Intravenous metoclopramide for increasing endoscopic mucosal visualization in patients with acute upper gastrointestinal bleeding: a multicenter, randomized, double-blind, controlled trial.

Acute upper gastrointestinal hemorrhage (UGIH) is the most common emergency condition that requires rapid endoscopic treatment. This study aimed to evaluate the effects of pre-endoscopic intravenous metoclopramide on endoscopic mucosal visualization (EMV) in patients with acute UGIH. This was a multicenter, randomized, double-blind controlled trial of participants diagnosed with acute UGIH. All participants underwent esophagogastroduodenoscopy within 24 h. Participants were assigned to either the metoclopramide or placebo group. Modified Avgerinos scores were evaluated during endoscopy. In total, 284 out of 300 patients completed the per-protocol procedure. The mean age was 62.8 ± 14.3 years, and 67.6% were men. Metoclopramide group achieved a higher total EMV and gastric body EMV score than the other group (7.34 ± 1.1 vs 6.94 ± 1.6; P = 0.017 and 1.80 ± 0.4 vs 1.64 ± 0.6; P = 0.006, respectively). Success in identifying lesions was not different between the groups (96.5% in metoclopramide and 93.6% in placebo group; P = 0.26). In the metoclopramide group, those with active variceal bleeding compared with the control group demonstrated substantial improvements in gastric EMV (1.83 ± 0.4 vs 1.28 ± 0.8, P = 0.004), antral EMV (1.96 ± 0.2 vs 1.56 ± 0.6, P = 0.003), and total EMV score (7.48 ± 1.1 vs 6.2 ± 2.3, P = 0.02). Pre-endoscopic intravenous metoclopramide improved the quality of EMV in variceal etiologies of UGIH, which was especially prominent in those who had signs of active bleeding based on nasogastric tube assessment.Trial Registration: Trial was registered in Clinical Trials: TCTR 20210708004 (08/07/2021).

Palliative Management of Inoperable Malignant Bowel Obstruction: Prospective, Open Label, Phase 2 Study at an NCI Comprehensive Cancer Center.

CONTEXT: Malignant bowel obstruction (MBO) is a common complication of intra-abdominal cancer, frequently seen in advanced gastrointestinal and gynecologic cancer. Management of MBO can be challenging, particularly if the patient is not a surgical candidate. No consensus exists on how best to manage these patients medically. Retrospective studies suggest that the combination of dexamethasone, octreotide and metoclopramide may lead to relief of obstruction and improvement in symptoms associated with the obstruction. OBJECTIVES: This study seeks to prospectively evaluate the combination of drug "triple therapy" dexamethasone 4 mg BID, metoclopramide 10 mg Q6 and octreotide 300 mcg TID to assess tolerability, safety, and effect on symptoms and deobstruction. METHODS: Adults admitted at Roswell Park Comprehensive Cancer Center with malignant bowel obstruction were eligible. Eligible patients who constented to the study were started on the triple therapy with close monitoring of symptoms and for adverse effects. RESULTS: A total of 15 patients enrolled in the study. Two patients experienced bradycardia as adverse effect and there was no incidence of bowel perforation. All patients who completed the study had complete resolution of their nausea, and improvement in other symptoms including pain, constipation, tolerance of oral intake and resumption of bowel movements. Only two of the 15 patients were alive to complete the six-month post study follow up. CONCLUSION: "Triple therapy" with dexamethasone, metoclopramide, and octreotide for management of nonsurgical MBO in this small sample size appears safe and well tolerated however a diagnosis of inoperable MBO remains associated with poor prognosis and death within months.

Is enhanced recovery after surgery essential?

BACKGROUND: The enhanced recovery after surgery (ERAS) method is designed for the patient to recover quickly, have less pain and have a more comfortable period after the surgery; that includes preoperative, intra and postoperative processes. ERAS has been started to be applied in cesarean section surgeries as the patients need to recover quickly. In the literature, there is no study about the results of ERAS in cesarean section about pain scores and complications. OBJECTIVES: It is aimed to compare the results of cesarean section patients using the ERAS method completely in patients who have had cesarean section without meeting some of the postoperative conditions of the ERAS criteria. STUDY DESIGN: It is a prospective study designed as postoperative metoclopramide, enema and routine opioids in group 1, enema and metoclopramide in group 2, metoclopramide only in group 3 and nothing in group 4. Postoperative pain scoring was done by using visual analog scale (VAS). Analysis of variance tests and t tests were used for results. RESULTS: There was no difference between groups according to age, parity, and birth weight. As a result, although there was no difference between the groups in terms of discharge time and complications, the VAS score used in pain scoring was found to be significantly lower in group 3 compared to the other groups (p: 0.000). Only metoclopramide group (group 3) had lowest VAS score. CONCLUSION: It has been revealed that the ERAS procedure does not need to be so detailed in the postoperative period, and the addition of metoclopramide may be sufficient. Since pain can be a subjective factor, other randomized studies are needed in terms of other criteria.

Pharmacologic treatment of gastroparesis: What is (still) on the horizon?

Gastroparesis is a neuromuscular disorder of the upper gastrointestinal tract. Patients typically complain about early satiety, postprandial fullness, nausea and vomiting. Etiology is multifactorial. Treatment strategies include nutritional support, pharmacologic agents or surgery for refractory cases. Metoclopramide is the first and only FDA approved pharmacologic agent for (diabetic) Gastroparesis. A couple of compounds are currently in clinical testing. Some beacons of hope have failed recently, however. Here we present an update on possible future treatment options.

Effects of combined dexamethasone and tranexamic acid in lower limb total arthroplasty: a systematic review and meta-analysis of randomized clinical trials.

PURPOSE: To evaluate the effectiveness of combined Tranexamic acid (TXA) and dexamethasone (DEX) in total hip and knee arthroplasty. METHODS: PUBMED, EMBASE, MEDLINE and CENTRAL database were systematically searched for randomized studies that utilized TXA and DEX administration of TXA in THA or TKA. RESULTS: A total of three randomized studies enrolling 288 patients were eligible for qualitative and quantitative analysis. DEX + TXA group demonstrated statistical significantly lesser usage of oxycodone (OR: 0.34, p < 0.0001), metoclopramide (OR: 0.21, p < 0.00001), lesser incidence of postoperative nausea and vomiting (OR: 0.27, p < 0.0001), better postoperative range of motion (MD: 2.30, p < 0.00001) and shorter length of hospital stay (MD: 0.31, p = 0.03). Comparable results were seen in total blood loss, transfusion rate and postoperative complications. CONCLUSION: In this meta-analysis, the combination of TXA and DEX has positive impacts on the usage of oxycodone and metoclopramide, postoperative range of motion, postoperative nausea and vomiting and reduces the length of hospital stay.

Primary bilateral macronodular adrenal hyperplasia: A series of 32 cases and literature review.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) accounts for <2% of cases of Cushing's syndrome. The majority of patients present with no obvious steroid excess it means with autonomous cortisol secretion (ACS). The classic treatment for patients with overt Cushing's syndrome is bilateral adrenalectomy, but unilateral resection of the larger adrenal gland can result in clinical and/or biochemical remission in >90% of cases, especially in cases of ACS. In this article, a series of 32 cases with PBMAH is described. Most of the cases of PBMAH had ACS, except for one case with overt Cushing's syndrome. A study of aberrant receptors was performed in six patients, being negative in three cases, positive in the metoclopramide test in two cases and positive in the metoclopramide test and in the mixed meal test in another patient. The patient with overt Cushing's syndrome was treated with adrenostatic therapy achieving biochemical control, while two patients with ACS underwent unilateral adrenalectomy with resection of the largest adrenal gland, demonstrating hypercortisolism remission and improvement of cardiovascular risk factors after surgery. This article describes a series of 32 cases of PBMAH and offers a comprehensive review of PBMAH.

Ultrasonographic assessment of metoclopramide effect on gastric volume in parturients females undergoing Caesarean section: a randomized double blind study.

BACKGROUND: The prokinetic effect of metoclopramide promotes gastric emptying and decreases stomach capacity. The aim of the present study was to assess the efficacy of metoclopramide in reducing gastric contents and volume using gastric point-of-care ultrasonography (PoCUS) in parturients females prepared for elective Cesarean section under general anesthesia. METHODS: A total of 111 parturient females were randomly allocated to one of two groups. The intervention group (Group M; N.=56) received 10 mg metoclopramide diluted in 10 mL 0.9% normal saline. The control group (Group C; N.=55): received 10 mL 0.9% normal saline. The cross-sectional area and volume of stomach contents were measured using ultrasound before and one hour after the administration of metoclopramide or saline. RESULTS: Statistically significant differences in mean antral cross-sectional area and gastric volume were observed between the two groups (P<0.001). Group M had significantly lower rates of nausea and vomiting compared to the control group. CONCLUSIONS: Metoclopramide decreases gastric volume, reduces postoperative nausea and vomiting, and may lower the risk of aspiration when used as premedication before obstetric surgery. Preoperative gastric PoCUS has utility in objectively assessing stomach volume and contents.

Effects of ondansetron, metoclopramide and granisetron on perioperative nausea and vomiting in patients undergone bariatric surgery: a randomized clinical trial.

INTRODUCTION: Post-operative nausea and vomiting (PONV) is a common problem after sleeve gastrectomy. In recent years, following the increase in the number of such operations, special attention has been paid to preventing PONV. Additionally, several prophylaxis methods have been developed, including enhanced recovery after surgery (ERAS) and preventive antiemetics. Nevertheless, PONV has not been completely eliminated, and the clinicians are trying to reduce the incidence of PONV yet. METHODS: After successful ERAS implementation, patients were divided into five groups, including control and experimental groups. Metoclopramide (MA), ondansetron (OA), granisetron (GA), and a combination of metoclopramide and ondansetron (MO) were used as antiemetics for each group. The frequency of PONV during the first and second days of admission was recorded using a subjective PONV scale. RESULTS: A total of 130 patients were enrolled in this study. The MO group showed a lower incidence of PONV (46.1%) compared to the control group (53.8%) and other groups. Furthermore, the MO group did not require rescue antiemetics, however, one-third of control cases used rescue antiemetics (0 vs. 34%). CONCLUSION: Using the combination of metoclopramide and ondansetron is recommended as the antiemetic regimen for the reduction of PONV after sleeve gastrectomy. This combination is more helpful when implemented alongside ERAS protocols.

Colostomy as a definitive treatment in an ALS patient with acute colonic Pseudo-obstruction refractory to medical management, a case report.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease, and ALS patients may experience disturbed gastrointestinal motility often resulting in acute colonic pseudo-obstruction (ACPO). There is currently a paucity in the literature to guide the treatment of patients with both ALS and ACPO. CASE PRESENTATION: Here we describe a 39-year-old male patient with advanced ALS who developed ACPO. His condition was refractory to both medical and procedural managements including polyethylene glycol, senna, and docusate suppository, metoclopramide, linaclotide, erythromycin, prucalopride, neostigmine, and repeated colonoscopies. He ultimately underwent successful colostomy for palliation. Here we report the peri-operative multidisciplinary approach taken with this case, the surgical procedures, the potential risks, and the outcome. CONCLUSION: The patient is delighted with the result and requested publication of this case to raise awareness of constipation in ALS patients and promote the consideration of colostomy as a treatment option for patients with ileus resistant to conservative management. Ultimately, a multidisciplinary team approach is required to properly assess the risks and benefits to achieve good clinical outcomes.

Hipo persistente: una rara complicación de una inyección epidural transforaminal de corticoides / Persistent hiccup: a rare complication of a transforaminal epidural corticoid injection / Soluços persistentes: uma complicação rara da injeção peridural transforaminal de corticosteroide

Se describe el caso de un paciente que instaló un hipo persistente luego de recibir una inyección epidural transforaminal lumbar de corticoides. Se destaca que es una complicación raramente reportada y por ende poco conocida por quienes practican intervencionismo en dolor. Se discuten los posibles mecanismos por los que puede presentarse, se reseña la evolución observada, y se describe el tratamiento instituido. Se señala el impacto que el hipo puede tener sobre la calidad de vida.

The case of a patient who installed a persistent hiccup after receiving a lumbar transforaminal epidural injection of corticosteroids is described. It is highlighted that it is a rarely reported complication and little known by those who practice interventional pain medicine. Possible mechanisms by which it may occur are discussed, the evolution observed and the treatment instituted are reviewed. The impact that hiccups can have on quality of life is pointed out.

Descrevemos o caso de um paciente que desenvolveu soluços persistentes após receber uma injeção peridural transforaminal lombar de corticosteróides. Ressalta-se que é uma complicação pouco relatada e, portanto, pouco conhecida por quem pratica o intervencionismo na dor. Discutem-se os possíveis mecanismos pelos quais pode ocorrer, revisa-se a evolução observada e descreve-se o tratamento instituído. O impacto que os soluços podem ter na qualidade de vida é apontado.

Safe Use of Erythromycin For Refractory Gastroparesis After Small Bowel Transplantation.

Current therapeutic options with prokinetic agents for posttransplant gastroparesis are limited. Erythromycin is associated with adverse reactions, including corrected QT interval prolongation and cytochrome P450 3A4 isoenzyme inhibition. The use of erythromycin has been avoided in patients undergoing treatment with cyclosporine or tacrolimus because of significant fluctuations in therapeutic immunosuppression levels. We report herein the successful use of erythromycin after visceral transplant to treat delayed gastric emptying. Two patients were managed with oral erythromycin (initial dose of 750 mg/d divided into 3 doses) for gastroparesis after visceral transplant. Patient 1 was a woman aged 42 years with a history of chronic intestinal pseudo-obstruction syndrome who underwent isolated small bowel transplant with dual (gastric and duodenal) proximal allograft anastomosis. Posttransplant gastroparesis was initially managed with oral metoclopramide. The patient also required high doses of tacrolimus (36 mg/d) to maintain adequate immunosuppression levels. The decision was made to change metoclopramide to erythromycin, which significantly decreased the daily tacrolimus dose requirement (from 36 to 9 mg/d), with resolution of nausea and intermittent bloating symptoms. Patient 2 was a woman aged 35 years with ultra-short gut syndrome after extensive enterectomy due to intestinal volvulus who underwent uneventful combined intestinal and colon transplant. Conventional pharmacologic therapy for gastroparesis was initiated after surgery without success. Erythromycin was started 15 days posttransplant, with significant improvement in her symptoms, and discontinued 47 days post-transplant. To maintain therapeutic levels (8-10 mg/dL), daily tacrolimus dose was decreased 75.8% and 36.5% for patients 1 and 2, respectively. No significant side effects associated with erythromycin use were observed in either patient. Our findings here suggest that erythromycin may be safely used for gastroparesis after small bowel transplant. Close monitoring of immunosuppressive drug levels and dose adjustments of other medications affected by inhibition of cytochrome P450 3A4 are advised.

Reversal of Feed Intolerance by Prokinetics Improves Survival in Critically Ill Cirrhosis Patients.

BACKGROUND AND AIMS: Feed intolerance (FI) is common in cirrhosis patients in intensive care units (ICU). Prokinetics are the first line treatment for FI but their efficacy and safety in critically ill patient with cirrhosis is unknown. We evaluated the role of prokinetics in reversal of FI and clinical outcomes. METHODS: Consecutive patients admitted in ICU developing new-onset FI, were randomized to receive either intravenous metoclopramide (Gr.A, n = 28), erythromycin (Gr.B, n = 27) or placebo (Gr.C, n = 28). FI was defined with the presence of 3 of 5 variables- absence of bowel sounds, gastric residual volume ≥ 500 ml, vomiting, diarrhoea and bowel distension. Primary end-point was complete resolution of FI (≥ 3 variables resolved) within 24-h and secondary end-points included resolution within 72-h and survival at 7-days. RESULTS: Of the 1030 ICU patients, 201 (19.5%) developed FI and 83 patients were randomized. Baseline parameters between the groups were comparable. Complete resolution at 24-h was higher in Gr.A (7.14%) and B (22.2%) than C (0%, p = 0.017). Overall, 58 (69.9%) patients achieved resolution within 72 h, more with metoclopramide (n = 24, 85.7%) and erythromycin (n = 25, 92.6%) than with placebo (n = 9, 32.1%, p < 0.001). The 7-day survival was better in patients who achieved resolution within 72-h (65.5 vs. 36%, p = 0.011) than non-responders. High lactate (OR-3.32, CI-1.45-7.70, p = 0.005), shock at baseline (OR-6.34, CI-1.67-24.1, p = 0.007) and resolution of FI within 72 h (OR-0.11, CI, 0.03-0.51, p = 0.04) predicted 7-day mortality. CONCLUSIONS: FI is common in critically-ill cirrhosis patients and non-resolution carries high mortality. Early recognition and treatment with prokinetics is recommended to improve short-term survival.

Gastrointestinal dysmotility is common in cirrhosis and higher incidence in critically ill patients. Promotility drugs are the first line of medication especially in ICU patients. In our study, we found that feed intolerance is present in nearly one in five critically ill cirrhosis and is associated with higher mortality. Patients who achieve resolution had an improved short-term survival. Prokinetic medications are safe in critically ill cirrhosis and help in early resolution of feed intolerance. Feed intolerance in critically ill cirrhosis should be recognized as an organ dysfunction and approaches for prevention and early diagnosis of feed intolerance could help in improving the outcomes in critical illness.

Optimal management strategies for primary headache in the emergency department.

PURPOSE: We sought to evaluate the factors associated with better outcomes for emergency department (ED) patients treated for primary headache. METHODS: This was a health records review of consecutive patients over a 3-month period presenting to two tertiary EDs and discharged with a diagnosis of primary headache. The primary outcome was the need for second round medications, defined as medications received > 1 h after the initial physician-ordered medications were administered. We performed multivariate logistic regression analysis to determine treatment factors associated with need for second round medications. RESULTS: We included 553 patients, mean age was 42.2 years and 72.9% were females. The most common diagnoses were headache not otherwise specified (48.8%) and migraine (43%). Ketorolac IV (62.2%) and metoclopramide IV (70.2%) were the most frequently administered medications. 18% of patients met the primary outcome. Dopamine antagonists (OR 0.3 [95% CI 0.1-0.5]) and non-steroidal anti-inflammatory drugs (NSAIDs) (OR 0.5 [95% CI 0.3-0.8]) ordered with initial medications were associated with reduced need for second round medications. Intravenous fluid boluses ≥ 500 ml (OR 2.8 [95% CI: 1.5-5.2]) and non-dopamine antagonist antiemetics (OR 2.2 [95% CI 1.2-4.2]) were associated with increased need. Opioid use approached statistical significance for receiving second round medication (p = 0.06). CONCLUSION: We determined that use of dopamine antagonists and NSAIDs were associated with a reduced need for second round medications in ED primary headache patients. Conversely, non-dopamine antagonist antiemetic medications and intravenous fluids were associated with a significantly increased need for second round medications. Careful choice of initial therapy may optimize management for these patients.

RéSUMé: OBJECTIF: Nous avons cherché à évaluer les facteurs associés à de meilleurs résultats pour les patients des services d'urgence traités pour des céphalées primaires. MéTHODES: Il s'agissait d'un examen des dossiers médicaux de patients consécutifs sur une période de 3 mois se présentant à deux services d'urgence tertiaires et sortis avec un diagnostic de céphalée primaire. Le résultat primaire était la nécessité d'une deuxième série de médicaments, définis comme des médicaments reçus > 1 heure après l'administration des premiers médicaments prescrits par le médecin. Nous avons effectué une analyse de régression logistique multivariée pour déterminer les facteurs de traitement associés au besoin de médicaments de second tour RéSULTATS: Nous avons inclus 553 patients, l'âge moyen était de 42,2 ans et 72,9 % étaient des femmes. Les diagnostics les plus fréquents étaient les céphalées non spécifiées autrement (48,8 %) et la migraine (43 %). Le kétorolac IV (62,2%) et le métoclopramide IV (70,2 %) étaient les médicaments les plus fréquemment administrés. 18 % des patients ont atteint le résultat primaire. Les antagonistes de la dopamine (OR 0,3 [IC 95 % : 0,1-0,5]) et les anti-inflammatoires non stéroïdiens (AINS) (OR 0,5 [IC 95 % : 0,3-0,8]) commandés avec les médicaments initiaux étaient associés à un besoin réduit de médicaments de deuxième série. Les bolus liquidiens intraveineux ≥ 500 ml (OR 2,8 [IC 95 % : 1,5-5,2]) et les antiémétiques non antagonistes de la dopamine (OR 2,2 [IC 95 % : 1,2-4,2]) étaient associés à un besoin accru. L'utilisation d'opioïdes a approché la signification statistique pour la réception d'un médicament de deuxième série (p = 0,06). CONCLUSION: Nous avons déterminé que l'utilisation d'antagonistes de la dopamine et d'AINS était associée à un besoin réduit de médicaments de second tour chez les patients souffrant de céphalées primaires aux urgences. À l'inverse, les médicaments antiémétiques non antagonistes de la dopamine et les fluides intraveineux étaient associés à un besoin significativement accru de médicaments de second tour. Un choix judicieux du traitement initial peut optimiser la prise en charge de ces patients.

MASCC antiemetics in advanced cancer updated guideline.

BACKGROUND: Nausea and vomiting are a common clinical symptom in the advanced cancer patient. Pharmacologic management is important. Evidence for drug choices and guidelines are needed to help clinicians manage nausea and vomiting in this population METHODS: Evidence from a systematic review published in 2010, initial MASCC guidelines developed from a systematic review of literature to 2015, and a new systematic review of randomized trials published between 2015 and February 2, 2021, was combined to establish a new guideline. RESULTS: A search of the literature between 2015 and February 2, 2021, revealed 257 abstracts of which there was one systematic review and 4 randomized trials which were used to modify the guideline. The new guideline is as follows: First Line: Metoclopramide (II) multiple small RCTs including a placebo-controlled trial, haloperidol (II) multiple non-placebo-controlled RCTs, high consensus. Second line: Methotrimeprazine (II) 1 well-powered non-placebo-controlled RCT, olanzapine (II) 1 placebo-controlled pilot RCT, high consensus. Third line: Tropisetron (II) large unblinded lower quality non-placebo-controlled RCT, levosulpiride (II) 1 blinded non-placebo-controlled pilot RCT, high consensus. DISCUSSION: Haloperidol, metoclopramide, methotrimeprazine, olanzapine tropisetron, and levosulpiride have been antiemetics used in randomized trials with antiemetic activity demonstrated. There are only three placebo-controlled randomized trials we could find in our literature review. Placebo responses varied significantly between two randomized trials. More randomized placebo-controlled trials with either metoclopramide or haloperidol rescue are needed to clarify antiemetic choices in advanced cancer. CONCLUSION: First-line antiemetics for nausea and vomiting in advanced cancer are metoclopramide and haloperidol, and second-line medications are methotrimeprazine and olanzapine.

Digestion-Specific Acupuncture Effect on Feeding Intolerance in Critically Ill Post-Operative Oral and Hypopharyngeal Cancer Patients: A Single-Blind Randomized Control Trial.

Malnourishment is prevalent in patients suffering from head and neck cancer. The postoperative period is crucial in terms of nutritional support, especially after composite resection and reconstruction surgery. These patients present with a number of risk factors that aggravate feeding intolerance, including postoperative status, prolonged immobility, decreased head elevation, mechanical ventilation, and applied sedative agents. Routine management protocols for feeding intolerance include prokinetic drug use and post-pyloric tube insertion, which could be both limited and accompanied by detrimental adverse events. This single-blind clinical trial aimed to investigate the effects of acupuncture in postoperative feeding intolerance in critically ill oral and hypopharyngeal cancer patients. Twenty-eight patients were randomized into two groups: Intervention group and Control group. Interventions were administered daily over three consecutive postoperative days. The primary outcome revealed that the intervention group reached 70% and 80% of target energy expenditure (EE) significantly earlier than the control group (4.00 ± 1.22 versus 6.69 ± 3.50 days, p = 0.012), accompanied by higher total calorie intake within the first postoperative week (10263.62 ± 1086.11 kcals versus 8384.69 ± 2120.05 kcals, p = 0.004). Furthermore, the intervention group also needed less of the prokinetic drug (Metoclopramide, 20.77 ± 48.73 mg versus 68.46 ± 66.56 mg, p = 0.010). In conclusion, digestion-specific acupuncture facilitated reduced postoperative feeding intolerance in oral and hypopharyngeal cancer patients.

Metoclopramide treatment blocks CD93-signaling-mediated self-renewal of chronic myeloid leukemia stem cells.

Self-renewal is a key characteristic of leukemia stem cells (LSCs) responsible for the development and maintenance of leukemia. In this study, we identify CD93 as an important regulator of self-renewal and proliferation of murine and human LSCs, but not hematopoietic stem cells (HSCs). The intracellular domain of CD93 promotes gene transcription via the transcriptional regulator SCY1-like pseudokinase 1 independently of ligation of the extracellular domain. In a drug library screen, we identify the anti-emetic agent metoclopramide as an efficient blocker of CD93 signaling. Metoclopramide treatment reduces murine and human LSCs in vitro and prolongs survival of chronic myeloid leukemia (CML) mice through downregulation of pathways related to stemness and proliferation in LSCs. Overall, these results identify CD93 signaling as an LSC-specific regulator of self-renewal and proliferation and a targetable pathway to eliminate LSCs in CML.

Gastrointestinal dysmotility in a patient with advanced lung cancer: paraneoplastic or drug-induced?

A 75-year-old man was hospitalised for bronchoscopy with biopsy due to a suspicious pulmonary mass at chest tomography. He had significant dyspnoea, constipation, nausea, vomiting, anorexia and a 33% loss of weight in the past 3 months. Biopsy revealed a pulmonary squamous cell carcinoma, which was inoperable. Tramadol used at home for 3 months was replaced by morphine on admission. The patient remained constipated despite prokinetics and laxatives, leading to the diagnostic hypothesis of paraneoplastic motility disorder and opioid-induced constipation. Abdominal tomography ruled out the possibility of mechanical obstruction. As complications, the patient presented superior vena cava syndrome and opioid (morphine) intoxication. The patient died a few days later. The management of this case highlights the importance of multidisciplinary care and the challenges of palliative oncology care. Paraneoplastic motility disorder must always be considered among the mechanisms of intestinal dysfunction in patients with advanced oncological disease.

High-flow oxygen and pro-serotonin agents for non-interventional treatment of post-dural-puncture headache.

OBJECTIVE: Post dural puncture headache (PDPH) is a common complication in patients following diagnostic or therapeutic lumbar puncture, procedures requiring epidural access, and spinal surgery. Epidural blood patch (EBP), the gold standard for the treatment of this pathology requires training not provided to emergency physicians. In addition, the presence of concomitant pathology and abnormal laboratory values are contraindications to perform EBP. In presence of these limitations, we sought for a non-interventional management of PDPH utilizing high-flow oxygen and pro-serotonin agents. We reviewed the mechanism of action of this therapy METHODS: To illustrate our proposal, we report a series of twelve consecutive patients with PDPH treated with high-flow oxygen therapy at 12 L/min via a non-rebreathing mask and intravenous metoclopramide. RESULTS: All patients were treated with this conservative therapy, no adverse reactions were observed. After the intervention, the headache resolved without further indications for PDPH. CONCLUSION: Our series suggests that combining high-flow oxygen and pro-serotonin agents such metoclopramide in the ED might be a feasible option as effective as the invasive methods used in treating PDPH. This therapy appears to be efficient and to minimize risk, cost and side effects. It presents an easily accessible alternative that should be considered when PDPH is not a viable option.