Nathaniel E. Wiest

Bio: Nathaniel E. Wiest is an academic researcher from Mayo Clinic. The author has contributed to research in topics: Medicine & Internal medicine. The author has an hindex of 1, co-authored 5 publications receiving 2 citations.

Screening for pancreatic cancer: a review for general clinicians.

Abstract: Pancreatic cancer (PC) is an exceptionally lethal malignancy with increasing incidence and mortality worldwide. One of the principal challenges in the treatment of PC is that the diagnosis is usually made at a late stage when potentially curative surgical resection is no longer an option. General clinicians including internists and family physicians are well positioned to identify high-risk individuals and refer them to centers with expertise in PC screening and treatment where screening modalities can be employed. Here, we provide an up-to-date review of PC precursor lesions, epidemiology, and risk factors to empower the general clinician to recognize high-risk patients and employ risk reduction strategies. We also review current screening guidelines and modalities and preview progress that is being made to improve screening tests and biomarkers. It is our hope that this review article will empower the general clinician to understand which patients need to be screened for PC, strategies that may be used to reduce PC risk, and which screening modalities are available in order to diminish the lethality of PC.

Role of Immune Checkpoint Inhibitor Therapy in Advanced EGFR-Mutant Non-Small Cell Lung Cancer

Abstract: Over the last decade, the treatment of advanced non-small cell lung cancer (NSCLC) has undergone rapid changes with innovations in oncogene-directed therapy and immune checkpoint inhibitors. In patients with NSCLC that harbors an epidermal growth factor receptor (EGFR) gene mutation (EGFRm), newer-generation tyrosine kinase inhibitors (TKIs) are providing unparalleled survival benefit and tolerability. Unfortunately, most of these patients will experience disease progression and thus an urgent need exists for improved subsequent lines of therapies. The concurrent revolution in immune checkpoint inhibitor (ICI) therapy is providing novel first and second line treatment options with improved clinical outcomes in wild-type EGFR (EGFRwt) NSCLC; however, the application of ICI therapy to advanced EGFRm NSCLC patients is controversial. Early studies demonstrated the inferiority of ICI monotherapy to EGFR TKI therapy in the first line setting and inferiority to chemotherapy in the second line setting. Additionally, combination ICI and EGFR TKI therapies have demonstrated increased toxicities, and EGFR TKI therapy given after first-line ICI therapy has been correlated with severe adverse events. Nonetheless, combination ICI therapies including dual-ICI blockade and ICI, chemotherapy, and angiogenesis inhibitors are areas of active study with some intriguing signals in preliminary studies. Here, we review previous and ongoing clinical studies of ICI therapy in advanced EGFRm NSCLC. We reviewed the data on ICI therapy in NSCLC with ALK, ROS1, BRAF, c-MET, RET, and NTRK mutations in a separate manuscript. We discuss advances in understanding the differences in the tumor biology and tumor microenvironment (TME) of EGFRm NSCLC tumors that may lead to novel approaches to enhance ICI efficacy. It is our goal to equip the reader with a knowledge of current therapies, past and current clinical trials, and exciting avenues of research that provide the promise of novel approaches and improved outcomes for patients with advanced EGFRm NSCLC.

Lactobacillus rhamnosus sepsis, endocarditis and septic emboli in a patient with ulcerative colitis taking probiotics

Abstract: A man in his 60s presented to the emergency room with fever and fatigue after a 2.5-month course of corticosteroids. His medical history was significant for bioprosthetic aortic valve replacement and moderately severe ulcerative colitis treated with balsalazide and daily lactobacillus-containing probiotics. Initial investigations revealed Lactobacillus rhamnosus bacteraemia without complication. Four days after hospital discharge, the patient experienced acute-onset right-sided paraesthesia and lower-limb paresis. On return to the emergency room, MRI of the brain demonstrated innumerable ring-enhancing lesions with haemorrhagic transformation. Transoesophageal echocardiogram revealed a small mobile density on the bioprosthetic aortic valve, raising the suspicion for L. rhamnosus infective endocarditis with secondary septic emboli to the brain. The patient was subsequently treated with intravenous gentamycin and ampicillin, with transition to indefinite oral amoxicillin suppressive therapy. The current case highlights the potential risk of lactobacilli translocation in an immunosuppressed patient with ulcerative colitis taking probiotics.

Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan)

Abstract: A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer However, uncertainty remains about the strength of this association Results from previous studies suggest a family history of select cancers (ie, ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium Cases and controls were from cohort studies from the United States, Europe and China, and a case-control study from the Mayo Clinic Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate-adjusted odds ratios (ORs) = 176, 95% confidence interval (CI) = 119-261] A family history of prostate cancer was also associated with increased risk (OR = 145, 95% CI = 112-189) There were no statistically significant associations with a family history of ovarian cancer (OR = 082, 95% CI = 052-131), breast cancer (OR = 121, 95% CI = 097-151) or colorectal cancer (OR = 117, 95% CI = 093-147) Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study

Use of Bacteriocins and Bacteriocinogenic Beneficial Organisms in Food Products: Benefits, Challenges, Concerns

Abstract: This review’s objective was to critically revisit various research approaches for studies on the application of beneficial organisms and bacteriocins as effective biopreservatives in the food industry. There are a substantial number of research papers reporting newly isolated bacterial strains from fermented food products and their application as potential probiotics, including partial characterization of bacteriocins produced by these microorganisms. Most of these studies follow scientific community-accepted standard procedures and propose various applications of the studied strains and bacteriocins as potential biopreservatives for the food industry. A few investigations go somewhat further, performing model studies, exploring the application of expressed bacteriocins in a designed food product, or trying to evaluate the effectiveness of the studied potential probiotics and bacteriocins against foodborne pathogens. Some authors propose applications of bacteriocin producers as starter cultures and are exploring in situ bacteriocin production to aid in the effective control of foodborne pathogens. However, few studies have evaluated the possible adverse effects of bacteriocins, such as toxicity. This comes from well-documented reports on bacteriocins being mostly non-immunogenic and having low cytotoxicity because most of these proteinaceous molecules are small peptides. However, some studies have reported on bacteriocins with noticeable cytotoxicity, which may become even more pronounced in genetically engineered or modified bacteriocins. Moreover, their cytotoxicity can be very specific and is dependent on the concentration of the bacteriocin and the nature of the targeted cell. This will be discussed in detail in the present review.

Lung cancer immunotherapy: progress, pitfalls, and promises

Abstract: Abstract Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are gaining ground in the treatment of lung cancer. Recent advances in adoptive cell therapy (CAR T, TCR, TIL), the associated clinical trials on lung cancer, and associated hurdles are discussed in this review. Recent trials on lung cancer patients (without a targetable oncogenic driver alteration) reveal significant and sustained responses when treated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint blockade immunotherapies. Accumulating evidence indicates that a loss of effective anti-tumor immunity is associated with lung tumor evolution. Therapeutic cancer vaccines combined with immune checkpoint inhibitors (ICI) can achieve better therapeutic effects. To this end, the present article encompasses a detailed overview of the recent developments in the immunotherapeutic landscape in targeting small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Additionally, the review also explores the implication of nanomedicine in lung cancer immunotherapy as well as the combinatorial application of traditional therapy along with immunotherapy regimens. Finally, ongoing clinical trials, significant obstacles, and the future outlook of this treatment strategy are also highlighted to boost further research in the field.

CD63-positive extracellular vesicles are potential diagnostic biomarkers of pancreatic ductal adenocarcinoma

Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest gastrointestinal cancers with a 5-year survival rate of less than 10%. Biomarkers for early PDAC detection are useful in treating patients with PDAC. Extracellular vesicles (EVs) are lipid-bound vesicles that are potential biomarkers of various diseases such as PDAC. In this study, we quantitatively measured the serum levels of EVs (CD63+-EVs) or platelet-derived EVs (CD41+- and CD61+-EVs) and evaluated their potential use as biomarkers of PDAC.We measured the serum levels of CD63+-, CD41+-, CD61+-EVs using sandwich enzyme-linked immunosorbent assay based on Tim4 with specificity for phosphatidylserine on EVs in age- and sex-matched healthy controls (HCs, n = 39) and patients with PDAC (n = 39). We also examined the effect of tumor burden on the serum EV levels after surgical resection (n = 28). CA19-9, a clinical PDAC biomarker, was also measured for comparison.Serum levels of CD63+-EVs, CD41+-EVs, and CD61+-EVs were significantly increased in patients with PDAC compared to HCs. Receiver operating characteristic analysis revealed that CD63+-EVs exhibited the highest diagnostic performance to discriminate patients with PDAC from HCs (area under the curve (AUC): 0.846), which was comparable to CA19-9 (AUC: 0.842). CA19-9 showed lower AUC values in early stages (I-II, AUC: 0.814) than in late stages (III-IV, AUC: 0.883) PDAC. Conversely, CD63+-EVs, CD41+-EVs, and CD61+-EVs showed comparable AUCs between early- and late-stage PDAC. The combined use of CA19-9 and CD63+-EVs showed a higher diagnostic performance for early-stage PDAC (AUC: 0.903) than CA19-9. The serum levels of CD63+-EVs, CD41+-EVs, CD61+-EVs, and CA19-9 decreased significantly after surgical resection, demonstrating that EVs are increased in sera of patients depending on the tumor burden.The serum levels of CD63+-EVs and platelet-derived EVs (CD41+-EVs, CD61+-EVs) are increased in patients with PDAC than HCs. Since CD63+-EVs showed a high AUC to discriminate patients with PDAC from HCs; they might be useful as potential biomarkers for PDAC.