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Medical Principles and Practice :... 2022Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among...
INTRODUCTION
Several forms of cannabinoids are currently being used to manage nausea and vomiting (N/V). Emerging cases of refractory N/V associated with chronic cannabis use among adults and older patients have been reported named cannabis hyperemesis syndrome (CHS). CHS is a condition that leads to repeated and severe N/V in long-term users of cannabinoids.
OBJECTIVE
The aim of this study was to outline current treatments for the management of CHS.
METHODS
A systematic review was conducted using PubMed, Ovid MEDLINE, Cochrane Central, EMBASE, and Google Scholar. Databases were used to search for articles on CHS published from January 2009 to June 2021, yielding 225 results of which 17 were deemed relevant and underwent review by 2 separate reviewers.
RESULTS
The duration of cannabis administration ranged between 6 months to 11 years may precipitate symptoms of CHS. The Rome IV diagnostic criteria of CHS require cannabinoid use and persistence of N/V symptoms for at least the past 6 months. Cannabis cessation is noted to be the most successful management, but other treatments also demonstrated symptom relief; these include hot water hydrotherapy, topical capsaicin cream, haloperidol, droperidol, benzodiazepines, propranolol, and aprepitant administration.
CONCLUSION
More research on CHS is needed to enhance knowledge translation, education, and create awareness in the medical community on the side effects of cannabinoids and to propose the best treatment options.
Topics: Adult; Analgesics; Cannabinoids; Cannabis; Humans; Marijuana Abuse; Syndrome; Vomiting
PubMed: 34724666
DOI: 10.1159/000520417 -
Science Translational Medicine Sep 2016CD19-specific chimeric antigen receptor (CAR)-modified T cells have antitumor activity in B cell malignancies, but factors that affect toxicity and efficacy have been...
CD19-specific chimeric antigen receptor (CAR)-modified T cells have antitumor activity in B cell malignancies, but factors that affect toxicity and efficacy have been difficult to define because of differences in lymphodepletion and heterogeneity of CAR-T cells administered to individual patients. We conducted a clinical trial in which CD19 CAR-T cells were manufactured from defined T cell subsets and administered in a 1:1 CD4(+)/CD8(+) ratio of CAR-T cells to 32 adults with relapsed and/or refractory B cell non-Hodgkin's lymphoma after cyclophosphamide (Cy)-based lymphodepletion chemotherapy with or without fludarabine (Flu). Patients who received Cy/Flu lymphodepletion had increased CAR-T cell expansion and persistence, and higher response rates [50% complete remission (CR), 72% overall response rate (ORR)] than patients who received Cy-based lymphodepletion without Flu (8% CR, 50% ORR). The CR rate in patients treated with Cy/Flu at the maximally tolerated dose was 64% (82% ORR; n = 11). Cy/Flu minimized the effects of an immune response to the murine single-chain variable fragment component of the CAR, which limited CAR-T cell expansion and clinical efficacy in patients who received Cy-based lymphodepletion without Flu. Severe cytokine release syndrome (sCRS) and grade ≥3 neurotoxicity were observed in 13 and 28% of all patients, respectively. Serum biomarkers, one day after CAR-T cell infusion, correlated with subsequent sCRS and neurotoxicity. Immunotherapy with CD19 CAR-T cells in a defined CD4(+)/CD8(+) ratio allowed identification of correlative factors for CAR-T cell expansion, persistence, and toxicity, and facilitated optimization of lymphodepletion that improved disease response and overall and progression-free survival.
Topics: Adult; Aged; Biomarkers, Tumor; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Proliferation; Cyclophosphamide; Female; Humans; Immunotherapy; Lymphocyte Depletion; Lymphocyte Subsets; Lymphoma, Non-Hodgkin; Male; Middle Aged; Receptors, Antigen, T-Cell; Syndrome; Transgenes; Treatment Outcome; Vidarabine; Young Adult
PubMed: 27605551
DOI: 10.1126/scitranslmed.aaf8621 -
Mycoses Sep 2019Breakthrough invasive fungal infections (IFIs) have emerged as a significant problem in patients receiving systemic antifungals; however, consensus criteria for defining... (Review)
Review
Defining breakthrough invasive fungal infection-Position paper of the mycoses study group education and research consortium and the European Confederation of Medical Mycology.
Breakthrough invasive fungal infections (IFIs) have emerged as a significant problem in patients receiving systemic antifungals; however, consensus criteria for defining breakthrough IFI are missing. This position paper establishes broadly applicable definitions of breakthrough IFI for clinical research. Representatives of the Mycoses Study Group Education and Research Consortium (MSG-ERC) and the European Confederation of Medical Mycology (ECMM) reviewed the relevant English literature for definitions applied and published through 2018. A draft proposal for definitions was developed and circulated to all members of the two organisations for comment and suggestions. The authors addressed comments received and circulated the updated document for approval. Breakthrough IFI was defined as any IFI occurring during exposure to an antifungal drug, including fungi outside the spectrum of activity of an antifungal. The time of breakthrough IFI was defined as the first attributable clinical sign or symptom, mycological finding or radiological feature. The period defining breakthrough IFI depends on pharmacokinetic properties and extends at least until one dosing interval after drug discontinuation. Persistent IFI describes IFI that is unchanged/stable since treatment initiation with ongoing need for antifungal therapy. It is distinct from refractory IFI, defined as progression of disease and therefore similar to non-response to treatment. Relapsed IFI occurs after treatment and is caused by the same pathogen at the same site, although dissemination can occur. These proposed definitions are intended to support the design of future clinical trials and epidemiological research in clinical mycology, with the ultimate goal of increasing the comparability of clinical trial results.
Topics: Antifungal Agents; Aspergillosis; Clinical Trials as Topic; Europe; Humans; Invasive Fungal Infections; Mucormycosis; Mycoses; Risk Factors; Treatment Failure
PubMed: 31254420
DOI: 10.1111/myc.12960 -
Blood Nov 2017Lymphodepletion chemotherapy followed by infusion of CD19-specific chimeric antigen receptor-modified (CAR) T cells has produced impressive antitumor responses in...
Lymphodepletion chemotherapy followed by infusion of CD19-specific chimeric antigen receptor-modified (CAR) T cells has produced impressive antitumor responses in patients with refractory CD19 B-cell malignancies but is often associated with cytokine release syndrome (CRS). Our understanding of CRS continues to evolve, and identification of the kinetics of CRS and predictive clinical and laboratory biomarkers of severity are needed to evaluate strategies to mitigate toxicity. We report the clinical presentation of and identify biomarkers of severe CRS in 133 adult patients who received CD19 CAR T cells. CRS developed in 70% of patients, including 62.5% with grade 1 to 3 CRS (grade 1, 26%; grade 2, 32%; grade 3, 4.5%), 3.8% with grade 4, and 3.8% with grade 5. A majority of cases of grade ≥4 CRS occurred during CAR T-cell dose finding. Multivariable analysis of baseline characteristics identified high marrow tumor burden, lymphodepletion using cyclophosphamide and fludarabine, higher CAR T-cell dose, thrombocytopenia before lymphodepletion, and manufacturing of CAR T cells without selection of CD8 central memory T cells as independent predictors of CRS. Severe CRS was characterized by hemodynamic instability, capillary leak, and consumptive coagulopathy. Angiopoietin-2 and von Willebrand factor, which are biomarkers of endothelial activation, were increased during severe CRS and also before lymphodepletion in patients who subsequently developed CRS. We describe a classification-tree algorithm to guide studies of early intervention after CAR T-cell infusion for patients at high risk of severe CRS. These data provide a framework for early intervention studies to facilitate safer application of effective CD19 CAR T-cell therapy.
Topics: Adult; Aged; Biomarkers, Tumor; Blood Coagulation Disorders; Cytokines; Endothelial Cells; Female; Fever; Hematopoiesis; Hemodynamics; Humans; Immunotherapy, Adoptive; Kinetics; Lymphocyte Count; Male; Middle Aged; Multivariate Analysis; Neurotoxicity Syndromes; Receptors, Antigen, T-Cell; Risk Factors; Syndrome; T-Lymphocytes; Treatment Outcome; Young Adult
PubMed: 28924019
DOI: 10.1182/blood-2017-06-793141 -
World Journal of Gastroenterology Jul 2022Proton pump inhibitors (PPIs), the most commonly used antisecretory medi-cations in the management of reflux illness, virtually eliminate elective surgery for ulcer... (Review)
Review
Proton pump inhibitors (PPIs), the most commonly used antisecretory medi-cations in the management of reflux illness, virtually eliminate elective surgery for ulcer disease, and relegate anti-reflux surgery to patients with gastroesophageal reflux disease (GERD) who are inadequately managed by medical therapy. However, PPI medications still leave some therapeutic demands of GERD unmet. Furthermore, up to 40%-55% of daily PPI users have chronic symptoms, due to PPI refractoriness. Potassium-competitive acid blockers (P-CABs) transcend many of the problems and limits of PPIs, delivering quick, powerful, and extended acid suppression and allowing for treatment of numerous unmet needs. Recently, it has become clear that compromised mucosal integrity plays a role in the etiology of GERD. As a result, esophageal mucosal protection has emerged as a novel and potential treatment approach. An increasing body of research demonstrates that when P-CABs are used as primary drugs or add-on drugs (to regular treatment), they provide a considerable extra benefit, particularly in alleviating symptoms that do not respond to PPI therapy.
Topics: Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Potassium; Proton Pump Inhibitors
PubMed: 36161043
DOI: 10.3748/wjg.v28.i28.3608 -
Cancers Dec 2022Although lenalidomide-based combinations, such as lenalidomide plus a proteasome inhibitor or an anti-CD38 monoclonal antibody, improve the overall response rate,... (Review)
Review
Although lenalidomide-based combinations, such as lenalidomide plus a proteasome inhibitor or an anti-CD38 monoclonal antibody, improve the overall response rate, progression-free survival, and overall survival of patients with relapsed/refractory multiple myeloma (RRMM), there is a tendency to use these regimens as a frontline treatment. This strategy has led to the development of refractoriness early in the disease course, usually after the patient's first treatment. Since lenalidomide-free regimens have so far shown limited efficacy in lenalidomide-refractory patients, there is an unmet need for other treatment options. In this review, we discuss the therapeutic options available to treat the general population of lenalidomide-refractory patients (mono, double and triple refractory) and the subpopulation of patients with other high-risk features such as renal failure, extramedullary disease, and high-risk cytogenetics. Moreover, new promising individual therapies and the possible impact of immunotherapy in RRMM patients are debated.
PubMed: 36612152
DOI: 10.3390/cancers15010155 -
Frontiers in Endocrinology 2022TEMPI (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) syndrome is... (Review)
Review
TEMPI (telangiectasias, elevated erythropoietin level and erythrocytosis, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting) syndrome is a rare and newly defined multisystemic disease, which belongs to "monoclonal gammopathy of clinical significances". Due to its rarity, the etiology, pathogenesis, and clinical features of this disease remain largely unknown. Owing to its hidden and diverse clinical manifestations, missed diagnosis and misdiagnosis are common. In recent years, as more patients (including three fatal cases) were identified, some special clinical manifestations other than the typical pentad of TEMPI syndrome have been reported. Meanwhile, several studies attempting to identify the pathogenesis of TEMPI syndrome were conducted. In this review, we summarize the reported clinical characteristics of TEMPI syndrome and discuss the current and potential treatment options for patients with TEMPI syndrome, including those with relapsed/refractory disease. Furthermore, we provide an overview of current knowledge on the pathophysiology of TEMPI syndrome.
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Polycythemia; Syndrome; Telangiectasis
PubMed: 35663307
DOI: 10.3389/fendo.2022.886961 -
Clinical and Experimental... 2016Intestinal inflammation and symptoms of celiac disease (CD) usually respond well to gluten withdrawal, but rare cases are refractory to diet. Two types of refractory CD... (Review)
Review
Intestinal inflammation and symptoms of celiac disease (CD) usually respond well to gluten withdrawal, but rare cases are refractory to diet. Two types of refractory CD are discriminated on the basis of the presence or absence of an atypical population of mucosal lymphocytes that may progress to enteropathy-associated T-cell lymphoma. Challenges remain in the secure diagnosis of both types of refractory disease, and evidence on which to base treatment recommendations is flawed by the small numbers of reported patients and the use of different diagnostic strategies. Recent advances in our understanding of the mechanisms of the condition in conjunction with the development of immunomodulatory agents for managing other inflammatory diseases are helping to shape future approaches to targeted therapy. Progression will depend on collaboration and recruitment to trials. In the meantime, there is evidence to suggest that earlier diagnosis and better follow-up and management of CD may prevent the development of refractoriness.
PubMed: 27536154
DOI: 10.2147/CEG.S87200 -
Blood Mar 2017Peripheral T-cell lymphoma, not otherwise specified, is a broad category of biologically and clinically heterogeneous diseases that cannot be further classified into any... (Review)
Review
Peripheral T-cell lymphoma, not otherwise specified, is a broad category of biologically and clinically heterogeneous diseases that cannot be further classified into any other of the existing entities defined by the World Health Organization classification. Anthracycline-containing regimens, namely cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), nowadays represent the standard first-line treatment; for patients who achieve a satisfactory response, a consolidation by means of autologous stem cell transplantation may offer a greater chance of long-term survival. Several patients, however, display treatment refractoriness or relapse soon after obtaining a response, and just a few of them are suitable transplant candidates. This is why several new agents, with innovative mechanisms of action, have been investigated in this context: pralatrexate, romidepsin, belinostat, and brentuximab vedotin have been approved for relapsed and refractory peripheral T-cell lymphomas based on their activity, although they do not significantly affect survival rates. The incorporation of such new drugs within a CHOP backbone is under investigation to enhance response rates, allow a higher proportion of patients to be transplanted in remission, and prolong survival.
Topics: Antineoplastic Combined Chemotherapy Protocols; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma, T-Cell, Peripheral
PubMed: 28115372
DOI: 10.1182/blood-2016-08-692566