausea and vomiting, and gives an overview of how common antiemetic drugs function to alleviate symptoms, alongside cautions and contraindications in their usage.

Purpose of Review: This review was undertaken to survey recent literature for research reports and comprehensive clinical reviews addressing the pharmacologic management of nausea and vomiting (N&V) in advanced cancer. The goal was to integrate findings in a comprehensive article that incorporates palliative care concepts into antiemetic treatment., Recent Findings: There are few published studies of N&V in advanced cancer; such research may be limited by the multicausal nature of N&V and participant burden to patients with life-limiting disease. Most articles are written by oncologists who also specialize in palliative care, and those addressing adverse effects of drugs used as antiemetics are found in other literature. Articles addressing more novel therapies, like cannabinoids and medical marijuana, are uncommon in the oncology literature. N&V in patients with progressive or advanced cancer is often multicausal. Nausea is more common and persistent, and even mild nausea is bothersome and may cause anxiety or depression. The mechanisms of nausea and vomiting overlap, but different neural pathways constitute the final pathway for each-the brainstem for vomiting and higher brain regions for nausea. Common causes of N&V in advanced cancer include constipation, opioids, and malignant bowel obstruction. About 40% have undetermined causes and may be exacerbated by impaired gastric emptying, chemical imbalances, or other factors. Several drugs that have antiemetic effects and act at different receptors are used to palliate N&V. There is a paucity of research that supports palliative antiemetic choices, and other research is needed to define potential therapeutic strategies that capitalize on differences between nausea and vomiting.

Purpose: The current work aimed to develop spray-dried silica xerogel nanoparticles (SXNs) as a gastroretentive carrier for the dual delivery of chlorambucil (CHL) and granisetron hydrochloride (GR). As a low-density system, it was proposed to float over gastric fluids; allowing for the retention of CHL in the acidic medium where it is more stable while ensuring the solubility of GR., Methods: Silica xerogels were developed by sol-gel process, using Tetraethyl orthosilicate (TEOS) water and acetic acid, followed by spray drying. SXNs were evaluated for particle size, zeta potential, entrapment efficiency (EE%), CHL and GR release after 1 hr (P 1h ) and after 8 hrs (P 8h ). The best achieved system (SXN4) was evaluated for morphology, pore diameter, total porosity, bulk density, wetting time, floating characteristics. Furthermore, the pharmacokinetics of the loaded drugs were evaluated in rats; relative to an aqueous CHL suspension containing GR., Results: SXN4 system had the highest desirability (0.69); showing spherical nanoparticles (181.63 nm), negative zeta potential (-5.18 mV), promising EE% of 59.39% and 73.94% (for CHL and GR, respectively) and sustained CHL and GR release profiles characterized by low P 1h (22.75% and 30.74%) and high P 8h (60.36% and 99.33%), respectively. It had a mean pore diameter of 8.622 nm, a total porosity of 62.27%, a bulk density of 0.605 g/mL, a wetting time of 292 sec, zero lag time and a floating duration of at least 8 h., Conclusion: The prolongation in the mean residence time (MRT (0-∞) ) and the promotion of the relative oral bioavailabilities of both drugs could unravel the potential of this system for the management of chemotherapy-induced nausea and vomiting., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Ghoneim et al.)

Background: The phase III TRIBE and TRIBE2 studies randomized metastatic colorectal cancer patients to first-line FOLFOXIRI/bevacizumab or a doublet (FOLFIRI or FOLFOX)/bevacizumab. The studies demonstrated a significant benefit from the triplet at the price of an increased incidence of chemotherapy-related adverse events (AEs). In both trials, males and females aged between 18 and 70 years with ECOG PS ≤2 and between 71 and 75 years with ECOG PS = 0 were eligible. We investigated the effect of FOLFOXIRI/bevacizumab versus doublets/bevacizumab according to age and gender., Patients and Methods: Subgroup analyses according to age (<70 versus 70-75 years) and gender were carried out for overall response rate (ORR), progression-free survival (PFS), and AE rates., Results: Of 1187 patients, 1005 (85%) were aged <70 years and 182 (15%) 70-75 years; 693 (58%) were males and 494 (42%) females. There was no evidence of interaction between age or gender and the benefit provided by the intensification of the upfront chemotherapy in terms of ORR and PFS, or the increased risk of experiencing G3/4 AEs. Elderly patients and females experienced higher rates of overall G3/4 AEs (73% versus 60%, P < 0.01 and 69% versus 57%, P < 0.01, respectively). Notably, in the FOLFOXIRI/bevacizumab subgroup, G3/4 diarrhea and febrile neutropenia occurred in 27% and 16% of elderly patients, respectively, while females reported high incidences of any grade nausea (67%) and vomiting (50%)., Conclusions: The improvements in terms of ORR and PFS of FOLFOXIRI/bevacizumab versus doublets/bevacizumab are independent of gender and age, with a similar relative increase in AEs among elderly patients and females. Initial dose reductions and possibly primary G-CSF prophylaxis should be recommended for patients between 70 and 75 years old treated with FOLFOXIRI/bevacizumab, and a careful management of antiemetic prophylaxis should be considered among females., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To assess the safety and efficacy of combined neurokinin-1 antagonist aprepitant treatment for multiple-day anthracycline chemotherapy-induced nausea and vomiting., Methods: One hundred patients with breast cancer from department of Medical Oncology of Ordos Central Hospital from June 2015 to February 2018 were selected and randomize subdivided into 2 groups. All cases received anthracycline (30 mg/m 2 /d for pirarubicin or 45 mg/m 2 /d for epirubicin) and cyclophosphamide adjuvant chemotherapy, along with either the standard therapy (dexamethasone and tropisetron) or the combined aprepitant therapy (aprepitant plus dexamethasone and tropisetron). The results of the observation between groups were presented by complete response in the overall phase (OP, 0-120 hours), acute phase (AP, 0-24 hours) and delay phase (DP, 25-120 hours). The Kaplan-Meier curves were plotted to exhibit the first time of vomiting, Functional Living Index-Emesis of patients' quality of life, and therapy-related adverse effects (AEs)., Results: The complete response of OP, AP, and DP were statistically different between aprepitant group and standard group (80.0% vs 48%, P = 0.001; 92.0% vs 74%, P = 0.017; 80.0% vs 48%, P = 0.001). The aprepitant group held a longer time reaching the first emesis after the relevant treatment than the standard group. The Functional Living Index-Emesis increased significantly in the aprepitant group compared with the standard group (24% vs 8.3%, P = 0.029). Fatigue and constipation were the only AEs of aprepitant, since no significant differences were observed in fatigue between the 2 groups (72% vs 70%, P = 0.826), while the incidence of constipation of aprepitant group was higher than the standard group (48% vs 28%, P = 0.039)., Conclusion: Combined aprepitant therapy is efficient and safe in the multiple-day anthracycline chemotherapy-induced nausea and vomiting control and is recommended for the clinical use., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Gemcitabine plus cisplatin (GC) is the standard treatment of advanced biliary tract cancer (BTC); however, it causes nausea, vomiting, and anorexia, and requires hydration. Gemcitabine plus S-1 (GS) reportedly has equal to, or better, efficacy and an acceptable toxicity profile. We aimed to confirm the non-inferiority of GS to GC for patients with advanced/recurrent BTC in terms of overall survival (OS)., Patients and Methods: We undertook a phase III randomized trial in 33 institutions in Japan. Eligibility criteria included chemotherapy-naïve patients with recurrent or unresectable BTC, an Eastern Cooperative Oncology Group Performance Status of 0 - 1, and adequate organ function. The calculated sample size was 350 with a one-sided α of 5%, a power of 80%, and non-inferiority margin hazard ratio (HR) of 1.155. The primary end point was OS, while the secondary end points included progression-free survival (PFS), response rate (RR), adverse events (AEs), and clinically significant AEs defined as grade ≥2 fatigue, anorexia, nausea, vomiting, oral mucositis, or diarrhea., Results: Between May 2013 and March 2016, 354 patients were enrolled. GS was found to be non-inferior to GC [median OS: 13.4 months with GC and 15.1 months with GS, HR, 0.945; 90% confidence interval (CI), 0.78-1.15; P = 0.046 for non-inferiority]. The median PFS was 5.8 months with GC and 6.8 months with GS (HR 0.86; 95% CI 0.70-1.07). The RR was 32.4% with GC and 29.8% with GS. Both treatments were generally well-tolerated. Clinically significant AEs were observed in 35.1% of patients in the GC arm and 29.9% in the GS arm., Conclusions: GS, which does not require hydration, should be considered a new, convenient standard of care option for patients with advanced/recurrent BTC., Clinical Trial Number: This trial has been registered with the UMIN Clinical Trials Registry (http://www.umin.ac.jp/ctr/index.htm), number UMIN000010667., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose of Review: Chemotherapy-induced nausea and vomiting (CINV) is a common cause of acute morbidity that impacts quality of life in children receiving cancer treatment. Here, we review the evolution of CINV prophylaxis guidelines in children, with an emphasis on the literature published in the last 5 years, to bring the reader up to date., Recent Findings: Recent studies have led to the adoption of the "triple therapy" regimen of antiemetic prophylaxis (a 5-HT3 antagonist, dexamethasone, and a neurokinin-1 antagonist) as the backbone of recommendations for the prevention of CINV in children. Areas of new data include the addition of aprepitant and inclusion of palonosetron as a non-inferior 5-HT3 antagonist. In addition, there are emerging pediatric data informing patient-derived risk factors associated with CINV risk and classification of antineoplastic drugs based on emetogenicity. Several recent pediatric studies have shaped published guidelines for CINV prophylaxis in children.

Background/aim: Risk factors for chemotherapy-induced nausea and vomiting (CINV) with anthracycline-containing regimen for breast cancer patients remain unknown. The risk factors for CINV with FEC100 were investigated., Patients and Methods: Data on CINV events and patient backgrounds of 180 patients were collected from the first cycle of FEC100 treatment. In this regimen, patients were administered various antiemetics (ADs). The combinations of ADs were classified into four categories, while body mass index (BMI) was stratified into three categories. Risk factors were selected based on patient characteristics and combination of ADs. Risks for CINV were analyzed by univariate and multivariate analyses., Results: In the univariate analysis of nausea, BMI was a significant factor, while BMI and combination of ADs were significant in vomiting. In the multivariate analysis concerning nausea, BMI was a significant factor. In the analysis concerning vomiting, the combination of ADs and BMI were significant., Conclusion: BMI was the most important risk factor for nausea and vomiting, while the combination of ADs was for vomiting., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Treatments for controlling delayed nausea after chemotherapy are inadequate, potentially inciting malnutrition. We sought to determine the incidence of nausea, anorexia, and food intake after chemotherapy., Patients and Methods: Subjects were females with gynecological cancers who underwent chemotherapy between 2008 and 2013. Nausea, anorexia, and food intake in the acute (day 1) and delayed phases (days 2 and 3) were retrospectively evaluated., Results: Subjects included 156 females. Chemotherapies were highly (HEC; n=24) and moderately emetogenic (MEC; n=132). There were no significant between-group differences for anorexia control during either the acute or the delayed phase and both groups demonstrated significantly worse control of nausea during the delayed phase. In the HEC group, food intake was significantly reduced on days 2 and 3 compared with day 1., Conclusion: Rates of nausea, anorexia, and food intake significantly worsened over time, particularly in the MEC group. Current supportive therapies appear inadequate and should be improved., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Medical marijuana (MM) is widespread in many medical fields, including oncology, with limited use in pediatric oncology where research is scarce and often shows conflicting results. This research focuses on alleviating side effects of anticancer treatment as an integral part of supportive and palliative care of children with cancer. We report our experience with MM treatment in 50 children, adolescents, and young adults with different types of cancer during 2010-2017. The main indications for prescriptions were nausea and vomiting, decreased mood, disturbed sleep, and pain. The medication was supplied to 30 patients via oil drops (60%) and 11 via smoking (22%), followed by vaporization, capsules, or combinations of various routes. Positive effects were reported by verbal children and parents in 80% of cases. MM was generally well tolerated with few patients reporting toxicity, with the most common adverse reactions being burning in the throat and anxiety attacks in subjects who chose to smoke the product. We conclude that MM may serve as a potentially useful complementary therapy to conventional supportive treatment of children suffering from cancer at the end of life. Further research is needed on the safety and efficacy and the consequences of prolonged use in pediatric populations.

Objective: To investigate the effects of the Chinese herbal medicine Xiaoaiping to treat chemotherapy-induced side effects in breast cancer patients., Methods: Ninety-three adult patients who attended our hospital and met the entry criteria from January 2016 to December 2017 were included. Patients were randomly divided into the control group (routine chemotherapy only) and the combined group (routine chemotherapy and Xiaoaiping). Demographic data and clinical variables were collected, and side effects including alopecia, nausea and vomiting, diarrhea, white blood cell (WBC) count, aspartate aminotransferase (AST) levels, and the quality of life were evaluated., Results: Basic clinical characteristics were not different between the groups. There were significantly fewer patients with alopecia grade 3-4, but significantly more patients with alopecia grade 1-2, in the combined group compared with the control group. Disease-free time for alopecia was longer in the combined compared with the control group. Overall, the side effects were significantly more serious in the control compared with the combined group. Patients in the combined group had better quality of life than the control patients., Conclusion: Xiaoaiping can improve alopecia, nausea and vomiting, and diarrhea symptoms, WBC count, AST levels, and the quality of life in breast cancer patients.

Purpose: To explore efficacy of short-course olanzapine with or without low-dose dexamethasone for prevention of delayed emesis in gynecologic cancer patients receiving carboplatin/paclitaxel., Methods: This was a prospective study in 81 chemo-naive patients receiving 0.25 mg intravenous palonosetron, 16 mg dexamethasone, and 10 mg oral olanzapine before chemotherapy. On days 2 and 3, patients randomly received 10 mg olanzapine (arm A; n=27), 10 mg olanzapine plus 4 mg dexamethasone (arm B; n=27), or 8 mg dexamethasone (reference arm C; n=27). The primary endpoint was total control (TC; no vomiting, no rescue antiemetics, and no nausea) on days 2-5, using a diary. Secondary endpoints included proportion of patients with no emesis impact on daily life using the Functional Living Index-Emesis (FLIE) questionnaire, and patient's satisfaction with antiemetic coverage., Results: Fifty-two percent of patients in arm A ( P =0.406), 59% in arm B ( P =0.779), and 67% in arm C had a delayed TC. Secondary analyses showed no significant difference across arms in any efficacy endpoint. FLIE scores as well as mean satisfaction scores were similar across arms., Conclusions: In this exploratory study with a small sample size, we did not find any clue about better control of delayed emesis with either olanzapine regimen in gynecologic cancer patients treated with carboplatin/paclitaxel and receiving the same prophylaxis for acute emesis.

Competing Interests: Competing interests: None declared.

Introduction: The area postrema in the caudal fourth ventricular floor is highly vascular without blood-brain or blood-cerebrospinal fluid barrier. In addition to its function as vomiting center, several others are part of the circumventricular organs for vasomotor/angiotensin II regulation, role in neuromyelitis optica related to aquaporin-4, and somatic growth and appetite regulation. Functions are immature at birth. The purpose was to demonstrate neuronal, synaptic, glial, or ependymal maturation in the area postrema of normal fetuses. We describe three area postrema tumors., Methods: Sections of caudal fourth ventricle of 12 normal human fetal brains at autopsy aged six to 40 weeks and three infants aged three to 18 months were examined. Immunocytochemical neuronal and glial markers were applied to paraffin sections. Two infants with area postrema tumors and another with neurocutaneous melanocytosis and pernicious vomiting also studied., Results: Area postrema neurons exhibited cytologic maturity and synaptic circuitry by 14 weeks'. Astrocytes coexpressed vimentin, glial fibrillary acidic protein, and S-100β protein. The ependyma is thin over area postrema, with fetal ependymocytic basal processes. A glial layer separates area postrema from medullary tegmentum. Melanocytes infiltrated area postrema in the toddler with pernicious vomiting; two children had primary area postrema pilocytic astrocytomas., Conclusions: Although area postrema is cytologically mature by 14 weeks, growth increases and functions mature during postnatal months. We recommend neuroimaging for patients with unexplained vomiting and that area postrema neuropathology includes synaptophysin and microtubule-associated protein-2 in patients with suspected dysfunction., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background/aim: The control of chemotherapy-induced nausea and vomiting during bleomycin, etoposide, and cisplatin (BEP) treatment is important for maintaining treatment intensity. The effects of palonosetron and granisetron were compared in BEP chemotherapy., Patients and Methods: The administration of palonosetron on days 1 and 5 (Pal method) and granisetron daily (days 1-5, Gra method) were compared in terms of their efficacy and cost-effectiveness., Results: Additional rescue antiemetic agents were used in 15 of 32 and 30 of 30 cycles in the Pal and Gra method groups, respectively (p<0.05). The complete response rate, defined as no vomiting and no rescue agent usage, in each cycle, was 50% and 0% in the Pal and Gra method groups, respectively (p<0.05). The average cost of antiemetic agents in a cycle was 50,759 and 54,555 yen in the Pal and Gra method groups, respectively (p<0.05)., Conclusion: The Pal method may be the standard method in BEP., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

A newborn girl presented within the first 24 hours after birth with a distended abdomen and bilious vomiting. These symptoms resolved spontaneously after a contrast enema, which showed obstruction of the left colon. This finding and the fact that the mother had been diagnosed with gestational diabetes mellitus led to the diagnosis of neonatal small left colon syndrome.

Background/aim: The incidence of delayed chemotherapy-induced nausea and vomiting (CINV), especially nausea, in gynecologic cancer patients who receive paclitaxel and carboplatin (TC) chemotherapy is unclear. We assessed risk factors for delayed CINV in these patients, and examined whether it was controlled with combination antiemetic therapy., Materials and Methods: Data were pooled from two prospective studies, and compared between the two antiemetic prophylaxis groups using inverse probability of treatment weighted (IPTW) analysis., Results: Among the 182 evaluable patients (mean age: 56.2 years), three antiemetics gave better overall control than two for delayed nausea (42.9% vs. 57.4%,) and vomiting (13.8% vs. 34.5%). Risk factor for delayed nausea was age [odds ratio (OR)=0.953; p=0.0898[and use of two antiemetics (vs. three antiemetics) for delayed vomiting (OR=0.304; p=0.0732)., Conclusion: A combination of three antiemetics controls delayed CINV among patients who undergo TC chemotherapy. Identification of risk factors can facilitate personalized treatments., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The aim of this study was to evaluate whether aprepitant is an effective antiemetic when combined with 5-hydroxytryptamine 3-(5-HT3) receptor antagonists and dexamethasone in patients with breast cancer receiving anthracycline-based chemotherapy., Patients and Methods: A retrospective study was carried out on 229 patients with breast cancer between 2004 and 2014. All the patients received three cycles of cyclophosphamide, epirubicin and 5-fluorouracil. 5-HT3 receptor antagonists and dexamethasone were used in 132 patients (cohort 1). 5-HT3 receptor antagonists, dexamethasone and aprepitant were used in 97 patients (cohort 2). The primary outcome was to compare the grades of emesis between cohorts 1 and 2., Results: The incidence of moderate and severe nausea was significantly lower in cohort 2 than in cohort 1 (p<0.05) during all three cycles. Additionally, the complete response rate (i.e. no nausea) was higher in cohort 2 (p<0.05)., Conclusion: The combination of 5-HT3 receptor antagonists, dexamethasone and aprepitant was more effective as an antiemetic treatment than the standard dual combination of 5-HT3 receptor antagonists and dexamethasone for patients with breast cancer receiving anthracycline-based adjuvant chemotherapy., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To assess the emetogenic potential of different chemotherapy (CT) regimens in daily clinical practice in an outpatient setting. To optimize antiemetic prophylaxis if necessary METHODS: Prospective and retrospective review of the emetogenic potential of CT regimens used in adult patients in an outpatient setting RESULTS: We assess the chemotherapy-induced nausea and vomiting (CINV) of 50 different CT regimens used on 157 different patients in an outpatient setting. We found that the CT usually classified as highly emetogenic, including cisplatin and anthracycline-cyclophosphamide combination, had the higher incidence of CINV (37.5 and 54.4% respectively). The antineoplastic drugs usually considered to be moderately emetogenic had, as expected, lower rates of emesis with the exception of irinotecan, which presented a pattern of nausea and/or vomiting (NV) similar to the highly emetogenic CT with a global incidence of 48.5%. The appearance of emetic symptoms had impact on quality of life in 70% of the patients, with nausea being the main emetic symptom., Conclusion: Antiemetic prophylaxis for highly emetogenic CT could be improve. Irinotecan CT regimens have a high emetogenic potential more than moderate and require more intensive antiemetic prophylaxis too.

Cases of vomiting and diarrhoea were reported in racing pigeons in Western Australia in May, 2016. Morbidity and mortality rates were high. Similar clinical disease was seen in Victoria in December and by early 2017 had been reported in all states except the Northern Territory, in different classes of domestic pigeon-racing, fancy and meat bird-and in a flock of feral pigeons. Autopsy findings were frequently unremarkable; histological examination demonstrated significant hepatic necrosis as the major and consistent lesion, often with minimal inflammatory infiltration. Negative contrast tissue suspension and thin section transmission electron microscopy of liver demonstrated virus particles consistent with a member of the Reoviridae. Inoculation of trypsin-treated Vero, MDBK and MA-104 cell lines resulted in cytopathic changes at two days after infection. Next generation sequencing was undertaken using fresh liver samples and a previously undescribed group A rotavirus (genotype G18P[17]) of avian origin was identified and the virus was isolated in several cell lines. A q-RT-PCR assay was developed and used to screen a wider range of samples, including recovered birds. Episodes of disease have continued to occur and to reoccur in previously recovered lofts, with variable virulence reported. This is the first report of a rotavirus associated with hepatic necrosis in any avian species., Competing Interests: The authors have declared that no competing interests exist.

Ca 2+ plays a major role in maintaining cellular homeostasis and regulates processes including apoptotic cell death and side-effects of cancer chemotherapy including vomiting. Currently we explored the emetic mechanisms of FPL64176, an L-type Ca 2+ channel (LTCC) agonist with maximal emetogenic effect at its 10 mg/kg dose. FPL64176 evoked c-Fos immunoreactivity in shrew brainstem sections containing the vomit-associated nuclei, nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus. FPL64176 also increased phosphorylation of proteins ERK1/2, PKCα/βII and Akt in the brainstem. Moreover, their corresponding inhibitors (PD98059, GF 109203X and LY294002, respectively) reduced FPL64176-evoked vomiting. A 30 min subcutaneous (s.c.) pretreatment with the LTCC antagonist nifedipine (10 mg/kg) abolished FPL64176-elicited vomiting, c-Fos expression, and emetic effector phosphorylation. Ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP 3 Rs) mediate intracellular Ca 2+ release from the sarcoplasmic/endoplasmic reticulum. The RyR antagonist dantrolene (i.p.), or a combination of low doses of nifedipine and dantrolene, but not the IP 3 R antagonist 2-APB, significantly attenuated FPL64176-induced vomiting. The serotonin type 3 receptor (5-HT 3 R) antagonist palonosetron (s.c.), the neurokinin 1 receptor (NK 1 R) antagonist netupitant (i.p.) or a combination of non-effective doses of netupitant and palonosetron showed antiemetic potential against FPL64176-evoked vomiting. Serotonin (5-HT) and substance P immunostaining revealed FPL64176-induced emesis was accompanied by an increase in 5-HT but not SP-immunoreactivity in the dorsomedial subdivision of the NTS. These findings demonstrate that Ca 2+ mobilization through LTCCs and RyRs, and subsequent emetic effector phosphorylation and 5-HT release play important roles in FPL64176-induced emesis which can be prevented by 5-HT 3 R and NK 1 R antagonists., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is a distressing adverse effect. Neurokinin-1 receptor antagonist (NK1RA)-containing regimens are the standard regimens for CINV prophylaxis in patients with cancer receiving highly or moderately emetogenic chemotherapy (HEC or MEC). NK1RA agents are expensive and were not registered in Sudan. Recently, regimens containing olanzapine, the available and affordable medication in Sudan, were introduced as another option. This study aimed to compare the efficacy of an olanzapine-containing regimen with the antiemetic regimen that was currently used in our institute for CINV prophylaxis in HEC/MEC settings., Patients and Methods: The study prospectively compared an olanzapine-containing regimen (acute phase: olanzapine, ondansetron, dexamethasone; delayed phase: olanzapine, ondansetron) with an ondansetron/dexamethasone regimen (acute phase: ondansetron, dexamethasone; delayed phase: ondansetron) in adult patients with cancer receiving HEC or MEC. The study outcomes were complete response (CR; no emesis and no rescue medications) and nausea control (no nausea), which were assessed in the acute (0 to 24 hours), delayed (24 to 120 hours), and overall (0 to 120 hours) phases., Results: The study included 131 patients (olanzapine-containing: 50 patients; ondansetron/dexamethasone: 81 patients). CR and nausea control were higher in the olanzapine-containing than in the ondansetron/dexamethasone regimen (CR: acute phase, 86% v 71.6%; P = .086; delayed phase, 72% v 30.9%; P < .001; overall phase, 66% v 25.9%; P < .001; nausea control: acute phase, 86% v 74.1%; P = .127; delayed phase, 76% v 34.6%; P < .001; overall phase, 72% v 29.6%; P < .001). The major toxicity of olanzapine was grade 1 and 2 sedation or drowsiness (25 patients)., Conclusion: An olanzapine-containing regimen has better efficacy for prevention of CINV in the HEC/MEC setting. Oncologists working in a limited-resource setting should be familiar with olanzapine-containing regimens, because NK1RA agents are not affordable and not easily available.

Aim: We compare neurokinin-1 receptor antagonist (NK-1RA)-based triple regimen and conventional duplex regimen for antiemetic efficacy for patients with moderately emetogenic chemotherapy (MEC). Patients & methods: Pooled risk ratios (RRs) were used to evaluate the complete response and no significant nausea. The results were separately analyzed for pure MEC regimens, carboplatin-based regimens and oxaliplatin-based regimens., Results: Ten trials focused on MEC involving 2928 cancer patients using NK-1RA triple regimens or conventional duplex regimen were included. NK-1RA-based triple regimen showed significant better complete responses in overall (RR: 1.14; 95% CI: 1.05-1.24), acute (RR: 1.02; 95% CI: 1.00-1.04) and delayed (RR: 1.13; 95% CI: 1.04-1.23) phase compared with duplex regimen in patients with MEC. Similar results were found for no significant nausea. Subgroup analyses showed that triple regimen showed superior antiemetic efficacy significantly in patients with carboplatin-based chemotherapy, instead of oxaliplatin-based chemotherapy., Conclusion: NK-1RA is recommended to use in carboplatin-based chemotherapy, not oxaliplatin-based chemotherapy.

Objective To investigate the effects of polaprezinc (PZ) on cyclophosphamide (CTX)- or cisplatin (DDP)-induced gastric mucosal injury and on a rat model of neurotransmitter-mediated vomiting. Methods Sprague-Dawley rats were divided at random into Control, CTX, DDP, PZ+CTX, and PZ+DDP groups. After 20 days, brain tissues and sera were analyzed for the levels of dopamine (DA), 5-hydroxytryptamine (5-HT), and nuclear factor kappa B (NF-κB). Hematoxylin and eosin-stained sections of stomach, intestine, and brain tissues were examined using light microscopy. Results The levels of DA, 5-HT, and NF-κB in brain and serum samples of rats treated with CTX or DDP were significantly increased compared with those of rats in the Control group. There was a significant decrease in these values in the PZ group. Moreover, PZ reduced damage to brain tissue caused by CTX or DDP. Conclusions PZ decreased the levels of DA, 5-HT, and NF-κB in blood and brain tissues caused by CTX or DDP and reduced the chemotherapy-induced damage to the small intestine, stomach, and brain. These findings can be translated to the clinic to enhance the efficacy and safety of chemotherapy.

Background: This study assessed the association between severe NVP and the risk of NTD in offspring compared with a population and a malformed control group. We also assessed whether folic acid supplements modified this association., Study Design and Setting: A case-control study was conducted with subjects enrolled from June 19, 2002, to November 18, 2014, from a population-based birth defects surveillance system that monitors major external structural birth defects through active case ascertainment in Shanxi Province, China. The main comparison was between women with NTD-affected offspring who experienced NVP in early pregnancy versus those who did not. A multivariable logistic regression model was used to examine the associations between severe NVP and the risk of NTD while adjusting for potential confounding factors. The risk was estimated by calculating the odds ratio (OR) and 95% confidence intervals (CIs)., Results: The adjusted OR (AOR) of severe NVP for NTDs was 3.25 (95%CI 2.56, 4.12) compared with the population control, and 1.65 (95%CI 1.00, 2.72) compared with the malformed controls. When stratified by intake of folic acid supplements, the AOR for severe NVP was 3.40 (95%CI 2.61, 4.42) in the non-intake of folic acid supplements stratum and 2.51 (95%CI 1.42, 4.43) in the intake of folic acid supplements stratum., Conclusion: We conclude that severe NVP is associated with NTDs, and that severe NVP may be a consequence, rather than a cause, of NTDs., (© 2017 Wiley Periodicals, Inc.)

Chemotherapy-induced nausea and vomiting (CINV) remains a challenge in cancer care. Improved understanding of CINV pathophysiology has triggered the development of new antiemetic therapeutic options, such as selective neurokinin-1 (NK 1 ) receptor antagonists (RAs), which effectively prevent CINV when added to a standard antiemetic regimen (serotonin-3 RA and dexamethasone). Aprepitant and its water-soluble prodrug, fosaprepitant dimeglumine, are the most widely used NK 1 RAs, with extensive clinical use worldwide. Recently, a Phase III trial prospectively evaluated fosaprepitant-based antiemetic therapy for CINV prevention in a large, well-defined nonanthracycline- and cyclophosphamide-based moderately emetogenic chemotherapy population. Fosaprepitant demonstrated significantly improved efficacy outcomes compared with a control regimen and was generally well tolerated, indicating that NK 1 RAs are a valuable therapeutic option in this setting.

Background: To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone-induced hiccup (DIH) in cancer patients treated with chemotherapy., Materials and Methods: Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone ( n  = 33) or methylprednisolone ( n  = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups., Results: No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group ( p  = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p  < .001). At the crossover phase, hiccup intensity was further decreased after the rotation of dexamethasone to methylprednisolone in the dexamethasone group (mean NRS, 3.5 to 0.9, p  < .001), while it was increased by rotating methylprednisolone to dexamethasone in the methylprednisolone group (mean NRS, 1.4 to 3.3, p  = .025). There were no differences in emesis intensity between the two groups at either the randomization or crossover phases. Clinicaltrials.gov identifier: NCT01974024., Conclusion: Dexamethasone-induced hiccup is a male-predominant phenomenon that can be ameliorated by rotating dexamethasone to methylprednisolone without compromising the antiemetic efficacy., Implications for Practice: In this randomized, multicenter, phase III trial, hiccup intensity was significantly lower when the antiemetic corticosteroid was rotated from dexamethasone to methylprednisolone without a change in emesis intensity than that when dexamethasone was maintained. At the crossover phase, hiccup intensity was increased again if dexamethasone was readministered instead of methylprednisolone. The present study demonstrated that dexamethasone-induced hiccup can be improved by rotating from dexamethasone to methylprednisolone without compromising its antiemetic efficacy., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2017.)

As neonates are brought to the emergency department (ED) for various complaints, it is challenging for emergency physicians to clinically determine the urgency of the visit. We sought to explore clinical characteristics associated with urgent visits to the ED. We conducted a retrospective study by reviewing medical records of neonatal visits to a tertiary pediatric regional emergency center for 5 years. Cases of patients who were discharged after checking only chest or abdominal X-ray or discharged without workup, were classified as non-urgent visits. Cases where more examinations were performed, or when the patient was hospitalized, were classified as urgent visits. Various clinical features and process in the ED were compared between the groups. Of the 1,008 cases enrolled in this study, 856 (84.9%) were urgent and 152 (15.1%) were non-urgent visits. After adjustment by multiple logistic regression analysis, non-urgent visits were associated with self-referrals rather than physician-referrals (odds ratio [OR], 5.96), visits in the evening rather than at night or daytime (OR, 2.51), patient visits from home rather than from medical facilities (OR, 2.19; 95). Fever and jaundice were the most common complaints (25.7% and 24.5%, respectively), and their OR of non-urgent visit was relatively low (adjusted OR 0.03 and 0.03, respectively). However, other common complaints, such as vomiting and cough (7.4% and 7.1%, respectively), were more likely to be non-urgent visits (adjusted OR 2.96 and 9.83, respectively). For suspected non-urgent visits, emergency physicians need to try to reduce unnecessary workup and shorten length of stay in ED., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2017 The Korean Academy of Medical Sciences.)