-
1.
Nephrotoxic Effects of Chemotherapeutic Agents.
Drury, Z, Ly, T, Abraham, J
Clinical journal of oncology nursing. 2022;(2):219-223
Abstract
Nephrotoxicity can be a severe complication of oncology treatment. The most common presentations of chemotherapy-related renal disorders include acute kidney injury, electrolyte abnormalities, acid base disturbances, hemolytic anemia, and hypertension. Oncology nurses should be aware of the potential renal complications of oncology therapeutics and advocate for appropriate monitoring and treatment of patients. This article reviews the most common chemotherapeutic agents that may cause nephrotoxicity.
-
2.
FOLFOXIRI and bevacizumab in patients with early-onset metastatic colorectal cancer. A pooled analysis of TRIBE and TRIBE2 studies.
Antoniotti, C, Germani, MM, Rossini, D, Lonardi, S, Pietrantonio, F, Santini, D, Marmorino, F, Allegrini, G, Daniel, F, Raimondi, A, et al
European journal of cancer (Oxford, England : 1990). 2022;:23-31
Abstract
BACKGROUND We performed a pooled analysis of TRIBE and TRIBE2 studies to assess the efficacy and safety of the intensification of upfront chemotherapy backbone - from doublets to the triplet FOLFOXIRI - in combination with bevacizumab (bev) in patients with early-onset metastatic colorectal cancer (EO-mCRC; aged <50 years) and to explore whether EO-mCRCs have a peculiar tumour genomic profiling. MATERIALS AND METHODS Subgroup analyses according to age (<50 versus ≥50 years) and treatment (FOLFOXIRI/bev versus doublets/bev) were carried out for rates of any grade and grade ≥3 (≥G3) overall and singular adverse events, progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Tumour genomic profiling was obtained using a DNA-based next-generation sequencing platform. RESULTS Of 1187 patients included, 194 (16%) patients were aged <50 years. Females were more frequently diagnosed with EO-mCRC (P = 0.04). Patients aged <50 years showed a lower risk of ≥G3 neutropenia (P = 0.07), diarrhoea (P = 0.04), asthenia (P = 0.008) and a higher risk of any grade nausea (P < 0.01) and vomiting (P < 0.01). Patients receiving FOLFOXIRI/bev more frequently experienced ≥G3 chemotherapy-related adverse events respect to doublets/bev, regardless of age (Pinteraction = 0.60). FOLFOXIRI/bev was associated to a lower incidence of neutropenia (P = 0.04) and asthenia (P = 0.01) in patients <50 years old, than those aged ≥50 years. PFS, OS and ORR did not differ according to age (PFS P = 0.81, OS P = 0.44, ORR P = 0.50) and no interaction between age and the benefit from the intensification of upfront chemotherapy was observed (PFS Pinteraction = 0.72, OS Pinteraction = 0.54, ORR Pinteraction = 0.65). Genomic profiling was assessed in 296 patients, showing an enrichment of FBXW7 and POLE mutations in EO-mCRC. CONCLUSIONS Upfront FOLFOXIRI/bev shows a favourable efficacy/safety balance in EO-mCRC. TRIAL REGISTRATION Clinicaltrials.gov Identifiers NCT00719797, NCT0233-9116.
-
3.
The Effects of Carbohydrate versus Fat Restriction on Lipid Profiles in Highly Trained, Recreational Distance Runners: A Randomized, Cross-Over Trial.
Buga, A, Welton, GL, Scott, KE, Atwell, AD, Haley, SJ, Esbenshade, NJ, Abraham, J, Buxton, JD, Ault, DL, Raabe, AS, et al
Nutrients. 2022;(6)
Abstract
A growing number of endurance athletes have considered switching from a traditional high-carbohydrate/low-fat (HCLF) to a low-carbohydrate/high-fat (LCHF) eating pattern for health and performance reasons. However, few studies have examined how LCHF diets affect blood lipid profiles in highly-trained runners. In a randomized and counterbalanced, cross-over design, athletes (n = 7 men; VO2max: 61.9 ± 6.1 mL/kg/min) completed six weeks of two, ad libitum, LCHF (6/69/25% en carbohydrate/fat/protein) and HCLF (57/28/15% en carbohydrate/fat/protein) diets, separated by a two-week washout. Plasma was collected on days 4, 14, 28, and 42 during each condition and analyzed for: triglycerides (TG), LDL-C, HDL-C, total cholesterol (TC), VLDL, fasting glucose, and glycated hemoglobin (HbA1c). Capillary blood beta-hydroxybutyrate (BHB) was monitored during LCHF as a measure of ketosis. LCHF lowered plasma TG, VLDL, and TG/HDL-C (all p < 0.01). LCHF increased plasma TC, LDL-C, HDL-C, and TC/HDL-C (all p < 0.05). Plasma glucose and HbA1c were unaffected. Capillary BHB was modestly elevated throughout the LCHF condition (0.5 ± 0.05 mmol/L). Healthy, well-trained, normocholesterolemic runners consuming a LCHF diet demonstrated elevated circulating LDL-C and HDL-C concentrations, while concomitantly decreasing TG, VLDL, and TG/HDL-C ratio. The underlying mechanisms and implications of these adaptive responses in cholesterol should be explored.
-
4.
Can Optimum Solar Radiation Exposure or Supplemented Vitamin D Intake Reduce the Severity of COVID-19 Symptoms?
Abraham, J, Dowling, K, Florentine, S
International journal of environmental research and public health. 2021;(2)
Abstract
The foremost mortality-causing symptom associated with COVID-19 is acute respiratory distress syndrome (ARDS). A significant correlation has been identified between the deficiency in vitamin D and the risk of developing ARDS. It has been suggested that if we can reduce or modify ARDS in COVID-19 patients, we may significantly reduce the severity of COVID-19 symptoms and associated mortality rates. The increased mortality of dark-skinned people, who have a reduced UV absorption capacity, may be consistent with diminished vitamin D status. The factors associated with COVID-19 mortality, such as old age, ethnicity, obesity, hypertension, cardiovascular diseases, and diabetes, are all found to be linked with vitamin D deficiency. Based on this review and as a precautionary measure, it is suggested that the adoption of appropriate and safe solar exposure and vitamin D enriched foods and supplements should be considered to reduce the possible severity of COVID-19 symptoms. Safe sun exposure is deemed beneficial globally, specifically in low and middle-income countries, as there is no cost involved. It is also noted that improved solar exposure and vitamin D levels can reduce the impact of other diseases as well, thus assisting in maintaining general human well-being.
-
5.
Antibody-Based Inhibition of Pathogenic New World Hemorrhagic Fever Mammarenaviruses by Steric Occlusion of the Human Transferrin Receptor 1 Apical Domain.
Ferrero, S, Flores, MD, Short, C, Vazquez, CA, Clark, LE, Ziegenbein, J, Zink, S, Fuentes, D, Payes, C, Batto, MV, et al
Journal of virology. 2021;(17):e0186820
Abstract
Pathogenic clade B New World mammarenaviruses (NWM) can cause Argentine, Venezuelan, Brazilian, and Bolivian hemorrhagic fevers. Sequence variability among NWM glycoproteins (GP) poses a challenge to the development of broadly neutralizing therapeutics against the entire clade of viruses. However, blockade of their shared binding site on the apical domain of human transferrin receptor 1 (hTfR1/CD71) presents an opportunity for the development of effective and broadly neutralizing therapeutics. Here, we demonstrate that the murine monoclonal antibody OKT9, which targets the apical domain of hTfR1, can sterically block cellular entry by viral particles presenting clade B NWM glycoproteins (GP1-GP2). OKT9 blockade is also effective against viral particles pseudotyped with glycoproteins of a recently identified pathogenic Sabia-like virus. With nanomolar affinity for hTfR1, the OKT9 antigen binding fragment (OKT9-Fab) sterically blocks clade B NWM-GP1s and reduces infectivity of an attenuated strain of Junin virus. Binding of OKT9 to the hTfR1 ectodomain in its soluble, dimeric state produces stable assemblies that are observable by negative-stain electron microscopy. A model of the OKT9-sTfR1 complex, informed by the known crystallographic structure of sTfR1 and a newly determined structure of the OKT9 antigen binding fragment (Fab), suggests that OKT9 and the Machupo virus GP1 share a binding site on the hTfR1 apical domain. The structural basis for this interaction presents a framework for the design and development of high-affinity, broadly acting agents targeting clade B NWMs. IMPORTANCE Pathogenic clade B NWMs cause grave infectious diseases, the South American hemorrhagic fevers. Their etiological agents are Junin (JUNV), Guanarito (GTOV), Sabiá (SABV), Machupo (MACV), Chapare (CHAV), and a new Sabiá-like (SABV-L) virus recently identified in Brazil. These are priority A pathogens due to their high infectivity and mortality, their potential for person-to-person transmission, and the limited availability of effective therapeutics and vaccines to curb their effects. While low homology between surface glycoproteins of NWMs foils efforts to develop broadly neutralizing therapies targeting NWMs, this work provides structural evidence that OKT9, a monoclonal antibody targeting a single NWM glycoprotein binding site on hTfR1, can efficiently prevent their entry into cells.
-
6.
Cystic fibrosis foundation consensus statements for the care of cystic fibrosis lung transplant recipients.
Shah, P, Lowery, E, Chaparro, C, Visner, G, Hempstead, SE, Abraham, J, Bhakta, Z, Carroll, M, Christon, L, Danziger-Isakov, L, et al
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2021;(7):539-556
Abstract
Cystic fibrosis (CF) is the indication for transplantation in approximately 15% of recipients worldwide, and Cystic Fibrosis Lung Transplant Recipients (CFLTRs) have excellent long-term outcomes. Yet, CFLTRs have unique comorbidities that require specialized care. The objective of this document is to provide recommendations to CF and lung transplant clinicians for the management of perioperative and underlying comorbidities of CFLTRs and the impact of transplantation on these comorbidities. The Cystic Fibrosis Foundation (CFF) organized a multidisciplinary committee to develop CF Lung Transplant Clinical Care Recommendations. Three workgroups were formed to develop focused questions. Following a literature search, consensus recommendations were developed by the committee members based on literature review, committee experience and iterative revisions, and in response to public comment. The committee formulated 32 recommendation statements in the topics related to infectious disease, endocrine, gastroenterology, pharmacology, mental health and family planning. Broadly, the committee recommends close coordination of care between the lung transplant team, the cystic fibrosis care center, and specialists in other disciplines with experience in the care of CF and lung transplant recipients. These consensus statements will help lung transplant providers care for CFLTRs in order to improve post-transplant outcomes in this population.
-
7.
Licorice (Glycyrrhiza glabra) Extracts-Suitable Pharmacological Interventions for COVID-19? A Review.
Abraham, J, Florentine, S
Plants (Basel, Switzerland). 2021;(12)
Abstract
Even though vaccination has started against COVID-19, people should continue maintaining personal and social caution as it takes months or years to get everyone vaccinated, and we are not sure how long the vaccine remains efficacious. In order to contribute to the mitigation of COVID-19 symptoms, the pharmaceutical industry aims to develop antiviral drugs to inhibit the SARS-CoV-2 replication and produce anti-inflammatory medications that will inhibit the acute respiratory distress syndrome (ARDS), which is the primary cause of mortality among the COVID-19 patients. In reference to these tasks, this article considers the properties of a medicinal plant named licorice (Glycyrrhiza glabra), whose phytochemicals have shown both antiviral and anti-inflammatory tendencies through previous studies. All the literature was selected through extensive search in various databases such as google scholar, Scopus, the Web of Science, and PubMed. In addition to the antiviral and anti-inflammatory properties, one of the licorice components has an autophagy-enhancing mechanism that studies have suggested to be necessary for COVID-19 treatment. Based on reviewing relevant professional and historical literature regarding the medicinal properties of licorice, it is suggested that it may be worthwhile to conduct in vitro and in vivo studies, including clinical trials with glycyrrhizic and glycyrrhetinic acids together with other flavonoids found in licorice, as there is the potentiality to provide natural interventions against COVID-19 symptoms.
-
8.
Can Copper Products and Surfaces Reduce the Spread of Infectious Microorganisms and Hospital-Acquired Infections?
Abraham, J, Dowling, K, Florentine, S
Materials (Basel, Switzerland). 2021;(13)
Abstract
Pathogen transfer and infection in the built environment are globally significant events, leading to the spread of disease and an increase in subsequent morbidity and mortality rates. There are numerous strategies followed in healthcare facilities to minimize pathogen transfer, but complete infection control has not, as yet, been achieved. However, based on traditional use in many cultures, the introduction of copper products and surfaces to significantly and positively retard pathogen transmission invites further investigation. For example, many microbes are rendered unviable upon contact exposure to copper or copper alloys, either immediately or within a short time. In addition, many disease-causing bacteria such as E. coli O157:H7, hospital superbugs, and several viruses (including SARS-CoV-2) are also susceptible to exposure to copper surfaces. It is thus suggested that replacing common touch surfaces in healthcare facilities, food industries, and public places (including public transport) with copper or alloys of copper may substantially contribute to limiting transmission. Subsequent hospital admissions and mortality rates will consequently be lowered, with a concomitant saving of lives and considerable levels of resources. This consideration is very significant in times of the COVID-19 pandemic and the upcoming epidemics, as it is becoming clear that all forms of possible infection control measures should be practiced in order to protect community well-being and promote healthy outcomes.
-
9.
High Rates of Fat Oxidation Induced by a Low-Carbohydrate, High-Fat Diet, Do Not Impair 5-km Running Performance in Competitive Recreational Athletes.
Prins, PJ, Noakes, TD, Welton, GL, Haley, SJ, Esbenshade, NJ, Atwell, AD, Scott, KE, Abraham, J, Raabe, AS, Buxton, JD, et al
Journal of sports science & medicine. 2019;(4):738-750
Abstract
A common belief is that high intensity exercise (>60%VO2max) is best sustained by high rates of carbohydrate oxidation. The belief is based, in part, on an idea developed by Krogh and Lindhard in 1920. In the 100 years since, few studies have tested its validity. We tested the null hypothesis that performance in competitive recreational athletes exercising at >80% VO2max, during simulated 5-km running time trials (5KTT) would be impaired during a 6-week period of adaption to a low-carbohydrate, high-fat (LCHF) diet, compared to their performances when they ate a diet higher in carbohydrate and lower in fat (HCLF). Seven male athletes (age 35.6 ± 8.4 years, height 178.7 ± 4.1 cm, weight 68.6 ± 1.6 kg) completed two maximal exercise (VO2max) tests (Day 1 and 39) and four 5KTT (Day 4, 14, 28, and 42) in a fasted state during two 6-week periods when they ate either a HCLF or a LCHF diet, in a randomized counterbalanced, crossover design. Exercise performance during the VO2max tests was unchanged on either diet (p = 0.251). Performance in the initial 5KTT was significantly slower on the LCHF diet (p = 0.011). There were no diet-related performance differences in the remaining three 5KTT (p > 0.22). Subjects exercised at ~82%VO2max. Carbohydrate oxidation provided 94% of energy on the HCLF diet, but only 65% on the LCHF diet. 5KTT performance at ~82%VO2max was independent of the runners' habitual diet. The HCLF diet offered no advantage over a diet with a high-fat content. Since these athletes run faster than 88% of recreational distance runners in the United States (U.S.), this finding may have wide general application.
-
10.
Safety and Efficacy of T-DM1 Plus Neratinib in Patients With Metastatic HER2-Positive Breast Cancer: NSABP Foundation Trial FB-10.
Abraham, J, Montero, AJ, Jankowitz, RC, Salkeni, MA, Beumer, JH, Kiesel, BF, Piette, F, Adamson, LM, Nagy, RJ, Lanman, RB, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019;(29):2601-2609
-
-
Free full text
-
Abstract
PURPOSE Patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer eventually develop resistance to dual-antibody therapy with trastuzumab plus pertuzumab. Mechanisms of resistance have not been well elucidated. We evaluated the safety, tolerability, and efficacy of ado-trastuzumab emtansine (T-DM1) plus neratinib in patients who progressed on trastuzumab plus pertuzumab. PATIENTS AND METHODS In this 3 + 3 dose-escalation study, patients with metastatic breast cancer who progressed on trastuzumab, pertuzumab, and a taxane were treated with T-DM1 at 3.6 mg/kg intravenously every 3 weeks and dose-escalating neratinib at 120, 160, 200, or 240 mg/d orally. RESULTS Twenty-seven patients were treated across four dose-levels of neratinib. Dose-limiting toxicity in cycle 1 was grade 3 diarrhea in six patients and grade 3 nausea in one; no patient experienced grade 4 diarrhea, and there were no grade 5 toxicities. Other grade 3 to 4 toxicities included nausea (11%), dehydration (11%), electrolyte abnormality (19%), thrombocytopenia (15%), elevated transaminase levels (7%), and fatigue (7%). Twelve (63%) of 19 evaluable patients had an objective response. Responses occurred at all neratinib doses. Plasma cell-free DNA at baseline showed ERBB2 (HER2) amplification in 10 of 27 patients. Deep and more durable responses occurred in patients with cell-free DNA ERBB2 amplification. Two complete responders had high expression of total HER2 and p95HER2 in baseline tissue. CONCLUSION We report the recommended phase II dose of T-DM1 3.6 mg/kg and neratinib 160 mg/d for this combination. Possible resistance mechanisms to HER2 antibodies may be loss of the HER2 receptor and high expression of p95HER2. These data provide the basis for an ongoing phase II study to better define the activity of this regimen.