The Nucleoside Analog BMS-986001 Shows Greater In Vitro Activity against HIV-2 than against HIV-1.

Treatment options for individuals infected with human immunodeficiency virus type 2 (HIV-2) are restricted by the intrinsic resistance of the virus to nonnucleoside reverse transcriptase inhibitors (NNRTIs) and the reduced susceptibility of HIV-2 to several protease inhibitors (PIs) used in antiretroviral therapy (ART). In an effort to identify new antiretrovirals for HIV-2 treatment, we evaluated the in vitro activity of the investigational nucleoside analog BMS-986001 (2',3'-didehydro-3'-deoxy-4'-ethynylthymidine; also known as censavudine, festinavir, OBP-601, 4'-ethynyl stavudine, or 4'-ethynyl-d4T). In single-cycle assays, BMS-986001 inhibited HIV-2 isolates from treatment-naive individuals, with 50% effective concentrations (EC50s) ranging from 30 to 81 nM. In contrast, EC50s for group M and O isolates of HIV-1 ranged from 450 to 890 nM. Across all isolates tested, the average EC50 for HIV-2 was 9.5-fold lower than that for HIV-1 (64 ± 18 nM versus 610 ± 200 nM, respectively; mean ± standard deviation). BMS-986001 also exhibited full activity against HIV-2 variants whose genomes encoded the single amino acid changes K65R and Q151M in reverse transcriptase, whereas the M184V mutant was 15-fold more resistant to the drug than the parental HIV-2ROD9 strain. Taken together, our findings show that BMS-986001 is an effective inhibitor of HIV-2 replication. To our knowledge, BMS-986001 is the first nucleoside analog that, when tested against a diverse collection of HIV-1 and HIV-2 isolates, exhibits more potent activity against HIV-2 than against HIV-1 in culture.

Sternoclavicular joint reconstruction for traumatic acute and chronic anterior and posterior instability: Patient-reported outcomes at a minimum of 2 years.

Background: Instability of the sternoclavicular joint (SCJ) is a rare problem that is often treated closed, with few published outcomes of surgical treatment with tendon graft reconstruction. Methods: We reviewed a consecutive series of patients who underwent tendon graft reconstruction for SCJ instability over a 7-year period. Cases with acute fractures or fewer than 2 years of follow-up were excluded. Pre- and postoperative function and pain were assessed using Single assessment numeric evaluation (SANE), simple shoulder test (SST), and visual analog scale (VAS) outcome measures. Results: Thirty cases were included, with 27 (90%) available for follow-up at a minimum of 2 years postoperatively. SANE scores improved from a median of 40 to 90. SST scores improved from a median of 3 positive responses to a median of 12 on a 12-point scale. VAS scores decreased from a median of 7 to 0 points. One patient underwent reoperation for recurrent instability and wound dehiscence. Three (11%) patients did not achieve a minimum 30% of maximum possible improvement in SST scores. Conclusions: Tendon graft reconstruction for SCJ instability is a safe procedure with a low complication rate and statistically and clinically significant improvements in patient-reported outcome measures at 2-year minimum follow-up. Level of evidence: Level IV: Therapeutic.

A Case for Acute Proximal Row Carpectomy for Perilunate Injuries.

Background: Perilunate injuries are complex injuries typically arising from high-energy injuries to the wrist. Standard treatment involves open reduction and internal fixation with ligamentous reconstruction; however, outcomes are fraught with complications including pain, stiffness, and arthrosis. Several case reports have demonstrated the role of proximal row carpectomy as a salvage procedure for complex carpal trauma in the setting of significant cartilage injury or bone loss. The authors believe that proximal row carpectomy may be an appropriate acute treatment in certain patient populations, with functional results similar to those obtained with ligamentous reconstruction. Methods: A retrospective review of two cases with perilunate dislocations managed with primary proximal row carpectomy are presented. Results: At greater than 1-year follow-up, both patients had stable radiocarpal alignment. Quick-DASH scores were 22.7 and 27.3. Conclusion: Primary proximal row carpectomy is a treatment option in the acute setting for perilunate injuries in elderly, lower-demand patients. Functional results are similar to those obtained with ligamentous reconstruction, with a shorter recovery period. Level of Evidence: IV.

Unicortical sternal graft reconstruction for anterior sternoclavicular joint instability.

Sternoclavicular joint (SCJ) injury represents 3%-5% of all shoulder girdle injuries, yet can produce significant pain and disability. While conservative management improves symptoms in most cases, surgical intervention may be indicated for patients with symptoms recalcitrant to nonoperative treatment. A wide range of surgical stabilisation techniques is documented in the literature; however, the scarcity of SCJ pathology has hindered development of a 'gold standard'.We present a minimalistic medial clavicle osteoplasty and SCJ reconstruction using semitendinosus autograft anchored with unicortical sternal tunnels in the 54 years old with chronic SCJ instability. This technique can be performed safely, resulting in joint stability and pain reduction, while avoiding risks and complications noted in the literature with other techniques.