Scapholunate ligament reconstruction using the palmaris longus tendon and suture anchor fixation in chronic scapholunate instability.

BACKGROUND: Multiple reconstruction techniques have been described in the management of chronic scapholunate (SL) instability, either based on the capsulodesis or tenodesis principle. It is uncertain which surgical method produces the best patient outcomes. We describe results of a technique using palmaris longus (PL) tendon for surgical reconstruction of the SL ligament and provide functional outcomes scores. MATERIALS AND METHODS: We surgically reconstructed the SL ligament using a PL tendon graft secured with Mitek® bone anchors. Surgical technique with photographs is provided in the main text. Functional outcomes were measured using the disabilities of the arm, shoulder, and hand and Mayo wrist scores. Patient satisfaction was assessed using a simple measure. RESULTS: Eleven patients attended mid-term followup (mean 45.8 months post-surgery) and had functional outcomes and satisfaction of this procedure that compared favorably to case series that used tenodesis for chronic SL ligament injuries. Almost all patients (n = 10) were able to return to regular employment. The majority of patients (n = 10) were satisfied with their primary reconstruction procedure. CONCLUSION: This technique avoids the use of drill holes to weave tendon through bone, uses an easy to access graft, and exploits the superior pullout strength of anchors while offering satisfactory functional outcomes that are comparable to alternative tenodesis techniques.

Heterogeneous Effects of Direct Hypoxia Pathway Activation in Kidney Cancer.

General activation of hypoxia-inducible factor (HIF) pathways is classically associated with adverse prognosis in cancer and has been proposed to contribute to oncogenic drive. In clear cell renal carcinoma (CCRC) HIF pathways are upregulated by inactivation of the von-Hippel-Lindau tumor suppressor. However HIF-1α and HIF-2α have contrasting effects on experimental tumor progression. To better understand this paradox we examined pan-genomic patterns of HIF DNA binding and associated gene expression in response to manipulation of HIF-1α and HIF-2α and related the findings to CCRC prognosis. Our findings reveal distinct pan-genomic organization of canonical and non-canonical HIF isoform-specific DNA binding at thousands of sites. Overall associations were observed between HIF-1α-specific binding, and genes associated with favorable prognosis and between HIF-2α-specific binding and adverse prognosis. However within each isoform-specific set, individual gene associations were heterogeneous in sign and magnitude, suggesting that activation of each HIF-α isoform contributes a highly complex mix of pro- and anti-tumorigenic effects.

Pan-genomic binding of hypoxia-inducible transcription factors.

Hypoxia-inducible transcription factors (HIFs) mediate the cellular response to hypoxia. HIF-DNA binding triggers a transcriptional program that acts to both restore oxygen homeostasis and adapt cells to low oxygen availability. In this context, HIF is centrally involved in many physiologic and pathophysiological processes such as development, high altitude adaptation, ischemic disease, inflammation, and cancer. The recent development of chromatin immunoprecipitation coupled to genome-wide DNA sequence analysis allows the position and extent of HIF binding to DNA to be characterized across the entire genome and correlated with genetic, epigenetic, and transcriptional analyses. This review summarizes recent pan-genomic analyses of HIF binding and HIF-dependent transcriptional regulation.

The von Hippel-Lindau tumor suppressor, hypoxia-inducible factor-1 (HIF-1) degradation, and cancer pathogenesis.

Recently, work on the mechanism of action of the von Hippel-Lindau tumour suppressor protein (pVHL) and studies on hypoxic gene regulation have converged, providing insights into both cellular oxygen sensing and cancer pathogenesis. pVHL is the recognition component of the E3-ubiquitin ligase complex involved in the degradation of hypoxia-inducible factor-1 (HIF) alpha-subunits, a process regulated by oxygen availability and blocked by disease causing pVHL mutations. In normoxic cells, pVHL targeting of HIF-alpha subunits follows hydroxylation of critical HIF prolyl residues by a group of oxygen, 2-oxoglutarate- and iron-dependent enzymes. In this review, we outline current understanding of HIF/pVHL/prolyl hydroxylase pathway and consider the implications for VHL-associated cancer.