Proximal superior mesenteric arterial and venous injuries

In a review of more than 1000 patients with operatively managed abdominal trauma, eight patients with injuries to the proximal parts of the superior mesenteric artery or vein were identified: three with either a superior mesenteric artery or vein injury and two with combined superior mesenteric vessel injuries. All patients were in shock on arrival, and had associated abdominal injuries. All six patients with solitary superior mesenteric artery or vein injuries underwent lateral suture repair of the injured vessel with good results. The combined injuries of both of the superior mesenteric vessels required more complex types of vascular repairs: an interposition saphenous vein graft for the arterial injury and ligation of the vein in one patient who later died of bowel necrosis, and an end-to-end arterial repair and lateral venorrhaphy in the other who had a viable bowel at a second look operation. The overall mortality rate was 13%. The various management options and guidelines for injuries to the proximal parts of the superior mesenteric vessels are discussed.     

Long-term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2-year follow-up of the CHRONOS-1 study

Safety profiles of oral PI3K inhibitors have resulted in US FDA black box warnings regarding fatal/serious toxicities. The approved intravenous PI3K inhibitor copanlisib has low incidence of severe toxicities and no black box warnings, but chronic treatment effects were unknown. We provide an update on safety and efficacy of copanlisib with a minimum 2-year follow-up of the CHRONOS-1 study. A total of 142 patients with histologically confirmed indolent B-cell lymphoma who had relapsed after or were refractory to ≥2 prior treatments received intravenous copanlisib 60 mg on days 1, 8, and 15 (28-day cycle). The primary efficacy endpoint was objective response rate (ORR) after ≥4 cycles (independent assessment). The predominant histology was follicular lymphoma (n = 104). The ORR was 60.6% (seven additional complete responses since primary analysis). Secondary endpoints of median duration of response, progression-free survival, and overall survival were 14.1 months (median follow-up, 16.1 months), 12.5 months (median follow-up, 14.0 months), and 42.6 months (median follow-up, 31.5 months), respectively. Median safety follow-up was 6.7 months; 26% of patients received treatment for >1 year. Common treatment-emergent adverse events (TEAEs) (all grade/grade 3/grade 4) were transient hyperglycemia (50.0%/33.1%/7.0%), diarrhea (35.2%/8.5%/0%), transient hypertension (29.6%/23.9%/0%), and neutropenia (28.9%/9.2%/14.8%). Serious AEs were largely unchanged, with no new cases of pneumonitis (4.2%), diarrhea (2.8%), or grade 5 events. Note, TEAEs showed no evidence for increased incidence or worsening following longer exposure in patients treated >1 year. Long-term follow-up of patients with relapsed/refractory indolent B-cell lymphoma treated with intravenous copanlisib demonstrated durable, enhanced responses without evidence of worsening TEAEs, as reported for orally administered PI3K inhibitors.     

Delayed presentation of blunt splenic injury

Eleven patients with delayed presentation of splenic injury after blunt abdominal trauma treated during a 10 year period have been described. They represented 24 percent of all patients treated for blunt splenic injury in our department in that time period. Ten patients required operative treatment and one was treated nonoperatively. There were no deaths. The value of computerized tomography and ultrasonography in the accurate preoperative assessment of splenic injury has been documented. In addition, the various diagnostic and therapeutic possibilities in blunt splenic trauma have been discussed.     

Revascularization of the limbs using vein grafts after vascular injuries

We report on 32 patients with vascular injury of a limb undergoing a total of 41 revascularization procedures with interposition vein grafts. A combined arterial and venous injury was present in nine cases, an isolated venous injury in four, and an isolated arterial injury in 19 cases. Eighteen per cent of patients with arterial injuries had normal distal pulses on initial examination. Preoperative arteriography was performed in 12 cases, and intraoperative arteriography in four. All venous injuries were diagnosed at operation. In most cases, the contralateral greater saphenous vein was used for grafting. Four patients had postoperative thrombosis after arterial reconstruction resulting in below knee amputation in two cases. Two patients suffered from postoperative swelling caused by venous insufficiency, one after ligation of an injured axillary vein, and the other one following venous thrombosis of a superficial femoral vein repair. It is concluded that revascularization of arterial and venous injuries of the extremities with interposition vein grafts is successful in most cases resulting in low amputation rates, and should be attempted in all major vascular injuries in viable limbs.     

Performance of a novel real-time respirator seal integrity monitor on firefighters: Simulated workplace pilot study

Millions of workers, including firefighters, use respiratory protective device. The key aspect in assuring the intended protection level of a respirator is its fit. However, even if the respirator originally fits well, the faceseal may be breached during its use. Until now, there have been no practically viable, inexpensive means to monitor the performance of a respirator during actual use. A novel Respirator Seal Integrity Monitor (ReSIM) was developed and recently evaluated on manikins by our team. The objective of this study was to evaluate the ReSIM effectiveness on respirator-wearing firefighters exposed to aerosols while performing simulated routine operational activities. Initially, 15 subjects were recruited for the study. Following a preliminary investigation that resulted in modifications in the ReSIM prototype and testing protocol, a subset of nine firefighters was chosen for a full-scale evaluation. The testing was conducted in a 24.3-m³ exposure chamber using NaCl as the challenge aerosol. Controlled faceseal leaks were established by opening a solenoid valve for 10, 15, or 20?sec. Leaks were also established as the tested firefighter slightly repositioned the respirator on his/her face. During the testing, the ReSIM measured particles inside a full-face elastomeric respirator with a 72.7% leak detection sensitivity (probability of correct leak identification) and an 84.2% specificity (probability of correct identification of the intervals which are absent of any leak). After adjusting for false negatives and persistent false positives, sensitivity and specificity increased to 83.6% and 92.2%, respectively. The factors causing minor limitations in leak detection sensitivity and specificity can be attributed to variability among subjects, moisture’s effect on the particle sensor, and some in-mask sampling bias. In conclusion, the ReSIM can promptly detect the breach in a respirator faceseal with high sensitivity and specificity. Due to its capability to alert the wearer of possible overexposure to hazardous aerosols, the ReSIM concept has a remarkable potential to be applied in various working environments, where respirators are used.     

Discordant expression of selectin ligands and sialyl Lewis x-related epitopes on murine myeloid cells

Murine leukocytes are thought to express alpha2-3-sialylated and alpha1-3-fucosylated selectin ligands such as sialyl Lewis x (sLe(x)), although monoclonal antibodies (mAbs) to sLe(x) or Le(x) reportedly do not bind to murine leukocytes. We observed that P- and E-selectin bound to pronase-sensitive ligands on murine monocytic WEHI-3 cells and murine neutrophils, indicating that the ligands for both selectins are glycoproteins. CSLEX-1, HECA-452, and other widely used mAbs to sLe(x) and Le(x) did not bind to WEHI-3 cells and bound at very low levels to murine neutrophils. Only the anti-sLe(x) mAbs 2H5 and KM93, which also recognize nonfucosylated glycans, bound to WEHI-3 cells. 2H5 and KM93 bound to pronase-resistant structures, indicating that the mAbs did not identify selectin ligands. Treatment of WEHI-3 cells with glycosidases or chlorate demonstrated that sialic acid modifications, alpha1-3-galactosylation, or sulfation did not mask epitopes for mAbs to sLe(x) or Le(x). Compared to human promyelocytic HL-60 cells, WEHI-3 cells and murine neutrophils expressed low alpha1-3-fucosyltransferase activities. Consistent with very low endogenous fucosylation, forced fucosylation of intact WEHI-3 cells or murine neutrophils by exogenous alpha1-3-fucosyltransferase FTVI and GDP-fucose created many new epitopes for anti-sLe(x) mAbs such as HECA-452 and CSLEX-1. Nevertheless, forced fucosylation of intact cells did not significantly augment their ability to bind to fluid-phase P- or E-selectin or to roll on immobilized P- or E-selectin under flow. These data suggest that murine myeloid leukocytes fucosylate only a few specific glycans, which interact preferentially with P- and E-selectin.