Antibiotics Versus Surgery in Treatment of Early Flexor Tenosynovitis.

BACKGROUND: Treatment of pyogenic flexor tenosynovitis (FTS) historically involved surgical debridement supplemented with antibiotic therapy. No consensus exists on either: (1) the treatment algorithm for this infection; or (2) the clinical definition of "early" FTS. We performed a retrospective study to clarify indications for nonoperative management. METHODS: We identified 40 patients with a diagnosis of FTS using Current Procedural Terminology and International Classification of Diseases, Tenth Revision, codes and a keyword search from an electronic medical record between 2011 and 2019. Patients underwent either surgical management (SG) (n = 20) or early antibiotics only (EAG) (n = 20). The surgical group was divided into patients with intraoperative purulence within the tendon sheath (PU) and those without purulence (NP). RESULTS: The number of Kanavel signs and duration of days of symptoms were significantly greater in SG compared with EAG. Subgroup analysis of SG showed a greater number of days of symptoms in the NP group when compared with the PU group. No statistical significance was found with respect to age, smoking, or specific individual Kanavel signs between SG and EAG. CONCLUSIONS: Both duration of symptoms and number of Kanavel signs should be considered in suspected early FTS. Patients with shorter duration of symptoms and fewer Kanavel signs were treated successfully with antibiotics alone. Operatively confirmed FTS presented more acutely with fewer days of symptoms and a higher number of Kanavel signs. Patients with subacute presentations may represent inflammatory conditions and hand infections other than FTS.

Neto-mediated intracellular interactions shape postsynaptic composition at the Drosophila neuromuscular junction.

The molecular mechanisms controlling the subunit composition of glutamate receptors are crucial for the formation of neural circuits and for the long-term plasticity underlying learning and memory. Here we use the Drosophila neuromuscular junction (NMJ) to examine how specific receptor subtypes are recruited and stabilized at synaptic locations. In flies, clustering of ionotropic glutamate receptors (iGluRs) requires Neto (Neuropillin and Tolloid-like), a highly conserved auxiliary subunit that is essential for NMJ assembly and development. Drosophila neto encodes two isoforms, Neto-α and Neto-ß, with common extracellular parts and distinct cytoplasmic domains. Mutations that specifically eliminate Neto-ß or its intracellular domain were generated. When Neto-ß is missing or is truncated, the larval NMJs show profound changes in the subtype composition of iGluRs due to reduced synaptic accumulation of the GluRIIA subunit. Furthermore, neto-ß mutant NMJs fail to accumulate p21-activated kinase (PAK), a critical postsynaptic component implicated in the synaptic stabilization of GluRIIA. Muscle expression of either Neto-α or Neto-ß rescued the synaptic transmission at neto null NMJs, indicating that Neto conserved domains mediate iGluRs clustering. However, only Neto-ß restored PAK synaptic accumulation at neto null NMJs. Thus, Neto engages in intracellular interactions that regulate the iGluR subtype composition by preferentially recruiting and/or stabilizing selective receptor subtypes.

Prodomain removal enables neto to stabilize glutamate receptors at the Drosophila neuromuscular junction.

Stabilization of neurotransmitter receptors at postsynaptic specializations is a key step in the assembly of functional synapses. Drosophila Neto (Neuropillin and Tolloid-like protein) is an essential auxiliary subunit of ionotropic glutamate receptor (iGluR) complexes required for the iGluRs clustering at the neuromuscular junction (NMJ). Here we show that optimal levels of Neto are crucial for stabilization of iGluRs at synaptic sites and proper NMJ development. Genetic manipulations of Neto levels shifted iGluRs distribution to extrajunctional locations. Perturbations in Neto levels also produced small NMJs with reduced synaptic transmission, but only Neto-depleted NMJs showed diminished postsynaptic components. Drosophila Neto contains an inhibitory prodomain that is processed by Furin1-mediated limited proteolysis. neto null mutants rescued with a Neto variant that cannot be processed have severely impaired NMJs and reduced iGluRs synaptic clusters. Unprocessed Neto retains the ability to engage iGluRs in vivo and to form complexes with normal synaptic transmission. However, Neto prodomain must be removed to enable iGluRs synaptic stabilization and proper postsynaptic differentiation.