C-clamp and pelvic packing for control of hemorrhage in patients with pelvic ring disruption.

BACKGROUND: Exsanguinating hemorrhage is the major cause of death in patients with pelvic ring disruption. AIMS: The aim of this study was to document outcomes after the stabilization of pelvic ring injuries by a C-clamp and control of hemorrhage by pelvic packing. Physiological parameters were tested as prognostic factors. SETTING AND DESIGN: This was a retrospective study at a level I trauma center. The study period was from January 1996 to December 2007. MATERIALS AND METHODS: Fifty patients with pelvic ring disruption and hemorrhagic shock were analyzed. The pelvic rings were fixed by a C-clamp, and patients with ongoing hemorrhage underwent laparotomy and extra- and/or intra-peritoneal pelvic packing. Clinical parameters (heart rate, mean arterial pressure) and physiological parameters (lactate levels, hemoglobin, hematocrit) were documented at admission and at different time points during the initial treatment (1, 2, 3, 4, 6, 8, and 12h after admission). RESULTS: Within 12 h of admission, 16 patients died (nonsurvivors) due to hemorrhagic shock (n=13) or head injuries (n=3). In this group, 12 patients underwent laparotomy with pelvic packing. Thirty-four patients survived the first 12 h (early survivors) after fixation by a C-clamp and additional packing in 23 patients. Four of these patients died 12.3±7.1 days later due to multiple organ failure (n=3) or severe head injury (n=1). The blood lactate level at admission was significantly higher in the group of nonsurvivors (7.2±0.8 mmol/L) compared to the early survivors (4.3±0.5 mmol/L, P<0.05). While hemoglobin values improved within the first 2 h in nonsurvivors, lactate levels continued to increase. CONCLUSION: Pelvic packing in addition to the C-clamp fixation effectively controls severe hemorrhage in patients with pelvic ring disruption. Early sequential measurements of blood lactate levels can be used to estimate the severity of shock and the response to the shock treatment.

Base excess determined within one hour of admission predicts mortality in patients with severe pelvic fractures and severe hemorrhagic shock.

BACKGROUND: Unstable pelvic ring fractures with exsanguinating hemorrhages are rare but potentially lifethreatening injuries. The aim of this retrospective study was to evaluate whether early changes in acid- base parameters predict mortality of patients with severe pelvic trauma and hemorrhagic shock. METHODS: Data for 50 patients with pelvic ring disruption and severe hemorrhage were analyzed retrospectively. In all patients, the pelvic ring was temporarily stabilized by C-clamp. Patients with ongoing bleeding underwent laparotomy with extra and/or intraperitoneal pelvic packing, as required. Base excess, lactate, and pH were measured upon admission and at 1, 2, 3, 4, 6, 8, and 12 h postadmission. Patients were categorized as early survivors (surviving the first 12 h after admission) and nonsurvivors. Statistical analysis was performed by Mann-Whitney test; significance was assumed at p < 0.05. Receiver operating characteristic curves were generated for early mortality from each acid-base variable. RESULTS: Sixteen patients (32%) were nonsurvivors due to hemorrhagic shock (n = 13) or severe traumatic brain injury (n = 3). Thirty-four patients were early survivors. Base excess, lactate, and pH significantly discriminated between early survivors and nonsurvivors. Base excess determined 1 h after admission discriminated most strongly, with an area under the receiver operating characteristic curve of 0.915 (95% confidence interval, 0.836-0.993; p < 0.001). CONCLUSION: Base excess, lactate, and pH discriminate early survivors from nonsurvivors suffering from severe pelvic trauma and hemorrhagic shock. Base excess measured 1 h after admission best predicted early mortality following pelvic trauma with concomitant hemorrhage.

In vitro norepinephrine significantly activates isolated platelets from healthy volunteers and critically ill patients following severe traumatic brain injury.

INTRODUCTION: Norepinephrine, regularly used to increase systemic arterial blood pressure and thus improve cerebral perfusion following severe traumatic brain injury (TBI), may activate platelets. This, in turn, could promote microthrombosis formation and induce additional brain damage. METHODS: The objective of this study was to investigate the influence of norepinephrine on platelets isolated from healthy volunteers and TBI patients during the first two post-traumatic weeks. A total of 18 female and 18 male healthy volunteers of different age groups were recruited, while 11 critically ill TBI patients admitted consecutively to our intensive care unit were studied. Arterial and jugular venous platelets were isolated from norepinephrine-receiving TBI patients; peripheral venous platelets were studied in healthy volunteers. Concentration-dependent functional alterations of isolated platelets were analyzed by flow cytometry, assessing changes in surface P-selectin expression and platelet-derived microparticles before and after in vitro stimulation with norepinephrine ranging from 10 nM to 100 microM. The thrombin receptor-activating peptide (TRAP) served as a positive control. RESULTS: During the first week following TBI, norepinephrine-mediated stimulation of isolated platelets was significantly reduced compared with volunteers (control). In the second week, the number of P-selectin- and microparticle-positive platelets was significantly decreased by 60% compared with the first week and compared with volunteers. This, however, was associated with a significantly increased susceptibility to norepinephrine-mediated stimulation, exceeding changes observed in volunteers and TBI patients during the first week. This pronounced norepinephrine-induced responsiveness coincided with increased arterio-jugular venous difference in platelets, reflecting intracerebral adherence and signs of cerebral deterioration reflected by elevated intracranial pressure and reduced jugular venous oxygen saturation. CONCLUSION: Clinically infused norepinephrine might influence platelets, possibly promoting microthrombosis formation. In vitro stimulation revealed a concentration- and time-dependent differential level of norepinephrine-mediated platelet activation, possibly reflecting changes in receptor expression and function. Whether norepinephrine should be avoided in the second post-traumatic week and whether norepinephrine-stimulated platelets might induce additional brain damage warrant further investigations.

Synchronous bilateral ductal carcinoma in situ of the male breast associated with gynecomastia in a 30-year-old patient following repeated injections of stanozolol.

We report a rare case of synchronous bilateral and multifocal ductal carcinoma in situ (DCIS) in a 30-year-old patient operated on for gynecomastia following repeated injections of stanozolol, a non-aromatizable androgen. The familial medical history was negative for breast cancer and work-up of serum hormone levels was normal. The patient underwent a modified radical mastectomy without axilla dissection 6 weeks following the primary procedure and recovered uneventfully. The role of synthetic androgens in the development of male breast neoplasia warrants further scrutiny.

Intussusception as a cause of bowel obstruction in adults.

BACKGROUND: Due to its unspecific presentation, intussusception is often diagnosed with delay in adults. METHODS: From 1986 to 2002, ten patients (men/women: 8/2, median age: 53.6 years) were managed for intussusception. Clinical, radiological and surgical management data were retrospectively analyzed. RESULTS: All patients presented with abdominal symptoms (pain: 10/10, nausea and vomiting: 3/10, diarrhoea: 2/10, "red-currant jelly stool": 2/10) during a median time of 8.3 months (2 days - 6 years) and with a trend for longer duration of symptoms for benign compared to malignant underlying disease (2 years vs 1 month). Two cases had developed acute bowel obstruction at the time of surgery. CT-scan was always performed, with correct diagnosis in seven cases. Ultrasonography (4/10), contrast enema (5/10) or coloscopy (4/10) either missed the intussusception or served merely to confirm the CT diagnosis. At surgery, an underlying lesion (six malignant and four benign tumours) was identified and removed in all cases (four small bowel, three right colon, two ileocaecal and one left colon resections). Eight were undiagnosed previously. CONCLUSIONS: Intussusception is rare in adults, but should be considered in cases of chronic or acute bowel obstructions. Early surgical management allows detection and potential cure of underlying tumours.

Inhibition of vascular endothelial growth factor receptor (VEGFR) signaling by BSF476921 attenuates regional cerebral edema following traumatic brain injury in rats.

PURPOSE: In the present study we assessed the ability of BSF476921, an inhibitor of vascular endothelial growth factor receptor (VEGFR) kinase signal transduction, to reduce edema formation and neurologic motor dysfunction following lateral fluid percussion (FP) brain injury in rats. METHODS: Anesthetized adult male rats were subjected to either lateral FP brain injury of moderate severity (n = 37) or sham injury (n = 22, surgery without brain injury). Animals were randomized to receive i.p. injections of either BSF476921 (30 mg/kg bw; injured n = 15, sham n = 11) or sterile water (injured n = 14, sham n = 11) at 1, 11 and 22 hours post-injury. After assessment of motor function using a standard 28-point neuroscore, animals were sacrificed 24 hours following trauma and their brains evaluated for regional water content using the wet-weight/dry-weight technique. RESULTS: Although brain-injured animals showed a significant motor deficit compared to uninjured animals, no differences were detected between BSF476921- and vehicle-treated animals at the acute 24 hour post-injury time point. However, BSF476921 significantly attenuated regional edema formation in brain-injured animals in the ipsilateral hippocampus (p < 0.05) and in the cortex adjacent to the injury (p < 0.05) when compared to vehicle treatment. CONCLUSIONS: To our knowledge, this is the first report of a small molecule VEGFR kinase inhibitor reducing cerebral edema in a widely accepted model of brain injury.

Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury.

OBJECTIVE: Using the neural stem cell (NSC) clone C17.2, we evaluated the ability of transplanted murine NSCs to attenuate cognitive and neurological motor deficits after traumatic brain injury. METHODS: Nonimmunosuppressed C57BL/6 mice (n = 65) were anesthetized and subjected to lateral controlled cortical impact brain injury (n = 52) or surgery without injury (sham operation group, n = 13). At 3 days postinjury, all brain-injured animals were reanesthetized and randomized to receive stereotactic injection of NSCs or control cells (human embryonic kidney cells) into the cortex-hippocampus interface in either the ipsilateral or the contralateral hemisphere. One group of animals (n = 7) was killed at either 1 or 3 weeks postinjury to assess NSC survival in the acute posttraumatic period. Motor function was evaluated at weekly intervals for 12 weeks in the remaining animals, and cognitive (i.e., learning) deficits were assessed at 3 and 12 weeks after transplantation. RESULTS: Brain-injured animals that received either ipsilateral or contralateral NSC transplants showed significantly improved motor function in selected tests as compared with human embryonic kidney cell-transplanted animals during the 12-week observation period. Cognitive dysfunction was unaffected by transplantation at either 3 or 12 weeks postinjury. Histological analyses showed that NSCs survive for as long as 13 weeks after transplantation and were detected in the hippocampus and/or cortical areas adjacent to the injury cavity. At 13 weeks, the NSCs transplanted ipsilateral to the impact site expressed neuronal (NeuN) or astrocytic (glial fibrillary acidic protein) markers but not markers of oligodendrocytes (2'3'cyclic nucleotide 3'-phosphodiesterase), whereas the contralaterally transplanted NSCs expressed neuronal but not glial markers (double-labeled immunofluorescence and confocal microscopy). CONCLUSION: These data suggest that transplanted NSCs can survive in the traumatically injured brain, differentiate into neurons and/or glia, and attenuate motor dysfunction after traumatic brain injury.

Prolonged intrathecal release of soluble Fas following severe traumatic brain injury in humans.

The mechanisms underlying cell death following traumatic brain injury (TBI) are not fully understood. Apoptosis is believed to be one mechanism contributing to a marked and prolonged neuronal cell loss following TBI. Recent data suggest a role for Fas (APO-1, CD95), a type I transmembrane receptor glycoprotein of the nerve growth factor/tumor necrosis factor superfamily, and its ligand (Fas ligand, FasL) in apoptotic events in the central nervous system. A truncated form of the Fas receptor, soluble Fas (sFas) may indicate activation of the Fas/FasL system and act as a negative feedback mechanism, thereby inhibiting Fas mediated apoptosis. Soluble Fas was measured in cerebrospinal fluid (CSF) and serum of 10 patients with severe TBI (GCS< or =8) for up to 15 days post-trauma. No sFas was detected in CSF samples from patients without neurological pathologies. Conversely, after TBI 118 out of 120 CSF samples showed elevated sFas concentrations ranging from 56 to 4327 mU/ml. Paired serum samples showed above normal (8.5 U/ml) sFas concentrations in 5 of 10 patients. Serum levels of sFas were always higher than CSF levels. However, there was no correlation between concentrations measured in CSF and in serum (r(2)=0.078, p=0.02), suggesting that the concentrations in the two compartments are independently regulated. Also, no correlation was found between sFas in CSF and blood brain barrier (BBB) dysfunction as assessed by the albumin CSF/serum quotient (Q(A)), and concentrations of the cytotoxic cytokine tumor necrosis factor-alpha in CSF, respectively. Furthermore, there was no correlation with two markers of immune activation (soluble interleukin-2 receptor and neopterin) in CSF. Maximal CSF levels of sFas correlated significantly (r(2)=0.8191, p<0.001) with the early peaks of neuron-specific enolase in CSF (a marker for neuronal cell destruction), indicating that activation of the Fas mediated pathway of apoptosis may be in part the direct result of the initial trauma. However, the prolonged elevation of sFas in CSF may be caused by the ongoing inflammatory response to trauma and delayed apoptotic cell death.