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 concerns an 84 year-old man, who presented with fever, malaise, and discoloration and pain in his fingers and toes ongoing for 2 weeks. He had no history of smoking. On physical examination, he was afebrile with blue-black discoloration on several fingers of his left hand and purpuric lesions on both hands and feet. He had palpable radial and dorsalis pedis pulses on both sides. What is the most likely diagnosis? You are offered Vibrio vulnificus infection, polyarteritis nodosa, necrotizing , Herpetic whitlow, and arterial embolism. We review these conditions. Among patients with metastatic pancreatic cancer, combination with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) leads to longer overall survival than gemcitabine therapy. Investigators now compared the efficacy and safety of a modified FOLFIRINOX regimen with gemcitabine as adjuvant therapy in patients with resected pancreatic cancer. They randomly assigned 493 patients with resected pancreatic ductal adenocarcinoma to receive a modified FOLFIRINOX regimen or gemcitibine for 24 weeks. Again, FOLFIRINOX beat gemcitibine but was more toxic. Bisphosphonates prevent fractures in patients with osteoporosis, but their efficacy in women with osteopenia is unknown. Most fractures in postmenopausal women occur in those with osteopenia, so therapies that are effective in women with osteopenia are needed. Invesitgators conducted a 6-year, double-blind trial involving 2000 women with osteopenia (defined by a T score of −1.0 to −2.5 at either the total hip or the femoral neck on either side) who were 65 years of age or older. Participants were randomly assigned to receive four infusions of either zoledronate at a dose of 5 mg (zoledronate group) or normal saline (placebo group) at 18-month intervals. Zoledronate was remarkable effective. No atypical femoral fractures or cases of osteonecrosis of the jaw were reported in either group. Desmoid tumors (also referred to as aggressive ) are connective tissue neoplasms that can arise in any anatomical location and infiltrate the mesentery, neurovascular structures, and visceral organs. There is no standard of care. In a double-blind, phase 3 trial, investigators randomly assigned 87 patients with progressive,

- 1 - symptomatic, or recurrent desmoid tumors to receive either sorafenib (400-mg tablet once daily) or matching placebo. Crossover to the sorafenib group was permitted for patients in the placebo group who had disease progression. The primary end point was investigator-assessed progression-free survival; rates of objective response and adverse events were also evaluated. Sorefenib was remarkably effective in inhibiting tumor growth. The lifetime risk of stroke has been calculated in a limited number of selected populations. Investigators sought to estimate the lifetime risk of stroke at the regional, country, and global level using data from a comprehensive study of the prevalence of major diseases. They used the Global Burden of Disease (GBD) Study 2016 estimates of stroke incidence and the competing risks of death from any cause other than stroke to calculate the cumulative lifetime risks of first stroke, ischemic stroke, or hemorrhagic stroke among adults 25 years of age or older. The global lifetime risk of stroke is approximately 25% starting at the age of 25 years among both men and women, and there is large geographic variation, with a particularly high lifetime risk of stroke in East Asia, Central Europe, and Eastern Europe. Advances in cancer screening and early detection, improvements in therapeutics, and supportive care all contribute to decreasing cancer mortality. As a result, physicians will be caring for more and more cancer survivors. N Engl J Med reviews the subject. We next learn that children and adolescents in the US are most commonly killed by motor vehicle accidents and gunshot wounds. We inspect a patient with a bullet lodged adjacent to his right knee joint. We learn that he has elevated blood lead levels and a minimental score of 24 (normal 30). The weekly case involves a young man with diplopia and proptosis of the left eye. We discover that he has a limited form of ANCA negative granulomatosis with polyangiitis. Uterus transplantation from live donors became a reality to treat infertility following a successful Swedish 2014 series, inspiring uterus transplantation centers and programs worldwide. However, no case of livebirth via deceased donor uterus has been successfully achieved, raising doubts about its feasibility and viability, including whether the womb remains viable after prolonged ischemia. In a Lancet report, we review a successful case from Brazil. Pegbelfermin (BMS-986036), a PEGylated human fibroblast growth factor 21 (FGF21) analog, has previously been shown to improve markers of metabolism and liver fibrosis in obese patients with type 2 diabetes. We inspect a controlled trial of

- 2 - this treatment in patients with non-alcoholic fatty liver disease. We then review a vaccine trial directed at Chikungunya fever. The UN Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) has provided support to Palestine refugees in Jordan, Lebanon, Syria, the Gaza Strip, and the West Bank since the 1950s. We learn that a multifaceted international response is needed to enable UNRWA to deliver sustainable services to Palestinian refugees and avert further loss of life, dignity, and hope, pending a just and lasting solution to their plight in accordance with applicable international law and UN General Assembly resolutions. We close with a patient who was shot by a friend. Since N Engl J Med and the Lancet eschew Christmas and New Year’s vacation, clinical journal club must soldier on in spite of the holidays. Join me on Wednesday in English and in German.

Yours, Fred Luft Check out the file pdf at https://www.mdc-berlin.de/cjc

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