In this section, we highlight the key high-impact studies, updates, and analyses published in medicine during the past week.
Past studies have shown that the outcomes of renal transplantation in HIV-positive patients are comparable to those of other high-risk candidates. In South Africa, where the rates of HIV infection remained high, and HIV infection was considered a contraindication for dialysis treatment or transplantation from an HIV-seronegative donor, a study was started in 2008 to evaluate the outcomes of HIV-positive-to-HIV-positive kidney transplantation. Previous results were favorable at one year, and the current study demonstrates the long term outcomes. In this prospective, nonrandomized trial lasting to 2014, 27 HIV-infected individuals on antiretroviral therapy with CD4 counts of 200 or higher and undetectable plasma HIV RNA levels received deceased donor kidneys from HIV positive patients who had either received no antiretroviral therapy or only first line antiretroviral therapy. Patients were followed for a median of 2.4 years, with survival rates of 84% at 1 year, 84% at 3 years, and 74% at 5 years. The viral load remained undetectable after transplantation. The rates of graft survival were 93% at 1 year, 84% at 3 years, and 84% at 5 years. Rejection rates were 8% at 1 year and 22% at 3 years. This study thus concluded that HIV-Positive-to-HIV-Positive Kidney transplantation appears to be a reasonable option.
This proof-of concept study describes the first live birth following a uterine transplantation from a post-menopausal donor. Prior studies have documented cases of uterine transplantation; however, no studies to date have reported successful pregnancies and deliveries following uterine transplantation. In this study, a 35 year old woman with congenital absence of a uterus has undergone a uterine transplantation using a uterus donated by a living 61 year old two-parous woman. The recipient was started on tacrolimus, azathioprine, and corticosteroids, with a total of 3 mild episodes of rejection, all reversed by corticosteroid treatment. The recipient started menstruating at regular intervals 43 days after transplantation. One year after uterine transplantation, the recipient successfully became pregnant after receiving an embryo transfer of one of the cryopreserved embryos prepared by in-vitro fertilization treatment by the recipient and her partner prior to uterine transplantation. Patient had a normal pregnancy until she was admitted for pre-eclampsia at 31 full weeks and 5 days. She had a caesarean section due to abnormal cardiotocography, with the delivery of a normal birth weight male baby with 9,9,10 APGAR scores. The uterine donor was also reported to undergo an uneventful recovery.
Transoralesophagogastric fundoplication (TF) is a treatment option for patients with gastroesophageal reflux disease (GERD) whose symptoms continue despite a maximal proton pump inhibitor (PPI) therapy. This prospective, sham controlled trial aimed to compare TF and PPI treatment in patients with GERD.Patients with persistent symptoms despite a daily PPI treatment and hiatal hernias greater than or equal to 2 cm were randomly assigned to undergo either TF followed by 6 months of placebo (n=87) or sham procedure followed by 6 months of once or twice daily omeprazole (n=42). TF reduced symptoms in 67% of patents and PPIs reduced symptoms in 45% of patients (p=0.023). TF lead to more significant decrease in esophageal acid exposure compared to PPIs. Both groups showed similar reductions in GERD symptoms scores, and severe complications were rare in both groups. Thus, TF was concluded to be an effective alternative for patients with uncontrolled GERD.
A controversy persists regarding the optimal induction and maintenance therapy in Crohn’s Disease (CD). In this meta-analysis, 39 randomized controlled trials have been identified studying methotrexate, azathioprine/6-mercaptopurine, infliximab, adalimumab, certolizumab, vedolizumab, or combined therapies. The pairwise treatment effects were evaluated with Bayesian random-effects network meta-analysis. For induction of remission, infliximab, infliximab+azathioprine, adalimumab, and vedolizumab were superior to placebo. Compared to certolizumab, infliximab+azathioprine were superior for induction of remission (OR, 3.1; 95% CI, 1.4-7.7) as was adalimumab (OR, 2.1; 95% CI, 1.0-4.6). For maintaining remission, all treatments were superior to placebo except infliximab+methotrexate. Compared to azathioprine/6 mercaptopurine, adalimumab (OR, 2.9; 95% CI, 1.6-5.1), infliximab (OR, 1.6; 95% CI 1.0-2.5), and infliximab+azathioprine (OR, 3.0; 95% CI, 1.7-5.5) were superior in maintaining remission. Compared to certolizumab, adalimumab (OR, 2.5; 95% CI, 1.4-4.6) and infliximab+azathioprine (OR, 2.6; 95% CI, 1.3-6.0) were superior in maintaining remission. Compared to vedolizumab, adalimumab was superior (OR, 2.4; 95% CI, 1.2-4.6). Overall, the study concluded that adalimumab and infliximab+azathioprine may be the best options for induction and maintenance of remission in CD.
Previously, lenvatinib, which is an oral inhibitor of vascular endothelial growth factors receptors 1,2 and 3, fibroblast growth factor receptors 1, 2, 3, and 4, platelet derived growth factor receptor alpha, RET, and KIT, has been shown to be efficacious in differentiated thyroid cancer resistant to radioiodine therapy in phase 2 trial. In this randomized, double blind, multicenter, phase 3 trial, 392 patients with thyroid cancer refractory to iodine therapy were assigned to receive either a daily dose of 24 mg of lenvatinib in 28 day cycles or a placebo. Progression-free survival, response rate, and safety were evaluated. Median progression free survival was 18.3 months in lenvatinib group compared to 3.6 months in the placebo group (hazard ratio, 0.21; 99% CI 0.14 – 0.31; p<0.001). Response rate was 64.8% in the lenvatinib group and 1.5% in the placebo group (p<0.001). In terms of side effects, 6 out of 20 deaths that occurred in the lenvatinib group were considered drug related. Other adverse events occurred in 40% of patients in lenvatinib group, ranging from hypertension, diarrhea, fatigue, decreased appetite, decreased weight, and nausea. 14.2% of patients in lenvatinib group discontinued treatment due to side effects as compared to 2.3% of patients in the placebo group. In conclusion, although lenvatinib was shown to have higher rates of adverse events, it increased progression-free survival and response rate in iodine treatment resistant thyroid cancer.
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