The earliest record of organ transplants is in the fourth century bc, when a surgeon named Tsin Yue-Jen exchanged the hearts of 2 soldiers.¹ In the 1940s, the groundbreaking experimentation in skin transplants of Medawar² and Merrill et al³ established the new field of transplantation immunology. Although other surgeons had attempted deceased-donor and living-donor kidney transplants, Joseph Murray, MD, performed the first successful kidney transplant in 1954 between identical twins, ushering in the new field of solid-organ transplantation.^4,5 Soon after came a succession of firsts, all remarkable technical achievements: the first successful lung transplant performed by James Hardy, MD, in 1963,⁶ the first successful pancreas transplant performed by Richard Lillehei, MD, in 1966,⁷ the first successful liver transplant performed by Thomas Starzl, MD, in 1967,⁸ and the first successful heart transplant performed by Christiaan Barnard, MD, in 1967.⁹

The role of nutritional supplements and dietary interventions in preventing mortality and cardiovascular disease (CVD) outcomes is unclear. To examine evidence about the effects of nutritional supplements and dietary interventions on mortality and cardiovascular outcomes in adults. PubMed, CINAHL, and the Cochrane Library from inception until March 2019; ClinicalTrials.gov (10 March 2019); journal Web sites; and reference lists. English-language, randomized controlled trials (RCTs) and meta-analyses of RCTs that assessed the effects of nutritional supplements or dietary interventions on all-cause mortality or cardiovascular outcomes, such as death, myocardial infarction, stroke, and coronary heart disease. Two independent investigators abstracted data, assessed the quality of evidence, and rated the certainty of evidence. Nine systematic reviews and 4 new RCTs were selected that encompassed a total of 277 trials, 24 interventions, and 992 129 participants. A total of 105 meta-analyses were generated. There was moderate-certainty evidence that reduced salt intake decreased the risk for all-cause mortality in normotensive participants (risk ratio [RR], 0.90 [95% CI, 0.85 to 0.95]) and cardiovascular mortality in hypertensive participants (RR, 0.67 [CI, 0.46 to 0.99]). Low-certainty evidence showed that omega-3 long-chain polyunsaturated fatty acid (LC-PUFA) was associated with reduced risk for myocardial infarction (RR, 0.92 [CI, 0.85 to 0.99]) and coronary heart disease (RR, 0.93 [CI, 0.89 to 0.98]). Folic acid was associated with lower risk for stroke (RR, 0.80 [CI, 0.67 to 0.96]; low certainty), whereas calcium plus vitamin D increased the risk for stroke (RR, 1.17 [CI, 1.05 to 1.30]; moderate certainty). Other nutritional supplements, such as vitamin B₆, vitamin A, multivitamins, antioxidants, and iron and dietary interventions, such as reduced fat intake, had no significant effect on mortality or cardiovascular disease outcomes (very low– to moderate-certainty evidence). Suboptimal quality and certainty of evidence. Reduced salt intake, omega-3 LC-PUFA use, and folate supplementation could reduce risk for some cardiovascular outcomes in adults. Combined calcium plus vitamin D might increase risk for stroke. None.

Objective: To systematically analyze the efficacy and safety of interleukin (IL)-12/23, IL-17, and selective IL-23 inhibitors in moderate to severe plaque psoriasis. Methods and results: Twenty-four randomized placebo-controlled trials were included. Compared to placebo, risk ratios (RR) of achieving PASI-75 and PGA/IGA 0/1 respectively were 20.20 (95% CI 13.82–29.54, p < .00001) and 14.55 (10.42–20.31, p < .00001) for ustekinumab 90 mg, 13.75 (8.49–22.28, p < .00001) and 9.81 (5.70–16.89, p < .00001) for ustekinumab 45 mg, 17.65 (12.38–25.17, p < .00001) and 26.13 (16.05–42.53, p < .00001) for secukinumab 300 mg, 15.36 (10.76–21.94, p < .00001) and 20.91 (12.82–34.13, p < .00001) for secukinumab 150 mg, 18.22 (10.63–31.23, p < .000001) and 18.82 (10.36–34.16, p < .00001) for ixekizumab 80 mg every 4 weeks, 19.83 (11.07–35.52, p < .00001) and 20.41 (11.01–37.81, p < .00001) for ixekizumab 80 mg every 2 weeks, 14.79 (9.86–22.16, p < .00001) and 21.93 (15.52–31.01, p < .00001) for brodalumab 210 mg, 11.55 (7.77–17.18, p < .00001) and 16.59 (11.72–23.49, p < .00001) for brodalumab 140 mg, 12.40 (8.87–17.34, p < .00001) and 10.84 (7.91–14.85, p < .00001) for guselkumab 100 mg, 11.45 (7.45–17.58, p < .00001) and 10.97 (6.44–18.69, p < .00001) for tildrakizumab 200 mg, 11.02 (7.17–16.93, p < .00001) and 10.03 (6.45–15.59, p < .00001) for tildrakizumab 100 mg. Similar outcomes were seen for PASI-90. Safety was satisfactory for each therapy at any dose, but a slightly increased risk of withdrawal due to toxicity was observed in individuals receiving ixekizumab compared to placebo. Conclusion: Ustekinumab, secukinumab, ixekizumab, brodalumab, guselkumab, and tildrakizumab were highly efficacious and generally well-tolerated when used as treatments for moderate to severe plaque psoriasis.