Pro/con debate: Should PaCO2 be tightly controlled in all patients with acute brain injuries?

You are the attending intensivist in a neurointensive care unit caring for a woman five days post-rupture of a cerebral aneurysm (World Federation of Neurological Surgeons Grade 4 and Fisher Grade 3). She is intubated for airway protection and mild hypoxemia related to an aspiration event at the time of aneurysm rupture, but is breathing spontaneously on the ventilator. Your patient is spontaneously hyperventilating with high tidal volumes despite minimal support and has developed significant hypocapnia. She has not yet developed the acute respiratory distress syndrome. You debate whether to tightly control her partial pressure of arterial carbon dioxide, weighing the known risks of acute hypocapnia in other forms of brain injury against the potential loss of clinical neuromonitoring associated with deep sedation and neuromuscular blockade in this patient who is at high risk of delayed ischemia from vasospasm. You are also aware of the potential implications of tidal volume control if this patient were to develop the acute respiratory distress syndrome and the effect of permissive hypercapnia on her intracranial pressure. In this paper we provide a detailed and balanced examination of the issues pertaining to this clinical scenario, including suggestions for clinical management of ventilation, sedation and neuromonitoring. Until more definitive clinical trial evidence is available to guide practice, clinicians are forced to carefully weigh the potential benefits of tight carbon dioxide control against the potential risks in each individual patient based on the clinical issues at hand.     

Rescue missions for totally buried avalanche victims: conclusions from 12 years of experience

Abstract Hohlreider, Matthias, Stephanie Thaler, Walter Wuertl, Wolfgang Voelckel, Hanno Ulmer, Hermann Brugger, and Peter Mair. Rescue missions for totally buried avalanche victims: conclusions from 12 years of experience. High Alt. Med. Biol. 9:229-234, 2008.-The planning and execution of avalanche rescue missions to search for totally buried avalanche victims are mostly based on personal experience and preference, as evidence-based information from literature is almost completely missing. Hence, the aim of this study was to identify major factors determining the survival probability of totally buried victims during avalanche rescue missions carried out by organized rescue teams (Austrian Mountain Rescue Service, Tyrol). During the 12-year period studied, 109 totally buried persons (56 off-piste, 53 backcountry), were rescued or recovered; 18.3% survived to hospital discharge. Median depth of burial was 1.25 m; median duration of burial was 85 min. The majority (61.6%) of the rescue missions were conducted under considerably dangerous avalanche conditions. The probability of survival was highest when located visually and lowest for those located by avalanche transceiver; survival did not significantly differ between those found by rescue dogs and those located with avalanche probes. Multivariate analysis revealed short duration of burial and off-piste terrain to be the two independent predictors of survival. Whenever companion rescue fails, snow burial in an avalanche is associated with extraordinarily high mortality. Searching the avalanche debris with probe lines seems to be equally effective as compared to searching with rescue dogs. The potential hazard for rescuers during avalanche rescue missions comes mainly from self-triggered avalanches, hence thorough mission planning and critical risk-benefit assessment are of utmost importance for risk reduction.     

Melatonin and prostate cancer cell proliferation: interplay with castration,epidermal growth factor,and androgen sensitivity

BACKGROUND: Potential modulatory effects of melatonin on the proliferation of androgen-sensitive LNCaP and androgen-insensitive PC-3 and DU 145 prostate cancer cells were reported recently. In this study, we investigated the effects of combined melatonin and castration on LNCaP tumor growth in vivo, the interactions between melatonin and epidermal growth factor (EGF) on LNCaP cell proliferation, and melatonin actions on the proliferation of PC-3 and DU 145 cells. METHODS: Tumor development and growth in castrated nude mice inoculated with LNCaP cells or in intact animals inoculated with DU 145 cells, with or without daily melatonin treatment, were monitored by observation and caliper measurement. MT(1) receptor expression in native or transfected prostate cancer cell lines was examined by immunocytochemistry or 2-[(125)I]iodomelatonin binding. Cyclin D1 expression in LNCaP cells was assessed by Western blotting, and cell proliferation was measured by thymidine incorporation and/or cell count. RESULTS: Melatonin treatment was associated with further decreases in LNCaP tumor incidence and growth rate in castrated nude mice. Melatonin and 2-iodomelatonin (a melatonin receptor agonist) attenuated EGF-stimulated increases in LNCaP cell proliferation and cyclin D1 levels. Melatonin had no effect on the proliferation or growth of MT(1) receptor-expressing DU 145 cells, and of PC-3 cells in which MT(1) receptor protein was undetectable. The proliferation of transfected PC-3 cells expressing MT(1) receptor was unaffected by 2-iodomelatonin. CONCLUSION: Together with previous data, the present results indicate synergistic action of melatonin and castration in inhibiting the growth of androgen-sensitive LNCaP tumor. Androgen-sensitive prostate cancer cell proliferation may be modulated by opposite changes in cyclin D1 levels induced by activated MT(1) and EGF receptors. In androgen-insensitive prostate cancer cells, MT(1) receptor-mediated signal transduction may become defective not only through changes in membrane receptor protein expression and/or functions, but also by means of alterations in downstream postreceptor signaling events.     

First metatarsophalangeal arthrodesis: a clinical,pedobarographic and gait analysis study

This study investigated the results of first metatarsophalangeal (MTP) arthrodesis in terms of clinical outcome measures, plantar pressure distribution, and gait patterns. Ten feet in nine patients with severe hallux rigidus (HR) who underwent first MTP arthrodesis were studied. The preoperative evaluation included a subjective questionnaire, physical exam, AOFAS hallux score, radiographs and dynamic pedobarography (EMED). At follow-up (average 34 months) these were repeated, and gait analysis studies were obtained. Patients showed significant clinical improvement based on the subjective criteria. The mean AOFAS score improved from 38 preoperatively to 90 postoperatively. Postoperative EMED analysis showed restoration of the weightbearing function of the first ray, with greater maximum force carried by the distal hallux at toe-off. Kinematic and kinetic gait analysis from each patient's operative limb were compared to the unaffected contralateral limb and to age- and sex-matched healthy subjects. The kinematic data indicated a significantly shorter step length with some loss in ankle plantar flexion at toe-off on the fused side. The kinetic data indicated a reduction in both ankle torque and ankle power at push-off. Clinical results indicated effective pain relief and a high level of patient satisfaction, consistent with previous reports in patients with symptomatic Hallux Rigidus.     

Risk factors leading to midurethral sling revision: a multicenter case-control study

Introduction and hypothesis

To determine risk factors for sling revision after midurethral sling (MUS) placement.

Methods

This multicenter case-control study included patients who underwent MUS placement and subsequent revision secondary to voiding dysfunction from January 1999–2007 from nine Urogynecology centers across the USA. Direct logistic regression analysis was used to determine which diagnostic variables predicted sling revision.

Results

Of the patients, 197 met the study criteria. Patient demographics, urodynamic findings, and operative differences did not increase the risk for sling revision. Risk factors for sling revision did include: pre-existing voiding symptoms (OR 2.76, 95% CI 1.32–5.79; p?=?0.004) retropubic sling type (OR?=?2.28, 95% CI 1.08–4.78; p?=?0.04) and concurrent surgery (OR?=?4.88, 95% CI 2.16–11.05; p?<?0.001)

Conclusions

This study determined that pre-existing obstructive voiding symptoms, retropubic sling type, and concurrent surgery at the time of sling placement are risk factors for sling revision.     

Expression of epithelial matrix molecules collagen and laminin and corresponding integrins in chronic wounds

Re-epithelialization of cutaneous wounds is a coordinated process of proliferation and migration of keratinocytes at the wound edge. The study objective was to identify the differences in epidermal morphology, keratinocyte proliferation and matrix molecules (laminin 1, laminin 5, type IV collagen) and their specific integrin (α3, α6) expression in biopsies of meshed split thickness grafted and chronic wounds. The mean mitotic index of keratinocytes (ratio of cell cycle associated antigen Ki-67 expressing keratinocytes to basal keratinocytes) was highest in chronic wounds (38.7%) compared to acute wounds (22.25%, range 5.7% to 54%). The mean thickness of the hyper-proliferative epithelium at the wound edge of chronic wounds was 0.69 mm compared to 0.15 mm at the wound margin of split thickness grafted wounds. Both chronic wounds and skin grafted wounds exhibited strong laminin 5 immunoreactivity at the basal side of the epithelium, which extended under the most forward keratinocytes. Laminin 1 and type IV collagen immunoreactivity did not extend to the wound margin in either skin grafted or chronic wounds. In both transplanted skin and chronic wounds, the integrin sub-units α3 and α6 exhibited a strong pericellular immunoreactivity on the leading keratinocytes of the wound margin. Our data demonstrates that the proliferation of keratinocytes and the expression of associated integrins are not impaired in chronic wounds. Presented at the 33rd Congress of the Association of German Plastic Surgeons, Germany, 18–21 September, 2002.     

Personality disorders evident by early adulthood and risk for anxiety disorders during middle adulthood

Data from the Children in the Community Study, a prospective longitudinal investigation, were used to investigate the association of personality disorder (PD) traits, evident by early adulthood, with risk for development of anxiety disorders by middle adulthood. Individuals without a history of anxiety disorders who met diagnostic criteria for >or=1 PD by early adulthood were at markedly elevated risk for agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, and panic disorder by middle adulthood. Antisocial, avoidant, borderline, dependent, depressive, histrionic, obsessive-compulsive, passive-aggressive, and schizotypal PD traits, evident by early adulthood, were associated with elevated risk for >or=1 anxiety disorder during middle adulthood. These associations remained significant after a history of anxiety disorder and co-occurring Axis I psychiatric disorder was controlled statistically. Findings of this study suggest that some types of PD traits that become evident by early adulthood may contribute to increased risk for the development of anxiety disorders by middle adulthood.     

Finite element analysis performed on radius and tibia HR‐pQCT images and fragility fractures at all sites in men

Few studies have investigated bone microarchitecture and biomechanical properties in men. This study assessed in vivo both aspects in a population of 185 men (aged 71 ± 10 years) with prevalent fragility fractures, compared to 185 controls matched for age, height, and weight, from the Structure of the Aging Men's Bones (STRAMBO) cohort. In this case‐control study, areal BMD (aBMD) was measured by DXA, bone microarchitecture was assessed by high resolution (HR)‐pQCT, and finite element (µFE) analysis was based on HR‐pQCT images of distal radius and tibia. A principal component (PC) analysis (PCA) was used to study the association of synthetic PCs with fracture by computing their odds ratio (OR [95%CI]) per SD change. Specific associations with vertebral fracture (n = 100), and nonvertebral fracture (n = 85) were also computed. At both sites, areal and volumetric BMD, cortical thickness and trabecular number, separation, and distribution were significantly worse in cases than in controls, with differences ranging from ?6% to 15%. µFE‐derived stiffness and failure load were 8% to 9% lower in fractures (p < .01). No difference in load distribution was found between the two groups. After adjustment for aBMD, only differences of µFE‐derived stresses, stiffness, and failure load at the tibia remained significant (p < .05). PCA resulted in defining 4 independent PCs, explaining 83% of the total variability of bone characteristics. Nonvertebral fractures were associated with PC1, reflecting bone quantity and strength at the radius (tibia) with OR = 1.64 [1.27–2.12] (2.21 [1.60–3.04]), and with PC2, defined by trabecular microarchitecture, with OR = 1.27 [1.00–1.61]. Severe vertebral fractures were associated with PC1, with OR = 1.56 [1.16–2.09] (2.21 [1.59–3.07]), and with PC2, with OR = 1.55 [1.17–2.06] (1.45 [1.06–1.98]). In conclusion, microarchitecture and biomechanical properties derived from µFE were associated with all types of fractures in men, showing that radius and tibia mechanical properties were relatively representative of distant bone site properties. © 2011 American Society for Bone and Mineral Research.     

Medical epidemiology of patients surviving ten years after liver transplantation

Simo KA, Sereika S, Bitner N, Newton KN, Gerber DA. Medical epidemiology of patients surviving ten years after liver transplantation.
Clin Transplant 2011: 25: 360–367. © 2010 John Wiley & Sons A/S. Abstract: The transition into extended long‐term follow‐up after liver transplantation raises a new series of issues with respect to continuing care of this population. A retrospective study was performed, analyzing patients who underwent orthotopic liver transplant (OLT) and survived ≥10 yr at a single institution. Long‐term comorbidities such as diabetes mellitus (DM), hypertension (HTN), chronic kidney disease (CKD), coronary artery disease (CAD), and obesity were identified and standardized prevalence ratios ([SPR]) utilized to compare with the general US population. There was an increased prevalence of HTN ([SPR] = 2.25 ± 0.61), DM ([SPR] = 2.67 ± 0.72), and CKD ([SPR] = 15.3 ± 4.04) but not CAD or obesity. In multivariate analysis, non‐viral etiology of end‐stage liver disease was associated with CKD (OR 3.42 CI 1.11–10.53), and an initial glomerular filtration rate (GFR) <60 mL/min per 1.73 m² (CKD stages III–V) was associated with HTN (OR 4.62 CI 1.14–18.73) after OLT. Creatinine ≥1.5 mg/dL at 10 yr was associated with an initial GFR <60 mL/min per 1.73 m² (p = 0.000) and CAD after OLT (p = 0.012). Patients, 10 yr after OLT, have a significantly higher prevalence of HTN, DM, and CKD than the general population, which is not confounded by obesity. Increased vigilance and proactive management are required to further improve long‐term outcomes.