Biopsy Method and Needle Size on Success of Next-Generation Sequencing in NSCLC: A Brief Report.

Introduction: Next-generation sequencing (NGS) is essential to the care of patients with NSCLC. Nevertheless, NGS is dependent on adequate material from biopsy. We evaluated the impact of biopsy method and needle gauge necessary for optimizing success in tissue NGS. Methods: A total of 1660 formalin-fixed, paraffin-embedded samples were submitted to Caris Life Sciences from 2007 to 2022 for tumor profiling. The results of NGS assays were linked with retrospective biopsy data for patients with lung cancer treated at USC/Norris Cancer Center to create a database with the following parameters: demographics, biopsy method, tumor location (lung mass versus lymph node versus metastasis), needle gauge, number of needle passes, complications, tumor volume, DNA content, and status of NGS. Fisher's exact test and analysis of variance were performed to determine the impact of biopsy method and needle gauge (G). Results: In total, 77 computed tomography (CT)-guided transthoracic core needle (CT-TTCN) biopsies, 74 endobronchial ultrasound (EBUS)-guided transbronchial needle aspirations (TBNAs), 27 bronchial forceps biopsies, and 107 surgical resections were included. Furthermore, 41 of 77 CT-TTCN biopsies (53.2%), 43 of 74 EBUS-TBNAs (58.1%), 22 of 27 bronchial forceps biopsies (81.5%), and 105 of 107 surgical resections (98.1%) underwent successful NGS assays. The probability of successful NGS completion for lung cancers was highest in surgical resections and bronchial forceps biopsies. Needle-based biopsies were more successful when a needle larger than 20G was used. Complication rates were higher for CT-TTCN biopsies compared with EBUS-TBNA (p < 0.0001). Overall, the DNA yield was significantly higher in EBUS-TBNA compared with CT-TTCN biopsies in primary lung sites (p = 0.0002). EBUS-TBNA was found to have higher success rates in NGS compared with CT-TTCN for both primary lung lesions (p = 0.023) and lymph node targets (p = 0.035). Conclusions: The less invasive EBUS-TBNAs had higher success rates in NGS than CT-TTCN biopsies and resulted in higher DNA concentrations. In CT-TTCN biopsies, use of 20G or smaller needles is associated with a higher risk of obtaining an inadequate specimen regardless of the number of passes taken. Surgical and bronchial forceps biopsies had highest success in achieving NGS.

Critical iron deficiency anemia with record low hemoglobin: a case report.

BACKGROUND: Anemia is a serious global health problem that affects individuals of all ages but particularly women of reproductive age. Iron deficiency anemia is one of the most common causes of anemia seen in women, with menstruation being one of the leading causes. Excessive, prolonged, and irregular uterine bleeding, also known as menometrorrhagia, can lead to severe anemia. In this case report, we present a case of a premenopausal woman with menometrorrhagia leading to severe iron deficiency anemia with record low hemoglobin. CASE PRESENTATION: A 42-year-old Hispanic woman with no known past medical history presented with a chief complaint of increasing fatigue and dizziness for 2 weeks. Initial vitals revealed temperature of 36.1 °C, blood pressure 107/47 mmHg, heart rate 87 beats/minute, respiratory rate 17 breaths/minute, and oxygen saturation 100% on room air. She was fully alert and oriented without any neurological deficits. Physical examination was otherwise notable for findings typical of anemia, including: marked pallor with pale mucous membranes and conjunctiva, a systolic flow murmur, and koilonychia of her fingernails. Her initial laboratory results showed a critically low hemoglobin of 1.4 g/dL and severe iron deficiency. After further diagnostic workup, her profound anemia was likely attributed to a long history of menometrorrhagia, and her remarkably stable presentation was due to impressive, years-long compensation. Over the course of her hospital stay, she received blood transfusions and intravenous iron repletion. Her symptoms of fatigue and dizziness resolved by the end of her hospital course, and she returned to her baseline ambulatory and activity level upon discharge. CONCLUSIONS: Critically low hemoglobin levels are typically associated with significant symptoms, physical examination findings, and hemodynamic instability. To our knowledge, this is the lowest recorded hemoglobin in a hemodynamically stable patient not requiring cardiac or supplemental oxygen support.

Clinical Dilemma - Cardiac Memory vs Myocardial Ischemia.

Cardiac memory (CM) is a commonly unrecognized entity in which electrocardiograph (EKG) changes demonstrate T wave inversions (TWI) that appear consistent with ischemia. Inability to recognize and distinguish CM from actual ischemia can be a burden for both patients and hospitals, leading to unnecessary hospital admission, cardiac testing, and cardiac catheterization. Simple EKG analysis and meticulous interpretation of T-wave axis and morphology can help differentiate between the two. We present a case with such a dilemma, and an overview literature and physiology behind this entity.

Silver Nanomaterials in Contemporary Molecular Physiology Research.

Silver nanoparticles have numerous potential applications in engineering, industry, biology and medicine. Because of their unique chemical properties, they have become the focus of many research teams all over the world. Silver nanoparticles may exhibit significant antimicrobial and anticancer effects, and they may be a valuable part of various bioassays and biosensors. However, the research on biological and medical uses of AgNPs is related with numerous potential problems and challenges that need to be overcome in the years ahead. Possible toxic effects of silver nanoparticles on living organisms represent a great concern, both in clinical medicine and public health. Nevertheless, in the future, it may be expected that all metallic nanomaterials, including the ones made from silver will greatly benefit almost all natural scientific fields. In this short review, we focus on the recent research on silver nanoparticles in experimental physiology, as well as other areas of fundamental and clinical medicine.

Austrian Syndrome - A Devastating Osler's Triad: Case Report and Literature Review.

Austrian syndrome is a rare triad of meningitis, pneumonia, and endocarditis caused by Streptococcus pneumoniae. We present a case of the Austrian syndrome in the oldest patient in the reviewed literature, with no other classically described risk factors. She had an unusual initial presentation and microorganism portal of entry. Her hospital course was complicated by the diagnosis of monoclonal gammopathy, septic knee joint, septic brain emboli and respiratory failure. We also provide an extensive review of available literature of this commonly unrecognized entity.

The relationship between right heart and aerobic capacity in large cohort of young elite athletes.

We sought to investigate right heart remodeling and function in elite athlees, as well as the relationship between parameters of right ventricular (RV) and right atrial (RA) remodeling and indices of aerobic capacity. Elite male athletes (n = 352) underwent echocardiographic examination including the evaluation of RV and RA parameters. Maximal cardiopulmonary exercise testing was performed to measure maximal oxygen consumption (VO2max), ventilatory anaerobic threshold (VAT) and heart rate reserve (HRR). The right heart remodeling was different between groups. Soccer players had significantly higher RV and RA diameters indexed for BSA. RV filling pressure assessed by tricuspid E/e' ratio was the lowest in soccer players, suggesting somewhat better RV diastolic function. Functional capacity also varies between groups of athletes. VO2max was the highest among soccer players, somewhat lower in basketball players and and the lowest among water polo players (55.3 ± 5.6 vs. 52.1 ± 5.9 vs. 53.5 ± 4.8 ml/kg/min, p < 0.001). Age, average weekly duration of training, percentage of body fat, as well as parameters of cardiopulmonary fitness (VO2max, O2 pulse, HRR), correlated well with parameters of RV and RA structure and function in the whole study population. However, systolic blood pressure at rest, VO2max and LV mass index are independently associated with RV and RA structure, whereas duration of training shows the best association with parameters of RV systolic and diastolic function. Even though soccer, water polo and basketball belong to the same group of sports, there is a significant difference in RV and RA remodeling between these three groups. It seems that right heart adaptation is the most pronounced in soccer players, who also have the highest maximal oxygen consumption. Further studies are necessary to investigate the mechanisms of these differences.

Erratum: Diet-Induced Obesity and Ghrelin Effects on Pituitary Gonadotrophs: Immunohistomorphometric Study in Male Rats.

[This corrects the article on p. 711 in vol. 17, PMID: 26862530.].

Diet-Induced Obesity and Ghrelin Effects on Pituitary Gonadotrophs: Immunohistomorphometric Study in Male Rats.

OBJECTIVE: The close relationship between energy metabolism, nutritional state, and reproductive physiology suggests that nutritional and metabolic disorders can disrupt normal reproductive function and fertility. Considering the importance of leptin and ghrelin effects in regulation of the hypothalamic-pituitary-gonadal axis, the objective of this study was to investigate the influence of obesity and centrally applied ghrelin on immunohistochemical appearance and quantitative morphology of the pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) producing cells in adult male rats. MATERIALS AND METHODS: In this experimental study, animals were given two differ- ent diets: normal-fat (NF) and high-fat (HF), for 4 weeks, corresponding to normal and positive energy balance (n=2×14), respectively. Each group was subsequently divided into two subgroups (n=7) receiving intracerebroventricular (ICV) injections of either ghrelin [G, 1 µg/5 µL phosphate buffered saline (PBS)] or vehicle (5 µL PBS, control group) every 24 hours for five consecutive days. RESULTS: Morphometric analyses showed that in HF control group, the percentage of FSH cells per unit volume of total pituitary gland tissue (in µm(3)), i.e. volume density (Vvc), was increased (P<0.05) by 9.1% in comparison with the NF controls. After ICV treatment with ghrelin, volume (Vc) and volume density (Vvc) of FSH cells in ghrelin+NF (GNF) and ghrelin+HF (GHF) groups remained unchanged in comparison with NF and HF controls. Volume of LH cells in HF control group was increased by 17% (P<0.05), but their Vvc was decreased by 8.3% (P<0.05) in comparison with NF controls. In GNF group, the volume of LH cells increased by 7% (P<0.05), in comparison with the NF controls, but in GHF group, the same parameter remained unchanged when compared with HF controls. The central application of ghrelin de- creased the Vvc of LH cells only in GNF group by 38.9% (P<0.05) in comparison with the NF control animals. CONCLUSION: The present study has shown that obesity and repetitive ICV administra- tion of low doses of ghrelin, in NF and HF rats, modulated the immunohistomorphometric features of gonadotrophs, indicating the importance of obesity and ghrelin in regulation of the reproductive function.

Central ghrelin treatment stimulates ACTH cells in normal-fed, food-restricted and high-fed rats: An immunohistomorphometric and hormonal study.

Changes in feeding regime represent serious stress, while ghrelin is considered a key player in energy balance. We investigated the effects of intracerebroventricular (ICV) ghrelin application on pituitary adrenocorticotropic (ACTH) cells in rats fed diets differing in energy content. Before the ICV treatment, male Wistar rats were subjected to three different feeding regimes for 4 weeks: normal-fed (NF), food-restricted (FR) or high-fed (HF) (n = 3 × 14). At the age of 8 weeks, rats from each group were divided into two subgroups and given ICV, either ghrelin (G; 1 µg ghrelin/5 µl PBS, n = 7) or solvent alone (5 µl PBS, n = 7) every 24 h for 5 days. The immunohistochemical appearance and quantitative morphology of pituitary ACTH cells were evaluated, as well as peripheral ACTH and corticosterone levels. Central ghrelin administration increased (p<0.05) ACTH cell volumes in GNF, GFR and GHF rats by 8.1%, 11.8% and 9.1%, respectively, compared to the controls, while significant increases in ACTH cell volume density were observed in GNF and GHF rats. Circulating ACTH and corticosterone levels were elevated (p<0.05) in GNF and GFR rats by 72.8% and 80.8%, respectively, when compared to the corresponding controls. Thus, central ghrelin administration stimulated the pituitary-adrenal axis under preserved and negative energy balance states.