Effects of Preemptive Analgesia on Pain and Cytokine Production in the Postoperative Period

Background: The postoperative period is associated with increased production of proinflammatory cytokines, which are known to augment pain sensitivity, among other effects. In a previous study, the authors found that patients treated with patient-controlled epidural analgesia (PCEA) exhibited attenuated proinflammatory cytokine response in the postoperative period. In the present study, the authors examined whether preemptive analgesia continued with PCEA may further attenuate the proinflammatory cytokine response and reduce pain sensitivity in the postoperative period. They compared cytokine production in two groups of patients, one receiving PCEA, the other receiving preemptive epidural analgesia continued by PCEA.

Methods: Female patients hospitalized for transabdominal hysterectomy were randomly assigned to one of two pain management techniques: PCEA or preemptive epidural analgesia followed by PCEA (PA + PCEA). Postoperative pain was assessed using the visual analog scale. Blood samples were collected before, 24, 48, and 72 h following surgery. Production of the following cytokines was assessed ex vivo in stimulated peripheral blood mononuclear cells: interleukin (IL)-1[beta], tumor necrosis factor [alpha], IL-6, IL-1ra, IL-10, and IL-2.

Results: Patients of the PA + PCEA group exhibited lower pain scores throughout the 72 h postoperatively, compared with patients of the PCEA group. In patients of the PA + PCEA group in the postoperative period, production of IL-1[beta], IL-6, IL-1ra, and IL-10 was significantly less elevated, while IL-2 production was significantly less suppressed.     

Hyperbaric Oxygen and Radiotherapy

BACKGROUND: Hyperbaric oxygen (HBO) therapy is the inhalation of 100% oxygen at a pressure of at least 1.5 atmospheres absolute (150 kPa). It uses oxygen as a drug by dissolving it in the plasma and delivering it to the tissues independent of hemoglobin. For a variety of organ systems, HBO is known to promote new vessel growth into areas with reduced oxygen tension due to poor vascularity, and therewith promotes wound healing and recovery of radiation-injured tissue. Furthermore, tumors may be sensitized to irradiation by raising intratumoral oxygen tensions. METHOD: A network of hyperbaric facilities exists in Europe, and a number of clinical studies are ongoing. The intergovernmental framework COST B14 action "Hyperbaric Oxygen Therapy" started in 1999. The main goal of the Working Group Oncology is preparation and actual implementation of prospective study protocols in the field of HBO and radiation oncology in Europe. RESULTS: In this paper a short overview on HBO is given and the following randomized clinical studies are presented: a) reirradiation of recurrent squamous cell carcinoma of the head and neck after HBO sensitization; b) role of HBO in enhancing radiosensitivity on glioblastoma multiforme; c) osseointegration in irradiated patients; adjunctive HBO to prevent implant failures; d) the role of HBO in the treatment of late irradiation sequelae in the pelvic region. The two radiosensitization protocols (a, b) allow a time interval between HBO and subsequent irradiation of 10-20 min. CONCLUSION: Recruitment of centers and patients is being strongly encouraged, detailed information is given on www.oxynet.org.     

Dental fractures on acute exposure to high altitude

There is little in the literature on dental restoration breakage in the aviation environment since reports of problems in combat aviators in War World II. We report two cases of dental fractures during acute exposure to a hypobaric environment. Case 1 was a young officer who suffered an amalgam restoration breakage during a 25,000-ft decompression chamber simulation. Case 2 occurred in an experienced aviator who had a tooth cusp fracture in a molar with a defective amalgam restoration during an unpressurized helicopter flight to 18,000 ft. In both cases, after removing the defective fillings, deep secondary caries were found; both teeth were successfully restored. Because hard-tissue tooth fracture during a high-altitude flight is a rare event, few flight surgeons or dentists are familiar with this phenomenon. We recommend regular dental examinations with careful assessment of previous dental restorations in aircrew subject to decompression.     

Spinal cord injury in the setting of traumatic thoracolumbar fracture is not reliably associated with increased risk of associated intra-abdominal injury following blunt trauma: An analysis of a National Trauma Registry database

Purpose: There is a common opinion that spinal fractures usually reflect the substantial impact of injuries and therefore may be used as a marker of significant associated injuries, specifically for intraabdominal injury (IAI). The impact of concomitant spinal cord injury (SCI) with the risk of associated IAI has not been well clarified. The aim of this study was to evaluate the incidence and severity of IAIs in patients suffering from spinal fractures with or without SCI. Methods: A retrospective cohort study using the Israeli National Trauma Registry was conducted. Patients with thoracic, lumbar and thoracolumbar fractures resulting from blunt mechanisms of injury from January 1, 1997 to December 31, 2018 were examined, comparing the incidence, severity and mortality of IAIs in patients with or without SCI. The collected variables included age, gender, mechanism of injury, incidence and severity of the concomitant IAIs and pelvic fractures, abbreviated injury scale, injury severity score, and mortality. Statistical analysis was performed using GraphPad InStat ® Version 3.10, with Chi-square test for independence and two sided Fisher’s exact probability test. Results: Review of the Israeli National Trauma Database revealed a total of 16,878 patients with spinal fractures. Combined thoracic and lumbar fractures were observed in 1272 patients (7.5%), isolated thoracic fractures in 4967 patients (29.4%) and isolated lumbar fractures in 10,639 patients (63.0%). The incidence of concomitant SCI was found in 4.95% (63/1272), 7.65% (380/4967) and 2.50% (266/10639) of these patients, respectively. The overall mortality was 2.5%, proving higher among isolated thoracic fracture patient than among isolated lumbar fracture counterparts (11.3% vs. 4.6%, p < 0.001). Isolated thoracic fractures with SCI were significantly more likely to die than non-SCI counterparts (8.2% vs. 3.1%, p < 0.001). There were no differences in the incidence of IAIs between patients with or without SCI following thoracolumbar fractures overall or in isolated thoracic fractures; although isolated lumbar fractures patients with SCI were more likely to have renal (3.4% vs. 1.6%, p = 0.02) or bowel injuries (2.3% vs. 1.0%, p = 0.04) than the non-SCI counterparts. Conclusion: SCI in the setting of thoracolumbar fracture does not appear to be a marker for associated IAI. However, in a subset of isolated lumbar fractures, SCI patient is associated with increased risks for renal and bowel injury.     

Clinical correlates of DHEA associated with post-traumatic stress disorder

OBJECTIVE: Increased plasma dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEAS) have been demonstrated in post-traumatic stress disorder (PTSD), but the documented beneficial effects of these steroids in enhancing mood and cognition, as well as neuroprotection, suggest their presence in PTSD may be associated with defensive rather than maladaptive effects. METHOD: We, therefore, examined plasma DHEA, DHEAS, cortisol, and the DHEA/cortisol ratio in 40 male veterans with or without PTSD, and determined their relationships to PTSD symptom severity and symptom improvement. RESULTS: The PTSD group showed significantly higher plasma DHEA and non-significantly higher DHEAS levels as well as a significantly lower cortisol/DHEA ratio, controlling for age. Regression analyses demonstrated that DHEA and DHEAS levels could be predicted by symptom improvement and coping, whereas the cortisol/DHEA ratio was predicted by severity of childhood trauma and current symptom severity. CONCLUSION: That greater symptom improvement was related to DHEA levels may suggest for a role for these hormones in modulating recovery from PTSD.     

Fukutin gene mutations in steroid-responsive limb girdle muscular dystrophy

OBJECTIVE: Defects in glycosylation of alpha-dystroglycan are associated with several forms of muscular dystrophy, often characterized by congenital onset and severe structural brain involvement, collectively known as dystroglycanopathies. Six causative genes have been identified in these disorders including fukutin. Mutations in fukutin cause Fukuyama congenital muscular dystrophy. This is the second most common form of muscular dystrophy in Japan and is invariably associated with mental retardation and structural brain defects. The aim of this study was to determine the genetic defect in two white families with a dystroglycanopathy. METHODS: The six genes responsible for dystroglycanopathies were studied in three children with a severe reduction of alpha-dystroglycan in skeletal muscle. RESULTS: We identified pathogenic fukutin mutations in these two families. Affected children had normal intelligence and brain structure and shared a limb girdle muscular dystrophy (LGMD) phenotype, had marked elevation of serum creatine kinase, and were all ambulant with remarkable steroid responsiveness. INTERPRETATION: Our data suggest that fukutin mutations occur outside Japan and can be associated with much milder phenotypes than Fukuyama congenital muscular dystrophy. These findings significantly expand the spectrum of phenotypes associated with fukutin mutations to include this novel form of limb girdle muscular dystrophy that we propose to name LGMD2L.     

Erythropoietin,a novel repurposed drug: An innovative treatment for wound healing in patients with diabetes mellitus

Developing a new drug is expensive: the cost of going from bench to bedside is about $US1 billion. Therefore, the repurposing of an approved drug is potentially rewarding because it expands the drug's existing therapeutic profile and preempts additional development costs. As the safety profile of a repurposed drug is already well known, any new investigations could then focus on its efficacy and other therapeutic benefits. Recombinant erythropoietin (EPO) is a potential candidate for repurposing because the results of numerous studies have shown that systemic and topical EPO is therapeutically beneficial when it is administered to healthy and diabetic animals with acute and chronic skin wounds and burns. Moreover, the molecular mechanisms of EPO's actions have been elucidated: EPO acts on those nonhematopoietic cells which are involved in the innate immune response where it promotes cellular proliferation and differentiation, exerts its cytoprotective actions, and inhibits apoptosis. In this review, the mechanism of EPO's action in skin wound healing is reviewed, and its potential for treating acute and chronic skin wounds and stimulating tissue regeneration in diabetic patients is discussed.