December 2019 – The Month of Magic

The CheckMate 227 trial is an open-label Phase III trial involving patients with Stage IV non-small-cell-lung cancer (NSCLC). Upon entry, patients with programmed death ligand 1 (PD-L1) expression levels ≥1% were randomly assigned in a 1:1:1 ratio to receive nivolumab plus ipilimumab, nivolumab alone, or chemotherapy alone. Patients with PD-L1 expression levels <1% were randomly assigned to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy alone. The primary endpoint reported concerned overall survival (OS) with nivolumab plus ipilimumab as compared to chemotherapy.

Among patients with PD-L1 expression levels ≥1%, the median OS was 17.1 months with nivolumab plus ipilimumab and 14.0 months with chemotherapy (P=0.007), with 2-year OS rates of 40.0% and 32.8%, respectively. An OS benefit was also noted in patients with PD-L1 expression levels <1%, with a median OS of 17.2 months with nivolumab plus ipilimumab versus 12.2 months with chemotherapy. When considering the overall study population, the median OS was 17.1 months with nivolumab plus ipilimumab versus 13.9 months with chemotherapy.

The percentage of patients who experienced Grade 3 or 4 treatment-related undesirable effects in the overall population was 32.8% with nivolumab plus ipilimumab versus 36.0% with chemotherapy. According to the authors, the treatment-related undesirable effects associated with nivolumab plus ipilimumab or chemotherapy were consistent with those reported in previous trials. Of note is that their incidence did not increase within a longer follow-up duration.

https://www.ncbi.nlm.nih.gov/pubmed/31562796

Reference: Hellmann MD, Paz-Ares L, Bernabe Caro R, et al.  Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2019. doi: 10.1056/NEJMoa1910231. [Epub ahead of print]

McCarthy and Savage collaborated intensely to condense McCarthy’s editing advice into several short statements. As these concepts have proven invaluable to us, we naturally wanted to share them with our readers. McCarthy’s main advice can be summarized as follows: Keep it simple while telling a coherent and compelling story. Below, you’ll find the first list of McCarthy’s principles as Part I.

• Use minimalism to achieve clarity. When you are writing, always ask yourself the following: Is it possible to preserve my original meaning without that punctuation mark, that word, that sentence, that paragraph, or even that section? Remove superfluous words or commas whenever you can.
• Decide on your readers’ theme and two to three points you want every reader to remember. This theme and these points form the single thread that runs through your paper.
• Limit each paragraph to a single message. Each paragraph should explore that message by first asking a question and then progressing to an idea and, at times, an answer.
• Keep sentences short, simply constructed, and direct. Concise, clear sentences work well for scientific explanations. Minimize clauses, compound sentences, and transition words such as “however” or “thus” so that the reader can focus on the main message.
• Don’t slow the reader down. Avoid footnotes, as they break the flow of thoughts. Don’t use jargon and overly technical language. And avoid using the same word repeatedly.

https://www.nature.com/articles/d41586-019-02918-5

The culprit: Queen Victoria of England, the Empress of the Indies.

This hereditary bleeding disorder has been associated with significant political consequences, the Bolshevik Revolution being the most significant one. As none of Victoria’s living descendants carry hemophilia, determining the exact causal mutation at the origin of the bleeding disease was rendered impossible for a long time.

In 1991, however, a tomb containing the remains of most of the Czar Nicolas II family was discovered, with a second tomb identified in 2007. Using the most up-to-date genetic tools along with the newest communication technology, Russian and American researchers were able to identify each body and obtain precious genetic material from young Czar Alexis.

The young Czar suffered from hemophilia B prior to being executed at age 14. Based on the major advances made in their respective research domains in recent years, the scientists were able to precisely identify the causal substitution in the Factor IX gene that brought such distress to European royal families.

A research team from the Neurology department of the Medicine and Health Sciences faculty and the German department of the Arts and Philosophy faculty of Ghent University, Ghent, Belgium, conducted in-depth investigations in 2008, using original letters from Nietzsche, descriptions by his relatives and friends, and biographical papers published in medical journals.

According to the research teams’ outcomes, Nietzsche suffered from migraine without aura since his childhood. In the second half of his life, he was afflicted by a psychiatric disorder with depressive episodes. During the last years of his life, Nietzsche exhibited a progressive cognitive decline that eventually led to profound dementia and stroke.

According to the Belgian research teams, all the signs and symptoms of Nietzsche’s disease could be accounted for by a medical condition described as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). According to the experts, there is insufficient evidence available to date to support the hypothesis that Nietzsche’s illness was caused by neurosyphilis.