Introduction In Europe, injectable collagenase clostridium histolyticum (CCH) is a novel, minimally invasive, non-surgical therapy with efficacy in correcting Dupuytren9s contracture (DC). We evaluated the efficacy and tolerability of 5 CCH injections using a protocol designed to follow clinical practice. Methods This was a 20-center, 9-month, open-label study in which DC patients with primary flexion deformities 20° (100° for MP; 80° for PIP) received 3 CCH (0.58 mg) injections/joint (5 injections/patient) at 30-day intervals. The primary endpoint was clinical success, defined as a reduction in contracture to 5° 30 days after the last injection (“Day 30”). After first injection into a prioritized joint, patients opted to receive up to 2 more injections into the same cord or cords from other affected joints whether or not they achieved clinical success with the first joint. Adverse events (AEs) were monitored. Results For the primary endpoint, 71% of MP (n=343) and 41% of PIP (n=244) joints showed a reduction in contracture to 5° with CCH injections. Of joints that did not achieve clinical success, 66% of MP (n=100) and 38% of PIP joints (n=144) showed 50% reduction in contracture after CCH. For range of motion (ROM), mean±SD increase from baseline to Day 30 was 33.0±16.2° for MP and 27.5±18.5° for PIP joints. Most commonly reported AEs were localized edema, bruising, pain, swelling, and tenderness; most resolved without intervention. Two serious AEs, deep vein thrombosis in the leg and tendonitis with partial tendon/ligament injury, were deemed possibly and probably related to treatment, respectively. Conclusions Results from this open-label study, designed to follow clinical practice, provide support for the efficacy of CCH in correcting the flexion deformity of MP/PIP joints caused by DC. Clinical success and ROM improvements were comparable to those observed in randomized, placebo-controlled trials. This study was funded by Auxilium Pharmaceuticals, Inc.
Prehospital intubation does not appear to result in a survival advantage for patients experiencing penetrating trauma; yet, there is still resistance to the practice of "scoop and run" to speed access to advanced care. An animal model was used to determine whether intubation provides a survival advantage during potentially lethal hemorrhage.The carotid arteries of Sprague-Dawley rats were cannulated, and mean arterial pressure (MAP) was measured. One group of animals (n = 10) was intubated and placed on a ventilator, whereas the other (n = 9) was administered with 100% oxygen via nose cone. Rats were exsanguinated to a MAP of 40 mm Hg and then bled periodically to maintain a MAP between 40 mm Hg and 45 mm Hg. The primary end-point was time until death. Secondary end-points included lactic acid and base excess levels measured in blood collected at 30-minute intervals after inducing shock.There was no significant difference in time until death between the intubated and nose cone groups (85.5 vs. 93.3 minutes, p = 0.60). Intubated animals had higher lactic acid levels at 90 minutes (6.1 vs. 3.5 mmol/L; p = 0.02) and 120 minutes (7.7 vs. 2.6 mmol/L, p = 0.03) after the initiation of shock. In addition, intubated animals had worse base excess at 90 minutes (-13.5 vs. -7.9 mmol/L, p = 0.04).Intubation does not result in a survival advantage in this rat model of hemorrhagic shock. Positive pressure ventilation may cause decreased venous return and accentuate end-organ hypoperfusion. Large animal studies are needed to further investigate these findings.
Prehospital intubation does not result in a survival advantage in patients experiencing penetrating trauma, yet resistance to immediate transportation to facilitate access to definitive care remains. An animal model was developed to determine whether intubation provides a survival advantage during severe hemorrhagic shock. We hypothesized that intubation would not provide a survival advantage in potentially lethal hemorrhage.After starting a propofol drip, Yorkshire pigs were intubated (n = 6) or given bag-valve mask ventilation (n = 7) using 100% oxygen. The carotid artery was cannulated with a 14-gauge catheter, and a Swan-Ganz catheter was placed under fluoroscopy using a central venous introducer. After obtaining baseline hemodynamic and laboratory data, the animals were exsanguinated through the carotid line until death. The primary end point was time until death, while secondary end points included volume of blood shed, temperature, cardiac index, mean arterial pressure, lactic acid, base excess, and creatinine levels measured in 10-minute intervals.There was no difference in time until death between the two groups (51.1 [2.5] minutes vs. 48.5 [2.4] minutes, p = 0.52). Intubated animals had greater volume of blood shed at 30 minutes (33.6 [4.4] mL/kg vs. 28.5 [4.3] mL/kg, p = 0.03), 40 minutes (41.7 [4.7] mL/kg vs. 34.9 [3.8] mL/kg, p = 0.04), and 50 minutes (49.2 [8.6] mL/kg vs. 40.2 [1.0] mL/kg, p = 0.001). In addition, the intubated animals were more hypothermic at 40 minutes (35.5°C [0.4°C] vs. 36.7°C [0.2°C], p = 0.01) and had higher lactate levels (2.4 [0.1] mmol/L vs. 1.8 [0.4] mmol/L, p = 0.04) at 10 minutes. Cardiac index (p = 0.66), mean arterial pressure (p = 0.69), base excess (p = 0.14), and creatinine levels (p = 0.37) were not different throughout the shock phase.Intubation does not convey a survival advantage in this model of severe hemorrhagic shock. Furthermore, intubation in the setting of severe hemorrhagic shock may result in a more profuse hemorrhage, worse hypothermia, and higher lactate when compared with bag-valve mask ventilation.
