[Brain metastases]. / Hirnmetastasen.

Cerebral metastases in patients with metastatic lung cancer are found in more than 30% of patients at baseline and manifest themselves in two out of three patients during disease evolution. For a long time, the cerebral manifestation of the disease was classified as prognostically unfavorable and hence such patients were regularly excluded from therapy studies. In the context of targeted molecular therapy strategies and established immuno-oncological systemic therapies, the blood-brain barrier no longer represents an insurmountable barrier. However, the treatment of brain metastases requires decision making in a multidisciplinary team within dedicated lung cancer and/or oncology centers. The differentiated treatment decision is based on the number, size and location of the brain metastases, neurology and general condition, comorbidities, potential life expectancy and the patient's wishes, but also tumor biology including molecular targets, extra-cranial tumor burden and availability of a CNS-effective therapy. Systemic therapies as well as neurosurgical and radiotherapeutic concepts are now often combined for optimized and prognosis-improving therapeutic strategies.

Pandemic's surgical sabotage.

Surgical care has steadily advanced and improved over hundreds of years. The evolution of surgical care in the past compared to advances in today's world was shockingly slow, with many interruptions and oppositions, but surgical advancement could only move forward if all other advancements in technology, scientific understanding, social and traditional concerns also progressed. This essay wishes to follow the incredible changes, that have enhanced or mitigated today's surgical services, but also events, like our present pandemic, that have interfered, even sabotaged the delivery of surgical services.

Impact of First-Line Antimicrobials on Chlamydia trachomatis-Induced Changes in Host Metabolism and Cytokine Production.

Urogenital infections with Chlamydia trachomatis (C. trachomatis) are the most common bacterial sexually transmitted diseases worldwide. As an obligate intracellular bacterium, chlamydial replication and pathogenesis depends on the host metabolic activity. First-line antimicrobials such as doxycycline (DOX) and azithromycin (AZM) have been recommended for the treatment of C. trachomatis infection. However, accumulating evidence suggests that treatment with AZM causes higher rates of treatment failure than DOX. Here, we show that an inferior efficacy of AZM compared to DOX is associated with the metabolic status of host cells. Chlamydial metabolism and infectious progeny of C. trachomatis were suppressed by therapeutic relevant serum concentrations of DOX or AZM. However, treatment with AZM could not suppress host cell metabolic pathways, such as glycolysis and mitochondrial oxidative phosphorylation, which are manipulated by C. trachomatis. The host cell metabolic activity was associated with a significant reactivation of C. trachomatis after removal of AZM treatment, but not after DOX treatment. Furthermore, AZM insufficiently attenuated interleukin (IL)-8 expression upon C. trachomatis infection and higher concentrations of AZM above therapeutic serum concentration were required for effective suppression of IL-8. Our data highlight that AZM is not as efficient as DOX to revert host metabolism in C. trachomatis infection. Furthermore, insufficient treatment with AZM failed to inhibit chlamydial reactivation as well as C. trachomatis induced cytokine responses. Its functional relevance and the impact on disease progression have to be further elucidated in vivo.

Unmasking the unmasked.

Facial maskings have been part of the human story since time began, and the reasons for their needs and the materials that went into their making would vary according to the reasons and materials available. The health-related needs took centuries to become established, but not until the germ theory of disease became recognized. The facial mask, seen as an essential defensive tool for prevention of respiratory transmitted disease continues to be the prime personal protective piece of equipment. With air-born contaminations, such as the present pandemic SARS- CoV-2 viral infestation, why would there be opposition to the use of this personal protective cover of our airways, when until an immunologic answer is available, it is the best single prevention we have. When supported with other measures, like distancing, washing and non-crowding, society would be much safer and secure, with probable less acute and drastic outcomes due to the spread of this virus.

Regulation of the Mitochondrion-Fatty Acid Axis for the Metabolic Reprogramming of Chlamydia trachomatis during Treatment with ß-Lactam Antimicrobials.

Infection with the obligate intracellular bacterium Chlamydia trachomatis is the most common bacterial sexually transmitted disease worldwide. Since no vaccine is available to date, antimicrobial therapy is the only alternative in C. trachomatis infection. However, changes in chlamydial replicative activity and the occurrence of chlamydial persistence caused by diverse stimuli have been proven to impair treatment effectiveness. Here, we report the mechanism for C. trachomatis regulating host signaling processes and mitochondrial function, which can be used for chlamydial metabolic reprogramming during treatment with ß-lactam antimicrobials. Activation of signal transducer and activator of transcription 3 (STAT3) is a well-known host response in various bacterial and viral infections. In C. trachomatis infection, inactivation of STAT3 by host protein tyrosine phosphatases increased mitochondrial respiration in both the absence and presence of ß-lactam antimicrobials. However, during treatment with ß-lactam antimicrobials, C. trachomatis increased the production of citrate as well as the activity of host ATP-citrate lyase involved in fatty acid synthesis. Concomitantly, chlamydial metabolism switched from the tricarboxylic acid cycle to fatty acid synthesis. This metabolic switch was a unique response in treatment with ß-lactam antimicrobials and was not observed in gamma interferon (IFN-γ)-induced persistent infection. Inhibition of fatty acid synthesis was able to attenuate ß-lactam-induced chlamydial persistence. Our findings highlight the importance of the mitochondrion-fatty acid interplay for the metabolic reprogramming of C. trachomatis during treatment with ß-lactam antimicrobials.IMPORTANCE The mitochondrion generates most of the ATP in eukaryotic cells, and its activity is used for controlling the intracellular growth of Chlamydia trachomatis Furthermore, mitochondrial activity is tightly connected to host fatty acid synthesis that is indispensable for chlamydial membrane biogenesis. Phospholipids, which are composed of fatty acids, are the central components of the bacterial membrane and play a crucial role in the protection against antimicrobials. Chlamydial persistence that is induced by various stimuli is clinically relevant. While one of the well-recognized inducers, ß-lactam antimicrobials, has been used to characterize chlamydial persistence, little is known about the role of mitochondria in persistent infection. Here, we demonstrate how C. trachomatis undergoes metabolic reprogramming to switch from the tricarboxylic acid cycle to fatty acid synthesis with promoted host mitochondrial activity in response to treatment with ß-lactam antimicrobials.

A History of Diagnostic Investigations in Epilepsy Surgery.

Epilepsy surgery has progressed significantly in the last 150 years. Functional brain maps allowed for the localization of epileptogenic lesions based on seizure patterns, allowing surgeons like McEwan and Horsely to treat epilepsy surgically. Berger's electroencephalogram marked the first modality directly identifying epileptic abnormalities. Penfield and Jasper collaborated, as neurosurgeon and neurologist, to use EEG for surgery. Meanwhile, Wada developed the amobarbital test, improving the protection of language and memory. Talairach and Bancaud pioneered invasive monitoring of deep brain activity with stereoelectroencephalography before the computer age made CT and MRI possible. Looking forward, AI and robotics hold promise for further improving outcomes.

Mechanizing medicine - Tomorrows history started yesterday.

History is by nature a retrospective subject, there usually being an interval between any event, a review or impact of the subject being considered. This NPSA Historian's paper, takes a long and quick historical view of influences that fostered changes resulting in the current state of affairs in the field of medicine and medical care. The fields of medicine and surgery, are undergoing rapid changes as a result of technological and other advances that are making tomorrow's medical history seemingly happening yesterday. Prospectively, the impact of current change and its rapidity has the potential to radically change the future practice of the art and craft of our profession.