Microbial Symphony: Exploring the Role of the Gut in Osteoarthritis-Related Pain. A Narrative Review.

One of the most common musculoskeletal disorders, osteoarthritis (OA), causes worldwide disability, morbidity, and poor quality of life by degenerating articular cartilage, modifying subchondral bone, and inflaming synovial membranes. OA pathogenesis pathways must be understood to generate new preventative and disease-modifying therapies. In recent years, it has been acknowledged that gut microbiota (GM) can significantly contribute to the development of OA. Dysbiosis of GM can disrupt the "symphony" between the host and the GM, leading to a host immunological response that activates the "gut-joint" axis, ultimately worsening OA. This narrative review summarizes research supporting the "gut-joint axis" hypothesis, focusing on the interactions between GM and the immune system in its two main components, innate and adaptive immunity. Furthermore, the pathophysiological sequence of events that link GM imbalance to OA and OA-related pain is broken down and further investigated. We also suggest that diet and prebiotics, probiotics, nutraceuticals, exercise, and fecal microbiota transplantation could improve OA management and represent a new potential therapeutic tool in the light of the scarce panorama of disease-modifying osteoarthritis drugs (DMOADs). Future research is needed to elucidate these complex interactions, prioritizing how a particular change in GM, i.e., a rise or a drop of a specific bacterial strain, correlates with a certain OA subset to pinpoint the associated signaling pathway that leads to OA.

Gut Microbiota Modulation and Its Implications on Neuropathic Pain: A Comprehensive Literature Review.

Neuropathic pain (NP) is a chronic pain disorder arising from somatosensory nervous system impairment. Extensive evidence supports the notion that the gut microbiota (GM) is crucial in maintaining human health by performing vital tasks. At the same time, its disruption has been linked to the emergence and advancement of an expanding range of disorders, including NP, in which GM could play a role in its pathophysiology. The crosstalk between the nervous system and GM happens through immune mediators, metabolites, and nervous structures and involves both central and peripheral nervous systems. This literature review aims to thoroughly investigate the function of modulating GM in the treatment of NP. It will achieve this by integrating existing knowledge, identifying underlying mechanisms, and evaluating the possible clinical consequences of exploiting the gut-brain axis. We will cover the main therapeutic applications of the described GM-modulators, such as probiotics, faecal microbiota transplantation, dietary supplements and emotional support, to the main kinds of NP in which any evidence, even if only pre-clinical, has been unravelled in recent years. The explored NP areas include chemotherapy-induced peripheral neuropathy, diabetic neuropathy, trauma-induced neuropathic pain, trigeminal neuralgia, postherpetic neuralgia and low back pain.

Effect of Preoperative Music Therapy Versus Intravenous Midazolam on Anxiety, Sedation and Stress in Stomatology Surgery: A Randomized Controlled Study.

BACKGROUND: Patients undergoing surgery and general anesthesia often experience anxiety, fear and stress, with negative bodily responses. These may be managed by the pre-procedural application of anxiolytic, analgesic, and anesthetic drugs that have, however, potential risks or side effects. Music therapy (MT) can be used as a complementary no-drug intervention alongside standard surgical care before, during and after medical procedures. The aim of this study was to evaluate the effects of preoperative MT intervention compared to premedication with midazolam on levels of anxiety, sedation and stress during general anesthesia for elective stomatology surgery. METHODS: A two-arm randomized and controlled single-center, parallel-group, pre-post event study was conducted. In total, 70 patients affected by stage I or II (both clinically and instrumentally N0) micro-invasive oral cancer and undergoing elective surgery under general anesthesia were assigned to the control group (CG) or to the music therapy group (MTG). MTG patients received preoperative music therapy intervention (MT) from a certified music therapist before surgery, while the CG patients did not receive MT but instead received premedication with intravenous midazolam, 0.02 mg/kg. Anesthesia was the same in both groups. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were recorded at the entrance to the operating room, just before the induction of anesthesia and every 5 min until the end of surgery. An anxiety visual analogues scale (A-VAS) was used to evaluate the level of anxiety. The bispectral index (BIS) monitor was used to measure the depth of sedation just before and 10 min after both music intervention and midazolam administration. Stress response was assessed 5 min before and 20 min after surgery via the control of plasma prolactin (PRL), growth hormone (GH), and cortisol levels. The patient global impression of satisfaction (PGIS) was tested 1 h after surgery. Participants in the MTG were asked to answer 3 questions concerning their experience with MT. RESULTS: No statistical differences among the PRL, GH and cortisol levels between the two groups were registered before and after the treatment, as well as for PAS, PAD and HR. Significant differences in the A-VAS scores between the MTG and CG (p < 0.01) was observed. Compared to the CG, MTG patients had a statistically significantly lower BIS score (p = 0.02) before induction. A PGIS score of 86.7% revealed that patients in the MTG were very satisfied, versus 80% in the CG (p < 0.05). CONCLUSION: Preoperative music therapy could be an alternative to intravenous midazolam when aiming to promote a preoperative and post-operative state of anxiolysis and sedation in stomatology surgery, even if no differences were found in terms of the surgery-related stress response according to physiological and hormonal determinations.

Low Back Pain and Radiofrequency Denervation of Facet Joint: Beyond Pain Control-A Video Recording.

Chronic low back pain is often due to L5S1 instability resulting in facet joint syndrome. Patients suffering from low back pain may also have a gait pattern characterized by a reduced speed and a shorter, asymmetrical step in order to reduce pain. This case is of a patient with L5S1 instability that occurred after L1 to L5 lumbar stabilization who was treated with radiofrequency (RF) denervation of the medial branch of L5S1 bilaterally. RF ablation outcome was tested by comparing its impact on pain, function, quality of life, and on gait pattern, before and 1 month after the procedure. To objectify the impact of a good pain control on gait, a video recording was performed (see Video 1).

Effects of an Intrathecal Drug Delivery System Connected to a Subcutaneous Port on Pain, Mood and Quality of Life in End Stage Cancer Patients: An Observational Study.

BACKGROUND: In cancer patients with limited life expectancy, an implant of an intrathecal (IT) drug delivery system connected to a subcutaneous port (IDDS-SP) has been proposed as a successful strategy, but conflicting results are reported on quality of life (QoL). The aim of this prospective observational study is to report the effects on pain, mood and QoL of an IT combination therapy delivered by an IDDS-SP in malignant refractory pain. METHODS: Adult patients in which IT therapy was recommended were recruited. An IT therapy with morphine and levobupivacaine was started: VASPI score, depression and anxiety (evaluated by the Edmonton Symptom Assessment System -ESAS-), the Pittsburgh Sleep Quality Index (PSQI), the 5-level EuroQol 5D version (EQ-5D-5L) and the requirements of breakthrough cancer pain (BTcP) medications were registered, with adverse events rate and the satisfaction of patients scored as Patient Global Impression of Change (PGIC). RESULTS: Fifty patients, (16 F/34 M) were enrolled (age 69 ± 12). All had advanced cancer with metastasis. The median daily VASPI score was 75, the median depression score was 6, and the median anxiety score was 4, median PSQI was 16. At 28 days, a significant reduction in VASPI score was registered as well as in depression and anxiety item. Also, PSQI decreased significantly. The EQ-5D-5 L showed a significant improvement in all components at 14 and 28 days. Patient Global Impression of Change scores showed high level of satisfaction. A low incidence of adverse events and a reduction in BTCP episodes were also registered. CONCLUSION: Intrathecal combination therapy delivered by an IDDS-SP could ensure adequate control of cancer related symptoms, such as pain, depression, anxiety and sleep disturbances. These effects, with low rate of AEs and reduced BTcP episodes, could explain the improvement in QoL and the overall high levels of patients' satisfaction.

The Routes of Administration for Acute Postoperative Pain Medication.

Effective treatment of postoperative acute pain, together with early mobilization and nutrition, is one of the perioperative strategies advocated to improve surgical outcome and reduce the costs of hospitalization. Moreover, adequate pain control reduces perioperative morbidity related to surgical stress and can also prevent the incidence of chronic postoperative pain syndromes, whose treatment is still a challenge. The choice of the most appropriate analgesics depends not only on the drug class, but also on the most suitable route of administration, the best dosage for that route, and unique limitations and contraindications for every patient. In the present review, a comprehensive analysis was performed on the different routes of administration of acute postoperative pain medications and their indications and limitations, focusing on recent evidence and international recommendations.

Successful Spinal Cord Stimulation for Necrotizing Raynaud's Phenomenon in COVID-19 Affected Patient: The Nightmare Comes Back.

Necrotizing Raynaud's phenomenon is a vascular clinical syndrome characterized by vasospasm of distal resistance vessels, usually triggered by cold temperatures or by psychological conditions such as anxiety and stress. Pain is the first reported symptom, related to insufficient oxygen delivery to the extremities that leads to ischemia of the peripheral tissues. The initial treatment is conservative, but if the symptoms persist, necrosis and distal amputation can occur. In selected patients, neuromodulation with spinal cord stimulation (SCS) can be an effective treatment by reducing pain and amputation rate. Recent evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause endotheliopathy with microvascular and macrovascular thrombotic events and can present as a systemic inflammatory vascular disease. We present a case of a severe necrotizing Raynaud's phenomenon successfully treated and controlled with SCS that abruptly reappeared during SARS-CoV-2 infection. The report of this case is suggestive for potential treatment in case of peripheral ischemia consequent to COVID-19 vasculopathy. The interaction between SCS and SARS-CoV-2-related endotheliopathy is unknown and would deserve further studies.

Pathophysiology of musculoskeletal pain: a narrative review.

Musculoskeletal pain (excluding bone cancer pain) affects more than 30% of the global population and imposes an enormous burden on patients, families, and caregivers related to functional limitation, emotional distress, effects on mood, loss of independence, and reduced quality of life. The pathogenic mechanisms of musculoskeletal pain relate to the differential sensory innervation of bones, joints, and muscles as opposed to skin and involve a number of peripheral and central nervous system cells and mediators. The interplay of neurons and non-neural cells (e.g. glial, mesenchymal, and immune cells) amplifies and sensitizes pain signals in a manner that leads to cortical remodeling. Moreover, sex, age, mood, and social factors, together with beliefs, thoughts, and pain behaviors influence the way in which musculoskeletal pain manifests and is understood and assessed. The aim of this narrative review is to summarize the different pathogenic mechanisms underlying musculoskeletal pain and how these mechanisms interact to promote the transition from acute to chronic pain.

Perioperative goal-directed therapy and postoperative complications in different kind of surgical procedures: an updated meta-analysis.

BACKGROUND: Goal-directed therapy (GDT) aims to assure tissue perfusion, by optimizing doses and timing of fluids, inotropes, and vasopressors, through monitoring of cardiac output and other basic hemodynamic parameters. Several meta-analyses confirm that GDT can reduce postoperative complications. However, all recent evidences focused on high-risk patients and on major abdominal surgery. OBJECTIVES: The aim of the present meta-analysis is to investigate the effect of GDT on postoperative complications (defined as number of patients with a least one postoperative complication) in different kind of surgical procedures. DATA SOURCES: Randomized controlled trials (RCTs) on perioperative GDT in adult surgical patients were included. The primary outcome measure was complications, defined as number of patients with at least one postoperative complication. A subgroup-analysis was performed considering the kind of surgery: major abdominal (including also major vascular), only vascular, only orthopedic surgery. and so on. STUDY APPRAISAL AND SYNTHESIS METHODS: Meta-analytic techniques (analysis software RevMan, version 5.3.5, Cochrane Collaboration, Oxford, England, UK) were used to combine studies using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In 52 RCTs, 6325 patients were enrolled. Of these, 3162 were randomized to perioperative GDT and 3153 were randomized to control. In the overall population, 2836 patients developed at least one complication: 1278 (40%) were randomized to perioperative GDT, and 1558 (49%) were randomized to control. Pooled OR was 0.60 and 95% CI was 0.49-0.72. The sensitivity analysis confirmed the main result. The analysis enrolling major abdominal patients showed a significant result (OR 0.72, 95% CI 0.59-0.87, p = 0.0007, 31 RCTs, 4203 patients), both in high- and low-risk patients. A significant effect was observed in those RCTs enrolling exclusively orthopedic procedures (OR 0.53, 95% CI 0.35-0.80, p = 0.002, 7 RCTs, 650 patients. Also neurosurgical procedures seemed to benefit from GDT (OR 0.40, 95% CI 0.21-0.78, p = 0.008, 2 RCTs, 208 patients). In both major abdominal and orthopedic surgery, a strategy adopting fluids and inotropes yielded significant results. The total volume of fluid was not significantly different between the GDT and the control group. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: The present meta-analysis, within the limits of the existing data, the clinical and statistical heterogeneity, suggests that GDT can reduce postoperative complication rate. Moreover, the beneficial effect of GDT on postoperative morbidity is significant on major abdominal, orthopedic and neurosurgical procedures. Several well-designed RCTs are needed to further explore the effect of GDT in different kind of surgeries.

Impact of COVID-19 pandemic on chronic pain management: Looking for the best way to deliver care.

Although pain treatment has been described as a fundamental human right, the Coronavirus disease 2019 (COVID-19) pandemic forced healthcare systems worldwide to redistribute healthcare resources toward intensive care units and other COVID-19 dedicated sites. As most chronic pain services were subsequently deemed non-urgent, all outpatient and elective interventional procedures have been reduced or interrupted during the COVID-19 pandemic in order to reduce the risk of viral spread. The shutdown of pain services jointly to the home lockdown imposed by governments has affected chronic pain management worldwide with additional impact on patients' psychological health. Therefore, the aim of this review is to analyze the impact of COVID-19 pandemic on chronic pain treatment and to address what types of strategies can be implemented or supported in order to overcome imposed limitations in delivery of chronic pain patient care.

An Ensemble of Psychological and Physical Health Indices Discriminates Between Individuals with Chronic Pain and Healthy Controls with High Reliability: A Machine Learning Study.

INTRODUCTION: Chronic pain (CP) is a complex multidimensional experience severely affecting individuals' quality of life. Multiple cognitive, affective, emotional, and interpersonal factors play a major role in CP. Furthermore, the psychological, social, and physical circumstances leading to CP show high inter-individual variability, thus making it difficult to identify core syndrome characteristics. In a biopsychosocial perspective, we aim at identifying a pattern of psycho-physical impairments that can reliably discriminate between CP individuals and healthy controls (HC) with high accuracy and estimated generalizability using machine learning. METHODS: A total of 118 CP and 86 HC were recruited. All individuals were administered several scales assessing quality of life, physical and mental health, personal functioning, anxiety, depression, beliefs about medical treatments, and cognitive ability. These features were trained to separate CP from HC using support vector classification and repeated nested cross-validation. RESULTS: Our psycho-physical classifier was able to discriminate CP from HC with 86.5% balanced accuracy and significance (p = 0.0001). The most reliable features characterizing CP were anxiety and depression scores, and belief of harm from prolonged pharmacological treatments; for HP, the most reliable features were physical and occupational functioning, and vitality levels. CONCLUSION: Our findings suggest that, using psychological and physical assessments, it is possible to classify CP from HC with high reliability and estimated generalizability via (i) a pattern of psychological symptoms and cognitive beliefs characteristic of CP, and (ii) a pattern of intact physical functioning characteristic of HC. We think that our algorithm enables novel insights into potential individualized targets for CP-related early intervention programs.

Vasopressor-Sparing Action of Methylene Blue in Severe Sepsis and Shock: A Narrative Review.

Shock is a serious acute circulatory failure leading to inadequate oxygen delivery to the cells. Its treatment is mainly based on circulating fluid optimization, and vasopressors to provide an adequate mean arterial pressure and microcirculatory flow. Norepinephrine is the drug of choice, but high dosages may be responsible for several side effects, including increased myocardial oxygen consumption, dysrhythmias, and peripheral and organ ischemia. Moreover, some patients are "non-responders" to first-line norepinephrine treatment. Hence, other drugs have been proposed to reach and maintain the hemodynamic target. In general, they are described as catecholamine-sparing agents. Among others, the most used are vasopressin, corticosteroids, and angiotensin II. Methylene blue (MB) represents a further option, even though its use is still a topic of controversy. This review article tries to summarize what is known and unknown about the actions of MB in patients in shock. It reduces excessive production of nitric oxide via blockade of guanylate cyclase in shock states. At present, it appears the MB provides positive results in septic shock, if administered early. Further randomized controlled trials are warranted regarding its use to provide more precise indications to physicians involved in the treatment of such patients.

A Bilateral Lumbar Multidermatomal Herpes Zoster in an Elderly Woman with Chronic Kidney Disease.

Herpes zoster (HZ) is a painful rash caused by the reactivation of the varicella-zoster virus (VZV) permanently latent within the cranial or dorsal root ganglia. Usually the rash presents in only one side of the body, in a single dermatome or restricted to a part of it. In immunocompromised patients, more than one contiguous unilateral dermatome, called multidermatomal HZ, has been described, usually in cervical dermatomes. Bilateral rash is rare. Besides immunosuppression, the major risk factors for virus reactivation are older age and female gender. This is a case of a bilateral lumbar multidermatomal HZ in an elderly woman with chronic renal failure.

Triple Intrathecal Combination Therapy for End-Stage Cancer-Related Refractory Pain: A Prospective Observational Study with Two-Month Follow-Up.

INTRODUCTION: In cancer-related pain refractory to systemic opioids, intrathecal (IT) administration of morphine can be a useful strategy. In clinical practice, IT morphine is usually combined with other drugs with different mechanisms of action, in order to obtain a synergistic analgesic effect. However, the discussion on efficacy and safety of IT combination therapy is still ongoing. The aim of this observational study was to report the effects of an IT combination of low doses of ziconotide, morphine, and levobupivacaine in end-stage cancer refractory pain. METHODS: Sixty adult patients, 21 females and 39 males, were enrolled to an IT device implant. The mean visual analogue scale of pain intensity (VASPI) score was 88 ± 20 mm. All patients started with a triple combination therapy: the initial IT dose of morphine was calculated for each patient based on the equivalent daily dose of morphine; an oral/IT ratio of 400/1 was used. For ziconotide, a standard slow titration schedule was started at 1.2 µg/day and the initial dose of levobupivacaine was 3 mg/day. RESULTS: The initial IT mean doses of morphine, ziconotide, and levobupivacaine were 0.8 ± 0.3 mg/day, 1.2 mcg/day and 3 mg/day, respectively. At day 2, a significant reduction in VASPI score was registered (49 ± 17, p < 0.001), and this significant reduction persisted at 56 days (mean VASPI score 44 ± 9, p < 0.001), with mean doses of morphine 2 ± 1 mg/day, ziconotide 2.8 ± 1 mcg/day, and levobupivacaine 3.8 ± 2 mg/day. Very few adverse effects (AEs) were observed. Patients' satisfaction was very high during the entire study period. CONCLUSIONS: Our results, within the limit of the study design, suggest that the IT combination of ziconotide, morphine, and levobupivacaine, at low doses, allows safe and rapid control of refractory cancer pain, with high levels of patient satisfaction.

Hemodynamic goal-directed therapy and postoperative kidney injury: an updated meta-analysis with trial sequential analysis.

BACKGROUND: Perioperative goal-directed therapy (GDT) reduces the risk of renal injury. However, several questions remain unanswered, such as target, kind of patients and surgery, and role of fluids and inotropes. We therefore update a previous analysis, including all studies published in the meanwhile, to clarify the clinical impact of this strategy on acute kidney injury. MAIN BODY: Randomized controlled trials enrolling adult patients undergoing major surgery were considered. GDT was defined as perioperative monitoring and manipulation of hemodynamic parameters to reach normal or supranormal values by fluids alone or with inotropes. Trials comparing the effects of GDT and standard hemodynamic therapy were considered. Primary outcome was acute kidney injury, whichever definition was used. Meta-analytic techniques (analysis software RevMan, version 5.3) were used to combine studies, using random-effect odds ratios (OR) and 95% confidence intervals (CI). Trial sequential analyses were performed including all trials and considering only low risk of bias trials. Sixty-five trials with an overall sample of 9308 patients were included. OR for the development of renal injury was 0.64 (95% CI, 0.62-0.87; p = 0.0003), with no statistical heterogeneity. Trial sequential analyses and sensitivity analysis including studies with low risk of bias confirmed the main results. A significant decrease in renal injury rate was observed in studies that adopted cardiac output and oxygen delivery as hemodynamic target and that used both fluids and inotropes. The postoperative kidney injury rate was significantly lower in trials enrolling "high-risk" patients and major abdominal and orthopedic surgery. SHORT CONCLUSION: The present meta-analysis suggests that targeting GDT to perioperative systemic oxygen delivery, by means of fluids and inotropes, can be the best way to improve renal perfusion and oxygenation in high-risk patients undergoing major abdominal and orthopedic surgery.

Perioperative hemodynamic goal-directed therapy and mortality: a systematic review and meta-analysis with meta-regression.

INTRODUCTION: Recent data found that perioperative goal directed therapy (GDT) was effective only in higher control mortality rates (>20%) with a relatively high heterogeneity that limited the strength of evidence. The aim of the present meta-analysis was to clearly understand which high risk patients may benefit of GDT. EVIDENCE ACQUISITION: Systematic review of randomized controlled trials with meta-analyses, including a meta-regression technique. MEDLINE, EMBASE, and The Cochrane Library databases were searched (1980-January 2015). Trials enrolling adult surgical patients and comparing the effects of GDT versus standard hemodynamic therapy were considered. The primary outcome measure was mortality. Data synthesis was obtained by using Odds Ratio (OR) with 95% confidence interval (CI) by random-effects model. EVIDENCE SYNTHESIS: Fifty eight studies met the inclusion criteria (8171 participants). Pooled OR for mortality was 0.70 (95% CI 0.56-0.88, P=0.002, no statistical heterogeneity). GDT significantly reduced mortality when it is >10% in control group (OR 0.43, 95% CI 0.30-0.61, P<0.00001). The meta-regression model showed that the cut off of 10% of mortality rate in control group significantly differentiates 43 studies from the other 15, with a regression coefficient b of -0.033 and a P value of 0.0001. The significant effect of GDT was driven by high risk of bias studies (OR 0.48, 95% CI 0.34-0.67, P<0.0001). CONCLUSIONS: The present meta-analysis, adopting the meta-regression technique, suggests that GDT significantly reduces mortality even when the event control rate is >10%.

The effects of goal-directed fluid therapy based on dynamic parameters on post-surgical outcome: a meta-analysis of randomized controlled trials.

INTRODUCTION: Dynamic predictors of fluid responsiveness, namely systolic pressure variation, pulse pressure variation, stroke volume variation and pleth variability index have been shown to be useful to identify in advance patients who will respond to a fluid load by a significant increase in stroke volume and cardiac output. As a result, they are increasingly used to guide fluid therapy. Several randomized controlled trials have tested the ability of goal-directed fluid therapy (GDFT) based on dynamic parameters (GDFTdyn) to improve post-surgical outcome. These studies have yielded conflicting results. Therefore, we performed this meta-analysis to investigate whether the use of GDFTdyn is associated with a decrease in post-surgical morbidity. METHODS: A systematic literature review, using MEDLINE, EMBASE, and The Cochrane Library databases through September 2013 was conducted. Data synthesis was obtained by using odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) by random-effects model. RESULTS: In total, 14 studies met the inclusion criteria (961 participants). Post-operative morbidity was reduced by GDFTdyn (OR 0.51; CI 0.34 to 0.75; P <0.001). This effect was related to a significant reduction in infectious (OR 0.45; CI 0.27 to 0.74; P = 0.002), cardiovascular (OR 0.55; CI 0.36 to 0.82; P = 0.004) and abdominal (OR 0.56; CI 0.37 to 0.86; P = 0.008) complications. It was associated with a significant decrease in ICU length of stay (WMD -0.75 days; CI -1.37 to -0.12; P = 0.02). CONCLUSIONS: In surgical patients, we found that GDFTdyn decreased post-surgical morbidity and ICU length of stay. Because of the heterogeneity of studies analyzed, large prospective clinical trials would be useful to confirm our findings.

Haemodynamic goal-directed therapy in cardiac and vascular surgery. A systematic review and meta-analysis.

In cardiovascular surgery, reduced organ perfusion and oxygen delivery contribute to increased postoperative morbidity and prolonged intensive care unit stay. Goal-directed therapy (GDT), a perioperative haemodynamic strategy aiming to increase cardiac output, is helpful in preventing postoperative complications, but studies in the context of cardiovascular surgery have produced conflicting results. The purpose of the present meta-analysis is to determine the effects of perioperative haemodynamic goal-directed therapy on mortality and morbidity in cardiac and vascular surgery. MEDLINE, EMBASE, The Cochrane Library and the DARE databases were searched until July 2011. Randomized controlled trials reporting on adult cardiac or vascular surgical patients managed with perioperative GDT or according to routine haemodynamic practice were included. Primary outcome measures were mortality and morbidity. Data synthesis was obtained by using odds ratio (OR) with 95% confidence interval (CI) by a random effects model. An OR <1 favoured GDT. Statistical heterogeneity was assessed by Q and I(2) statistics. Eleven articles (five cardiac surgery and six vascular procedures), enrolling a total sample of 1179 patients, were included in the analysis. As compared with routine haemodynamic practice, perioperative GDT did not reduce mortality in either cardiac or vascular surgery (pooled OR 0.87; 95% CI 0.37-2.02; statistical power 64%). GDT significantly reduced the number of cardiac patients with complications (OR 0.34; 95% CI 0.18-0.63; P = 0.0006), but no effect was observed in vascular patients (OR, 0.84; 95% CI 0.45-1.56; P = 0.58). Perioperative GDT prevents postoperative complications in cardiac surgery patients, while it has no effect in vascular surgery. The different characteristics and comorbidities of the population enrolled could explain these conflicting results. More trials conforming to the characteristics of low-risk-of-bias studies and enrolling a larger and well-defined population of patients are needed to better clarify the effect of GDT in the specific setting of cardiovascular surgery.

Oral nystatin prophylaxis in surgical/trauma ICU patients: a randomised clinical trial.

INTRODUCTION: Candida prophylaxis in ICU is still a matter of debate. Oral chemoprophylaxis has been advocated to reduce the incidence of Candida colonisation and infection. METHODS: We performed a randomised trial studying a single drug (nystatin) versus control in surgical/trauma ICU patients. Multiple-site testing for fungi was performed in each patient on ICU admission (T0) and subsequently every 3 days (T3, T6, T9, and so forth). The primary evaluation criterion was the time course of the corrected colonisation index. RESULTS: Ninety-nine patients were enrolled. At admission, 69 patients exhibited Candida colonisation: the most frequently colonised body sites were the stomach and the pharynx. The most frequent isolated species was Candida albicans. The corrected colonisation index was similar in the two groups at T0 (P = 0.36), while a significant statistical difference was observed between the treatment and control groups at T6 (median 0.14 and 0.33, respectively; P = 0.0016), at T9 (median 0.00 and 0.28, respectively; P = 0.0001), at T12 (median 0.00 and 0.41, respectively; P = 0.0008), and at T15 (median 0.00 and 0.42, respectively; P < 0.0003). The same results were obtained in the subgroup of patients already colonised at ICU admission. CONCLUSION: This trial shows that nystatin prophylaxis significantly reduces fungal colonisation in surgical/trauma ICU patients, even if already colonised. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01495039.