Sodium-glucose cotransporter 2 inhibitors: are they ready for prime time in the management of lupus nephritis?

PURPOSE OF REVIEW: Lupus nephritis is a common complication of systemic lupus erythematosus and is associated with significant morbidity and mortality. The utility of sodium-glucose cotransporter 2 (SGLT2) inhibitors in the management of lupus nephritis is currently uncertain. Here, we summarize the rationale for their use among patient with lupus nephritis. RECENT FINDINGS: SGLT2 inhibitors were initially developed as antihyperglycemic agents. They have since been shown to have additional, profound effects to slow the progression of chronic kidney disease and lessen the long-term risks of cardiovascular disease in large clinic trials of patients with chronic kidney disease, with and without diabetes, as well as in patients with and without proteinuria. Patients with recent exposure to immunosuppression were excluded from these trials due to concern for risk of infection. In the few, small trials of patients with lupus nephritis, SGLT2 inhibitors were found to be well tolerated. They have been shown to reduce proteinuria and to have modest beneficial effects on blood pressure and BMI among patients with lupus nephritis. They have not been shown to influence disease activity. SUMMARY: SGLT2 inhibitors may have a role in mitigating the chronic renal and cardiovascular effects of lupus nephritis. They should be introduced after kidney function has been stabilized with appropriate immunosuppression, in conjunction with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. They currently have no role in active disease.

Miltefosine Reduces the Cytolytic Activity and Virulence of Acinetobacter baumannii.

Stagnation in antimicrobial development has led to a serious threat to public health because some Acinetobacter baumannii infections have become untreatable. New therapeutics with alternative mechanisms of action to combat A. baumannii are therefore necessary to treat these infections. To this end, the virulence of A. baumannii isolates with various antimicrobial susceptibilities was assessed when the isolates were treated with miltefosine, a phospholipase C inhibitor. Phospholipase C activity is a contributor to A. baumannii virulence associated with hemolysis, cytolysis of A549 human alveolar epithelial cells, and increased mortality in the Galleria mellonella experimental infection model. While the effects on bacterial growth were variable among strains, miltefosine treatment significantly reduced both the hemolytic and cytolytic activity of all treated A. baumannii strains. Additionally, scanning electron microscopy of polarized A549 cells infected with bacteria of the A. baumannii ATCC 19606T strain or the AB5075 multidrug-resistant isolate showed a decrease in A549 cell damage with a concomitant increase in the presence of A549 surfactant upon administration of miltefosine. The therapeutic ability of miltefosine was further supported by the results of G. mellonella infections, wherein miltefosine treatment of animals infected with ATCC 19606T significantly decreased mortality. These data demonstrate that inhibition of phospholipase C activity results in the overall reduction of A. baumannii virulence in both in vitro and in vivo models, making miltefosine a viable option for the treatment of A. baumannii infections, particularly those caused by multidrug-resistant isolates.

Devices for Autonomic Regulation Therapy in Heart Failure With Reduced Ejection Fraction.

Heart failure (HF) is associated with significant morbidity and mortality and an increasing economic burden. The persistence of HF's risk factors, coupled with an aging population, also leads to an increase in its incidence and prevalence. It is well established that sympathetic hyperactivity and parasympathetic withdrawal are instrumental in the development and worsening of HF. Therefore, restoring autonomic balance to the cardiovascular system is an attractive therapeutic approach. The following is a review of current clinical trials of device-based autonomic regulation therapy in the management of HF with a reduced ejection fraction.

Locking Compression Pilon Plate for Fixation of Comminuted Posterior Wall Acetabular Fractures: A Novel Technique.

Posterior wall acetabular fractures involving a large portion the wall's width and with extensive comminution are difficult fractures to manage operatively. Cortical substitution with a pelvic reconstruction plate and supplemental spring plates has been the traditional means of fixation for these fractures. This option, however, requires the use of multiple, unlinked plates and provides no reliable option for peripheral fixation in comminuted fragments. We describe a novel technique for operative fixation of large, comminuted posterior wall fractures using a single distal tibia pilon plate with the option for peripheral locking screw fixation and report on a series of 20 consecutive patients treated with this method.

Orthopaedic trauma in the Anabaptist community: epidemiology and hospital charges.

This study aims to define the epidemiology of orthopaedic trauma in the rural Anabaptist community and analyze the hospital charges associated with their treatment. The authors performed a retrospective review of 79 Amish and 40 Mennonite patients who had been seen in their rural level I trauma center emergency department for an orthopaedic injury from January 2006 to May 2013. Data collection included baseline demographics, injury mechanism and severity, injury complex, operative interventions, outcomes, and hospital charges. Amish and Mennonite groups were similar except for a higher percentage of males in the Mennonite group. For Amish patients, occupational injuries (52%) and buggy accidents (16%) accounted for the highest percentage of admissions. Eighty-seven percent sustained at least one fracture, most commonly of the hand (11%). Amish patients were statistically more likely to sustain fractures of the spine, and Mennonite patients were more likely to sustain fractures of the foot and femur. Over half of patients required surgery (58%). Total hospital charges did not differ based between the groups. Amish patients completed outpatient follow-up less frequently than Mennonite patients. Anabaptist patients are at risk for a variety of orthopaedic injuries related to their unique lifestyle and vocations. Socioreligious beliefs must be taken into consideration when educating these patients regarding postinjury care, as attendance at outpatient follow-up is low. Understanding the types of injuries that these patients sustain can help create strategies to prevent costly transportation and agricultural accidents within the Anabaptist community.

Infections do not predict shedding in co-infections with two helminths from a natural system.

Given the health and economic burden associated with the widespread occurrence of co-infections in humans and agricultural animals, understanding how coinfections contribute to host heterogeneity to infection and transmission is critical if we are to assess risk of infection based on host characteristics. Here, we examine whether host heterogeneity to infection leads to similar heterogeneity in transmission in a population of rabbits single and co-infected with two helminths and monitored monthly for eight years. Compared to single infections, co-infected rabbits carried higher Trichostrongylus retortaeformis intensities, shorter worms with fewer eggs in utero, and shed similar numbers of parasite eggs. In contrast, the same co-infected rabbits harbored fewer Graphidium strigosum with longer bodies and more eggs in utero, and shed more eggs of this helminth. A positive density-dependent relationship between fecundity and intensity was found for T. retortaeformis but not G. strigosum in co-infected rabbits. Juvenile rabbits contributed to most of the infection and shedding of T. retortaeformis, while adult hosts were more important for G. strigosum dynamics of infection and transmission, and this pattern was consistent in single and co-infected individuals. This host-parasite system suggests that we cannot predict the pattern of parasite shedding during co-infections based on intensity of infection alone. We suggest that a mismatching between susceptibility and infectiousness should be expected in helminth coinfections and should not be overlooked.