A Current Review in the Orthopedic Management of Osteonecrosis of the knee Secondary to Treatment of Pediatric Hematologic Malignancy.

Acute Lymphoblastic Leukemia is the most prevalent pediatric hematologic malignancy. The treatment for this illness has advanced significantly, now touting a 90% cure rate. Although these patients often become disease free, treatment can leave devastating effects that last long after their disease burden is alleviated. A commonly experienced result of treatment is osteonecrosis (ON), often occurring in weight bearing joints. Uncertainty exists in the optimal treatment of this cohort of patients. In this review, we describe the etiology and suspected pathogenesis of ON, as well as treatment options described in the literature.

Subtrochanteric fracture after femoral neck system of femoral neck fractures: a report of four cases.

BACKGROUND: The femoral neck system (FNS) is commonly used for internal fixation of femoral neck fractures and has shown promising results. However, we have observed cases of peri-implant subtrochanteric femur fractures associated with the use of FNS at our institution. This case series aims to investigate four cases of peri-implant subtrochanteric fractures in patients treated with the FNS implant for femoral neck fractures. CASE PRESENTATION: We reviewed 35 patients who underwent treatment with FNS for femoral neck fractures between January 2017 and December 2021 at our level 1 trauma institution. Among these patients, four cases of peri-implant subtrochanteric femur fractures were identified. In contrast, no such fractures occurred in patients treated with cannulated screws or dynamic hip screws (DHS). Interestingly, all four cases of peri-implant fractures were seen in patients with incomplete nondisplaced femoral neck fractures. Only one case involved an identifiable technical error. CONCLUSIONS: This case series sheds light on peri-implant subtrochanteric femur fractures as a previously unreported complication associated with the use of FNS for femoral neck fractures. These fractures were observed exclusively in patients with incomplete nondisplaced fractures who received FNS fixation. No similar complications were observed in patients treated with other types of fixation. This finding suggests the need for caution and further investigation when considering FNS as a treatment option for this specific fracture pattern. The identification of peri-implant subtrochanteric femur fractures as a potential complication of FNS usage in incomplete nondisplaced femoral neck fractures raises important considerations for clinical decision-making and patient management in orthopedic trauma.

Management of Calcaneal Cysts in the Pediatric Population: A Review.

Cysts of the bone are a common pathology that, although benign, are frequently treated because of their tendency to compromise the integrity of affected bone. Two common entities are unicameral bone cysts and aneurysmal bone cysts. Although these are two distinct pathologies, they are treated similarly and thus will be discussed in tandem. The optimal treatment of calcaneal bone cysts in pediatric patients has long been debated among orthopaedic surgeons because of the relatively small number of cases and varied results within the literature. Currently, there are three lines of thought regarding treatment: observation, injection, and surgical intervention. When considering which course of treatment is best for an individual patient, the surgeon must consider the fracture risk without treatment, the risk of complications with treatment, and the recurrence rate with each treatment approach. There are limited data on pediatric calcaneal cysts specifically. Still, there are much data concerning simple bone cysts of long bones in the pediatric population and calcaneal cysts in the adult population. Because of the lack of literature on the subject, there is a need for a review of the available literature and a consensus on the approach to treating calcaneal cysts in the pediatric population.

PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis.

Following DNA damage, nuclear p53 induces the expression of PUMA, a BH3-only protein that binds and inhibits the antiapoptotic BCL-2 repertoire, including BCL-xL. PUMA, unique among BH3-only proteins, disrupts the interaction between cytosolic p53 and BCL-xL, allowing p53 to promote apoptosis via direct activation of the BCL-2 effector molecules BAX and BAK. Structural investigations using NMR spectroscopy and X-ray crystallography revealed that PUMA binding induced partial unfolding of two α-helices within BCL-xL. Wild-type PUMA or a PUMA mutant incapable of causing binding-induced unfolding of BCL-xL equivalently inhibited the antiapoptotic BCL-2 repertoire to sensitize for death receptor-activated apoptosis, but only wild-type PUMA promoted p53-dependent, DNA damage-induced apoptosis. Our data suggest that PUMA-induced partial unfolding of BCL-xL disrupts interactions between cytosolic p53 and BCL-xL, releasing the bound p53 to initiate apoptosis. We propose that regulated unfolding of BCL-xL provides a mechanism to promote PUMA-dependent signaling within the apoptotic pathways.

Intrinsic disorder mediates the diverse regulatory functions of the Cdk inhibitor p21.

Traditionally, well-defined three-dimensional structure has been thought to be essential for protein function. However, myriad biological functions are performed by highly dynamic, intrinsically disordered proteins (IDPs). IDPs often fold upon binding their biological targets and frequently show 'binding diversity' by targeting multiple ligands. We sought to understand the physical basis of IDP binding diversity and report here that the cyclin-dependent kinase (Cdk) inhibitor p21(Cip1) adaptively binds to and inhibits the various Cdk-cyclin complexes that regulate eukaryotic cell division. Using results from NMR spectroscopy and biochemical and cellular assays, we show that structural adaptability of a helical subdomain within p21, termed LH, enables two other subdomains, D1 and D2, to specifically bind conserved surface features of the cyclin and Cdk subunits, respectively, within otherwise structurally distinct Cdk-cyclin complexes. Adaptive folding upon binding is likely to mediate the diverse biological functions of the thousands of IDPs present in eukaryotes.

Mechanism of apoptosis induction by inhibition of the anti-apoptotic BCL-2 proteins.

Normal cellular lifespan is contingent upon preserving outer mitochondrial membrane (OMM) integrity, as permeabilization promotes apoptosis. BCL-2 family proteins control mitochondrial outer membrane permeabilization (MOMP) by regulating the activation of the pro-apoptotic BCL-2 effector molecules, BAX and BAK. Sustainable cellular stress induces proteins (e.g., BID, BIM, and cytosolic p53) capable of directly activating BAX and/or BAK, but these direct activators are sequestered by the anti-apoptotic BCL-2 proteins (e.g., BCL-2, BCL-xL, and MCL-1). In the event of accumulated or marked cellular stress, a coordinated effort between previously sequestered and nascent BH3-only proteins inhibits the anti-apoptotic BCL-2 repertoire to promote direct activator protein-mediated MOMP. We examined the effect of ABT-737, a BCL-2 antagonist, and PUMA, a BH3-only protein that inhibits the entire anti-apoptotic BCL-2 repertoire, with cells and mitochondria that sequestered direct activator proteins. ABT-737 and PUMA cooperated with sequestered direct activator proteins to promote MOMP and apoptosis, which in the absence of ABT-737 or PUMA did not influence OMM integrity or cellular survival. Our data show that the induction of apoptosis by inhibition of the anti-apoptotic BCL-2 repertoire requires "covert" levels of direct activators of BAX and BAK at the OMM.

The Current and Future Status of Lasers in Surgery.

Almost from the moment of its invention, the laser was destined to play a significant role in surgery. This intense new source of coherent, radiant energy inevitably attracted the attention of imaginative physicians and surgeons, who immediately recognised its potential for precise removal of diseased tissue.