Unexpected Diaphragmatic Hernia Among Patients Undergoing Video-Assisted Thoracic Surgery for Internal Fixation of Rib Fractures.

Traumatic blunt diaphragm injuries are a diagnostic challenge in trauma. They may be missed due to the increasing trend of non-operative management of patients. The purpose of this study was to review the rate of occult blunt diaphragm injuries in patients who underwent video assisted thoracic surgery (VATS) for rib fixation. This retrospective study included patients that received VATS as part of our institutional protocol for rib fracture management. This includes utilizing incentive spirometry, multimodal analgesia, and early consideration for VATS. Data was abstracted from the electronic medical record and included demographics, operative findings, and outcomes. Thirty patients received VATS per our rib fracture protocol. No patients had any identified diaphragm injury on pre-operative imaging. A concomitant diaphragm injury was identified in 20% (6/30) of the study population. All patients were alive at 30 days. For all patients, total hospital length of stay was 14.5 days, ICU length of stay was 8.9 days, and average ventilator days was 4.2 days. When comparing patients with and without concomitant diaphragm injuries, hospital length of stay was 16.8 days vs. 14.5 (P = 0.59), ICU length of stay was 11.8 days vs. 8.2 (P = 0.54), and ventilator days was 4.5 days vs. 4.2 (P = 0.93). This study revealed that 20% of patients undergoing VATS for rib fracture fixation had a concomitant diaphragm injury. This higher-than-expected prevalence suggests that groups of patients sustaining blunt trauma may have occult diaphragmatic injuries that are otherwise unidentified. This raises the need for improved diagnostic modalities to identify these injuries.

The dual role of tetraspanin CD63 in HIV-1 replication.

BACKGROUND: Previously, we showed that the tetraspanin membrane protein CD63 mediates both early and post-integration stages of the HIV-1 replication cycle. The temporal roles of CD63 were discerned using monoclonal antibodies and small interfering RNAs (siRNAs) to block CD63 function, and determining which of the sequential steps in HIV-1 replication were disrupted. Inhibition was shown to occur during early infection, suggestive of involvement in virus entry or reverse transcription. In addition, we have shown that treatment with CD63 siRNA post-infection, significantly inhibited virus production in supernatant, suggesting an important role for CD63 in macrophages during HIV-1 replication events occurring after proviral integration, and possibly during egress. RESULTS: In this study we used CD63 siRNA to investigate the infectivity of pseudotyped viruses (carrying an NL4-3 Env-negative luciferase backbone) in primary human macrophages. We demonstrated that lab adapted R5- and R5X4-tropic HIV-1 strains are significantly inhibited by CD63 silencing. However, the infectivity of MLV or VSV-pseudotyped strains, which enter though receptor-mediated endocytosis, is unaffected by silencing CD63. These results indicate that CD63 may support Env-mediated entry or fusion events facilitated though CD4 and CCR5. Also, antibody and siRNA-based CD63 inhibition studies indicate a potential role for CD63 following proviral integration. Further, we show that CD63 expression is key for efficient replication in primary CD4⁺ T cells, complementing our prior studies with primary human macrophages and immortalized cell lines. CONCLUSIONS: Collectively, these findings indicate that CD63 may support Env-mediated fusion as well as a late (post-integration) step in the HIV-1 replication cycle.