Spinal cord stimulation for chronic visceral abdominal pain.

BACKGROUND: Spinal cord stimulation (SCS) may reduce pain scores and improve function in patients with chronic visceral abdominal pain. We thus present our large clinical experience in SCS for visceral abdominal pain. METHODS: We trialed spinal cord stimulation in 35 patients, each of whom was shown by retrograde differential epidural block to have either visceral pain (n = 32) or mixed visceral and central pain (n = 3). SCS trials lasted 4 to 14 days (median 9 days). SCS lead tips were mostly positioned at T5 (n = 11) or T6 (n = 10). RESULTS: Thirty patients (86%) reported at least 50% pain relief upon completion of the trial. Among these, pretrial visual analog scale (VAS) pain scores averaged 8.2 +/- 1.6 (SD) and opioid use averaged 110 +/- 119 mg morphine sulfate equivalents. During the trial, VAS pain scores decreased to 3.1 +/- 1.6 cm (P < 0.001, Mann-Whitney Rank Sum Test) and opioid use decreased to 70 +/- 68 mg morphine equivalent a day (P = 0.212). Five patients failed the trial, one was lost to follow-up, and 19 were followed for the whole year. Seven patients were either followed for less than a year (n = 3) or the SCS system was removed due to infection or lead migration (n = 4). One patient despite the successful trial felt no improvements at 6 months after the implant and requested an explant of the SCS device. Among the 28 patients who received permanent implant, 19 were followed at least a year. Their VAS pain scores remained low (3.8 +/- 1.9 cm; P < 0.001) at 1 year, as did opioid use (38 +/- 48 mg morphine equivalents; P = 0.089). CONCLUSIONS: Spinal cord stimulation may be a useful therapeutic option for patients with severe visceral pain.

STAT3- and STAT5-dependent pathways competitively regulate the pan-differentiation of CD34pos cells into tumor-competent dendritic cells.

The clinical outcomes of dendritic cell (DC)-based immunotherapy remain disappointing, with DCs often displaying a tenuous capacity to complete maturation and DC1 polarization in the tumor host. Surprisingly, we observed that the capacity for successful DC1 polarization, including robust IL12p70 production, could be regulated by STAT-dependent events even prior to DC differentiation. Exposure of CD34(pos) cells to single-agent granulocyte-macrophage colony-stimulating factor (GMCSF) induced multilineage, STAT5-dependent differentiation, including DCs that failed to mature in the absence of further exogenous signals. In contrast, Flt3L induced nearly global differentiation of CD34(pos) cells into spontaneously maturing DCs. IL-6 synergized with Flt3L to produce explosive, STAT3-dependent proliferation of phenotypically undifferentiated cells that nevertheless functioned as committed DC1 precursors. Such precursors not only resisted many tumor-associated immunosuppressants, but also responded to tumor contact or TGFbeta with facilitated DC maturation and IL12p70 production, and displayed a superior capacity to reverse tumor-induced T-cell tolerance. GMCSF preempted Flt3L or Flt3L plus IL-6 licensing by blocking STAT3 activation and promoting STAT5-dependent differentiation. Paradoxically, following overt DC differentiation, STAT5 enhanced whereas STAT3 inhibited DC1 polarization. Therefore, nonoverlapping, sequential activation of STAT3 and STAT5, achievable by sequenced exposure to Flt3L plus IL-6, then GMCSF, selects for multilog expansion, programming, and DC1 polarization of tumor-competent DCs from CD34(pos) cells.

Transdermal oxygen does not improve sternal wound oxygenation in patients recovering from cardiac surgery.

BACKGROUND: Sternal wound dehiscence and infection complicate 1% of cardiac surgeries. Tissue oxygen tension (PsqO(2)) is the primary determinant of surgical wound infection risk and is often critically low in surgical incisions. We tested the hypothesis that local transdermal delivery of oxygen improves oxygenation in sternotomy wounds after cardiac surgery. Our secondary hypothesis was that supplemental inspired oxygen improves sternal wound PsqO(2). METHODS: After undergoing cardiopulmonary bypass, 30 patients randomly received (1) 2 EpiFlo oxygen generators (Ogenix, Inc., Beachwood, OH) that provided oxygen at 6 mL/h into an occlusive wound dressing or (2) identical-appearing inactive generators. PsqO(2) and temperature were measured in the wound approximately 5 mm below the skin surface. PsqO(2) and arterial oxygen (Pao(2)) were measured 1 h after intensive care unit admission (Fio(2) = 60%) and on the first and second postoperative mornings at Fio(2) of both 30% and 50% in random order. RESULTS: Data from four patients were excluded for technical reasons. Patient characteristics were similar in each group, as were type of surgery and perioperative management. Increasing Fio(2) from 30% to 50% improved Pao(2) from 99 [84-116] to 149 [128-174] mm Hg (P < 0.001, mean [95% CI]) and sternal wound PsqO(2) from 23 [16-33] to 27 [19-38] mm Hg (P < 0.001). In contrast, local oxygen delivery did not improve tissue oxygenation: 24 [14-41] vs 25 [16-41] mm Hg (P = 0.88). CONCLUSIONS: Additional inspired oxygen improved Pao(2) and sternal wound PsqO(2) after bypass and may, consequently, reduce infection risk. However, oxygen insufflated locally into an occlusive dressing did not improve wound PsqO(2) and, therefore, does not appear to be useful clinically in cardiac surgery patients to reduce sternal wound infections.