Summary Clinical Journal Club

Dear friends of clinical journal club - load the file down at https://www.mdc- berlin.de/cjc: The N Engl J Med image of the week shows a 4-year-old boy who was brought by his father to the ophthalmology clinic with a 1-year history of enlarging white deposits in both eyes and decreasing night vision. On examination, the conjunctivae of both the right eye and the left eye appeared dry and wrinkled, with foamy, cream-colored deposits near the outer corners. The corneas were clear, the fundi were normal, and the visual acuity was 20/30 in both eyes. The child appeared pale, with hypopigmented hair, a weight of 10.5 kg (z score of less than −3), and a height of 92 cm (z score of −2.8). These physical exam findings are associated with what underlying condition? You are offered Sjögren syndrome, pyridoxine deficiency, vitamin A deficiency, Loaisis, and type-1 diabetes. Concern about the use of epinephrine as a treatment for out-of-hospital cardiac arrest led the International Liaison Committee on Resuscitation to call for a placebo-controlled trial to determine whether the use of epinephrine is safe and effective in such patients. In a randomized, double-blind trial involving 8014 patients with out-of-hospital cardiac arrest in the United Kingdom, paramedics at five National Health Service ambulance services administered either parenteral epinephrine (4015 patients) or saline placebo (3999 patients), along with standard care. The primary outcome was the rate of survival at 30 days. Secondary outcomes included the rate of survival until hospital discharge with a favorable neurologic outcome, as indicated by a score of 3 or less on the modified Rankin scale. In the epinephrine group, 3.2% were alive at 30 days, in the placebo group 2.4%, a slight but significant difference. However, the survivors in the epinephrine group had a more severe neurological impairment. Brain metastases are a common cause of disabling neurologic complications and death in patients with metastatic melanoma. Previous studies of nivolumab combined with ipilimumab in metastatic melanoma have excluded patients with untreated brain metastases. Therefore, the next investigators evaluated the efficacy and safety of nivolumab plus ipilimumab in patients with melanoma who had untreated brain metastases. Yes, the combined treatment (against CTLA4 and PD-1) seemed effective. At 30 months 75% of the patients were still alive. The use of tranexamic acid reduces mortality due to postpartum hemorrhage. Obstetricians investigated - 1 - whether the prophylactic administration of tranexamic acid in addition to prophylactic oxytocin in women with vaginal delivery would decrease the incidence of postpartum hemorrhage. In a multicenter, double-blind, randomized, controlled trial, the investigators randomly assigned women in labor who had a planned vaginal delivery of a singleton live fetus at 35 or more weeks of gestation to receive 1 g of tranexamic acid or placebo, administered intravenously, in addition to prophylactic oxytocin after delivery. Unfortunately, tranexamic acid did not reduce postpartum blood loss. Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage, which is not available in many countries. In a large trial, investigators compared a novel formulation of heat-stable carbetocin with oxytocin. Carbetocin is an oxytocin analogue, does not require cold-chain transport and storage; it has been shown to maintain stability over a period of 36 months at 30°C and 75% relative humidity. The investigators enrolled women across 23 sites in 10 countries in a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin (at a dose of 100 μg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth. Both drugs were kept in cold storage (2 to 8°C) to maintain double-blinding. There were two primary outcomes: the proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml. Carbetocin was noninferior to oxytocin. The N Engl J Med review is about Lynch syndrome. Of all new cases of colorectal cancer, 3% are attributable to the Lynch syndrome. Although colorectal cancer is the most common cancer associated with the Lynch syndrome, extracolonic cancers, including cancers of the endometrium (the most common), small bowel, ureter and renal pelvis, stomach, hepatobiliary tract, and ovary, can occur. Variants of the Lynch syndrome include the Muir–Torre syndrome, which is characterized by sebaceous adenomas and other skin tumors (such as keratoacanthomas), and Turcot’s syndrome, which includes glioblastoma. The genetic mechanism involves DNA repair genes. Incidentally, Dr. Henry Lynch (ex high-school dropout, soldier, and boxer) is a genuine clinician-scientist hero, who will be 90 years old this year. The patient this week is a 48 year-old man who develops fever, chills, and an erythematous rash over half his body. He has eosinophilia, Herpes Virus 6, and ingests a variety of medicines for various reasons. - 2 - The condition is called Drug Rash with Eosinophilia and Systemic Symptoms (DRESS). In the Lancet, we learn that obesity is a major public health issue, and new pharmaceuticals for weight management are needed. Therefore, investigators evaluated the efficacy and safety of the glucagon-like peptide-1 (GLP-1) analogue semaglutide in comparison with liraglutide and a placebo in promoting weight loss. They did a randomised, double-blind, placebo and active controlled, multicentre, dose-ranging, phase 2 trial. The study was done in eight countries involving 71 clinical sites. Eligible participants were adults (≥18 years) without diabetes and with a body-mass index (BMI) of 30 kg/m2 or more. The estimated bodyweight reductions were 7·8% for participants receiving liraglutide and 2·3% for those receiving placebo. The highest dose of semaglutide was very impressive. The efficacy-safety relationship seemed very favorable. Risankizumab is a humanised IgG1 monoclonal antibody that binds to the p19 subunit of interleukin-23, inhibiting this key cytokine. The next investigators aimed to assess the efficacy and safety of risankizumab compared with placebo or ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. In each study, patients were stratified by weight and previous exposure to tumour necrosis factor inhibitor and randomly assigned (3:1:1) by use of interactive response technology to receive 150 mg risankizumab, 45 mg or 90 mg ustekinumab (weight-based per label), or placebo. Findings from these two phase 3 randomised, double-blind, controlled clinical studies showed that risankizumab was highly effective in treatment of patients with moderate-to-severe plaque psoriasis. About a third of women receiving pethidine (a synthetic opioid also known as meperidine) for labour pain subsequently require an epidural, which provides effective pain relief but increases the risk of instrumental vaginal delivery. Remifentanil (a highly potent shortacting opioid) patient-controlled analgesia (PCA) in labour is an alternative to pethidine, but is not widely used. We inspect a comparison. The Lancet reviews are on snake bite and AIDS. Both reviews are timely and helpful. We close with a 41-year-old woman presented to a clinic because of the sudden appearance of erosions on and swelling of her lips. Presentation from last week and this week will be on Wednesday. Otherwise please load-down the files and perhaps YouTube. Yours, Fred Luft - 3 - Check out the file pdf at https://www.mdc-berlin.de/cjc - 4 - .

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