Molecular Markers, Immune Therapy, and Non-Small Cell Lung Cancer-State-of-the-Art Review for Surgeons.

Background: Lung cancer is a leading cause of cancer deaths in the United States. An increasing understanding of relevant non-small cell lung cancer (NSCLC) biomarkers has led to the recent development of molecular-targeted therapies and immune checkpoint inhibitors that have revolutionized treatment for patients with advanced and metastatic disease. The purpose of this review is to provide surgeons with a state-of-the-art understanding of the current medical and surgical treatment trends and their implications in the future of management of NSCLC. Materials and Methods: A systematic search of PubMed was conducted to identify English language articles published between January 2010 and March 2024 focusing on molecular markers, tumor targeting, and immunotherapy in the diagnosis and treatment of NSCLC. Case series, observational studies, randomized trials, guidelines, narrative reviews, systematic reviews, and meta-analyses were included. Results: There is now increasing data to suggest that molecular-targeted therapies and immune therapies have a role in the neoadjuvant setting. Advances in intraoperative imaging allow surgeons to perform increasingly parenchymal-sparing lung resections without compromising tumor margins. Liquid biopsies can noninvasively detect targetable mutations in cancer cells and DNA from a blood draw, potentially allowing for earlier diagnosis, personalized therapy, and long-term monitoring for disease recurrence. Conclusions: The management of NSCLC has advanced dramatically in recent years fueled by a growing understanding of the cancer biology of NSCLC. Advances in medical therapies, surgical techniques, and diagnostic and surveillance modalities continue to evolve but have already impacted current treatment strategies for NSCLC, which are encompassed in this review.

Cinematic Rendering: Novel Tool for Improving Pancreatic Cancer Surgical Planning.

Pancreatic ductal adenocarcinoma is the third-leading cause of all cancer-related deaths in the US. While 20% of patients have resectable disease at diagnosis, improved control of systemic disease using effective chemotherapeutic regimens allows for aggressive operations involving complex vascular resection and reconstruction. A pancreas protocol computed tomography (PPCT) is the gold standard imaging modality in determining local resectability (degree of tumor-vessel involvement), however, it is limited by the inter-operator variability. While post-processing-3D-rendering helps, it does not allow for real-time dynamic assessment of resectability. A recent development in post-process-rendering called cinematic rendering (CR) overcomes this by utilizing advanced light modeling to generate photorealistic 3D images with enhanced details. Cinematic rendering allows for nuanced visualization of areas of interest. Our preliminary experience, as one of the first centers to incorporate the routine use of CR, has proven very useful in surgical planning. For local determination of resectability, vascular mapping allows for accurate assessment of major arteries and the portovenous system. For the portovenous anatomy it assists in determining the optimal surgical approach (extent of resection, appropriate technique for reconstruction, and need for mesocaval shunting). For arterial anatomy, vessel encasement either represents dissectible involvement via periadventitial dissection or true vessel invasion that is unresectable. CR could potentially provide superior ability than traditional PPCT to discern between the two. Additionally, CR allows for better 3D visualization of arterial anatomic variants which, if not appreciated preoperatively, increases risk of intraoperative ischemia and postoperative complications. Lastly, CR could help avoid unnecessary surgery by enhanced identification of occult metastatic disease that is metastatic disease that is otherwise not appreciated on a standard PPCT.

Twisting: Incidence and Risk Factors of an Intraprocedural Challenge Associated With Pipeline Flow Diversion of Cerebral Aneurysms.

BACKGROUND: Pipeline Embolization Device (PED; Medtronic) "twisting" manifests with the appearance of a "figure 8" in perpendicular planes on digital subtraction angiography. This phenomenon has received little attention in the literature, requires technical precision to remediate, and has potential to cause ischemic stroke if not properly remediated. OBJECTIVE: To report incidence, risk factors, and sequelae of PED twisting and to discuss techniques to remediate a PED twist. METHODS: Case images were reviewed for instances of twisting from a prospectively-maintained, Institutional Review Board-approved cohort of patients undergoing flow diversion for cerebral aneurysm. RESULTS: From August 2011 to December 2017, 999 PED flow diverting stents were attempted in 782 cases for 653 patients. A total of 25 PED twists were observed while treating 20 patients (2.50%, 25/999). Multivariate analysis revealed predictors of twisting to be: Large and giant aneurysms (odds ratio (OR) = 9.66, P = .005; OR = 27.47, P < .001), increased PED length (OR = 1.14, P < .001), and advanced patient age (OR = 1.07, P = .002). Twisted PEDs were able to be remediated 75% of the time, and procedural success was achieved in 90% of cases. PED twisting was not found to be a significant cause of major or minor complications. However, at long-term follow-up, there was a trend towards poor occlusion outcomes for the cases that encountered twisting. CONCLUSION: Twisting is a rare event during PED deployment that was more likely to occur while treating large aneurysms with long devices in older patients. While twisting did not lead to major complications in this study, remediation can be challenging and may be associated with inferior occlusion outcomes.

Aspirin Monotherapy in Flow Diversion of Selected Internal Carotid Artery Aneurysms.

BACKGROUND: Dual antiplatelet therapy has been adopted as the standard of care for intracranial stenting, including flow diversion of cerebral aneurysms, to reduce the risk of acute and delayed ischemic complications. CASE DESCRIPTION: This is a report of 2 cases in which patients who underwent flow diversion of unruptured internal carotid artery aneurysms were treated with aspirin monotherapy. Neither patient tolerated dual antiplatelet therapy, one because of nosebleeds due to hereditary hemorrhagic telangiectasia and one because of an unnamed bleeding disorder. The lesions-a previously coiled, recanalizing dorsal internal carotid artery aneurysm and a small superior hypophyseal aneurysm-were each treated with a single Pipeline Flex embolization device and were completely occluded with normal-appearing parent vessel on 12-month follow-up digital subtraction angiography. CONCLUSIONS: This is the first report of patients electively treated with flow diversion using Pipeline Flex embolization device on aspirin monotherapy in the literature.

Flow diversion covering the M1 origin as a last resort.

INTRODUCTION: Internal carotid artery termination (ICAT) and proximal A1 aneurysms can be challenging for open surgical clipping or endovascular coiling. Treatment with flow diversion covering the middle cerebral artery (MCA), an end vessel supplying a terminal circulation, has not been reported. METHODS: A prospective, Institutional Review Board-approved database was analysed for patients with pipeline embolisation device (PED) placement from the anterior cerebral artery (ACA) to the ICA during cerebral aneurysm treatment. RESULTS: Nine cases were identified, including five proximal A1, three posterior communicating artery and one ICAT aneurysm locations. Average aneurysm size was 8.3 mm (range 3-17), with 67% saccular and 78% right-sided. Primary indication for treatment was significant dome irregularity (44%), recurrence or enlargement (33%), underlying collagen vascular disorder (11%) and traumatic pseudoaneurysm (11%). Preservation of the ipsilateral ACA (with PED placed in A1) was performed when the anterior communicating artery (67%) or contralateral A1 (33%) were absent on angiography. Adjunctive coiling was done in four cases (44%). There was one major stroke leading to mortality (11%) and one minor stroke (11%). Clinical follow-up was 27 months on average. Follow-up digital subtraction angiography (average interval 15 months) showed complete aneurysm obliteration (88%) or dome occlusion with entry remnant (12%). The jailed MCA showed minimal or mild delay (primarily anterograde flow) in 75% of cases and significant delay (reliance primarily on ACA and external carotid artery collaterals) in 25%. CONCLUSIONS: Covering the MCA with a flow diverting stent should be reserved for select rare cases. Strict attention to blood pressure augmentation during the periprocedural period is necessary to minimise potential ischaemic compromise.

Multiple pipeline twists encountered during treatment of a symptomatic fusiform ICA aneurysm.

Pipeline embolisation device (PED) 'twisting' is an intra-operative complication that manifests with the appearance of a 'figure-8' in perpendicular planes on digital subtraction angiography. A twisted PED causes narrowing and/or complete occlusion of the vessel lumen and poses significant risks for thrombus formation and downstream ischaemia. Here, we present a case in which three unique PED implants become twisted during pipeline embolisation of a large fusiform internal carotid artery aneurysm. The twists were remediated by balloon angioplasty and a combination of techniques that allowed the PED to rotate and restore its original axis. Six-month and twelve-month follow-up angiography demonstrated complete aneurysm occlusion with preservation of the parent vessel, proving that proper remediation of PED twisting can still result in successful long-term outcomes.

Workshop Report on Atomic Bomb Dosimetry--Review of Dose Related Factors for the Evaluation of Exposures to Residual Radiation at Hiroshima and Nagasaki.

Groups of Japanese and American scientists, supported by international collaborators, have worked for many years to ensure the accuracy of the radiation dosimetry used in studies of health effects in the Japanese atomic bomb survivors. Reliable dosimetric models and systems are especially critical to epidemiologic studies of this population because of their importance in the development of worldwide radiation protection standards. While dosimetry systems, such as Dosimetry System 1986 (DS86) and Dosimetry System 2002 (DS02), have improved, the research groups that developed them were unable to propose or confirm an additional contribution by residual radiation to the survivor's total body dose. In recognition of the need for an up-to-date review of residual radiation exposures in Hiroshima and Nagasaki, a half-day technical session was held for reports on newer studies at the 59 th Annual HPS Meeting in 2014 in Baltimore, MD. A day-and-a-half workshop was also held to provide time for detailed discussion of the newer studies and to evaluate their potential use in clarifying the residual radiation exposure to atomic bomb survivors at Hiroshima and Nagasaki. The process also involved a re-examination of very early surveys of radioisotope emissions from ground surfaces at Hiroshima and Nagasaki and early reports of health effects. New insights were reported on the potential contribution to residual radiation from neutron-activated radionuclides in the airburst's dust stem and pedestal and in unlofted soil, as well as from fission products and weapon debris from the nuclear cloud. However, disparate views remain concerning the actual residual radiation doses received by the atomic bomb survivors at different distances from the hypocenter. The workshop discussion indicated that measurements made using thermal luminescence and optically stimulated luminescence, like earlier measurements, especially in very thin layers of the samples, could be expanded to detect possible radiation exposures to beta particles and to determine their significance plus the extent of the various residual radiation areas at Hiroshima and Nagasaki. Other suggestions for future residual radiation studies are included in this workshop report.

Prevention of lung injury in cardiac surgery: a review.

Inflammatory lung injury is an inevitable consequence of cardiac surgery with cardiopulmonary bypass. The lungs are particularly susceptible to the effects of the systemic inflammatory response to cardiopulmonary bypass. This insult is further exacerbated by a pulmonary ischemia-reperfusion injury after termination of bypass. Older patients and those with pre-existing lung disease will clearly be less tolerant of any lung injury and more likely to develop respiratory failure in the postoperative period. A requirement for prolonged ventilation has implications for morbidity, mortality, and cost of treatment. This review contains a summary of recent interventions and changes of practice that may reduce inflammatory lung injury after cardiac surgery. The review also focuses on a number of general aspects of perioperative management, which may exacerbate such injury, if performed poorly.

Workshop report on atomic bomb dosimetry-residual radiation exposure: recent research and suggestions for future studies.

There is a need for accurate dosimetry for studies of health effects in the Japanese atomic bomb survivors because of the important role that these studies play in worldwide radiation protection standards. International experts have developed dosimetry systems, such as the Dosimetry System 2002 (DS02), which assess the initial radiation exposure to gamma rays and neutrons but only briefly consider the possibility of some minimal contribution to the total body dose by residual radiation exposure. In recognition of the need for an up-to-date review of the topic of residual radiation exposure in Hiroshima and Nagasaki, recently reported studies were reviewed at a technical session at the 57th Annual Meeting of the Health Physics Society in Sacramento, California, 22-26 July 2012. A one-day workshop was also held to provide time for detailed discussion of these newer studies and to evaluate their potential use in clarifying the residual radiation exposures to the atomic-bomb survivors at Hiroshima and Nagasaki. Suggestions for possible future studies are also included in this workshop report.

Hyperoxia: a review of the risks and benefits in adult cardiac surgery.

Perioperative hyperoxia has been claimed to have a number of therapeutic advantages. However, in the setting of cardiac surgery and cardiopulmonary bypass (CPB), enthusiasm for its use has been tempered by concerns regarding the effect of high partial pressures of oxygen on cardiac, vascular, and respiratory function and the potential for exacerbation of ischemia-reperfusion injury. There is encouraging evidence from animal studies that hyperoxia is effective in myocardial preconditioning, at least in nondiseased hearts. There is also evidence that hyperoxia reduces gas microemboli production and longevity during CPB, although it is unclear whether this translates into a clinical benefit in terms of a reduction in postoperative neurological morbidity. Hyperoxia leads to changes in cardiovascular function. However, the effects of these changes remain unclear. At a tissue level, there is evidence that hyperoxia does not lead to improvement in partial pressure of oxygen. Indeed, the opposite may be the case with reductions in capillary density leading to areas of reduced tissue oxygenation. The risks of hyperoxia in association with CPB include lung injury, increased systemic reactive oxygen species generation, and exacerbation of reactive oxygen species-mediated myocardial injury at the time of reperfusion. Again, it is difficult to know whether the changes demonstrated are temporary or if they translate into a worsening of clinical outcomes. In conclusion, perhaps the key to the use of hyperoxia is in the timing. In the period pre-CPB, hyperoxia may precondition the myocardium and, paradoxically, confer a degree of protection against reactive oxygen species-induced injury at the time of reperfusion. Hyperoxia during CPB is probably harmful and should be avoided unless the risk from gas microemboli is thought to be significant, in which case the risks and benefits to the individual patient must be weighed.

An efficient and inexpensive refrigerated LC system for H/D exchange mass spectrometry.

Loss of deuterium label during the LC step in amide hydrogen/deuterium exchange mass spectrometry (H/D-MS) is minimized by maintaining an acidic mobile phase pH and low temperature (pH 2.5, 0 °C). Here we detail the construction and performance of a low-cost, thermoelectrically refrigerated enclosure to house high-performance liquid chromatography (HPLC) components and cool mobile phases. Small volume heat exchangers rapidly decrease mobile phase temperature and keep the temperature stable to ±0.2 °C. Using a superficially porous reversed-phase column, we obtained excellent chromatographic performance in the separation of peptides with a median peak width of 4.4 s. Average deuterium recovery was 80.2% with an average relative precision of 0.91%.

Anxiolytic effects of nicotine in a rodent test of approach-avoidance conflict.

RATIONALE: Nicotine has been reported to produce both anxiolytic and/or anxiogenic effects in humans and animals. OBJECTIVES: This study examined whether pretreatment with nicotine would alter anxiety in a unique runway model of approach-avoidance conflict. MATERIALS AND METHODS: Food-restricted rats were trained to run a straight alley once a day to obtain food upon goal-box entry. Beginning on trial 11, food reward was followed by a series of five foot shocks (0.3-0.4 mA, 0.5 s) in the goal box. Non-shocked control rats continued to run for food only. The resulting association of the goal box with both a positive (food) and negative (foot shock) stimulus produced an approach-avoidance conflict (subjects exhibited "retreat behaviors" in which they would approach the goal box, stop, and then retreat back towards the start box). Once retreats were established, their sensitivity to nicotine pretreatment (0.0, 0.03, 0.045, 0.06, or 0.075 mg/kg, i.v.) was compared to saline. In subsequent tests, the effects of nicotine (0.06 or 0.03 mg/kg) were examined on spontaneous activity (locomotion) and center-square entries in an open field (anxiety). RESULTS: Doses of 0.06 and 0.075 mg/kg, but not lower doses of nicotine, reduced the number of runway retreats, and 0.06 mg/kg nicotine increased the number of open-field center entries relative to saline. No effects on locomotion were observed. CONCLUSIONS: Nicotine reduced approach-avoidance conflict and increased the rats' willingness to enter the center of an open field, suggesting that the drug can produce anxiolytic properties and that such effects may serve as an important factor in the persistence of smoking behavior.

Detection of back random responding: effectiveness of MMPI-2 and Personality Assessment Inventory validity indices.

Two experiments examined the detection and effects of back random responding (BRR) on the Minnesota Multiphasic Personality Inventory--2 (MMPI-2) and the Personality Assessment Inventory (PAI). Experiment 1 revealed that MMPI-2 Clinical and Content scales were relatively resistant to the effects of BRR. Fb--F > or = 20T was the most effective index for identifying invalid protocols. Experiment 2 revealed greater susceptibility of the PAI interpretive scales to the effects of BRR and less successful detection of BRR. The most effective PAI validity index was the combined indicator, ICN > or = 73T or INF > or = 75T. Clinical and empirical implications of these findings are discussed, and tentative modifications to the MMPI-2 interpretative guidelines are provided.

Development and validation of the Pain Outcomes Questionnaire-VA.

The development of effective pain treatment strategies requires the availability of precise and practical measures of treatment outcomes, the importance of which has been noted in the Veterans Health Administration's (VHA's) National Pain Initiative. This paper presents the results of a 5-year collaborative effort to develop and validate a comprehensive and efficient self-report measure of pain treatment outcomes. Two samples of veterans (957 total subjects) undergoing inpatient or outpatient pain treatment at six VHA facilities completed Pain Outcomes Questionnaire-VA (POQ-VA) items and several additional measures. We used a comprehensive, multistage analytic procedure to evaluate the psychometric properties of the instrument. Results provided strong support for the reliability, validity, and clinical use of the POQ-VA when used to evaluate the effectiveness of treatment for veterans experiencing chronic noncancer pain.

Psychological consequences of military operations in low-level radiation environments.

Military operations have produced neuropsychiatric (NP) casualties throughout history. The same is true for radiation accidents. Although we have not carried out military operations in nuclear environments, related experience suggests that operations performed under low-level radiation conditions could serve to compound the factors that are known to produce NP casualties. Historically, military NP casualty rates have varied widely depending on a complex array of factors, ranging from the actual conditions of the operation and experiences of the soldiers to the perception of the conflict by both the soldiers and the people back home. History has also shown that lack of preparation contributes to NP casualties. The number and severity of NP casualties can be minimized by ensuring that the equipment, training, and leadership are in place to instill in our soldiers the confidence that they can cope with the types of threats that are part of modern-day missions.

Sonic booms of space shuttles approaching Edwards Air Force Base, 1988-1993.

From 1988 to 1993 13 sonic booms of space shuttles approaching Edwards Air Force Base were measured at a site 10 miles west of EAFB, with one to seven different sound level meters for each measurement. Results from five of these measurements are here presented. Maximum differences in measured levels between instruments for the same flight varied from 0 to 6 dB depending on the measurement descriptor and model of sound level meter. The average difference between predicted and measured values was 0.7+/-1.5 dB. For sound level meters with adequate bandwidth the waveforms measured varied from a near perfect N-wave to a more distorted form reflecting the influence of the varying condition of the atmosphere during propagation to the ground.