Advancing neoadjuvant therapies in resectable non-small cell lung cancer: implications for novel treatment strategies and biomarker discovery.

The delivery of neoadjuvant and perioperative therapies for non-small cell lung cancer has been radically altered by significant advances and by the incorporation of targeted therapies as well as immune checkpoint inhibitors alone or alongside conventional chemotherapy. This evolution has been particularly notable in the incorporation of immunotherapy and targeted therapy into the treatment of resectable NSCLC, where recent FDA approvals of drugs such as nivolumab and pembrolizumab, in combination with platinum doublet chemotherapy, have led to considerable improvements in pathological complete response rates and the potential for enhanced long-term survival outcomes. This review emphasizes the growing importance of biomarkers in optimizing treatment selection and explores the impact of emerging studies that challenge existing treatment paradigms and investigate novel therapeutic combinations poised to redefine standard of care practices. Furthermore, the discussion extends to the unmet needs within perioperative treatment assessment and prognostication, highlighting the prospective value of biomarkers in evaluating treatment responses and prognosis.

Neurological Adverse Effects of Immune Checkpoint Inhibitors and Chimeric Antigen Receptor T-Cell Therapy.

Immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor (CAR) T-cell constitute recently approved novel therapies targeted to treat a wide number of malignancies. Both the treatments modulate the immune system and can cause a number of immune-related adverse events (irAEs), including polyendocrinopathies, gastrointestinal and neurological complications. This literature review focuses on the neurological side effects of these therapies as these are uncommon and alter the course of the treatment. Neurological complications involve the peripheral and central nervous system, including polyneuropathy, myositis, myasthenia gravis, demyelinating polyradiculopathy, myelitis, and encephalitis. If early recognized, the neurological complications can be treated effectively with steroids to reduce the potential of short-term and long-term complications. Therefore, early identification and treatment of irAEs are needed to optimize the outcomes associated with ICPI and CAR T-cell therapies.

Ischemic gastropathy with "leopard skin" stomach.

Ischemic gastropathy is a rare, underreported phenomenon that is associated with a poor prognosis. Patients often present with signs of shock, gastrointestinal bleeding, and anemia. We describe a patient with alcoholic cirrhosis who presented after a fall in hemorrhagic shock. Initial endoscopy revealed evidence of ongoing bleeding, with subsequent endoscopy revealing the "leopard skin" appearance in the stomach. The patient was treated supportively but eventually succumbed to his condition. Prompt diagnosis, treatment, and awareness of the delayed changes on upper endoscopy are imperative in diagnosing ischemic gastropathy. Patients with risk factors for the condition need to be given additional consideration for this diagnosis.

A Systematic Review of the Role of Runt-Related Transcription Factor 1 (RUNX1) in the Pathogenesis of Hematological Malignancies in Patients With Inherited Bone Marrow Failure Syndromes.

Somatic runt-related transcription factor 1 (RUNX1) mutations are the most common mutations in various hematological malignancies, such as myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Mono-allelic RUNX1 mutations in germline cells may cause familial platelet disorder (FPD), an inherited bone marrow failure syndrome (IBMFS) associated with an increased lifetime risk of AML. It is suspected that additional RUNX1 mutations may play a role in the pathogenesis of hematological malignancies in IBMFS. This review aims to study the role of RUNX1 mutations in the pathogenesis of hematological malignancies in patients with IBMFS. A PubMed database search was conducted using the following medical subject heading (MeSH) terms: "inherited bone marrow failure syndromes," "hematological neoplasms," "gene expression regulation, leukemic," "RUNX1 protein, human," "RUNX1 protein, mouse," and "Neutropenia, Severe Congenital, Autosomal recessive." Three studies published in 2020 were identified as meeting our inclusion and exclusion criteria. Leukemic progression in severe congenital neutropenia was used as a disease model to evaluate the clinical, molecular, and mechanistic basis of RUNX1 mutations identified in hematological malignancies. Studies in mice and genetically reprogrammed or induced pluripotent stem cells (iPSCs) have shown that isolated RUNX1 mutations are weakly leukemogenic and only initiate hyperproduction of immature hematopoietic cells when in combination with granulocyte colony-stimulating factor 3 receptor (GCSF3R) mutations. Despite this, whole-exome sequencing (WES) performed on leukemogenic transformed cells revealed that all AML cells had an additional mutation in the CXXC finger protein 4 (CXXC4) gene that caused hyperproduction of the ten-eleven translocation (TET2) protein. This protein causes inflammation in cells with RUNX1 mutations. This process is thought to be critical for clonal myeloid malignant transformation (CMMT) of leukemogenic cells. In conclusion, the combinations of GCSF3R and RUNX1 mutations have a prominent effect on myeloid differentiation resulting in the hyperproduction of myeloblasts. In other studies, it has been noted that the mutations in GCSF3R and RUNX1 genes are not sufficient for the full transformation of leukemogenic cells to AML, and an additional clonal mutation in the CXXC4 gene is essential for full transformation to occur. These data have implicitly demonstrated that RUNX1 mutations are critical in the pathogenesis of various hematological malignancies, and further investigations into the role of RUNX1 are paramount for the development of new cancer treatments.

Elucidating the Intriguing Association Between Systemic Lupus Erythematosus and Cardiovascular Disease.

Systemic lupus erythematosus (SLE) patients have demonstrated a higher risk of developing cardiovascular disease (CVD), resulting in it being one of the leading causes of death in SLE patients. SLE itself acts as a sole risk factor influencing the prevalence and progression of CVD. However, conventional risk factors, such as age, hypertension, smoking, and obesity, play a crucial role as well. Therefore, this systematic review attempts to unravel the association of CVD in SLE patients while evaluating the role of conventional risk factors. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed to search the PubMed database starting from March 2021 systematically. Original studies that evaluated the prevalence and progression of CVD in SLE patients were extracted by two reviewers independently. Quality in Prognostic Studies (QUIPS) tool was used to assess the risk of bias. Most studies have a moderate to low risk of bias. Among 3,653 studies identified by our search, 10 studies were included in the review. Strong epidemiologic evidence of SLE patients having an increased relative risk of CVD compared to controls was found. Traditional CVD risk factors, such as age, hypertension, obesity, and smoking, influence the prevalence of CVD among SLE patients. Several SLE-specific factors such disease activity, duration, and certain medications also acted as influencing factors. However, the relative risk of CVD was still higher in SLE patients after adjustment of certain risk factors. One study found that the odds of having a Coronary Artery Calcification (CAC) score greater than zero in women with SLE aged less than or equal to 45 years was 12.6 times higher than women in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort (95% CI 5.2 to 30.7) (participants of CARDIA cohort acted as control). This finding was made after age, hypertension, total cholesterol levels, and aspirin use were adjusted, and the study was restricted to women. Although conventional risk factors increase CVD prevalence, SLE itself also dramatically increases the prevalence of CVD. Therefore, we recommend that SLE should be treated as a "CVD risk equivalent." SLE patients should be managed more extensively with greater emphasis given to cardiac health for better clinical outcomes.

D-Dimer: A Potential Solution to Problems of Cancer Screening, Surveillance, and Prognosis Assessment.

Research has established a direct link between the plasma level of D-dimer and underlying malignancy. D-dimer has a strong association with the detection and prognosis of several cancers. For these reasons, this literature review aimed to evaluate the usefulness of elevated D-dimer levels in the initial screening of cancer, cancer recurrence surveillance, and for use as a cancer prognostic tool. A search of PubMed up to February 1, 2021, was carried out by reviewers. This literature review includes studies investigating the relationship between pretreatment plasma D-dimer levels and cancer. From the findings, pretreatment D-dimer levels can assist with cancer screening and prognosis assessment. Pretreatment plasma D-dimer levels can function as an effective cancer recurrence control. Elevated pre-treatment plasma D-dimer concentration is valuable in facilitating cancer screening, predicting an augmented risk of cancer recurrence, and anticipating a worse cancer prognosis.

Unraveling the Role of Hypothyroidism in Non-alcoholic Fatty Liver Disease Pathogenesis: Correlations, Conflicts, and the Current Stand.

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common causes of chronic liver diseases globally. Because thyroid hormones play a crucial role in lipid metabolism, thyroid dysfunction has been implicated in NAFLD pathogenesis in the past decade, with hypothyroidism-induced NAFLD being regarded as a distinct disease entity. However, there has been no common consensus yet, and several studies have found contradictory results. Hence, we conducted this systematic review to represent the current view on the role of hypothyroidism (HT) and individual thyroid function parameters such as thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) in NAFLD pathogenesis. We searched PubMed, PubMed Central, and Semantic Scholar databases from inception until January 2021 to identify relevant observational (case-control, cross-sectional, and longitudinal) studies. A total of 699 articles were recognized through our database search. After applying the eligibility criteria and performing quality assessment, 10 studies involving 42,227 participants were included in the final systematic review. Each of these studies assessed different thyroid function parameters, and NAFLD was found to be associated with HT in two studies, elevated TSH in three studies, suppressed T4 in three studies, elevated T3 in one study, and elevated TPOAb in one study. There was also a wide heterogeneity in HT definition, study population characteristics, and study design among these studies, making a direct comparison difficult. Because the recognition of HT-induced NAFLD has possible diagnostic, therapeutic, and prognostic implications, we recommend that comprehensive, long-term prospective studies be carried out to determine if HT or thyroid function parameters are causally associated with NAFLD.

The Advancement in Detecting Sepsis and Its Outcome: Usefulness of Procalcitonin in Diagnosing Sepsis and Predicting Fatal Outcomes in Patients Admitted to Intensive Care Unit.

Sepsis still remains a big challenge in patients admitted to intensive care units (ICUs) despite stellar advances made in the field of medicine. We can achieve better clinical outcomes in patients by diagnosing sepsis earlier. Procalcitonin (PCT), an inflammatory biomarker, has shown promising results in this regard. Therefore, this systematic review was done to assess the use of PCT in diagnosing and predicting severe outcomes in patients admitted to ICU and to assess if introducing PCT as a routine biochemical tool in hospitals would be helpful to achieve better clinical course in ICU patients. To identify relevant articles, we searched PubMed, Google Scholar, and references of included articles. Eligible studies were identified by two investigators independently and data were extracted. Original articles that evaluated the diagnostic and prognostic value of serum PCT levels in predicting sepsis, the severity of sepsis, and mortality among adult patients admitted to ICU were included in this study. A total of 2,063 citations were identified by the search, among which 10 studies (five prospective cohort, three retrospective cohort, one cross-sectional, and one case-control study) met the inclusion criteria. Most studies showed moderate-to-low risk of bias which was evaluated using the Quality in Prognosis Studies tool. All studies showed a positive correlation between initial PCT levels and detecting mortality resulting from sepsis, six studies found PCT helpful in detecting sepsis, and four studies evaluated the role of PCT in detecting severity in patients with sepsis. One study found area under the curve of serum PCT level for predicting 28-day mortality to be 0.82 (95% confidence interval [CI]: 0.70-0.94; p < 0.001) in adults and 0.83 (95% CI: 0.73-0.92; p < 0.001) in the elderly having an optimal cut-off level of serum PCT of 0.2 ng/mL in both the adult and elderly groups, with a sensitivity of 81 and 75% and specificity of 81.7 and 80.4%, respectively. PCT has shown promising results in detecting sepsis and its clinical course. For early diagnosis and management of sepsis, severe sepsis, and mortality in patients admitted to the ICU for a more favorable clinical outcome, PCT can be used.