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Following France’s entry into World War I on August 3, 1914, Thierry de Martel (1875–1940), the French neurosurgery pioneer, served on the front line and was wounded on October 3, 1914. He was then assigned as a surgeon in temporary hospitals in Paris, where he published his first observations of cranioencephalic war wounds. In 1915, de Martel met Harvey Cushing at the American Hospital in Neuilly, where de Martel was appointed chief surgeon in 1916. In 1917, he published with the French neurologist Charles Chatelin a book (Blessures du crâne et du cerveau. Clinique et traitement) with the aim to optimize the practice of wartime brain surgery. This book, which included the results of more than 5000 soldiers with head injuries, was considered the most important ever written on war neurology at that time and was translated into English in 1918 (Wounds of the Skull and Brain; Their Clinical Forms and Medical and Surgical Treatment). In this book, de Martel detailed the fundamentals of skull injuries, classified the various craniocerebral lesions, recommended exploratory craniectomy for cranioencephalic injuries, recommended the removal of metal projectiles from the brain using a magnetic nail, and advocated for the prevention of infectious complications. Between the World Wars, de Martel undertook several developments for neurosurgery in France alongside neurologists Joseph Babinski and Clovis Vincent. Following France’s entry into World War II on September 3, 1939, de Martel took over as head of the services of the American Hospital of Paris in Neuilly. He updated his work on war surgery with the new cases he personally treated. Together with Vincent, de Martel presented his new approach in "Le traitement des blessures du crâne pendant les opérations militaires" ("The treatment of skull injuries during military operations") on January 30, 1940, and published his own surgical results in April 1940 in "Plan d’un travail sur le traitement des plaies cranio-cérébrales de guerre" ("Work Plan on the Treatment of Cranio-Cerebral Wounds of War"), intended for battlefield surgeons. On June 14, 1940, the day German troops entered Paris, de Martel injected himself with a lethal dose of phenobarbital. Thierry de Martel played a central role in establishing modern neurosurgery in France. His patriotism led him to improve the management of wartime cranioencephalic injuries using his own experience acquired during World Wars I and II.

The present investigation aimed to characterize the protein profile of cavitating ultrasound aspirator fluid of newly diagnosed and recurrent glioblastoma comparing diverse zones of collection, i.e., tumor core and tumor periphery, with the aid of 5-aminolevulinic acid fluorescence. The samples were pooled and analyzed in triplicate by LC-MS following the shotgun proteomic approach. The identified proteins were then grouped to disclose elements exclusive and common to the tumor state or tumor zones and submitted to gene ontology classification and pathway overrepresentation analysis. The proteins common to the distinct zones were further investigated by relative quantitation, following a label free approach, to disclose possible differences of expression. Nine proteins, i.e., tubulin 2B chain, CD59, far upstream element-binding, CD44, histone H1.4, caldesmon, osteopontin, tropomyosin chain and metallothionein-2, marked the core of newly diagnosed glioblastoma with respect to tumor periphery. Considering the tumor zone, including the core and the fluorescence positive periphery, the serine glycine biosynthesis, pentose phosphate, 5-hydroxytryptamine degredation, de novo purine biosynthesis and huntington disease pathways resulted statistically significantly overrepresented with respect to the human genome of reference. The fluorescence negative zone shared several protein elements with the tumor zone, possibly indicating the presence of pathological aspects of glioblastoma rather than of normal brain parenchyma. On the other hand, its exclusive protein elements were considered to represent the healthy zone and, accordingly, exhibiting no pathways overrepresentation. On the contrary to newly diagnosed glioblastoma, pathway overrepresentation was recognized only in the healthy zone of recurrent glioblastoma. The TGF&beta, signaling pathway, exclusively classified in the fluorescence negative periphery in newly diagnosed glioblastoma, was instead the exclusive pathway classified in the tumor core of recurrent glioblastoma. These results, preliminary obtained on sample pools, demonstrated the potential of cavitron ultrasonic sur