Clinicopathological significance of unraveling mitochondrial pathway alterations in non-small-cell lung cancer.

Early detection, accurate monitoring, and therapeutics are major problems in non-small-cell lung cancer (NSCLC) patients. We identified genomic copy number variation of a unique panel of 40 mitochondria-targeted genes in NSCLCs (GEOGSE #29365). Validation of mRNA expression of these molecules revealed an altered panel of 34 genes in lung adenocarcinomas (LUAD) and 36 genes in lung squamous cell carcinomas (LUSC). In the LUAD subtype (n = 533), we identified 29 upregulated and 5 downregulated genes, while in the LUSC subtype (n = 502), a panel of 30 upregulated and 6 downregulated genes were discovered. The majority of these genes are associated with mitochondrial protein transport, ferroptosis, calcium signaling, metabolism, OXPHOS function, TCA cycle, apoptosis, and MARylation. Altered mRNA expression of SLC25A4, ACSF2, MACROD1, and GCAT was associated with poor survival of the NSCLC patients. Progressive loss of SLC25A4 protein expression was confirmed in NSCLC tissues (n = 59), predicting poor survival of the patients. Forced overexpression of SLC25A4 in two LUAD cell lines inhibited their growth, viability, and migration. A significant association of the altered mitochondrial pathway genes with LC subtype-specific classical molecular signatures was observed, implicating the existence of nuclear-mitochondrial cross-talks. Key alteration signatures shared between LUAD and LUSC subtypes including SLC25A4, ACSF2, MACROD1, MDH2, LONP1, MTHFD2, and CA5A could be helpful in developing new biomarkers and therapeutics.

A snapshot of lung cancer: where are we now?-a narrative review.

Background and Objective: The global impact of cancer and cancer-related deaths has been a huge challenge and continues to be a setback in the health sector and beyond even in recent times. Cancer is the second leading cause of death globally with lung cancer (LC) being the second most prevalent malignancy and the leading cause of mortality amongst cancers in men and women worldwide. LC still constitutes a major burden despite recent advances in diagnostic and treatment tools. In this article, we review the trends in LC with an emphasis on non-small cell LC. We aimed to identify nuclear and mitochondrial genetic alterations, microbiome dysbiosis, and their significance in non-small cell LC tumorigenesis as well as its relevance in the future management of LCs. Methods: We identified studies for this review by searching the PubMed, Cochrane, Education Resources Information Center (ERIC), and Surveillance, Epidemiology, and End Results (SEER) databases for English-Language articles published from January 1, 2000 through to July 30, 2022, using keywords: lung cancer, non-small cell lung cancer, early detection, treatment, mitochondria, microbiome and epigenetics. Key Content and Findings: This review will highlight the genomic environment, mitochondrial and nuclear alterations that play a role in the etiopathogenesis of LC and its application in the progression as well as management of the disease. We also elaborate on current molecular tumor biomarkers and their therapeutic targets. Conclusions: LC remains the leading cause of cancer-related deaths globally with poor prognosis despite available treatment options and even recent advances in both diagnostic tools and management guidelines. Human nuclear and mitochondrial alterations clearly play a role in tumorigenesis and progressive genomic evolution is crucial in the early carcinogenesis of LC which is strongly influenced by host immune surveillance. It is imperative that more research and clinical trials be undertaken to appreciate an in-depth understanding of LC from the molecular level to facilitate the discovery of more targeted therapy and overall better management of LC.

Implementation of a Low-Cost Quality Improvement Intervention Increases Adherence to Cancer Screening Guidelines and Reduces Healthcare Costs at a University Medical Center.

Adherence to US Preventative Services Task Force (USPSTF) cancer screening guidelines remains considerably lower than the recommendation of the Healthy People 2020 initiative. Patient populations recommended for screening are not screened at an appropriate rate, and populations not recommended for screening are inappropriately screened. Closer adherence to guidelines should improve outcomes and reduce costs, estimated to reach $158 billion/year by 2020. We evaluated whether a use of low-cost educational health maintenance (HM) card by medical residents at a university hospital could impact education and adherence to updated cancer screening guidelines. We also analyzed savings to the healthcare system. Adherence to cervical, breast, and colorectal cancer screening guidelines, defined as percentage that was screened (or not screened) in accordance with the USPSTF guidelines, in clinic visits from December 2012 (n = 336) was compared to those from December 2013 (n = 306) after a quality improvement intervention. Post-intervention, adherence to screening guidelines increased by 40.8% (p < 0.01) for cervical, 33.2% (p < 0.01) for breast, and 20.5% (p < 0.01) for colorectal cancer in average-risk patients. Inappropriate screening was reduced by 26.8% (p < 0.01) for cervical and 32.8% (p < 0.01) for breast cancer. A non-significant 1.1% decrease (p = 0.829) was observed for colorectal cancer. The annual potential savings from avoiding inappropriate screenings were $998,316 (95% CI; $644,484-$1,352,148). We showed a significant absolute increase in USPSTF knowledge of 28.3% irrespective of the house staff level that remained high at 2 years from the educational intervention. The low-cost HM card increased appropriate knowledgeable cancer screening adherence while reducing unnecessary testing and producing substantial savings to the healthcare system.

Decreasing Time to Initiation of Chemotherapy for Patients Electively Admitted to a Hematologic Malignancy Service.

PURPOSE: Delays in initiating elective inpatient chemotherapy can decrease patient satisfaction and increase length of stay. At our institution, we observed that 86% of patients who were admitted for elective chemotherapy experienced a delay-more than 6 hours-with a median time to chemotherapy of 18.9 hours. We developed a process improvement initiative to improve time to chemotherapy for elective chemotherapy admissions. METHODS: Our outcome measure was the time from admission to chemotherapy administration in patients who were admitted for elective chemotherapy. Process measures were identified and monitored. We collected baseline data and used performance improvement tools to identify key drivers. We focused on these key drivers to develop multiple plan-do-study-act cycles to improve our outcome measure. Once we started an intervention, we collected data every 2 weeks to assess our intervention. RESULTS: At the time of interim analysis, we observed a median decrease in time to chemotherapy administration from 18.9 hours to 8.85 hours (P = .005). Median time to laboratory results resulted decreased from 3.17 hours to 0.00 hours. There was no change in time from signing chemotherapy to nurse releasing the chemotherapy. We noted that more providers were signing the chemotherapy before patient admission. CONCLUSION: By implementing new admission workflows, optimizing our use of the electronic medical record to communicate among providers, and improving preadmission planning we were able to reduce our median time to chemotherapy for elective admissions by 53.2%. Improvement is still needed to meet our goals and to ensure the sustainability of these ongoing efforts.

Enhancing evaluation of sarcopenia in patients with non-small cell lung cancer (NSCLC) by assessing skeletal muscle index (SMI) at the first lumbar (L1) level on routine chest computed tomography (CT).

PURPOSE: Ongoing cancer cachexia trials evaluate sarcopenia by skeletal muscle index (SMI) at the L3 vertebrae level, commonly used as a standard. Routine chest CT institutional protocols widely differ in including L3. We investigated whether SMI at L1 assessment, rather than L3, would be reliable and more practicable for non-small cell lung cancer (NSCLC). METHODS: NSCLC patients with routine CT chest had SMI measurements performed at L1 using Slice-O-Matic software. Accuracy of including L1 level, imaging quality, and ability to detect sarcopenia was collected and correlation of L1 SMI with body mass index (BMI) was performed. RESULTS: Thirty-seven patients with NSCLC (73 CT assessments) were enlisted at three institutions. Characteristics: 47% female; medians: age 59, KPS 80%; BMI 25.49, weight 72.97 kg, SMI 59.24. Sarcopenia was detected in 14.7% of patients; 20% had sarcopenic obesity. Of the 73 CTs, 94.5% included L1 (95% CI 86.6-98.5%). Three images (4%) were difficult to evaluate. Inclusion of L1 was similar among the three participating institutions (90.4 to 96.7% inclusion). BMI correlation with SMI was weak (r = 0.329). CONCLUSIONS: SMI assessment at L1 is achievable in patients with NSCLC receiving routine chest CT, with 96% having acceptable quality evaluations. Similar to results previously reported at L3, BMI showed poor correlation and low sensitivity to detect muscle mass loss. The use of CT at L1 is reliable and presents the opportunity for easier patient evaluation of sarcopenia in patients with lung cancer without the need for additional testing or radiation exposure.

Aortocavitary fistula as a complication of infective endocarditis and subsequent complete heart block in a patient with severe anemia.

Infective endocarditis has different presentations depending on the involvement of valvular and perivalvular structures, and it is associated with high morbidity and mortality. Aortocavitary fistula is a rare complication. We introduce the case of a 48-year-old female with native valve endocarditis, complicated by aortocavitary fistula to the right atrium, and consequently presented with syncope.