Cell-free DNA in the surveillance of heart transplant rejection

BackgroundCirculating cell-free deoxyribonucleic acid (cfDNA) is promptly materializing as a highly useful tool for the surveillance of solid-organ transplant rejection. Donor-specific fraction (DF) cfDNA is a potential marker of selective donor organ injury. It is emerging as a promising analytical target in the near future. The aim of this systematic review is to throw light on the importance of cfDNA and future perspective in detecting acute rejection in heart transplantation.MethodsAn exhaustive search was carried out for this review article on the basis of literature available including scientific databases of PubMed, Embase, and ClinicalTrials.gov. The search engines were systematically explored using the search terms “cell free DNA,” “Heart transplant,” and “Rejection” from inception until August 2020, and narrative analysis was accomplished. Majority of the studies described endomyocardial biopsy-proven acute rejection as reference standard.ResultsAfter initial screening of 331 articles, 11 studies were included and discussed in detail in the present review article. Majority of the studies showed prospective designs. A firm correlation was noted between acute rejection (identified on endomyocardial biopsy) and cfDNA levels by most of the studies.ConclusionscfDNA is a promising tool to replace repeated biopsies to detect rejection. The development in the area of digital droplet polymerase chain reaction and massive parallel sequencing, along with the overall reduction in cost of sequencing with its automation, has helped establish its role in the transplant population.     

The Metabolic Syndrome and Microvascular Complications in a Murine Model of Type 2 Diabetes

To define the components of the metabolic syndrome that contribute to diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM), we treated the BKS db/db mouse, an established murine model of T2DM and the metabolic syndrome, with the thiazolidinedione class drug pioglitazone. Pioglitazone treatment of BKS db/db mice produced a significant weight gain, restored glycemic control, and normalized measures of serum oxidative stress and triglycerides but had no effect on LDLs or total cholesterol. Moreover, although pioglitazone treatment normalized renal function, it had no effect on measures of large myelinated nerve fibers, specifically sural or sciatic nerve conduction velocities, but significantly improved measures of small unmyelinated nerve fiber architecture and function. Analyses of gene expression arrays of large myelinated sciatic nerves from pioglitazone-treated animals revealed an unanticipated increase in genes related to adipogenesis, adipokine signaling, and lipoprotein signaling, which likely contributed to the blunted therapeutic response. Similar analyses of dorsal root ganglion neurons revealed a salutary effect of pioglitazone on pathways related to defense and cytokine production. These data suggest differential susceptibility of small and large nerve fibers to specific metabolic impairments associated with T2DM and provide the basis for discussion of new treatment paradigms for individuals with T2DM and DPN.     

Carbapenem-resistant Pseudomonas aeruginosa in malaysia producing IMP-7 beta-lactamase

We have isolated and identified a carbapenem-resistant Pseudomonas aeruginosa strain from Malaysia that produces an IMP-7 metallo-beta-lactamase. This isolate showed high-level resistance to meropenem and imipenem, the MICs of which were 256 and 128 micro g/ml, respectively. Isoelectric focusing analyses revealed pI values of >9.0, 8.2, and 7.8, which indicated the possible presence of IMP and OXA. DNA sequencing confirmed the identity of the IMP-7 determinant.     

Innovations in treating aortic diseases: the abdominal aorta

Patients with an abdominal aortic aneurysm (AAA) could benefit from earlier diagnosis to improve long-term outcomes. Candidate serum biomarkers for earlier AAA diagnosis include D-dimer, fibrinogen, low-density lipoprotein, high-density lipoprotein, lipoprotein(a), and the proteolytic enzymes known as matrix metalloproteinases. Furthermore, biomarkers such as brain natriuretic peptide significantly stratify perioperative risk in AAA repair. Statins significantly improve outcomes after AAA repair. They may also significantly slow AAA growth to allow pharmacologic arrest of AAA development. Recent trials have focused attention on fluid management for AAA repair. Although restrictive fluid management may significantly improve clinical outcomes, current evidence does not clearly support crystalloid or colloid for AAA repair. There may be an increased risk of renal dysfunction associated with hetastarch therapy. Endovascular repair has revolutionized the clinical management of AAAs. Recent trials have shown its significant outcome advantages. Furthermore, it is also applicable in high-risk operative cohorts and, in the future, may be suited for earlier AAA repair. This technology continues to advance with the development of branched and fenestrated grafts as well as total percutaneous endovascular AAA repair. Regardless of these advances, the clinical management of endoleaks will remain a major clinical focus. Taken together, these advances in the management of AAAs likely will significantly influence future clinical approaches to this challenging patient cohort.     

Repeatability of hypoxia PET imaging using [<Superscript>18</Superscript>F]HX4 in lung and head and neck cancer patients: a prospective multicenter trial

Purpose

Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [¹⁸F]HX4 in patients with head and neck and lung cancer.

Methods

Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [¹⁸F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUV_max and SUV_mean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV_1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.

Results

All parameters of [¹⁸F]HX4 uptake were significantly correlated between scans: SUV_max (r?=?0.958, p?<?0.001), SUV_mean (r?=?0.946, p?<?0.001), TBR_max (r?=?0.962, p?<?0.001) and HV_1.2 (r?=?0.995, p?<?0.001). The relative coefficients of repeatability were 15 % (SUV_mean), 17 % (SUV_max) and 17 % (TBR_max). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65?±?0.14.

Conclusion

Repeated hypoxia PET scans with [¹⁸F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [¹⁸F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.