A novel pilot study to evaluate the efficacy and safety of a wireless patch system in patients with chronic nausea and vomiting.

BACKGROUND: Gastric sensorimotor disorders (functional dyspepsia [FD] and gastroparesis [GP]) are prevalent and burdensome. Prolonged ambulatory recording using a wireless patch may provide novel information in these patients. METHODS: Consecutive adult patients (age ≥ 18 years) referred for gastric emptying scintigraphy (GES) were eligible for study inclusion. Patients were excluded if they had prior foregut surgery; were taking opioids or other medications known to affect gastric emptying; had a HgbA1C > 10; or were recently hospitalized. Three wireless motility patches were applied to the skin prior to GES. Patients wore the patches for 6 days while recording meals, symptoms, and bowel movements using an iPhone app. KEY RESULTS: Twenty-three consecutive adults (87% women; mean age = 43.9 years; mean BMI = 26.7 kg/m2) were enrolled. A gastric histogram revealed three levels of gastric myoelectric activity: weak, moderate, and strong. Patients with delayed gastric emptying at 4 h had weak gastric myoelectrical activity. Patients with nausea and vomiting had strong intestinal activity. Those with FD had weak gastric and intestinal myoelectric activity, and a weak meal response in the stomach, intestine, and colon compared to those with nausea alone or vomiting alone. CONCLUSIONS AND INFERENCES: Patients with FD, and those with delayed gastric emptying, had unique gastrointestinal myoelectrical activity patterns. Reduced postprandial pan-intestinal myoelectric activity may explain the symptoms of FD in some patients. Recording gastrointestinal activity over a prolonged period in the outpatient setting has the potential to identify unique pathophysiologic patterns and meal-related activity that distinguishes patients with distinct gastric sensorimotor disease states.

Clinical characteristics and outcomes of children with COVID-19 in Saudi Arabia.

OBJECTIVES: To determine the demographic and clinical characteristics, underlying comorbidities, and outcomes of children with coronavirus disease 2019 (COVID-19) infection. METHODS: In this retrospective study, we reported 62 pediatric patients (age <14 years) with confirmed COVID-19 between March 2 and July 1, 2020, at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. RESULTS: Comorbid conditions, including cardiac, neurological, respiratory, and malignant disorders, were reported in 9 patients (14.5%). The most prominent presenting complaints were fever (80.6%) and cough (48.4%). Most of our patients (80.6%) had mild disease, 11.3% had moderate disease, and 8.1% exhibited severe and critical illness. Twenty-one patients (33.9%) were hospitalized, with 4 patients (6.5%) admitted to the pediatric intensive care unit, and 3 (4.8%) patients died. CONCLUSION: All pediatric age groups are susceptible to COVID-19, with no gender difference. COVID-19 infection may result in critical illness and even mortality in subsets of pediatric patients.

Central and peripheral emetic loci contribute to vomiting evoked by the Akt inhibitor MK-2206 in the least shrew model of emesis.

Akt (protein kinase B) signaling is frequently activated in diverse cancers. Akt inhibitors such as perifosine and MK-2206 have been evaluated as potential cancer chemotherapeutics. Although both drugs are generally well tolerated, among their most common side-effects vomiting is a major concern. Here we investigated whether these Akt inhibitors evoke emesis in the least shrew model of vomiting. Indeed, both perifosine and MK-2206 induced vomiting with maximal efficacies of 90% at 50 mg/kg (i.p.) and 100% at 10 mg/kg (i.p.), respectively. MK-2206 (10 mg/kg, i.p.) increased c-Fos immunoreactivity both centrally in the shrew brainstem dorsal vagal complex (DVC) emetic nuclei, and peripherally in the jejunum. MK-2206 also evoked phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in both the DVC emetic nuclei and the enteric nervous system in the jejunum. The ERK1/2 inhibitor U0126 suppressed MK-2206-induced emesis dose-dependently. We then evaluated the suppressive efficacy of diverse antiemetics against MK-2206-evoked vomiting including antagonists/inhibitors of the: L-type Ca2+ channel (nifedipine at 2.5 mg/kg, subcutaneously (s.c.)); glycogen synthase kinase 3 (GSK-3) (AR-A014418 at 10 mg/kg and SB216763 at 0.25 mg/kg, i.p.); 5-hydroxytryptamine 5-HT3 receptor (palonosetron at 0.5 mg/kg, s.c.); substance P neurokinin NK1 receptor (netupitant at 10 mg/kg, i.p.) and dopamine D2/3 receptor (sulpride at 8 mg/kg, s.c.). All tested antagonists/blockers attenuated emetic parameters to varying degrees. In sum, this is the first study to demonstrate how pharmacological inhibition of Akt evokes vomiting via both central and peripheral mechanisms, a process which involves multiple emetic receptors.

Distinguishing active pediatric COVID-19 pneumonia from MIS-C.

IMPORTANCE: Active pediatric COVID-19 pneumonia and MIS-C are two disease processes requiring rapid diagnosis and different treatment protocols. OBJECTIVE: To distinguish active pediatric COVID-19 pneumonia and MIS-C using presenting signs and symptoms, patient characteristics, and laboratory values. DESIGN: Patients diagnosed and hospitalized with active COVID-19 pneumonia or MIS-C at Children's of Alabama Hospital in Birmingham, AL from April 1 through September 1, 2020 were identified retrospectively. Active COVID-19 and MIS-C cases were defined using diagnostic codes and verified for accuracy using current US Centers for Disease Control case definitions. All clinical notes were reviewed for documentation of COVID-19 pneumonia or MIS-C, and clinical notes and electronic medical records were reviewed for patient demographics, presenting signs and symptoms, prior exposure to or testing for the SARS-CoV-2 virus, laboratory data, imaging, treatment modalities and response to treatment. FINDINGS: 111 patients were identified, with 74 classified as mild COVID-19, 8 patients as moderate COVID-19, 8 patients as severe COVID-19, 10 as mild MIS-C and 11 as severe MIS-C. All groups had a male predominance, with Black and Hispanic patients overrepresented as compared to the demographics of Alabama. Most MIS-C patients were healthy at baseline, with most COVID-19 patients having at least one underlying illness. Fever, rash, conjunctivitis, and gastrointestinal symptoms were predominant in the MIS-C population whereas COVID-19 patients presented with predominantly respiratory symptoms. The two groups were similar in duration of symptomatic prodrome and exposure history to the SARS-CoV-2 virus, but MIS-C patients had a longer duration between presentation and exposure history. COVID-19 patients were more likely to have a positive SAR-CoV-2 PCR and to require respiratory support on admission. MIS-C patients had lower sodium levels, higher levels of C-reactive protein, erythrocyte sedimentation rate, d-dimer and procalcitonin. COVID-19 patients had higher lactate dehydrogenase levels on admission. MIS-C patients had coronary artery changes on echocardiography more often than COVID-19 patients. CONCLUSIONS AND RELEVANCE: This study is one of the first to directly compare COVID-19 and MIS-C in the pediatric population. The significant differences found between symptoms at presentation, demographics, and laboratory findings will aide health-care providers in distinguishing the two disease entities.

Factors that contribute to the impairment of quality of life in gastroparesis.

BACKGROUND: Understanding factors that impair quality of life (QOL) in gastroparesis is important for clinical management. AIMS: (a) Determine QOL in patients with gastroparesis; (b) Determine factors that impair QOL. METHODS: Gastroparetic patientsAQ6 underwent history and questionnaires assessing symptoms (PAGI-SYM and Rome III), QOL (SF-36v2 and PAGI-QOL), depression (Beck Depression Inventory [BDI]), and anxiety (State Trait Anxiety InventoryAQ7). KEY RESULTS: 715 gastroparesis patients (256 diabetic (DG), 459 idiopathic (IG)) were evaluated. SF-36 physical component (PC) score averaged 33.3 ± 10.5; 41% had impaired score <30. SF-36 PC scores were similar between diabetic and idiopathic gastroparesis. Impaired SF-36 PC associated with increased nausea/vomiting and upper abdominal pain subscores, acute onset of symptoms, higher number of comorbidities, use of narcotic pain medications, and irritable bowel syndrome (IBS). SF-36 mental component (MC) score averaged 38.9 ± 13.0; 26% had impaired score <30. Poor SF-36 MC associated with diabetic etiology, higher Beck depression inventory, and state anxiety scores. PAGI-QOL score averaged 2.6 ± 1.1; 50% had a score of <2.6. Low PAGI-QOL associated with higher fullness, bloating, and upper abdominal pain subscores, more depression and Trait anxiety, smoking cigarettes, need for nutritional support, progressively worsening symptoms and periodic exacerbations. CONCLUSIONS & INFERENCES: Multiple measures show poor QOL present in gastroparesis. Several areas impacted on reduced QOL: (a) Symptoms of nausea, vomiting, and abdominal pain, as well as IBS; (b) Etiology and acute onset and progressively worsening symptoms; (c) Comorbidities and psychological factors such as anxiety and depression; (d) Patient-related factors such as smoking. Targeting the modifiable factors may improve patient outcomes in gastroparesis.

Hot-Water Bathing Improves Symptoms in Patients with Cyclic Vomiting Syndrome and Is Modulated by Chronic Cannabis Use.

BACKGROUND: Cyclic vomiting syndrome (CVS) is a chronic functional GI disorder; a characteristic compulsive "hot-water bathing" pattern is reported to alleviate symptoms during an acute episode. There is limited data on this bathing pattern: proposed mechanisms include core temperature increase via effects on cannabinoid type 1 receptors in the brain, skin transient receptor potential vanilloid 1 receptor stimulation, and blood flow shift from viscera to skin. AIMS: We thus sought to characterize the hot-water bathing pattern in patients with CVS and identify differences between heavy cannabis users in comparison to occasional and non-users. METHODS: We conducted a cross-sectional study of 111 patients with CVS at a single tertiary referral center. Questionnaires regarding clinical characteristics, hot-water bathing, and cannabis use were administered. Patients were classified based on cannabis usage into regular cannabis users (≥ 4 times/week), and occasional + non-users (< 4 times/week and no current use). RESULTS: A total of 81 (73%) respondents reported the hot-water bathing behavior during an episode. The majority (> 80%) noted a marked improvement in nausea, vomiting, abdominal pain and symptoms associated with panic. Regular cannabis users were more likely to use "very-hot" water (50% vs. 16%, p = 0.01) and time to relief of symptoms was longer (> 10 min) in this group, compared to the rest of the cohort. CONCLUSIONS: Hot-water bathing relieves both GI and symptoms related to panic in most patients which appear to be modulated by chronic cannabis use. These findings can help inform future physiologic studies in CVS pathogenesis.

The Surgical Resection of Brainstem Glioma: Outcomes and Prognostic Factors.

BACKGROUND: The management of brainstem glioma remains controversial, with increasing evidence supporting surgical resection as the primary treatment for a select subgroup of tumors. However, there remains no consensus on the specific benefits and risks, the selection of surgical candidates, and prognostic factors that may further refine surgical indications. METHODS: A retrospective single-surgeon chart review was performed for all patients who underwent surgical treatment for radiographically suspected brainstem glioma between 2000 and 2017. Preoperative and postoperative radiographic evaluations on magnetic resonance imaging were conducted. Survival outcomes were collected, and machine-learning techniques were used for multivariate analysis. RESULTS: Seventy-seven patients with surgical treatment of brainstem glioma were identified, with a median age of 9 years (range, 0-58 years). The cohort included 64% low-grade (I and II) and 36% high-grade (III and IV) tumors. For all patients, the 1-year and 5-year overall survival were 76.4% and 62.3%, respectively. Transient neurologic deficit was present in 34% of cases, and permanent deficit in a further 29%. CONCLUSIONS: The radical surgical resection of brainstem gliomas can be performed with acceptable risk in well-selected cases and likely confers survival advantage for what is otherwise a rapidly and universally fatal disease. Various radiographic features are useful during patient selection and may guide treatment selection.

Vomiting and retching as presenting signs of focal epilepsy in children.

Ictal vomiting is a rare condition easily misdiagnosed as a common disease. We report two children presenting with retching and vomiting as the main ictal manifestation. Patient 1 was a four-year-old girl with a history of daily nocturnal vomiting for two months, first interpreted as a functional disorder, then as a viral infection. She presented with vomiting accompanied by focal right-sided hemifacial clonic jerking, occurring multiple times per day. Video-EEG demonstrated ictal discharges associated with the retching and vomiting, over a normal background, and occasional interictal focal spikes. MRI was normal. PET demonstrated left-sided opercular hypometabolism. Patient 2 was a girl with a history of focal epilepsy, secondary to a right central dysembryoplastic tumour, first resected with subsequent seizure freedom at the age of three years. At five years of age, she presented with recurrent episodes of retching and vomiting initially diagnosed as migraine. Video-EEG showed ictal discharges, clinically correlating with retching, vomiting and clonic facial jerking, with normal interictal activity. Brain MRI showed a progression of the tumour. A second resection resulted in seizure freedom. Ictal vomiting often goes undiagnosed, especially in children, causing treatment delays. An ictal origin should be considered, particularly when the episodes are recurrent and stereotyped. [Published with video sequences].

Effect of paroxetine on intestinal motility in the presence of ondansetron.

Chemotherapy, radiotherapy, surgery and depression are the conditions that run in parallel fashions. All these conditions cause the release of an increased amount of serotonin in the body. Serotonin acts on these 5HT3 receptors and causes nausea and vomiting. Ondansetron acts by blocking serotonin from acting on the receptors and thus is useful in decreasing episodes of nausea and vomiting but when used concomitantly with SSRIs (selective serotonin reuptake inhibitors) as cancer patient also suffered from depression. This combination tends to decrease the efficacy of ondansetron. The present study was carried out to observe the modulatory role of ondansetron on ileal smooth muscle motility in vitro. Experiments were performed in four groups (n=6) and ileal smooth muscle activity was recorded on the power lab (USA). The effects of increasing concentrations of serotonin, ondansetron and paroxetine alone were observed. In the fourth group effects of paroxetine in the presence of fixed concentration (1ml) of ondansetron (10-6M) was observed. The maximum response obtained by serotonin served as a control for our study (100%). Paroxetine response on intestinal motility was completely blocked in the presence of ondansetron. Our findings hence, reinforce the hypothesis that paroxetine decreases the antiemetic activity of serotonin antagonist ondansetron, by super sensitization of serotonergic receptors resulting in an increased incidence of nausea and vomiting in cancer patient despite adequate antiemetic prophylaxis.

How should our testing behaviour change with time in children in current COVID-19 pandemic?

BACKGROUNDS: More paediatric-confirmed cases have been reported with the global pandemic of COVID-19. This study aims to summarize the key points and supply suggestions on screening paediatric COVID-19 patients more appropriately. MATERIALS AND METHODS: We retrospectively included paediatric patients who have accepted SARS-CoV-2 RT-PCR testing in Children's Hospital of Chongqing Medical University (30 January 2020 to 13 February 2020) and compared them with paediatric-confirmed COVID-19 cases. Besides, a review was carried out by analysing all current literature about laboratory-confirmed paediatric cases with COVID-19. RESULTS: There were 46 suspected cases included in the descriptive study. The results of SARS-CoV-2 RT-PCR testing were all negative. Compared with paediatric-confirmed cases, the incidence of epidemic history was lower in suspected cases (P < .001). The rate of fever (P < .001), cough (P < .001), headache or dizziness (P < .001), vomiting (P < .001) and abdominal discomfort or distention (P = .01) were more observed in the included suspected children. There were more children having decreased WBC count in the confirmed group. In the literature review, twenty-nine studies were obtained with 488 paediatric COVID-19 cases. 88.6% of them had epidemiological history. Cough and fever were the most common symptoms. Compared with older patients, the incidence of fever, respiratory symptoms, lethargy and headache or dizziness was lower, while gastrointestinal symptoms were reported more. CONCLUSIONS: Children with a history of close contact with confirmed cases, manifested as cough and fever should be paid more attention to after excluding infection of other common pathogens. Atypical symptoms should not be over-emphasized in screening paediatric COVID-19. More studies are needed for guiding efficient recognition in paediatric COVID-19.

Gender-Related Differences in Gastroparesis.

Gastroparesis is a disorder where the stomach empties contents too slowly into the small intestine with associated symptoms of nausea, vomiting, postprandial fullness, bloating, early satiety and/or abdominal pain. It is a well-established fact that the female gender is more susceptible to developing gastroparesis compared to males, although the significance and rationale behind this gender inequality remains an unresolved mystery. Several hypotheses have been proposed including an intrinsically slower stomach in females, elevated levels of sex steroid hormones, loss of neuronal nitric oxide (nNOS) expression, and possibly due to altered serotonergic signaling. Recently, our group investigated gender-associated differences in the number of interstitial cells of Cajal in the antral and pyloric smooth muscle of diabetic patients with severe refractory gastroparesis and found there was no significant difference between the 2 genders. Targeting these gender-specific mechanisms may lead towards future therapeutic options that might alleviate and/or prevent gastroparesis. Furthermore, a better-understanding of the sex-related differences in gastroparesis can allow medical practitioners to better tailor treatment options for their patients. This article will attempt to explain why females are more vulnerable to developing gastroparesis by examining the pathogenesis and molecular basis of gender-related factors that have been identified to play a role in the gender disparity of this entity.

Clinical Insights into the Gastrointestinal Manifestations of COVID-19.

The month of December 2019 became a critical part of the time of humanity when the first case of coronavirus disease 2019 (COVID-19) was reported in the Wuhan, Hubei Province in China. As of April 13th, 2020, there have been approximately 1.9 million cases and 199,000 deaths across the world, which were associated with COVID-19. The COVID-19 is the seventh coronavirus to be identified to infect humans. In the past, Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome were the two coronaviruses that infected humans with a high fatality, particularly among the elderly. Fatalities due to COVID-19 are higher in patients older than 50 years of age or those with multimorbid conditions. The COVID-19 is mainly transmitted through respiratory droplets, with the most common symptoms being high fever, cough, myalgia, atypical symptoms included sputum production, headache, hemoptysis and diarrhea. However, the incubation period can range from 2 to 14 days without any symptoms. It is particularly true with gastrointestinal (GI) symptoms in which patients can still shed the virus even after pulmonary symptoms have resolved. Given the high percentage of COVID-19 patients that present with GI symptoms (e.g., nausea and diarrhea), screening patients for GI symptoms remain essential. Recently, cases of fecal-oral transmission of COVID-19 have been confirmed in the USA and China, indicating that the virus can replicate in both the respiratory and digestive tract. Moreover, the epidemiology, clinical characteristics, diagnostic procedures, treatments and prevention of the gastrointestinal manifestations of COVID-19 remain to be elucidated.

Role of Cannabis and Its Derivatives in Gastrointestinal and Hepatic Disease.

Medical and recreational cannabis use has increased dramatically over the last decade, resulting from mainstream cultural acceptance and legalization in several countries worldwide. Cannabis and its derivatives affect many gastrointestinal processes via the endocannabinoid system (ECS). The ECS influences gastrointestinal homeostasis through anti-inflammatory, anti-nociceptive, and anti-secretory effects. Some gastrointestinal disorders might therefore be treated with cannabinoids. Despite numerous studies in cell lines and animals, few human studies have evaluated the therapeutic effects of cannabinoids. Cannabis' schedule 1 drug status has limited its availability in research; cannabis has been legalized only recently, in some states, for medicinal and/or recreational use. Cannabinoids can alleviate chemotherapy-induced nausea and emesis and chronic pain. Studies have demonstrated the important roles of the ECS in metabolism, obesity, and nonalcoholic fatty liver disease and the anti-inflammatory effects of cannabis have been investigated in patients with inflammatory bowel diseases. Despite its potential benefits, undesired or even detrimental effects of cannabis can limit its use. Side effects such as cannabinoid hyperemesis syndrome affect some users. We review the ECS and the effects of cannabis and its derivatives on gastrointestinal and hepatic function in health and disease.

Delayed Hyponatremia Following Surgery for Pituitary Adenomas: An Under-recognized Complication.

BACKGROUND: Delayed hyponatremia is a serious complication seen after pituitary surgery. We document the incidence, presentation, outcome and risk factors for this condition. MATERIALS AND METHODS: This was a retrospective study involving 222 patients operated for nonfunctioning pituitary macroadenomas between 2007-2016. Delayed hyponatremia was defined as serum sodium <135 mmol/L, occurring after the third post-operative day. Hyponatremia was categorized as mild (134-130 mmol/L), moderate (129-125 mmol/L) and severe (<125 mmol/L). All patients received intravenous (0.9%) saline, intravenous hydrocortisone and 12g oral salt over 24 hours. Patients with severe hyponatremia were given 3% saline. RESULTS: Fifty eight patients (26%) developed delayed hyponatremia; thirty (13.5%) had severe hyponatremia. Delayed hyponatremia usually (43.1%) occurred on the seventh post-operative day (range, 3-15 days). Most patients (81%) remained asymptomatic; 11 patients developed vomiting (5), seizures (3), lethargy (1), fever (1) and paralytic ileus (1). One patient developed status epilepticus. Patients who manifest symptoms had lower sodium levels as compared to those who did not have symptoms (mean 117.7 mmol/L vs. 123 mmol/L; P < 0.01). Male gender (P = 0.002) and intra-operative CSF leak (P = 0.003) were risk factors for developing delayed hyponatremia. Other factors like, age, pre-operative cortisol levels, extent of resection and post-operative diabetes insipidus did not correlate with the occurrence of delayed hyponatremia. Patients who maintained their mean serum sodium levels >138 mmol/L (day 1-day 3) were unlikely to develop delayed hyponatremia (sensitivity, 55.2% and specificity, 83.9%), positive predictive value, 63.2% [confidence interval (CI) 48, 76.7%] and negative predictive value, 78.8% (CI 70.6, 85.5%). In most patients (57%) hyponatremia was corrected within 48 hours (h). CONCLUSIONS: We recommend routine serum sodium testing on the seventh post-operative day for all patients undergoing pituitary surgery. Most patients remain asymptomatic and unless they are detected early they can go on to develop serious complications.

Rathke Cleft Cysts with Apoplexy-Like Symptoms: Clinicoradiologic Comparisons with Pituitary Adenomas with Apoplexy.

BACKGROUND: Rathke cleft cyst (RCC) can cause acute symptoms mimicking pituitary adenoma (PA) apoplexy. We evaluated the clinicoradiologic features for distinguishing RCC from PA apoplexy. METHODS: We retrospectively evaluated 22 patients with RCC and 24 patients with PA with apoplexy-like symptoms who underwent surgery via a transsphenoidal approach between November 1999 and December 2016. We compared the clinical data and magnetic resonance (MR) images between the 2 groups. RESULTS: The RCC group was younger and had smaller tumors compared with the PA group (P = 0.02 and 0.001, respectively). The incidences of visual deficits and cranial nerve palsy were lower in the RCCs than in the PAs (P ≤ 0.02 for all). MR images showed more frequent intracystic nodules in the RCCs (P < 0.001), whereas nodular enhancement and lateral deviation of the pituitary stalk were more commonly seen in the PAs (P ≤ 0.003 for both). However, the presence of endocrine dysfunction or decreased consciousness, and the recurrence ratio, were not significantly different between the groups (P ≥ 0.48 for all). In the multivariable logistic regression analysis, patients without nodular enhancement had a 15.84-fold greater risk of RCC than did those with nodular enhancement (P = 0.031). The probability of RCC decreased 0.59-fold with each 1-cm3 increase in tumor volume. CONCLUSIONS: RCC with apoplexy-like symptoms has different clinicoradiologic features compared with PA apoplexy. Patients with RCC present with milder ocular symptoms and smaller tumor volumes compared with those with PA apoplexy. The absence of nodular enhancement on MR images could suggest RCC.

Neurological Etiologies and Pathophysiology of Cyclic Vomiting Syndrome.

Cyclic vomiting syndrome is an idiopathic chronic periodic disorder of childhood which may persist into the adult years. Although cyclic vomiting syndrome is considered a central nervous system disorder, it is often managed by a pediatric gastroenterologist. The practitioner should not assume a gastrointestinal or non-neurological cause of symptoms especially if there are coexisting neurological symptoms and signs or if vomiting does not bring relief; this suggests a possible central nervous system cause, which may necessitate a pediatric neurology consultation. Examples of central nervous system causes of cyclic vomiting syndrome that can have subjective and objective neurological findings include abdominal migraine, certain types of epilepsy, structural lesions (tumors, Chiari malformation, demyelinating disease), mitochondrial disease, autonomic disorders, fatty acid/organic acid disorders, urea cycle defects, and cannabinoid hyperemesis syndrome. Improved familiarity with cyclic vomiting syndrome and its mimics may improve the time to appropriate diagnosis and may reduce morbidity related to cyclic vomiting syndrome.

Pathophysiology of Vomiting and Esophageal Perforation in Boerhaave's Syndrome.

BACKGROUND AND AIMS: Boerhaave's syndrome, involving esophagus rupture, is considered a pathological response to vomiting that may occur just before perforation. However, the mechanism of vomiting and occurrence of this disease have not been clearly demonstrated. METHODS: We identified patients with esophageal perforation between 1995 and 2017 and reviewed endoscopic findings at retching during upper gastrointestinal endoscopy. Finally, we proposed a theory for the underlying pathological mechanism. RESULTS: We retrospectively investigated 10 patients with esophageal perforation between 1995 and 2017. All patients presented after vomiting associated with large volumes of food and alcohol intake. Nine were treated by primary closure of the perforation and drainage of the thoracic cavity, and one was conservatively treated. In all cases, the perforations were longitudinal tears (1-4 cm) and located in the left of the esophagus, just above the gastric cardia. CONCLUSIONS: We hypothesize that vomiting occurred by retrograde propagation of gastrointestinal motor contraction from the jejunum to the gastric antrum, followed by prolapse of the gastric fornix mucosal into the esophagus. Subsequent esophageal perforation probably resulted from excessive prolapse due to strong contraction and destruction of the muscularis mucosa of the left side of abdominal esophagus, with longitudinal stretching of the whole left esophageal wall due to traction. We also propose that Boerhaave's syndrome is defined as "post-emetic esophageal perforation" to ensure broader recognition and more expedient diagnosis and treatment. Remaining conditions without any definite causes may be labeled "idiopathic" or "spontaneous" rupture of the esophagus.

Revisiting the physiology of nausea and vomiting-challenging the paradigm.

PURPOSE: The predominant neurotransmitters and receptors for acute and delayed chemotherapy-induced nausea and vomiting (CINV) are represented in the current paradigm, which reflects successful control of emesis. However, control of nausea (N) lags behind management of vomiting (V). This review aims to re-examine and incorporate new information about the mechanisms of V and N. METHODS: The initial literature search focused on CINV. Keywords in articles led to subsequent discovery of publications focused on N&V in other medical and scientific fields (e.g., gastroenterology, neurology, cannabinoid science, neuropharmacology, and motion sickness). Using keywords to identify other sources continued until no further recent, meaningful publications were found. RESULTS: More than 86% of references were from recent non-oncology journals and books, suggesting there are many areas for cross-fertilization research into mechanisms and management of N&V-particularly of N, which involves overlapping and dissimilar CNS areas from V. Information from cited articles was incorporated into visual representation of N&V, which is certainly not exhaustive but supports highly complex processes in the stomach and gut, the vagus nerve and spinal cord neurons, the nucleus tractus solitarii, and the anterior insular cortex and anterior cingulate cortex with input from the amygdala. CONCLUSIONS: These data support the idea that mechanisms for N, whatever the cause, must be highly similar. Continued research into nausea, including patient-reported evaluation and outcomes, is important; interventions for nausea could be considered adjuvants to current standard of care antiemetics and be individualized, depending on patient-reported efficacy and adverse effects and preferences.

Oesophageal eosinophilia accompanies food allergy to hen egg white protein in young pigs.

BACKGROUND: Esophagitis with eosinophilia, inflammation, and fibrosis represent a chronic condition in humans with food allergies. OBJECTIVE: In this investigation, we asked whether esophagitis with an eosinophilic component is observed in young pigs rendered allergic to hen egg white protein (HEWP). METHODS: Food allergy was induced in young pigs using two protocols. In one protocol, sensitized pigs were challenged by gavage with a single dose of HEWP. Clinical signs were monitored for 24 hours, and then, gastrointestinal (GI) tissues were collected for histological examination. The phenotype of circulating, ovalbumin (OVA)-specific T cells also was examined in HEWP challenged animals. In the second protocol, sensitized animals were fed HEWP for 28 days. Animals were then examined by endoscopy and gastrointestinal tissues collected for histological examination. RESULTS: In pigs challenged by gavage with HEWP, clinical signs were noted in 5/6 pigs including diarrhoea, emesis, and skin rash. Clinical signs were not seen in any control group. Histological analysis revealed significant levels of oesophageal eosinophilic infiltration (P < .05) in 4/6 of these animals, with two also displaying eosinophilic infiltration in the stomach. Eosinophils were not increased in ileum or colon samples. Increased numbers of circulating, OVA-specific CD4+ T cells also were observed in pigs that received HEWP by gavage. In the group of animals fed HEWP, endoscopy revealed clinical signs of esophagitis including oedema, granularity, white spots, and furrowing, while histology revealed oedema, immune cell infiltration, and basal zone hyperplasia. CONCLUSIONS AND CLINICAL RELEVANCE: Food allergy in the pig can be associated with esophagitis based on histological and endoscopic findings, including eosinophilic infiltration. The young pig may, therefore, be a useful large animal model for the study of eosinophilic esophagitis in humans.