Gregory C. Makris

Statins for infection and sepsis: a systematic review of the clinical evidence

INTRODUCTION Statins are currently used for hyperlipidaemia control and considered useful for protection from cardiovascular events. In addition, there is increasing evidence for the potential use of statins in preventing and treating infections. METHODS We performed a systematic review of the literature that compared the outcome between statin and non-statin users among patients suffering from sepsis or other infections. The relevant studies were identified from searches of PubMed, Scopus and the Cochrane Library databases. RESULTS Twenty studies were identified (13 of them were retrospective), out of which 9 examined the use of statins in patients with sepsis, bacteraemia or multiorgan dysfunction syndrome, 4 community-acquired pneumonia (CAP), 1 ICU infections, 2 other bacterial infections and 4 viral infections. Eleven studies had data regarding mortality as the main outcome: 8 showed decreased mortality in statin users (3 of them reported on patients with bacteraemia), 2 showed no difference in mortality and 1 reported an increased mortality in patients who received statins. Seven studies examined the risk of sepsis as the main outcome; six of these studies showed a decreased risk of sepsis in patients receiving statins, whereas one study found no difference. CONCLUSIONS The majority of the studies suggest that statins may have a positive role in the treatment of patients with sepsis and infection. However, the majority of the reviewed studies have the inherent methodological limitations of retrospective studies. Conclusions regarding this important clinical question should wait for the results of ongoing relevant randomized controlled trials.

Probiotics for the prevention of respiratory tract infections: a systematic review

We evaluated the clinical evidence regarding probiotic use for the prevention of respiratory tract infections (RTIs). Randomised controlled trials (RCTs) studying the effects of probiotics for the prevention of upper or lower RTIs were systematically identified. Fourteen RCTs (twelve involving healthy subjects and two involving patients with RTIs) were included. Various Lactobacillus strains were used in seven RCTs, combinations of Lactobacillus and Bifidobacterium strains were used in five RCTs, and a Bifidobacterium strain and a non-pathogenic Enterococcus faecalis strain were used in one RCT, respectively. In ten RCTs no difference was found regarding the incidence of RTIs in the probiotic arm compared with the control arm, whereas the remaining four RCTs favoured the use of probiotics. Reduction in the severity of symptoms related to RTIs was noted in five of six RCTs that provided relevant data. In three of nine RCTs that provided relevant data, the clinical course of RTIs was shorter in the probiotic arm, whereas no difference was found in the remaining six RCTs. In conclusion, probiotics may have a beneficial effect on the severity and duration of symptoms of RTIs but do not appear to reduce the incidence of RTIs.

The effect of statins on carotid plaque morphology: A LDL-associated action or one more pleiotropic effect of statins?

INTRODUCTION The early identification of the unstable carotid plaque together with the best medical treatment, are two missing parts of the stroke-prevention puzzle. This review summarizes the available evidence on the effects of statins on carotid plaque morphology. METHODS A systematic review of the PubMed, Scopus and Cochrane Library databases was performed. Studies evaluating the effect of statins on plaque imaging features other than intima media thickness as well as on the serum inflammatory profile were eligible for inclusion. RESULTS Seventeen studies were eligible for inclusion. The majority of the studies used MRI and ultrasound imaging. Plaque composition (fibrous cap and lipid core size), and size (plaque area and volume) were mainly used to evaluate the changes in plaque morphology. All studies showed slower progression, remodelling or even regression of the plaque even after only 1 month of statin administration, although the type, dosage and duration of treatment varied significantly between them. Intensive statin treatment was suggested to have a more pronounced effect on plaque morphology, however, that was mainly associated with maintaining LDL-levels <100 mg/mL and not with the intensity of the dosage. Seven studies measured CRP, four of which found significantly decreased levels with statin use. CONCLUSION This review suggests that statins may have a beneficial effect on plaque morphology and the inflammatory response. Further validation of whether this is an LDL-associated effect or a separate pleiotropic phenomenon of statins is needed. There are significant inherent limitations to the safe extraction of solid conclusions from the studies due to data heterogeneity and publication bias.

Bacterial interference for the prevention and treatment of infections

Bacterial interference refers to the antagonism between bacterial species during the process of surface colonisation and acquisition of nutrients. The clinical evidence on the potential applications of microorganisms for the prevention and/or treatment of infections in the upper respiratory, urogenital and gastrointestinal tracts was reviewed through the PubMed and Scopus databases. Data regarding factors that may affect the human microflora, thus contributing to tissue colonisation from potential pathogens, were also retrieved. The clinical evidence for application of the interfering ability of non-virulent bacteria to prevent or treat infections has been rather limited, although promising for certain purposes. A number of relevant preliminary trials suggest that in the upper respiratory tract the rate of recurrence of otitis media or streptococcal pharyngotonsillitis appears to decrease using selected bacteria with inhibitory ability against common pathogens of upper respiratory tract in combination with appropriate antibiotic treatment. Regarding the urogenital tract, specific non-pathogenic strains of Escherichia coli and probiotic organisms were successfully applied to decrease the recurrence of local infections. The interfering ability of specific probiotic organisms (strains of Lactobacilli and Bifidobacteria) within the gastrointestinal tract against common pathogens was also demonstrated. In conclusion, randomised controlled trials are warranted to investigate the effectiveness and safety of potential applications of the principle of bacterial interference in the prevention and treatment of infections of various sites. Such trials should initially employ selected strains of probiotics for which there are preliminary data regarding their effectiveness and lack of common or serious toxicity.

Three-dimensional ultrasound imaging for the evaluation of carotid atherosclerosis

INTRODUCTION Emerging data suggests that 3-dimensional (D) ultrasound (US) may provide us with a new tool for the identification of the vulnerable carotid plaque. METHODS A systematic review of the PubMed, Scopus and Cochrane databases regarding the reproducibility and effectiveness of 3D US in evaluation of carotid plaque disease (CPD) was performed. RESULTS Seven studies on the reproducibility of 3D ultrasound evaluation of plaque volume (PV) were identified. All studies reported good intra- and inter-observer reproducibility ranging from 2.8-6.0% to 4.2-7.6%, respectively. In addition, ten studies evaluating 3D carotid plaque progression with and without treatment were retrieved. In the 4 studies where 2D and 3D US features were compared, PV rather than intima media thickness (IMT) was a more sensitive marker of plaque change as a response to treatment. However, there were no studies evaluating changes in plaque morphology or specific composition features post-treatment with both 2 and 3D US. Finally, only one study was identified regarding the 3D composition differences of CPD between symptomatic and asymptomatic patients. CONCLUSION The current evidence supports the good reproducibility of the 3D US on the evaluation of carotid plaque volume, however with high heterogeneity between studies. There is also preliminary evidence that PV measurements may be more sensitive than IMT in the identification of plaque change post-treatment, though, more plaque-related evidence is necessary. Further research is needed to establish if 3D is superior to 2D US in the identification of the vulnerable carotid plaque in clinical settings.

Compression stockings significantly improve hemodynamic performance in post-thrombotic syndrome irrespective of class or length

BACKGROUND Graduated elastic compression (GEC) stockings have been demonstrated to reduce the morbidity associated with post-thrombotic syndrome. The ideal length or compression strength required to achieve this is speculative and related to physician preference and patient compliance. The aim of this study was to evaluate the hemodynamic performance of four different stockings and determine the patients preference. METHODS Thirty-four consecutive patients (40 legs, 34 male) with post-thrombotic syndrome were tested with four different stockings (Mediven plus open toe, Bayreuth, Germany) of their size in random order: class 1 (18-21 mm Hg) and class II (23-32 mm Hg), below-knee (BK) and above-knee thigh-length (AK). The median age, Venous Clinical Severity Score, Venous Segmental Disease Score, and Villalta scale were 62 years (range, 31-81 years), 8 (range, 1-21), 5 (range, 2-10), and 10 (range, 2-22), respectively. The C of C0-6EsAs,d,pPr,o was C0 = 2, C2 = 1, C3 = 3, C4a = 12, C4b = 7, C5 = 12, C6 = 3. Obstruction and reflux was observed on duplex in 47.5% legs, with deep venous reflux alone in 45%. Air plethysmography was used to measure the venous filling index (VFI), venous volume, and time to fill 90% of the venous volume. Direct pressure measurements were obtained while lying and standing using the PicoPress device (Microlab Elettronica, Nicolò, Italy). The pressure sensor was placed underneath the test stocking 5 cm above and 2 cm posterior to the medial malleolus. At the end of the study session, patients stated their preferred stocking based on comfort. RESULTS The VFI, venous volume, and time to fill 90% of the venous volume improved significantly with all types of stocking versus no compression. In class I, the VFI (mL/s) improved from a median of 4.9 (range, 1.7-16.3) without compression to 3.7 (range, 0-14) BK (24.5%) and 3.6 (range, 0.6-14.5) AK (26.5%). With class II, the corresponding improvement was to 4.0 (range, 0.3-16.2) BK (18.8%) and 3.7 (range, 0.5-14.2) AK (24.5%). Median stocking pressure (mm Hg) as measured with the PicoPress in class I was 23 (range, 12-33) lying and 27 (range, 19-39) standing (P < .0005) and in class II was 28 (range, 21-40) lying and 32 (range, 23-46) standing (P < .0005). There was a significant but weak correlation (Spearman) between stocking interface pressure measured directly with the PicoPress and the VFI improvement (baseline VFI-compression VFI) at r = .237; P = .005. Twenty-one patients (legs) changed their preference of compression and 38% of these (8/21 patients, 9/21 legs) preferred an AK-GEC stocking. CONCLUSIONS Compression significantly improved all hemodynamic parameters on air plethysmography. However, the hemodynamic benefit did not significantly change with the class or length of stocking. These results support the liberal selection of a GEC stocking based on patient preference.

Meta-analysis: ertapenem for complicated intra-abdominal infections

Background  Ertapenem is a new member of the carbapenem class of antibiotics, with a favourable pharmacokinetic profile, but a narrower spectrum of antimicrobial activity, compared with older representatives of this class.

Do PubMed and Google searches help medical students and young doctors reach the correct diagnosis? A pilot study

BACKGROUND In the era of the World Wide Web we sought to examine whether the use of PubMed and Google can help physicians to improve their diagnostic skills. METHODS Twenty-six diagnostic cases presented in the case records of the New England Journal of Medicine during 2005 were used for our analysis. Three investigators (one trainee doctor and two final year medical students), tried determining the diagnosis, initially without and afterwards with the use of PubMed and Google. RESULTS A slight increase in the proportion of correct diagnoses obtained was seen following the employment of the formerly mentioned Internet resources, specifically 15.4%, 2.9%, and 11.5% increase for the 3 investigators respectively (from 17 correct diagnoses out of the 26 cases to 21 correct diagnoses out of 26 for investigator A, from 11/26 to 12/26 for investigator B, and from 11/26 to 13/26 for investigator C). This increase was not statistically significant. One investigator was helped more by Google, one by PubMed, and one was equally assisted by the two resources. CONCLUSIONS We believe that these preliminary findings justify the induction of further studies in order to clarify whether resources such as PubMed and Google may substantially aid physicians and medical students in the differential diagnosis process.

Saphenous pulsation on duplex may be a marker of severe chronic superficial venous insufficiency

BACKGROUND Pulsatile flow in deep, perforating veins and varicose veins (VVs) has been described previously to support a hypothesis of arteriovenous (AV) fistulae in the pathogenesis of VVs. Its presence has also been suggested as a cause of failure of VV treatments. However, AV communications have never been adequately visualized and direct pressure tracings within leg veins have been inconclusive. The present study was observational aiming to investigate the prevalence and rate of spontaneous pulsation within the great saphenous vein (GSV) in volunteers and patients using color duplex and compare this to reflux and markers of disease severity. METHODS Twenty-seven consecutive patients (32 legs, median Venous Clinical Severity Score (VCSS) = 5 [0-11]) attending the VV clinic and 23 consecutive ambulatory normal volunteers (46 legs) had their GSV assessed at midthigh using color duplex. Subjects were examined standing with the hips resting against an adjustable couch, bearing weight on the contralateral leg, with the test leg touching the ground. The presence of flow and reflux were initially determined using manual calf compression. Saphenous pulsation (SP) was defined as a cyclical change in velocity. The GSV diameter and SP rate were then recorded after 2 minutes of dependency. The number of pulsations was counted from video recordings. RESULTS The resting SP, if present, was discrete, monophasic, of variable amplitude, antegrade, and irregular, irrespective of respiration. Pulsation was detected in 2/44 (4.5%) legs with C(0-1) (C part of CEAP), 9/17 (52.9%) legs with C(2-3), and 16/17 (94.1%) legs with C(4-6) (P < .05, z test of column proportions). Reflux occurred in 8/32 (25%) legs without SP (C(0) = 2, C(1) = 1, C(2) = 3, C(3) = 2). The median GSV diameter was significantly elevated in the presence of SP (no pulse: 3.5 [range, 1.5-8.1] mm; pulse: 7 [range, 4-9.4] mm; P < .0005). The median refluxing GSV diameter in GSV pulsators compared with nonpulsators was 7 (range, 4-9.4) mm; vs 5.1 (range, 2.7-8.1) mm, respectively (P = .003). The median SP rate in refluxing GSVs was 52 (range, 22-95) beats per minute. CONCLUSIONS The high prevalence of pulsatile antegrade saphenous flow is a novel observation in patients with severe superficial chronic venous insufficiency. It is detectable in 75% of patients with GSV reflux and significantly increases with clinical severity and saphenous diameter. It may be a marker of advanced venous disease and, as it is easy to record, it could supplement duplex evaluations of reflux. Further work is needed to establish the clinical relevance of the SP in terms of disease progression, recurrence after treatment, and as a hemodynamic marker of severity.

Do Changes in Antimicrobial Resistance Necessitate Reconsideration of Surgical Antimicrobial Prophylaxis Strategies

BACKGROUND The potential need for re-evaluation of guidelines on surgical antimicrobial prophylaxis (AMP) in an era of advancing antimicrobial resistance is a matter of a considerable controversy. METHOD Review of the pertinent literature. RESULTS Over the last decade, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has increased significantly, as illustrated by several surveillance studies. The blending of community acquisition and long-term carriage may increase the probability of unrecognized MRSA carriers being admitted to the hospital. Thus, MRSA is considered a major epidemiological threat in most parts of the world, exerting pressure for reconsideration of the guidelines for surgical AMP. The use of a glycopeptide as first-choice prophylaxis in major procedures such as cardiac surgery generally is not recommended but is not ruled out. Current recommendations are based on trials performed almost a decade ago at the latest and do not reflect the contemporary epidemiology of resistance. A few recent studies suggested that vancomycin in combination with gentamicin and rifampicin reduces the incidence of surgical site infections significantly in high-risk patients. These developments led some surgeons and infectious diseases clinicians to consider advanced antimicrobial coverage in surgical AMP. On the other hand, other clinicians are rightfully skeptical about extensive administration of glycopeptides or other agents beyond first- or second-generation cephalosporins because of the risk of further emergence and dissemination of antimicrobial resistance. CONCLUSION Properly designed randomized trials are needed urgently to determine whether standard perioperative AMP should be reconsidered in settings with changing etiology of surgical infections.