SOHO State of the Art Update and Next Questions: IDH Therapeutic Targeting in AML

Mutations in isocitrate dehydrogenase isoform (IDH) 1 and 2 occur in approximately 25% of patients with acute myeloid leukemia (AML). These mutations lead to a block in myeloid differentiation and ultimately, to the development of AML. Inhibitors of mutant IDH1 and 2 have recently been approved by the US Food and Drug Administration and their use has led to clinical responses with prolonged duration of response. IDH inhibitors in combination with standard-of-care therapy and other small molecular inhibitors are now being used.     

Increased morbidity and mortality in cardiac patients undergoing fundoplication

Background

Infants with congenital cardiac disease (CCD) often require gastrostomy tube placement (GT) and need antireflux procedures, such as fundoplications. Our purpose was to compare morbidity/mortality rates among infants with CCD undergoing GT, fundoplication, or both.

Methods

Using the NSQIP-Pediatric, we identified 4070 patients <1-year-old who underwent GT and/or fundoplication from 2012 to 2014. 2346 infants (58%) had CCD categorized as minor, major or severe. Regression models were used to estimate the association of CCD with morbidity/mortality.

Results

Among all patients undergoing fundoplication, there were increased odds of morbidity/mortality among CCD patients compared to non-CCD patients (OR 2.15; p < 0.001). Odds of complications decreased when procedures were performed laparoscopically or later in the first year of life. Using GT alone as a reference, fundoplication alone (OR 1.67; p < 0.001) and GT with fundoplication (OR 1.82; p < 0.001) had increased odds of morbidity/mortality among cardiac patients. Increased risk persisted after stratification by severity of CCD and after accounting for surgical approach.

Conclusion

Fundoplication is associated with increased odds of morbidity/mortality in infants with CCD compared to GT alone. Risks are lower with laparoscopic approach and if surgery is delayed until later in the first year of life. Timing and surgical approach for patients with CCD requires further investigation.

     

The silent overall burden of foot disease in a representative hospitalised population

The aims of this study were to investigate the point prevalence, and associated independent factors, for foot disease (ulcers, infections and ischaemia) in a representative hospitalised population. We included 733 (83%) of 883 eligible adult inpatients across five representative Australian hospitals on one day. We collected an extensive range of self‐reported characteristics from participants. We examined all participants to clinically diagnose foot disease (ulcers, infections and ischaemia) and amputation procedures. Overall, 72 participants (9·8%) [95% confidence interval (CI):7·2–11·3%] had foot disease. Foot ulcers, in 49 participants (6·7%), were independently associated with peripheral neuropathy, peripheral arterial disease, previous foot ulcers, trauma and past surgeon treatment (P < 0·05). Foot infections, in 24 (3·3%), were independently associated with previous foot ulcers, trauma and past surgeon treatment (P < 0·01). Ischaemia, in 33 (4·5%), was independently associated with older age, smokers and past surgeon treatment (P < 0·01). Amputation procedures, in 14 (1·9%), were independently associated with foot infections (P < 0·01). We found that one in every ten inpatients had foot disease, and less than half of those had diabetes. After adjusting for diabetes, factors linked with foot disease were similar to those identified in diabetes‐related literature. The overall inpatient foot disease burden is similar in size to well‐known medical conditions and should receive similar attention.     

Intra-Articular Knee Injections Before Total Knee Arthroplasty: Outcomes and Complication Rates

Background

The relationship between intra-articular injections and complication rates after total knee arthroplasty (TKA) remains controversial. This study's purpose was to determine the relationship between the number and timing of intra-articular injections with complications and outcomes after TKA from a single surgeon's database.

Complications Following Outpatient Total Joint Arthroplasty: An Analysis of a National Database

Background

As outpatient total hip (THA) and knee arthroplasties (TKA) increase in popularity, concerns exist about the safety of discharging patients home the same day. The purpose of this study is to determine the complications associated with outpatient total joint arthroplasty (TJA) and to identify high-risk patients who should be excluded from these protocols.

Connexin43 Mutant Patient‐Derived Induced Pluripotent Stem Cells Exhibit Altered Differentiation Potential

We present for the first time the generation of induced pluripotent stem cells (iPSCs) from a patient with a connexin‐linked disease. The importance of gap junctional intercellular communication in bone homeostasis is exemplified by the autosomal dominant developmental disorder oculodentodigital dysplasia (ODDD), which is linked to mutations in the GJA1 (Cx43) gene. ODDD is characterized by craniofacial malformations, ophthalmic deficits, enamel hypoplasia, and syndactyly. In addition to harboring a Cx43 p.V216L mutation, ODDD iPSCs exhibit reduced Cx43 mRNA and protein abundance when compared to control iPSCs and display impaired channel function. Osteogenic differentiation involved an early, and dramatic downregulation of Cx43 followed by a slight upregulation during the final stages of differentiation. Interestingly, osteoblast differentiation was delayed in ODDD iPSCs. Moreover, Cx43 subcellular localization was altered during chondrogenic differentiation of ODDD iPSCs compared to controls and this may have contributed to the more compact cartilage pellet morphology found in differentiated ODDD iPSCs. These studies highlight the importance of Cx43 expression and function during osteoblast and chondrocyte differentiation, and establish a potential mechanism for how ODDD‐associated Cx43 mutations may have altered cell lineages involved in bone and cartilage development. © 2017 American Society for Bone and Mineral Research.