Defining Fluoroquinolone Resistance-Mediating Mutations from Non-Resistance Polymorphisms in Mycoplasma hominis Topoisomerases

Often dismissed as a commensal, Mycoplasma hominis is an increasingly prominent target of research due to its role in septic arthritis and organ transplant failure in immunosuppressed patients, particularly lung transplantation. As a mollicute, its highly reductive genome and structure render it refractile to most forms of treatment and growing levels of resistance to the few sources of treatment left, such as fluoroquinolones. We examined antimicrobial susceptibility (AST) to fluoroquinolones on 72 isolates and observed resistance in three (4.1%), with corresponding mutations in the quinolone resistance-determining region (QRDR) of S83L or E87G in gyrA and S81I or E85V in parC. However, there were high levels of polymorphism identified between all isolates outside of the QRDR, indicating caution for a genomics-led approach for resistance screening, particularly as we observed a further two quinolone-susceptible isolates solely containing gyrA mutation S83L. However, both isolates spontaneously developed a second spontaneous E85K parC mutation and resistance following prolonged incubation in 4 mg/L levofloxacin for an extra 24–48 h. Continued AST surveillance and investigation is required to understand how gyrA QRDR mutations predispose M. hominis to rapid spontaneous mutation and fluoroquinolone resistance, absent from other susceptible isolates. The unusually high prevalence of polymorphisms in M. hominis also warrants increased genomics’ surveillance.

Case Report: Capillary Leak Syndrome With Kidney Transplant Failure Following Autologous Mesenchymal Stem Cell Therapy

Mesenchymal stem cells (MSCs) have attracted great interest in the field of kidney transplantation due to their immunomodulatory and reparative properties. In registered clinical trials, MSCs have been used before, at the time of, or early after transplantation and have been reported to be well-tolerated with no serious safety concerns. No results are available on the use of MSCs in the late post-transplant period. Here, we present a case report of a severe systemic complication mimicking capillary leak syndrome with ultimate kidney transplant failure after autologous transplantation of MSCs used as rescue treatment of late antibody-mediated kidney allograft rejection.

Allo-Specific Humoral Responses: New Methods for Screening Donor-Specific Antibody and Characterization of HLA-Specific Memory B Cells

Antibody-mediated allograft rejection (AMR) causes more kidney transplant failure than any other single cause. AMR is mediated by antibodies recognizing antigens expressed by the graft, and antibodies generated against major histocompatibility complex (MHC) mismatches are especially problematic. Most research directed towards the management of clinical AMR has focused on identifying and characterizing circulating donor-specific HLA antibody (DSA) and optimizing therapies that reduce B-cell activation and/or block antibody secretion by inhibiting plasmacyte survival. Here we describe a novel set of reagents and techniques to allow more specific measurements of MHC sensitization across different animal transplant models. Additionally, we have used these approaches to isolate and clone individual HLA-specific B cells from patients sensitized by pregnancy or transplantation. We have identified and characterized the phenotypes of individual HLA-specific B cells, determined the V(D)J rearrangements of their paired H and L chains, and generated recombinant antibodies to determine affinity and specificity. Knowledge of the BCR genes of individual HLA-specific B cells will allow identification of clonally related B cells by high-throughput sequence analysis of peripheral blood mononuclear cells and permit us to re-construct the origins of HLA-specific B cells and follow their somatic evolution by mutation and selection.

Optimizing Transplant Approaches and Post-Transplant Strategies for Patients With Acute Myeloid Leukemia

Acute Myeloid Leukemia (AML) is the commonest indication for allogeneic stem cell transplantation (allo-SCT) worldwide. The increasingly important role of allo-SCT in the management of AML has been underpinned by two important advances. Firstly, improvements in disease risk stratification utilizing genetic and Measurable Residual Disease (MRD) technologies permit ever more accurate identification of allo-mandatory patients who are at high risk of relapse if treated by chemotherapy alone. Secondly, increased donor availability coupled with the advent of reduced intensity conditioning (RIC) regimens has substantially expanded transplant access for patients with high risk AML In patients allografted for AML disease relapse continues to represent the commonest cause of transplant failure and the development of novel strategies with the potential to reduce disease recurrence represents a major unmet need.

The application of an allogeneic bone screw for osteosynthesis in hand and foot surgery: a case series

Introduction The allogeneic bone screw transplant is a new osteosynthesis device making the use of foreign fixation material obsolete for various kinds of indications. Moreover, it is integrated into the recipient bone by natural bone remodeling without harming the surrounding tissue. The aim of this study was to determine the efficacy and safety of the transplant for osteotomy and arthrodesis in hand and foot surgery and to evaluate the clinical importance of the device. Materials and methods A single-surgeon case series of 32 patients who had undergone hand or foot surgery with the application of an allogeneic bone screw with an average follow-up time of 1 year is reported. Clinical data were reviewed to evaluate the pain levels and satisfaction of the patients and the frequency and type of complications occurring during the healing process. Routine radiography and computed tomography were reviewed to determine the fusion rate, the ingrowth behavior of the transplant and the possible occurrence of transplant failure. Results High patient satisfaction was paired with low postoperative pain levels and a low complication rate. 97% of the patients were free of pain at the timepoint of the second follow-up examination, the mean time of recovery of full mobility was 50.1 ± 26.1 days after surgery. Wound healing disturbance occurred only in two cases. Bony consolidation of the osteotomy or arthrodesis gap as well as osseointegration of the transplant was seen in all cases. No transplant failure or transplant loosening occurred. Conclusions The application of the allogeneic bone screw resulted in a 100% fusion rate while the patient burden was low. The transplant is safe and suited for various kinds of osteosynthesis in hand and foot surgery.

Managing Patients with Failing Kidney Allograft

Patients who receive a kidney transplant commonly experience failure of their allograft. Transplant failure often comes with complex management decisions, such as when and how to wean immunosuppression and start the transition to a second transplant or to dialysis. These decisions are made in the context of important concerns about competing risks, including sensitization and infection. Unfortunately, the management of the failed allograft is, at present, guided by relatively poor-quality data and, as a result, practice patterns are variable and suboptimal given that patients with failed allografts experience excess morbidity and mortality compared with their transplant-naive counterparts. In this review, we summarize the management strategies through the often-precarious transition from transplant to dialysis, highlighting the paucity of data and the critical gaps in our knowledge that are necessary to inform the optimal care of the patient with a failing kidney transplant.

Delayed renal transplant failure secondary to renal vein thrombosis in a patient with a permanent IVC filter

Renal vein thrombosis is a rare, but potentially serious complication in patients with renal transplantation as it can lead to non-reversible graft injury and failure. Often this clinical entity is found in the early transplantation period, and the available management strategies are associated with favourable patient outcomes. The incidence, pathophysiology and outcomes for the delayed occurrence of renal vein thrombosis are unknown. The case here describes a unique situation with an excellent clinical outcome related to early diagnosis and appropriate care.