Oncologic Emergencies: Immune-Based Cancer Therapies and Complications

Cancer therapies have undergone several recent advancements. Current cancer treatments include immune-based therapies comprised of checkpoint inhibitors, and adoptive immunotherapy; each treatment has the potential for complications that differ from chemotherapy and radiation. This review evaluates immune-based therapies and their complications for emergency clinicians. Therapy complications include immune-related adverse events (irAE), cytokine release syndrome (CRS), autoimmune toxicity, and chimeric antigen receptor (CAR) T-cell-related encephalopathy syndrome (CRES). Immune-related adverse events are most commonly encountered with checkpoint inhibitors and include dermatologic complications, pneumonitis, colitis/diarrhea, hepatitis, and endocrinopathies. Less common irAEs include nephritis, myocardial injury, neurologic toxicity, ocular diseases, and musculoskeletal complications. CRS and CRES are more commonly associated with CAR T-cell therapy. CRS commonly presents with flu-like illness and symptoms resembling sepsis, but severe myocardial and pulmonary disease may occur. Critically ill patients require resuscitation, broad-spectrum antibiotics, and hematology/oncology consultation

Crush syndrome

AbstractThe first detailed cases of crush syndrome were described in 1941 in London after victims trapped beneath bombed buildings presented with swollen limbs, hypovolemic shock, dark urine, renal failure, and ultimately perished. The majority of the data and studies on this topic still draw from large databases of earthquake victims. However, in Africa, a continent with little seismic activity, the majority of crush syndrome cases are instead victims of severe beatings rather than earthquake casualties, and clinical suspicion by emergency personnel must be high in this patient group presenting with oliguria or pigmenturia. Damaged skeletal muscle fibres and cell membranes lead to an inflammatory cascade resulting in fluid sequestration in the injured extremity, hypotension, hyperkalemia and hypocalcemia and their complications, and renal injury from multiple sources. Elevations in the serum creatinine, creatine kinase (CK), and potassium levels are frequent findings in these patients, and can help guide critical steps in management. Fluid resuscitation should begin prior to extrication of trapped victims or as early as possible, as this basic intervention has been shown to in large part prevent progression of renal injury to requiring haemodialysis. Alkalinization of the urine and use of mannitol for forced diuresis are recommended therapies under specific circumstances and are supported by studies done in animal models, but have not been shown to change clinical outcomes in human crush victims. In the past 70years the crush syndrome and its management have been studied more thoroughly, however clinical practice guidelines continue to evolve

Clinical review of malaria for the emergency physician

AbstractMalaria is a disease caused by parasites of the Plasmodium genus, and is one of the most prevalent diseases in Africa and around the world. Emergency physicians in both endemic and non-endemic regions often encounter initial presentations of malaria, and knowledge about the pathophysiology, diagnosis, and treatment of this disease is crucial in caring for these patients. This article covers briefly the epidemiology of malaria and the lifecycle of the Plasmodium parasite. This is followed by a discussion of the clinical evaluation, diagnosis, and management of patients with malaria, as pertinent to the African emergency physician

The Somatic Genomic Landscape of Glioblastoma

We describe the landscape of somatic genomic alterations based on multi-dimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer

Emergency Centre care for sexual assault victims

Sexual assault is a topic of importance worldwide to health professionals that provide emergency care. Victims of sexual assault include adult men, adult women, and children. The prevalence of sexual assault is likely under-reported. These patients should be offered comprehensive medical care upon arrival to the emergency centre. This includes assessment for acute injuries; medical history; physical examination; and possible collection of evidence. Depending on the patient's situation, he or she may be offered prophylactic and therapeutic management, which includes pregnancy testing and emergency contraception, prophylaxis for sexually transmitted infections, and HIV post-exposure prophylaxis. This article addresses the most up-to-date information on this management. Patients should also be offered mental health counselling on-site if appropriate health professionals are available. A number of countries have national protocols for care of the sexual assault patient. Implementing these protocols can be strengthened through such interventions as hiring sexual assault nurse examiners or creating a sexual assault centre within the emergency centre. The patient's immediate and future safety and emotional needs should be evaluated and a plan formulated for safety when the patient is discharged. Medical follow up is recommended and should be strongly encouraged

Meningococcal disease

The first cases of meningococcal meningitis were described in Geneva in 1805 and in New England in 1806, the causative agent finally being identified by Anton Weichselbaum in 1887. The first meningococcal epidemics occurred in sub-Saharan Africa in the early 1900s and periodic outbreaks continue to occur worldwide today. Neisseria meningitidis colonizes the naso-oropharyngeal mucosa in approximately 10–20% of healthy individuals. When it invades the bloodstream, meningococcus has the potential to cause devastating disease. It can affect people of any age, but primarily infects children and adolescents. Meningococcemia classically follows an upper respiratory illness consisting of myalgias, fever, headache, and nausea. It can present as an indolent infection with rapid recovery or progress within a few hours into a fulminant illness affecting multiple organ systems. As such, meningococcemia is one of the important causes of sepsis. Prior to antibiotic therapy, the disease carried a 70% mortality rate. Despite advances in early diagnosis and treatment, 10–15% of affected patients die from the disease and another 10–20% are left with severe morbidities (neurologic disability, hearing loss, loss of a limb). Meningococcal disease remains a significant global health threat

Methamphetamine and MDMA: ‘Safe’ drugs of abuse

Methamphetamine and MDMA have been called safe drugs of abuse. Worldwide there is an increased consumption of these drugs, which has become a focus of research in South Africa. As the number of methamphetamine users has increased in many African countries, it is essential that emergency care practitioners are able to diagnose and manage intoxication with methamphetamine, MDMA, and other derivatives. The most common presentations include restlessness, agitation, hypertension, tachycardia, and headache while hyperthermia, hyponatraemia, and rhabdomyolysis are among the most common serious complications. Most deaths are secondary to hyperthermia complicated by multiple organ failure. A number of laboratory analyses should be obtained if locally available. We provide a review of the current recommended general and specific management approaches. Benzodiazepines are the first line therapy for hyperthermia, agitation, critical hypertension, and seizures. Patients with serious complications are best managed in an intensive care unit if available. Emergency centres should create protocols and/or further train staff in the recognition and management of intoxication with these ‘not so safe’ drugs