He was also one of the first to understand the importance of pathology, the danger of the spread of infection and how the problem of inflammation of the wound, bone lesions and even tuberculosis often undid any benefit that was gained from the intervention. He consequently adopted the position that all surgical procedures should be used only as a last resort.Other important 18th- and early 19th-century surgeons included Percival Pott (1713–1788) who described tuberculosis on the spine and first demonstrated that a cancer may be caused by an environmental carcinogen (he noticed a connection between chimney sweeps exposure to soot and their high incidence of scrotal cancer). Astley Paston Cooper (1768–1841) first performed a successful ligation of the abdominal aorta, and James Syme (1799–1870) pioneered the Symes Amputation for the ankle joint and successfully carried out the first hip disarticulation. Modern pain control through anesthesia was discovered in the mid-19th century. Before the advent of anesthesia, surgery was a traumatically painful procedure and surgeons were encouraged to be as swift as possible to minimize patient suffering. This also meant that operations were largely restricted to amputations and external growth removals. Beginning in the 1840s, surgery began to change dramatically in character with the discovery of effective and practical anaesthetic chemicals such as ether, first used by the American surgeon Crawford Long, and chloroform, discovered by Scottish obstetrician James Young Simpson and later pioneered by John Snow, physician to Queen Victoria.
Mobocertinib, sold under the brand name Exkivity, is used for the treatment of non-small cell lung cancer.The most common side effects include diarrhea, rash, nausea, stomatitis, vomiting, decreased appetite, paronychia, fatigue, dry skin, and musculoskeletal pain.Mobocertinib is a small molecule tyrosine kinase inhibitor. Its molecular target is epidermal growth factor receptor (EGFR) bearing mutations in the exon 20 region. Mobocertinib is an irreversible kinase inhibitor, forming a covalent bond with the cysteine 797 in the EGFR active site, leading to sustained inhibition of EGFR enzymatic activity. The irreversible binding leads to increased potency via higher affinity binding, more sustained EGFR kinase activity inhibition, and greater overall selectivity, as only a limited number of other kinases possess a cysteine in the equivalent position.Mobocertinib was approved for medical use in the United States in September 2021. It is a first-in-class oral treatment to target EGFR Exon20 insertion mutations. Medical uses
Mobocertinib is indicated for adults with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. Mechanism of action
Mobocertinib acts to inhibit EGFR exon 20 insertion mutations at a lower concentration than it does on wild-type proteins. Pharmacokinetics
The volume of distribution of Mobocertinib at steady state is 3,509 L.  The mean oral bioavailability of Mobocertinib is 37%. The median Tmax is 4 hours. The average half-life of Mobocertinib and its metabolites is 18 hours. Mobocertinib is metabolized by CYP3A enzymes.