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Appendiceal cancer most commonly metastasizes to the peritoneum. Cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) is the standard of care for appendiceal cancer with peritoneal metastases. Adverse events postoperatively have been associated with reduced survival. We analyzed clinical outcomes, including complications after CRS and HIPEC in patients with appendiceal cancer, in a recent cohort of patients to identify prognostic factors. Patients undergoing CRS with HIPEC for appendix cancer with peritoneal metastases between January 2007 and December 2009 were identified. Prospectively collected data were analyzed, including preoperative, intraoperative, and postoperative variables, and multivariate Cox regression models were developed to identify factors independently predicting overall survival (OS). A total of 133 consecutive patients with a median age of 51 years were analyzed; 53.4 % were female. Pre-, intra-, and postoperative clinical variables analyzed for their impact on survival included sex, age, prior surgical score, Peritoneal Cancer Index, completeness of cytoreduction score, histology, lymph node metastases, operative time, blood transfusion, fresh frozen plasma transfusion, perioperative chemotherapy, postoperative complications, length of hospitalization, and disease recurrence. OS at 5 years was 74.4 %, and 5-year recurrence-free survival (RFS) of patients with a complete cytoreduction (CC ≤ 1) was 65.5 %. Factors independently predicting shorter survival included peritoneal mucinous adenocarcinoma (PMCA) histology (hazard ratio [HR] 15.2, 95 % confidence interval [CI] 3.38–69.0), lymph node metastasis (HR 3.82, 95 % CI 1.13–12.8), and incomplete cytoreduction [CC3; HR 13.7, 95 % CI 3.18–59.1). An incomplete cytoreduction was associated with the PMCA variant (p

Benchmarking the quality of intraoperative care by comparing the rates of intraoperative adverse events (iAEs) necessitates adequate risk adjustment. We sought to identify the patient- and procedure-related risk factors for iAEs.Our 2007 to 2012 institutional American College of Surgeons NSQIP and administrative databases were linked and then screened for iAEs using the Patient Safety Indicator "Accidental Puncture/Laceration." Intraoperative adverse events were confirmed by systematic review of medical records. Comorbidities were assessed using American College of Surgeons NSQIP variables. Adhesiolysis was determined using CPT codes for lysis of adhesions. Operative complexity was determined using relative value units. Multivariable models were constructed to identify independent predictors of iAEs. Sensitivity analyses were performed in uniform samples of operations.Of 9,292 patients, 218 iAEs were confirmed in 183 patients. Median patient age was 56 years old and 54% were female. Compared with patients without iAEs, iAE patients were older (median 61 vs 56 years; p0.001), more functionally dependent (9% vs 5%; p = 0.028), and had higher American Society of Anesthesiologists class (≥3 in 45% vs 35%; p = 0.004); their procedures were more complex (median relative value units 29 vs 23; p0.001), more likely open (48% vs 21%; p0.001), and more often required adhesiolysis (44% vs 18%; p0.001). In multivariable analyses, adhesiolysis (odds ratio = 2.34; 95% CI, 1.71-3.21; p0.001), higher operative complexity (third vs first relative value units quartile: odds ratio = 3.36; 95% CI, 1.66-6.78; p0.001; fourth vs first quartile: odds ratio = 5.97; 95% CI, 3.01-11.86; p0.001), and open surgical approach (odds ratio = 2.04; 95% CI, 1.39-3.01; p0.001) independently predicted iAEs. Sensitivity analyses confirmed adhesiolysis and higher operative complexity as independent iAE predictors.Adhesiolysis and higher operative complexity predict an increased risk for iAE. Attempts to benchmark the quality of intraoperative care need to adequately risk adjust for these factors.

The contribution of radionuclide therapies (RNTs) to effective patient treatment is widely appreciated. The administration of high doses has necessitated investigating the potential radiation hazard to caregivers from patients undergoing RNTs. This work aimed to review the literature regarding measured effective doses to caregivers from such patients. The main selection criterion was the presence of real radiation exposure measurements. The results were categorised according to the treatment protocol and dose parameters. Analysis of the collected data demonstrated that the measured effective dose values were within the dose constraints defined by the International Commission on Radiological Protection, provided that the radiation protection instructions were followed by both patients and caregivers. In conclusion, the radiation risk for caregivers was almost negligible. In this context, treatments could be administered more often on an outpatient basis, once cost-effectiveness criteria were established and radiation protection training and procedures were appropriately applied.

Background In recent years, the management of synchronous colorectal liver metastasis has changed significantly. Alternative surgical strategies to the classical colorectal-first approach have been proposed. These include the liver-first and combined resections approaches. The objectives of this review were to compare the short- and long-term outcomes for all three approaches. Methods A systematic review of comparative studies was performed. Evaluated endpoints included surgical outcomes (5-year overall survival, 30-day mortality, and post-operative complications). Pair-wise and network meta-analysis (NMA) were performed to compare survival outcomes. Results Eighteen studies were included in this review, reporting on 3,605 patients. NMA and pair-wise meta-analysis of the 5-year overall survival did not show significant difference between the three surgical approaches: combined versus colorectal-first, mean odds ratio (OR) 1.02 (95% CI 0.8–1.28, P = 0.93); liver-first versus colorectal-first, mean OR 0.81 (95% CI 0.53–1.26, P = 0.37); liver-first versus combined, mean OR 0.80 (95% CI 0.52–1.24, P = 0.41). In addition NMA of the 30-day mortality among the three approaches also did not observe statistical difference. Analysis of variance showed that mean post-operative complications of all approaches were comparable (P = 0.51). Conclusion There are considerable differences in the peri-operative management of synchronous CLM patients. This meta-analysis demonstrated no clear statistical surgical outcome or survival advantage towards any of the three approaches. J. Surg. Oncol. 2015 111:341–351. © 2014 Wiley Periodicals, Inc.

There is currently no systematic approach to evaluating the severity of intraoperative adverse events (iAEs).A 3-phase project was designed to develop and validate a novel severity classification scheme for iAEs. Phase 1 created the severity classification using a modified Delphi process. Phase 2 measured the classification's internal consistency by calculating inter-rater reliability among 91 surgeons using standardized iAEs scenarios. Phase 3 measured the classification's construct validity by testing whether major iAEs (severity class ≥3) correlated with worse 30-day postoperative outcomes compared with minor iAEs (severity class3). This was achieved by creating a matched database using American College of Surgeons NSQIP and administrative data, querying for iAEs using the Patient Safety Indicator #15 (Accidental Puncture/Laceration), and iAE confirmation by chart review.Phase 1 resulted in a 6-point severity classification scheme. Phase 2 revealed an inter-rater reliability of 0.882. Of 9,292 patients, phase 3 included 181 confirmed with iAEs. All preoperative/intraoperative variables, including demographics, comorbidities, type of surgery performed, and operative length, were similar between patients with minor (n = 110) vs major iAEs (n = 71). In multivariable logistic analysis, severe iAEs correlated with higher risks of any postoperative complication (odds ratio [OR] = 3.8; 95% CI, 1.9-7.4; p0.001), surgical site infections (OR = 3.7; 95% CI, 1.7-8.2; p = 0.001), systemic sepsis (OR = 6.0; 95% CI, 2.1-17.2; p = 0.001), failure to wean off the ventilator (OR = 3.2; 95% CI, 1.2-8.9; p = 0.022), and postoperative length of stay ≥7 days (OR = 3.0; 95% CI, 1.5-5.9; p = 0.002). Thirty-day mortalities were similar (4.5% vs 7.1%; p = 0.46).We propose a novel iAE severity classification system with high internal consistency and solid construct validity. Our classification scheme might prove essential for benchmarking quality of intraoperative care across hospitals and/or individual surgeons.

Surgery remains the only potentially curative option for patients with hepatocellular carcinoma (HCC) and fibrolamellar carcinoma (FLC). We sought to investigate the differences over time in surgically managed FLC compared with conventional HCC using population-based data.Using SEER data, we identified 7,225 patients with surgically managed FLC or HCC from 1986 to 2008. We examined differences in clinicopathologic and surgical factors associated with long-term survival.Of the 7,225 patients, the majority had HCC (n = 7,135; 99%) vs FLC (n = 90; 1%). Patients with FLC were younger (25 years vs 59 years) and more often were women (44% vs 27%) than patients with HCC (both p0.001). Regional disease was more common among patients with FLC (42.2%) vs patients with HCC (22.1%) (p0.001). More than one-third of patients with FLC (36.9%) were operatively managed with a hemihepatectomy compared with patients with HCC, who were more often managed with a liver transplant (p0.001). On univariable analysis, there was a marked difference in overall survival, with patients with FLC surviving a median of 75 months vs 43 months for HCC (hazard ratio [HR]: 0.59; p = 0.001). There was a marked difference in survival when patients were stratified by localized (FLC, 78 months vs HCC, 49 months; p = 0.012) vs regional disease (FLC, 46 months vs HCC, 23 months; p = 0.002.Patients with FLC have many clinicopathologic features that are different from those of patients with HCC, including younger age and female sex. Despite a higher likelihood of advanced disease at the time of diagnosis, surgically treated FLC patients had better long-term outcomes than patients with conventional HCC.

Surgical site infection (SSI) after pilonidal disease surgery can lead to serious complications. We systematically searched the PubMed, Scopus, and ClinicalTrials.gov databases for studies evaluating the use of antimicrobials as an adjunct to pilonidal disease surgery. We identified 12 eligible studies [nine randomized controlled trials (RCTs), three retrospective cohort studies], enrolling a total of 1,172 patients. No difference was observed when single-dose prophylaxis was compared to no prophylaxis or to a long course of antibiotics (seven studies, 690 patients). Similarly, gentamicin collagen sponges (GCS) did not appear to be beneficial when compared with no GCS (with primary or secondary closure; four studies, 402 patients). One study (80 patients) reported faster healing and lower SSI and recurrence rates with GCS than a 7-day course of antibiotics. The clinical heterogeneity precluded a formal meta-analysis. Although the generalization of our findings may be limited by the relative paucity and clinical heterogeneity of the existing studies, prophylactic antibiotics or GCS did not appear to be beneficial in promoting healing or reducing SSI or recurrence rates. Large, double-blind, placebo-controlled RCTs are warranted in order to further elucidate this issue.

Background Postoperative complications may have an adverse effect not only on short-term but also long-term outcome among patients having surgery for cancer. A retrospective series of patients who had surgery for colorectal liver metastases (CLM) was used to assess this association. Methods Patients who had surgery with curative intent for CLM from 2000 to 2009 were included. The impact of postoperative complications, patient characteristics, disease stage and treatment on long-term survival was analysed using multivariable Cox regression models. Results A total of 251 patients were included. The median age was 58 (interquartile range 51–68) years and there were 87 women (34·7 per cent). A minor or major postoperative complication developed in 41 and 14 patients respectively, and five patients (2·0 per cent) died after surgery. The 5-year recurrence-free (RFS) and overall survival rates were 19·5 and 41·9 per cent respectively. Multivariable analysis revealed that postoperative complications independently predicted shorter RFS (hazard ratio (HR) 2·36, 95 per cent confidence interval 1·56 to 3·58) and overall survival (HR 2·34, 1·46 to 3·74). Other independent predictors of shorter RFS and overall survival included lymph node metastasis, concomitant extrahepatic disease, a serum carcinoembryonic antigen level of at least 100 ng/dl, and the use of radiofrequency ablation (RFS only). The severity of complications also correlated with RFS (P = 0·006) and overall survival (P = 0·001). Conclusion Postoperative complications were independently associated with decreased long-term survival after surgery for CLM with curative intent. The prevention and management of postoperative adverse events may be important oncologically.

We sought to assess the impact of intraoperative adverse events (iAEs) on 30-day postoperative mortality, 30-day postoperative morbidity, and postoperative length of stay (LOS) among patients undergoing abdominal surgery. We hypothesized that iAEs would be associated with significant increases in each outcome.The relationship between iAEs and postoperative clinical outcomes remains largely unknown.The 2007 to 2012 institutional ACS-NSQIP and administrative databases for abdominal surgeries were matched then screened for iAEs using the Agency for Healthcare Research and Quality's 15 Patient Safety Indicator, "Accidental Puncture/Laceration". Each chart flagged during the initial screen was then manually reviewed to confirm whether an iAE occurred. Univariate then multivariable logistic regression models were constructed to assess the independent impact of iAEs on 30-day mortality, 30-day morbidity, and prolonged (≥7 days) postoperative LOS, controlling for preoperative/intraoperative variables (eg, age, comorbidities, ASA, wound classification), procedure type (eg, laparoscopic vs open, intestinal, foregut, hepatopancreaticobiliary vs abdominal wall procedure), and complexity (eg, adhesions; relative value units). Propensity score analyses were conducted with each iAE patient matched with 5 non-iAE patients. Sensitivity analyses were performed.A total of 9288 cases were included; 183 had iAEs. Most iAEs consisted of bowel (44%) or vessel (29%) injuries and were addressed intraoperatively (92%). In multivariable analyses, iAEs were independently associated with increased 30-day mortality [OR = 3.19, 95% confidence interval (CI) 1.52-6.71, P = 0.002], 30-day morbidity (OR = 2.68, 95% CI 1.89-3.81, P0.001), and prolonged postoperative LOS (OR = 1.85, 95% CI 1.27-2.70, P = 0.001). Postoperative complications associated with iAEs included deep/organ-space surgical site infection (OR = 1.94, 95% CI 1.20-3.14), P = 0.007), sepsis (OR = 2.14, 95% CI 1.32-3.47, P = 0.002), pneumonia (OR = 2.18, 95% CI 1.11-4.26, P = 0.023), and failure to wean ventilator (OR = 3.88, 95% CI 2.17-6.95, P0.001). Propensity score matching confirmed these findings, as did multiple sensitivity analyses.iAEs are independently associated with substantial increases in postoperative mortality, morbidity, and prolonged LOS. Quality improvement efforts should focus on iAE prevention, mitigation of harm after iAEs occur, and risk/severity-adjusted iAE tracking and benchmarking.

Background Desmoid tumors are rare soft-tissue neoplasms with limited data on their management. We sought to determine the rates of recurrence following surgery for desmoid tumors and identify factors predictive of disease-free survival.

Acute cystitis is one of the most common health-related problems in the female population. Over the last few decades, a number of drugs labeled as 'urinary tract analgesics' were released; these are available over the counter and are gaining widespread resonance among the North American population. The main representatives of this class of drugs are phenazopyridine and methenamine hippurate. Methenamine's efficacy and side effects have been well studied in a recent systematic review. On the other hand, in contrast to its widespread use, the published clinical evidence regarding phenazopyridine's effectiveness and safety is scarce. In addition, consumers (potentially patients) appear to ignore the limitations of this kind of treatment. In this article, concerns regarding the use of over-the-counter uroanalgesics, with a focus on the relevant clinical evidence, are discussed.

The reevaluation of “forgotten” antibiotics can identify new therapeutic options against extensively drug-resistant Gram-negative pathogens. We sought to investigate isepamicin in this regard. We retrospectively evaluated the antimicrobial susceptibility to isepamicin of Enterobacteriaceae sp. isolates from unique patients, collected at the microbiological laboratory of the University Hospital of Heraklion, Crete, Greece, from 2004 to 2009. Susceptibility testing was done with the automated Vitek 2 system. The breakpoints for susceptibility to isepamicin, tigecycline, and other antibiotics were those proposed by the Comité de l'Antibiogramme de la Société Française de Microbiologie (CA-SFM), the FDA, and the CLSI, respectively. A total of 6,296 isolates were studied, including primarily 3,401 (54.0%) Escherichia coli , 1,040 (16.5%) Klebsiella pneumoniae , 590 (9.4%) Proteus mirabilis , and 460 (7.3%) Enterobacter sp. isolates. Excluding the species with intrinsic resistance to each antibiotic, antimicrobial susceptibility was highest for colistin (5,275/5,441 isolates [96.9%]) and isepamicin (6,103/6,296 [96.9%]), followed by meropenem (5,890/6,296 [93.6%]), imipenem (5,874/6,296 [93.3%]), and amikacin (5,492/6,296 [87.2%]). The antimicrobial susceptibility of the 1,040 K. pneumoniae isolates was highest for isepamicin (95.3%), followed by colistin (89.3%) and meropenem (63.0%). Regarding resistant K. pneumoniae isolates, susceptibility to isepamicin was observed for 91.1% of the 392, 87.7% of the 375, and 85.6% of the 111 isolates that were nonsusceptible to the carbapenems, all other aminoglycosides, and colistin, respectively. Isepamicin exhibited high in vitro activity against almost all of the Enterobacteriaceae species. It could particularly serve as a last-resort therapeutic option for carbapenem-resistant K. pneumoniae in our region, where it is endemic, as it does not show considerable cross-resistance with other aminoglycosides.

The objective of this investigation was to document clinicians’ awareness regarding the incidence and severity of Clostridium difficile-associated diarrhea (CDAD). An international electronic survey was conducted among corresponding authors of articles indexed by PubMed and published during the last 10 years in ‘Core Clinical Journals’. A total of 1,163 clinicians answered (response rate 59%); most of the responses were submitted from North America (54.6%), Europe (32.2%), and Asia/Pacific (11.6%). Only 2.2% of the participants answered correctly all four questions, while 14.1% answered all questions incorrectly. Regarding each question, 10.8% of the participants correctly estimated current CDAD treatment failure or recurrence rates to be around 40%, 33.4% correctly estimated the ratio of antibiotic-associated colitis attributed to C. difficile to be around 60%, 72.7% correctly responded that almost all antibiotics are associated with CDAD, and 41.7% correctly responded that any patient is at risk for CDAD. Almost half (44.4%) of the respondents considered CDAD to be underestimated. Participants from North America scored higher than those from Europe or Asia/Pacific (p

Summary Background: In our clinical practice, we have experienced a consistent increase in the morbidity of elderly in Greece during August. Methods: We prospectively analysed and compared the morbidity of elderly patients (≥ 75 years old) between August and November of the same year (2010), using data from the SOS Doctors (a network of physicians performing house call visits). Results: We analysed data on 739 and 738 elderly patient house-calls in August and November, respectively. Overall, the most common diagnoses were cardiovascular (17.6%), musculoskeletal (10.7%), gastrointestinal (9.5%), respiratory (8.5%), renal/genitourinary (8.1%), and neurologic/psychiatric (7.9%). In August, patients were older (p

Aminoglycosides constitute one of the oldest classes of antimicrobials. Despite their toxicity, mainly nephrotoxicity and ototoxicity, aminoglycosides are valuable in current clinical practice, since they retain good activity against multidrug-resistant Gram-negative pathogens, such as Pseudomonas aeruginosa and Acinetobacter spp. Time-kill studies have shown a concentration-dependent and partially concentration-dependent bacterial killing against Gram-negative and Gram-positive bacteria, respectively. Pharmacodynamic data gathered over recent decades show that the administration of aminoglycosides by an extended-interval dosing scheme takes advantage of the maximum potential of these agents, with the goal of achieving an area under the concentration-time curve (AUC) of 100 mg · h/L over 24 hours and a peak plasma drug concentration (C(max)) to minimum inhibitory concentration (MIC) ratio of 8-10. Several clinical conditions that are common in seriously ill patients result in expansion of the extracellular space and can lead to a lower than desirable C(max) with the usual loading dose. Extended-interval dosing schemes allow adequate time to decrease bacterial adaptive resistance, a phenomenon characterized by slow concentration-independent killing. Adaptive resistance is minimized by the complete clearance of the drug before the subsequent dose, thus favouring the extended-interval dosing schemes. The efficacy of these schemes is also safeguarded by the observed post-antibiotic sub-MIC effect and post-antibiotic leukocyte enhancement, which inhibit bacterial regrowth when the serum aminoglycoside levels fall below the MIC of the pathogen. In everyday clinical practice, aminoglycosides are usually used empirically to treat severe sepsis and septic shock while awaiting the results of antimicrobial susceptibility testing. The European Committee on Antimicrobial Susceptibility Testing acknowledges the regimen-dependent nature of clinical breakpoints for aminoglycosides, i.e. of MIC values that classify bacterial isolates into sensitive or resistant, and bases its recommendations on extended-interval dosing. To a large extent, the lack of correlation between in vitro antimicrobial susceptibility testing and clinical outcome is derived from the fact that the available clinical breakpoints for aminoglycosides are set based on mean pharmacokinetic parameters obtained in healthy volunteers and not sick patients. The nephrotoxicity associated with once- versus multiple-daily administration of aminoglycosides has been assessed in numerous prospective randomized trials and by several meta-analyses. The once-daily dosing schedule provides a longer time of administration until the threshold for nephrotoxicity is met. Regarding ototoxicity, no dosing regimen appears to be less ototoxic than another. Inactivation of aminoglycosides inside the bacterial pathogens occurs by diverse modifying enzymes and by operation of multidrug efflux systems, making both of these potential targets for inhibition. In summary, despite their use for several decades, the ideal method of administration and the preferred dosing schemes of aminoglycosides for most of their therapeutic indications need further refinement. Individualized pharmacodynamic monitoring has the potential of minimizing the toxicity and the clinical failures of these agents in critically ill patients.

Background. The authors evaluated the available evidence regarding the use of adhesive strips for the management of surgical incisions and compared them with sutures and other closure materials. Study design. Systematic review and meta-analysis of randomized controlled trials (RCTs). Results. Twelve RCTs studying 1317 incisions in 1023 patients were included. No difference was found regarding the development of infection (odds ratio [OR] = 0.47; 95% Confidence interval [CI] = 0.12-1.85), dehiscence (OR = 1.22; 95% CI = 0.32-4.64), and overall cosmetic result (standardized mean difference = 0.01; 95% CI = −0.19 to 0.20). Closure with strips resulted in significantly lower incidence of redness (OR = 0.57; 95% CI = 0.37-0.89). The available data on pain, need for resuturing, swelling, patient satisfaction, and closure time with the use of strips could not be synthesized; however, regarding the latter 2 outcomes, application of strips seemed favorable. There was significant heterogeneity among the studies. Conclusions. The findings suggest that adhesive strips may be an efficient closure material for certain small-length incisions. Further research is warranted on outcomes such as dehiscence and the need for resuturing.

Background Atelectasis is considered to be the most common cause of early postoperative fever (EPF) but the existing evidence is contradictory. We sought to determine if atelectasis is associated with EPF by analyzing the relevant published evidence. Methods We performed a systematic search in PubMed and Scopus databases to identify studies examining the association between atelectasis and EPF. Results A total of eight studies, including 998 cardiac, abdominal, and maxillofacial surgery patients, were eligible for analysis. Only two studies specifically examined our question, and six additional articles reported sufficient data to be included. Only one study reported a significant association between postoperative atelectasis and fever, whereas the remaining studies indicated no such association. The performance of EPF as a diagnostic test for atelectasis was also assessed, and EPF performed poorly (pooled diagnostic OR, 1.40; 95% CI, 0.92-2.12). The significant heterogeneity among the studies precluded a formal metaanalysis. Conclusion The available evidence regarding the association of atelectasis and fever is scarce. We found no clinical evidence supporting the concept that atelectasis is associated with EPF. More so, there is no clear evidence that atelectasis causes fever at all. Large studies are needed to precisely evaluate the contribution of atelectasis in EPF.

Once daily dosing (ODD) of aminoglycosides has become a standard of care for most patient populations. However, the use of ODD of aminoglycosides has not been clarified in febrile neutropenia.We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared the effectiveness and safety of ODD versus multiple daily dosing (MDD) of aminoglycosides in patients with febrile neutropenia. We searched the PubMed, Scopus, Cochrane Central Register of Trials and clinicaltrials.gov databases up to July 2010.A total of five and eight RCTs were included in the effectiveness and safety analyses, respectively. We observed a trend towards better effectiveness of the ODD regimen in the clinically evaluable population {five RCTs, 403 patient-episodes, risk ratio (RR) = 1.18 [95% confidence interval (95% CI): 0.98, 1.42]}, but not in the microbiologically evaluable population [three RCTs, 119 patient-episodes, RR = 1.11 (95% CI: 0.84, 1.48)]. The occurrence of nephrotoxicity was similar between the two groups [seven RCTs, 1643 patient-episodes, RR = 0.74 (95% CI: 0.36, 1.50)], as was ototoxicity [six RCTs, 862 patient-episodes, RR = 1.05 (95% CI: 0.51, 2.19)]. There was no difference in mortality [four RCTs, 403 patient-episodes, RR = 0.77 (95% CI: 0.21, 2.78)].Although the generalization of our findings may be restricted by the relatively small sample size and other methodological limitations of the included RCTs, ODD appears to be at least as effective and as safe as MDD in patients with febrile neutropenia. RCTs comparing ODD versus MDD in patients with bacteraemia and profound or prolonged neutropenia would be of additional value.

Background: Infectious mononucleosis usually runs a mild self-limiting course. Complications arise rarely and when so, corticosteroids are the mainstay of their treatment. The role of antivirals in the management of severe EBV infections is debatable. Methods: We sought to review the usage of antivirals for severe EBV infection in apparently immunocompetent patients. For this reason a search in PubMed and Scopus was performed for the time period from 1982 to 2009. Results: 45 patients with severe manifestations of infectious mononucleosis received antivirals (as an adjunct to steroids in 26 of them). Specifically 21 patients with CNS involvement (meningoencephalitis, cerebellitis), 4 with peripheral nervous system involvement (Guillain-Barre, myeloradiculitis, facial nerve palsy), 5 with hepatitis and 15 with other afflictions (including adult respiratory distress syndrome, thrombocytopenia, aplastic anemia, acute renal failure, ulcerations, myocarditis, and frosted branch vasculitis) received antiviral medications. Thirty-nine out of these 45 patients had a favourable outcome (27 were cured and 12 showed clinical improvement) while 6 patients died. The most commonly prescribed antiviral regimen was acyclovir monotherapy (35 patients). Three patients received combinations of acyclovir with other antivirals and 1 received famciclovir. Three patients received ganciclovir monotherapy, 1 ganciclovir plus foscarnet, 1 foscarnet and 1 vidarabine. Conclusion: The available data derive from case reports and case series and thus the deduction of conclusions regarding the effect, if any, of antiviral treatment is debatable. However, physicians may consider using antiviral agents in severe manifestations of EBV infections in immunocompetent patients as an adjunct to steroid treatment.

Background We sought to investigate the penetration of the H1N1v vaccine in Greek medical students, as well as their approach to the vaccination. Methods A survey was conducted among the students of the University of Athens, School of Medicine, 1 month after the initiation of the vaccination programme. Participants were asked to fill in a questionnaire regarding their status of vaccination and their approach to the H1N1v vaccine. Results We handed a questionnaire to 1000 students (out of 1700 officially enrolled in the medical school) and retrieved 922 answers. Only 74 (8%) medical students had been vaccinated and 78 (9%) planned to (probably or definitely) do so in the future, while 641 (67%) would (probably or definitely) not get vaccinated. The highest coverage was among the sixth year students (37/234, 16%). The most common reasons for not having received the vaccine were perception of the disease as mild (387/848, 46%), and concern regarding long-term adverse events (370/848, 44%). Thirty percent (258/848) of the students doubted the vaccine's effectiveness, and 197 (23%) worried about possible short-term adverse events. One hundred and thirty-three respondents (16%) believed the whole story is a conspiracy while 102 (12%) reported to have had the flu. Almost half (43%) of the participants considered their knowledge on the subject inadequate. Conclusion Our findings confirmed the low penetration of the H1N1 vaccine in Greece, as in most European countries, even in medical students. Better education of the students and the public might aid in increasing the immunization rates.

Summary Background: Studies evaluating the association of economic variables with mortality have produced mixed findings. Objective: We sought to evaluate whether economic crises confer increase in mortality. Methods: We reviewed studies analysing mortality in the general population in periods of economic crisis compared with periods prior to or after the crisis, by searching PubMed, Scopus, Cochrane and the World Wide Web. Results: Eleven studies were included in this review; they referred to economic crises that occurred in Russia, South Korea, as well as South or Central American, African or European countries (5, 2, 2, 1 and 1 studies respectively). Periods of economic crises were associated with the increase in all-cause mortality in seven out of eight studies that reported specific relevant data and increase in cardiovascular mortality in six out of seven studies. Increase in mortality because of respiratory infections, chronic liver disease, suicides, homicides and mortality in infants was noted in association with economic crises in all 5, 4, 6, 5 and 3 studies, respectively, that reported specific relevant data. Mortality from transport accidents decreased with economic crises in five out of six studies. Conclusion: Economic crises in less affluent countries are accompanied with the increase in all-cause mortality, as well as mortality from most of the major specific causes. Further data are needed to establish the effect of economic crises on mortality in more affluent countries. We believe that the above-mentioned association could be attributed to increased psychosocial stress during such periods, among other factors. Public health authorities should be aware of this issue and consider appropriate preventive and control measures.

The value of additional imaging in clearing the cervical spine (C-spine) of alert trauma patients with tenderness on clinical exam and a negative computed tomographic (CT) scan is still unclear.All adult trauma patients with a Glasgow Coma Scale of 15, C-spine tenderness in the absence of neurologic signs, and a negative C-spine CT were included. The study period extended from September 2011 to June 2012. C-spine CT scans were interpreted in detail and considered negative in the absence of any findings indicating bony, ligamentous, or soft tissue injury around the C-spine. The incidence of C-spine injury was evaluated using early (24 h) repeat physical examination, MRI, and/or flexion-extension films.Of 2015 patients with a C-spine CT, 383 (19 %) fulfilled the inclusion criteria. The median age was 43 (IQR: 30-53) and 44.7 % were female. Thirty-six patients (9.4 %) underwent MRI (3.7 %), flexion-extension imaging (5.2 %), or both (0.5 %), with no significant injuries identified and subsequent removal of the collar allowed. The remaining patients were clinically cleared within 24 h of presentation. None of the patients developed neurological signs following removal of the collar. On bivariate analysis, no variable except for evaluation by trauma surgery was associated with performance of additional imaging.C-spine precautions can be withdrawn without additional imaging in most blunt trauma patients with C-spine tenderness but negative neurologic evaluation and C-spine CT. Focus should be placed on the detailed and comprehensive interpretation of the C-spine CT.

Little is known about intraoperative adverse events (iAEs) in emergency surgery (ES). We sought to describe iAEs in ES and to investigate their clinical and financial impact.The 2007 to 2012 administrative and American College of Surgeons-National Surgical Quality Improvement Program databases at our tertiary academic center were: (1) linked, (2) queried for all ES procedures, and then (3) screened for iAEs using the ICD-9-CM-based Patient Safety Indicator "accidental puncture/laceration". Flagged cases were systematically reviewed to: (1) confirm or exclude the occurrence of iAEs (defined as inadvertent injuries during the operation) and (2) extract additional variables such as procedure type, approach, complexity (measured by relative value units), need for adhesiolysis, and extent of repair. Univariate and multivariate analyses were performed to assess the independent impact of iAEs on 30-day morbidity, mortality, and hospital charges.Of a total of 9,288 patients, 1,284 (13.8%) patients underwent ES, of which 23 had iAEs (1.8%); 18 of 23 (78.3%) of the iAEs involved the small bowel or spleen, 10 of 23 (43.5%) required suture repair, and 8 of 23 (34.8%) required tissue or organ resection. Compared with those without iAEs, patients with iAEs were older (median age 62 vs 50; P = .04); their procedures were more complex (total relative value unit 46.7, interquartile range [27.5 to 52.6] vs 14.5 [.5 to 30.2]; P.001), longer in duration (3 hours: 52% vs 8%; P.001), and more often required adhesiolysis (39.1% vs 13.5% P = .001). Patients with iAEs had increased total charges ($31,080 vs $11,330, P.001), direct charges ($20,030 vs $7,387, P.001), and indirect charges ($11,460 vs $4,088, P.001). On multivariable analyses, iAEs were independently associated with increased 30-day morbidity (odds ratio, 3.56 [CI, 1.10 to 11.54]; P = .03) and prolonged postoperative length of stay (LOS; LOS7 days; odds ratio, 5.60 [1.54 to 20.35]; P = .01]. A trend toward increased mortality did not reach statistical significance.In ES, iAEs are independently associated with significantly higher postoperative morbidity and prolonged LOS.

Little evidence currently exists regarding the clinical or financial impact of intraoperative adverse events (iAEs). We sought to study the additional health care charges attributable to the occurrence of an iAE.The administrative and ACS-NSQIP databases at our tertiary academic medical center were linked for all patients undergoing abdominal surgery (January 2007-October 2012). The ICD-9-CM-based Patient Safety Indicator "accidental puncture/laceration" was used to screen the linked database for potential iAEs. All iAEs were confirmed subsequently through standardized review of all flagged medical records. Multivariate analyses controlling for demographics, comorbidities/laboratory values, procedure type, and approach and complexity of surgery were performed to assess the increase in health care charges independently predicted by the occurrence of iAEs.Of 9,111 patients, 183 were confirmed to have iAEs. Patients in the iAE group had higher median total charges ($27,169 [IQR, 17,302-44,952] vs $13,312 [IQR, 8,586-22,012]; P.001), direct charges ($17,808 [IQR, 11,520-28,930] vs $8,738 [IQR, 5,686-14,227]; P.001) and indirect charges ($9,396 [IQR, 5,932-16,144] vs $4,568 [IQR, 2,887-7,824]; P.001) when compared with patients without iAEs. Multivariate analyses demonstrated that iAEs independently predict an increase in total hospitalization charges by 41% (95% CI, 30-52%; P.001). Specifically, the direct, indirect, operating room, laboratory/radiology, and alimentation/medical therapy charges increased by 42, 39, 27, 54, and 48%, respectively (all P.001).In addition to the morbidity incurred by patients, the occurrence of an iAE is associated with major additional health care charges. In an era of value-based health care, understanding and preventing iAEs can lead to major cost savings alongside improvements in patient safety and surgical quality.

Perioperative blood transfusion (PBT) is common in pancreatic surgery. Recent studies have suggested that PBT may be associated with worse long-term outcomes. A systematic review and meta-analysis of studies comparing long-term clinical outcomes of cancer patients undergoing curative-intent pancreatic surgery with regard to occurrence of PBT was performed. A total of 23 studies (4339 patients) were included in the systematic review, and 19 studies (3646 patients) were included in the meta-analysis. Nearly half (45.8 %) of all patients were female (range 25–60 %), and median age ranged from 59 to 72 years. About half (46.5 %, range 19–72 %) of the patients were transfused. Most had pancreatic ductal adenocarcinoma (69.5 %), while others had ampullary carcinoma (15.0 %), cholangiocarcinoma (7.4 %), or exocrine tumors of pancreas (8.1 %). Most (91.1 %) underwent pancreaticoduodenectomy, while the remaining patients underwent a total or distal pancreatectomy. The 5-year overall survival for all patients ranged from 0 to 65 %. Thirteen and nine of 19 studies reported a detrimental effect of PBT on survival on univariable and multivariable analysis, respectively. Overall, PBT was associated with shorter overall survival (pooled odds ratio 2.43, 95 % confidence interval 1.90–3.10); this finding was reproduced in sensitivity analysis. Patients receiving PBT had significantly lower 5-year survival after curative-intent pancreatic surgery. Further research should focus on implementing guidelines for and discerning factors associated with the poor outcomes after PBT.

Background We sought to assess the independent effect of concomitant adhesions (CAs) on patient outcome in abdominal surgery. Materials and methods Using the American College of Surgeons National Surgical Quality Improvement Program data, we created a uniform data set of all gastrectomies, enterectomies, hepatectomies, and pancreatectomies performed between 2007 and 2012 at our tertiary academic center. American College of Surgeons National Surgical Quality Improvement Program data were supplemented with additional variables (e.g., procedure complexity–relative value unit). The presence of CAs was detected using the Current Procedural Terminology codes for adhesiolysis (44005, 44180, 50715, 58660, and 58740). Cases where adhesiolysis was the primary procedure (e.g., bowel obstruction) were excluded. Multivariable logistic regression analyses were performed to assess the independent effect of CAs on 30-d morbidity and mortality, while controlling for age, comorbidities and the type/complexity/approach/emergency nature of surgery. Results Adhesiolysis was performed in 875 of 5940 operations (14.7%). Operations with CAs were longer (median duration 3.2 versus 2.7 h, P

Importance Data on outcomes following surgical management of intrahepatic cholangiocarcinoma (ICC) are limited. The incidence of ICC is increasing and it has a poor prognosis. No consensus has been reached regarding the optimal treatment modalities. Objective To systematically review and synthesize the available evidence regarding treatment and prognosis in patients with ICC. Data Sources The PubMed database was searched for relevant articles published between January 1, 2000, and April 1, 2013. Study Selection Only studies assessing predictors of survival or recurrence in patients undergoing curative-intent surgical treatment of ICC were included. Small series, studies reporting on mixed types of cholangiocarcinoma, or exclusively on hepatolithiasis-associated cholangiocarcinoma, and those published in a language other than English, French, German, Italian, or Greek, were excluded. Fifty-seven of 960 articles were therefore analyzed. Data Extraction and Synthesis Data on preoperative, intraoperative, and postoperative variables were extracted by 3 independent reviewers. Multiple studies reporting on the same population were excluded. Data were pooled using a random-effects model. Main Outcomes and Measures We hypothesized that preoperative variables and tumor characteristics affect patient survival. The outcomes of the study were overall survival and recurrence-free survival. The hypothesis was formulated before data collection. Results Fifty-seven studies (4756 patients) were included in the review. Median patient age ranged from 49 to 67 years, and 57% were male. Most patients had a solitary (69%), large (median size, 4.5-8.0 cm) tumor of the mass-forming type (86%). Approximately one-third of the patients had lymph node metastasis (34%) or vascular (38%), perineural (29%), or biliary invasion (29%). Most underwent a major hepatectomy (82%), often accompanied by lymphadenectomy (67%) and sometimes by extrahepatic bile duct resection (23%). Median and 5-year overall survival (OS) generally were approximately 28 months (range, 9-53 months) and 30% (range, 5%-56%), respectively; factors predicting shorter OS included large tumor size, multiple tumors, lymph node metastasis, and vascular invasion. Adjuvant chemotherapy or radiotherapy did not appear to be beneficial. Seven studies (2132 patients) provided data for the meta-analysis. Factors associated with shorter OS included older age (pooled hazard ratio, 1.10; 95% CI, 1.03-1.17), larger tumor size (1.09; 1.02-1.16), presence of multiple tumors (1.70; 1.43-2.02), lymph node metastasis (2.09; 1.80-2.43), vascular invasion (1.87; 1.44-2.42), and poor tumor differentiation (1.41; 1.17-1.71). Conclusions and Relevance The prognosis of ICC is dictated mainly by tumor factors. Future research could focus on the usefulness of adjuvant treatment as well as other multidisciplinary treatment modalities.

Multidisciplinary cancer clinics may improve patient care. We examined how a single-day multidisciplinary liver clinic (mdlc) affected care recommendations for patients compared with the recommendations provided before presentation to the mdlc. We analyzed the demographic and clinicopathologic data of 343 patients assessed in the Johns Hopkins Liver Tumor Center from 2009 to 2012, comparing imaging and pathology interpretation, diagnosis, and management plan between the outside provider (osp) and the mdlc. Most patients were white (n = 259, 76%), median age was 60 years, and 146 were women (43%). Outside providers referred 182 patients (53%), the rest were self-referred. Patients travelled median of 83.4 miles (interquartile range: 42.7&ndash, 247 miles). Most had already undergone imaging (n = 338, 99%) and biopsy (n = 194, 57%) at the osp, and a formal management plan had been formulated for about half (n = 168, 49%). Alterations in the interpretation of imaging occurred for 49 patients (18%) and of biopsy for 14 patients (10%). Referral to the mdlc resulted in a change of diagnosis in 26 patients (8%), of management plan in 70 patients (42%), and of tumour resectability in 7 patients (5%). Roughly half the patients (n = 174, 51%) returned for a follow-up, and 154 of the returnees (89%) received treatment, primarily intraarterial therapy (n = 88, 57%), systemic chemotherapy (n = 60, 39%), or liver resection (n = 32, 21%). Enrollment in a clinical trial was proposed to 34 patients (10%), and 21 of the 34 (62%) were accrued. Patient assessment by our multidisciplinary liver clinic had a significant impact on management, resulting in alterations to imaging and pathology interpretation, diagnosis, and management plan. The mdlc is an effective and convenient means of delivering expert opinion about the diagnosis and management of liver tumours.

Hepatocellular carcinoma (HCC) primarily affects patients with a cirrhotic liver. Reports on the characteristics of patients with HCC in noncirrhotic liver, as well as predictors of recurrence and survival, are scarce.Between 1992 and 2011, 334 patients treated for HCC in noncirrhotic liver were identified from three major hepatobiliary centers. Clinicopathological characteristics were analyzed and independent predictors of recurrence and overall survival were identified using Cox proportional hazards models.Median patient age was 58 years and 77 % were male. Most patients had a solitary (81 %) and poorly or undifferentiated tumor (56 %); median size was 6.5 cm. The majority of patients (96 %) underwent liver resection (microscopically negative margins in 94 %), whereas a few had transarterial chemoembolization or transplantation (4 %). Median recurrence-free survival (RFS) was 2.5 years, and 1- and 5-year RFS was 71.1, and 35 %, respectively. Elevated alkaline phosphatase levels [hazards ratio (HR) = 1.82], poor tumor differentiation (HR = 1.4), macrovascular invasion (HR = 2.18), and the presence of satellite lesions (HR = 1.9), or intrahepatic metastases (HR = 2.59) were independently associated with shorter RFS; in contrast, an intact tumor capsule independently prolonged RFS (HR = 0.46). Median overall survival was 5.9 years, and 1- and 5-year overall survival was 86.9, and 54.5 %, respectively. Tumor size ≥5 cm (HR = 2.27), macrovascular (HR = 2.72) or adjacent organ invasion (HR = 3.34), and satellite lesions (HR = 2.18) were independently associated with shorter overall survival, whereas an intact tumor capsule showed a protective effect (HR = 0.51).Following resection of HCC in the setting of no cirrhosis, more than one-half of patients were alive after 5 years. However, even among patients with no cirrhosis, recurrence was common. Factors associated with RFS and overall survival included tumor characteristics, such as tumor capsule, satellite lesions, and vascular invasion.

The liver is one of the most common sites for metastatic disease, and optimal management of hepatic metastases often requires a multidisciplinary approach. Most commonly, liver metastases are derived from a colorectal or neuroendocrine primary tumor. Liver resection with curative intent is standard for resectable cases, but unfortunately most patients are not initially resectable because of the size, location, and/or extent of disease; inadequate remnant liver volume; or comorbidities. For patients with liver-limited or liver-dominant colorectal liver metastases (CRLM), the current challenges are to use different locoregional treatments to convert some borderline unresectable cases to resectable, and improve local control and overall survival. Although neuroendocrine liver metastases (NELM) may behave in a relatively indolent manner from an oncologic perspective, significant morbidity may be caused by excess hormone production when compared with metastatic liver disease from other primaries, and liver-directed treatment may be beneficial in reducing symptoms and perhaps extending survival. In the multidisciplinary management of patients with liver metastases, local therapies are especially important. Local approaches may be complementary (ie, portal vein embolization) or an alternative (ie, ablation, hepatic arterial infusion, selective radioembolization, and stereotactic body radiotherapy) to surgical resection. This article evaluates the available evidence on current regional strategies for managing patients with liver metastases, with an emphasis on CRLM and NELM, highlighting the clinical usefulness and limitations of each modality.

Objective Biomedical literature is increasingly enriched with literature reviews and meta-analyses. We sought to assess the understanding of statistical terms routinely used in such studies, among researchers. Methods An online survey posing 4 clinically-oriented multiple-choice questions was conducted in an international sample of randomly selected corresponding authors of articles indexed by PubMed. Results A total of 315 unique complete forms were analyzed (participation rate 39.4%), mostly from Europe (48%), North America (31%), and Asia/Pacific (17%). Only 10.5% of the participants answered correctly all 4 “interpretation” questions while 9.2% answered all questions incorrectly. Regarding each question, 51.1%, 71.4%, and 40.6% of the participants correctly interpreted statistical significance of a given odds ratio, risk ratio, and weighted mean difference with 95% confidence intervals respectively, while 43.5% correctly replied that no statistical model can adjust for clinical heterogeneity. Clinicians had more correct answers than non-clinicians (mean score ± standard deviation: 2.27±1.06 versus 1.83±1.14, p

Objective. To review the published evidence on technology-assisted liver resection regarding operative time, intraoperative bleeding, mortality, hospital stay, postoperative bile leak, and other outcomes. Method. A systematic review of clinical studies comparing liver resection using vessel sealing systems (VSSs—LigaSure), Cavitron Ultrasonic Surgical Aspirator (CUSA), or radiofrequency dissecting sealer (RFDS) with the conventional clamp-crushing technique (CC) was performed. Data for each modality were synthesized and individually compared with CC with the methodology of meta-analysis. Result. In all, 8 randomized controlled trials (RCTs) and 7 nonrandomized studies evaluating 1539 patients were included. Compared with CC, the VSS group (3 RCTs and 3 nonrandomized studies) had significantly lower blood loss by a mean of 109 mL (weighted mean difference [WMD] = −109; 95% confidence interval [CI] = −192, −26; data on 494 patients), lower risk for postoperative bile leak by 63% (odds ratio [OR] = 0.37; CI = 0.17, 0.78; 559 patients), and shorter total hospital stay by 2 days (WMD = −2.04; CI = −3.08, −1; 340 patients); no difference was noted for liver parenchyma transection time and mortality. No difference was noted between CUSA (4 RCTs and 1 nonrandomized study) or RFDS (3 RCTs and 3 nonrandomized studies) versus CC for any of the studied outcomes. Conclusion. Of the 3 modalities used in liver resection (VSS, CUSA, and RFDS), only VSS appeared to offer significant benefit over standard CC. However, the generalization of our findings is limited by the scarcity and clinical heterogeneity of the published studies. Large, well-designed and implemented RCTs are warranted to further investigate the usefulness of novel modalities used in liver resection.

Elderly individuals are more susceptible to excess summer heat. We sought to examine whether the use of cooling systems (air-conditioning or fan) affected the clinical outcomes of elderly febrile patients. We prospectively followed elderly (≥75 years old) febrile patients requesting the medical services of the SOS Doctors (a network of physicians performing house-call visits) from July 10 to August 20, 2011. Patients who used cooling systems (“users”) were compared with those who did not (“non-users”) regarding mortality, clinical outcome of primary illness (improvement or deterioration), and emergency hospitalization. Prospectively collected data were available for 339 individual elderly febrile patients. “Users” had lower mortality (10 % vs. 19 %, p < 0.05) than “non-users”; no difference was noted on clinical improvement (85 % vs. 76 %, p = 0.11) and emergency hospitalization rates (21 % vs. 30 %, p = 0.16). No difference was noted between users of air-conditioning and fan regarding mortality or clinical improvement, but fan use was associated with more hospitalizations (37 % vs. 19 %, p < 0.05). On multivariate analysis (assessing daily ambient temperature, use of cooling systems, patient age, and living conditions), the sole variable significantly associated with mortality was the non-use of cooling systems [odds ratio (OR): 2.18, 95 % confidence interval (CI): 1.06–4.50]. The use of air-conditioning or fan during hot summer periods appeared to be beneficial for elderly febrile patients living in a large city. Large prospective studies are warranted in order to provide further insight into potential individual and public health initiatives aiming to alleviate the impact of excess summer heat on the health of elderly patients.

In this era of increasing antimicrobial resistance, infections caused by multi-drug-resistant (MDR) gram-negative bacilli (GNB) are becoming more common and pose a challenge to all clinicians, including surgeons.We evaluated the epidemiology and antimicrobial sensitivities of GNB isolated from patients treated on surgical wards at the University Hospital of Heraklion, Crete, Greece, from 2004 to 2009. The MDR isolates were defined according to an international expert proposal supported by the U.S. Centers for Disease Control and Prevention and the European Centre for Disease Prevention and Control.A total of 1,153 GNB were isolated; 536 (46.5%) were MDR. The most common isolates were Escherichia coli (312 [27.8%]; MDR rate 50.2%), Pseudomonas aeruginosa (298 [25.8%]; MDR rate 39.6%), Acinetobacter baumannii (137 [11.9%]; MDR rate 83.9%), and Klebsiella pneumoniae (112 [9.7%]; MDR rate 44.6%). Most pathogens were isolated from patients hospitalized in the Departments of Surgical Oncology (32.3%), Orthopedic and Trauma Surgery (31.8%), General Surgery (18.1%), and Pediatric Surgery (15.5%). The clinical specimens comprised pus (45.1%), normally sterile fluids (22.5%), urine (16.8%), blood (6.3%), and other body fluids. Most effective in vitro against all MDR pathogens were colistin (83%), meropenem (57%), and imipenem-cilastatin (56%). The MDR P. aeruginosa was susceptible most often to colistin (94%) and aminoglycosides (tobramycin 56%, amikacin 55%), MDR A. baumannii only to colistin (94%), and MDR K. pneumoniae to meropenem (92%) and aminoglycosides (amikacin 76%, gentamicin 74%).In a region with a high prevalence of antibiotic resistance, almost one-half of GNB isolated from surgical patients were MDR. Surgeons may consider these developments to guide empiric antibiotic therapy for infections caused by gram-negative pathogens.

Although the vancomycin minimum inhibitory concentration (VMIC) susceptibility breakpoint for Staphylococcus aureus was recently lowered to ≤2 mg/L, it is argued that isolates in the higher levels of the susceptible range may bear adverse clinical outcomes. Clinical outcomes (all-cause mortality and treatment failure) of patients with S. aureus infections by 'high-VMIC' (conventionally defined as VMIC >1 mg/L but ≤2 mg/L) and 'low-VMIC' (VMIC≤1 mg/L) isolates were compared by performing a systematic review and meta-analysis. The effect of potential confounders was assessed by univariate meta-regression analyses. In total, 33 studies (6210 patients) were included. Most studies were retrospective (28/33), used the Etest (22/33) and referred to meticillin-resistant S. aureus (MRSA) infections (26/33) and bacteraemia (23/33). Irrespective of VMIC testing method, meticillin resistance and site of infection, the high-VMIC group had higher mortality [relative risk (RR)=1.21 (95% confidence interval 1.03-1.43); 4612 patients] and more treatment failures [RR=1.67 (1.26-2.21); 2049 patients] than the low-VMIC group. The results were not affected by the potential confounders and were reproduced in the subset of patients with MRSA infections [mortality, RR=1.19 (1.02-1.40), 2956 patients; treatment failure, RR=1.69 (1.26-2.25), 1793 patients]. In conclusion, infection by vancomycin-susceptible S. aureus with VMIC>1mg/L appears to be associated with higher mortality than VMIC≤1mg/L. Further research is warranted to verify these results and to assess the impact of VMIC on meticillin-susceptible S. aureus infections. Evaluation of alternative antimicrobial agents also appears justified.

The presence of extra-hepatic disease (EHD) is no longer an absolute contraindication to surgery in patients with colorectal liver metastases (CRLM). Recently, a novel prognostic model predicting overall survival in such patients was proposed using five risk factors (EHD other than isolated lung metastases, CEA ≥10 ng/ml,5 liver metastases, right colon as the primary CRC location, and diagnosis of EHD concomitant to CRLM recurrence). A bi-institutional database was used to perform an external validation of this model.Ninety-seven patients operated for CRLM and EHD between 1982 and 2011 in two institutions was analyzed. The proposed prognostic model was validated in this cohort using Cox proportional hazards models and the concordance index (c).Of the five proposed risk factors, only EHD other than isolated lung metastases was found to independently predict overall survival [Hazards Ratio (HR) = 2.10 (95% CI: 1.01-4.40)]. Although, the number of risk factors was marginally associated with overall survival in univariate analysis (P = 0.049), the performance of the proposed prognostic model was poor when applied to our cohort (c = 0.64).The examined prognostic model of survival in patients with CRLM and EHD had poor performance. Further research is warranted to delineate the subset of patients who will benefit from surgery.

Background Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver tumor presenting earlier in life than nonfibrolamellar hepatocellular carcinoma (NFL-HCC), with distinct epidemiologic and clinical characteristics. Although FLC is believed to have a better prognosis than NFL-HCC, data on treatment and prognosis are scarce. We performed a systematic review to investigate treatment options and clinical outcomes of patients with FLC. Study Design The study is a systematic review of the literature and pooled analysis of individual patient data. Results A total of 35 series were analyzed, reporting on 575 patients (52% female, elevated alpha-fetoprotein in 10%, cirrhosis in 3%, hepatitis B in 2%), most of whom were treated with partial hepatectomy (55%) or orthotopic liver transplantation (23%). Nineteen studies provided data on 206 individual patients with a median age of 21 years and tumor size of 12 cm. Median overall survival (OS) was 39 months; 1-year, 3-year, and 5-year OS rates were 85%, 53%, and 44%, respectively. For patients treated with liver resection, median OS was 18.5 years and 1-year, 3-year, and 5-year OS were 93%, 80%, and 70%, respectively. Based on data from 15 studies, FLC appeared to follow a relatively indolent course compared with NFL-HCC. Conclusions Patients with FLC treated with partial hepatectomy have excellent long-term survival, with 5-year overall survival reaching 70%. Patients fared worse with the use of other therapeutic options including chemotherapy, intra-arterial therapy, and transplantation, although data directly comparing resection vs transplantation were limited.

Introduction The epidemiology and antibiotic resistance of Staphylococcus aureus have evolved, underscoring the need for novel antibiotics, particularly against methicillin-resistant S. aureus (MRSA). Telavancin is a bactericidal lipoglycopeptide with potent activity against Gram-positive pathogens. Objective To systematically review and synthesize the available evidence from randomized controlled trials (RCTs) evaluating telavancin in the treatment of patients with infections due to Gram-positive organisms with the methodology of meta-analysis. Results Six RCTs comparing telavancin with vancomycin were included; 4 (2229 patients) referred to complicated skin and soft tissue infections (cSSTIs) and 2 (1503 patients) to hospital-acquired pneumonia (HAP). Regarding cSSTIs, telavancin and vancomycin showed comparable efficacy in clinically evaluable patients (odds ratio [OR] = 1.10 [95% confidence intervals: 0.82–1.48]). Among patients with MRSA infection, telavancin showed higher eradication rates (OR = 1.71 [1.08–2.70]) and a trend towards better clinical response (OR = 1.55 [0.93–2.58]). Regarding HAP, telavancin was non-inferior to vancomycin in terms of clinical response in two Phase III RCTs; mortality rates for the pooled trials were comparable with telavancin (20%) and vancomycin (18.6%). Pooled data from cSSTIs and HAP studies on telavancin 10 mg/kg indicated higher rates of serum creatinine increases (OR = 2.22 [1.38–3.57]), serious adverse events (OR = 1.53 [1.05–2.24]), and adverse event-related withdrawals (OR = 1.49 [1.14–1.95]) among telavancin recipients. Conclusion Telavancin might be an alternative to vancomycin in cases of difficult-to-treat MRSA infections. The potent antistaphylococcal activity of telavancin should be weighted against the potential for nephrotoxicity.

Immunization during pregnancy has the potential to protect the mother and the newborn from preventable diseases. Current recommendations suggest that inactivated vaccines might be considered during pregnancy when the benefits outweigh the risks. In this review, we aimed to evaluate the safety of hepatitis B (HB) vaccine, pneumococcal polysaccharide vaccine (PPSV) and meningococcal polysaccharide vaccine (MPSV) administration during pregnancy by systematically reviewing the available evidence in PubMed and Scopus databases, as well as postmarketing surveillance data (including the Vaccine Adverse Event Reporting System [VAERS] database). A total of 18 studies were eligible for inclusion in the review. Six studies provided data on HB vaccine, six on PPSV and three on MPSV; three additional studies compared PPSV with MPSV. Additionally, 91 reports on vaccinations of pregnant women were identified from postmarketing surveillance data (88 on HB vaccine, 2 on PPSV, 1 on MPSV). The most common complaints were local reactions, including tenderness and swelling. Overall, immunization during pregnancy did not seem to be associated with a teratogenic effect on the fetus, preterm labour or spontaneous abortion. However, the lack of randomized, placebo-controlled trials, or even large cohort studies, in addition to the inherent limitations of the reviewed observational studies with small statistical power, precluded safe conclusions. Large, prospective, population-based cohort studies are needed to elucidate this issue.

Mesh infection, although infrequent, is a devastating complication of mesh hernioplasties. The aim of this study was to systematically review and synthesize the available evidence on risk factors for synthetic mesh infection after hernioplasty. A systematic search was performed in PubMed and Scopus databases. The extracted data were synthesized with the methodology of meta-analysis. We identified six eligible studies that reported on 2,418 mesh hernioplasties. The crude mesh infection rate was 5%. Statistically significant risk factors were smoking (risk ratio [RR] = 1.36 [95% confidence interval (CI): 1.07, 1.73]; 1,171 hernioplasties), American Society of Anesthesiologists (ASA) score ≥3 (RR = 1.40 [1.15, 1.70]; 1,682 hernioplasties), and emergency operation (RR = 2.46 [1.56, 3.91]; 1,561 hernioplasties). Also, mesh infections were significantly correlated with patient age (weighted mean difference [WMD] = 2.63 [0.22, 5.04]; 2,364 hernioplasties), ASA score (WMD = 0.23 [0.08, 0.38]; 1,682 hernioplasties), and the duration of the hernioplasty (WMD = 44.92 [25.66, 64.18]; 833 hernioplasties). A trend toward higher mesh infection rates was observed in obese patients (RR = 1.41 [0.94, 2.11]; 2,243 hernioplasties) and in patients operated on by a resident (in contrast to a consultant; RR = 1.18 [0.99, 1.40]; 982 hernioplasties). Mesh infections usually resulted in mesh removal, and common pathogens included Staphylococcus spp., Enterococcus spp., and gram-negative bacteria. Patient age, ASA score, smoking, and the duration and emergency setting of the operation were found to be associated with the development of synthetic mesh infection. The heterogeneity of the available evidence should be taken under consideration. Prospective studies with a meticulous follow-up are warranted to further investigate mesh-related infections.

Objective To study the effectiveness and safety of vancomycin compared with that of other antibiotics for the treatment of gram-positive infections. Methods Major electronic databases were searched. Data from published randomized controlled trials (January 1, 1950, to September 15, 2011) were pooled using a meta-analytic method. Results Fifty-three trials comparing vancomycin with linezolid, daptomycin, quinupristin-dalfopristin, tigecycline, ceftaroline, ceftobiprole, telavancin, teicoplanin, iclaprim, and dalbavancin were included in the meta-analysis. Individual antibiotics were as effective as vancomycin, except for linezolid, which was more effective than vancomycin for the treatment of skin and soft tissue infections (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.07-2.43). Comparators were as effective as vancomycin in the intent-to-treat population (OR, 1.08; 95% CI, 0.98-1.18) but were more effective in the clinically evaluable population (OR, 1.14; 95% CI, 1.02-1.27) when all infections were pooled. When available data from all trials were pooled, no differences were noted when patients with febrile neutropenia (OR, 1.07; 95% CI, 0.82-1.39), pneumonia (OR, 1.10; 95% CI, 0.87-1.37), bacteremia (OR, 1.05; 95% CI, 0.76-1.45), and skin and soft tissue infections (OR, 1.11; 95% CI, 0.89-1.39) were studied. Comparators were more effective in open-label (OR, 1.28; 95% CI, 1.08-1.50) but not in double-blind trials (OR, 1.04; 95% CI, 0.90-1.20). Total adverse events attributed to studied antibiotics (OR, 1.07; 95% CI, 0.90-1.28) and patients withdrawn from trials (OR, 0.86; 95% CI, 0.68-1.09) were similar in the compared groups. Mortality was not different between vancomycin and comparator antibiotics when all trials were included in the analysis (OR, 1.09; 95% CI, 0.96-1.23). Comparators were associated with higher mortality in open-label (OR, 1.27; 95% CI, 1.05-1.54) but not double-blind trials (OR, 0.96; 95% CI, 0.80-1.14). Conclusion On the basis mainly of data from open-label trials, vancomycin is a treatment choice that is as effective as other available antibiotics for patients with gram-positive infections. Study design seems to make a major contribution to the outcome.

Atelectasis is considered to be the most common cause of early postoperative fever (EPF) but the existing evidence is contradictory. We sought to determine if atelectasis is associated with EPF by analyzing the relevant published evidence.We performed a systematic search in PubMed and Scopus databases to identify studies examining the association between atelectasis and EPF.A total of eight studies, including 998 cardiac, abdominal, and maxillofacial surgery patients, were eligible for analysis. Only two studies specifically examined our question, and six additional articles reported sufficient data to be included. Only one study reported a significant association between postoperative atelectasis and fever, whereas the remaining studies indicated no such association. The performance of EPF as a diagnostic test for atelectasis was also assessed, and EPF performed poorly (pooled diagnostic OR, 1.40; 95% CI, 0.92-2.12). The significant heterogeneity among the studies precluded a formal metaanalysis.The available evidence regarding the association of atelectasis and fever is scarce. We found no clinical evidence supporting the concept that atelectasis is associated with EPF. More so, there is no clear evidence that atelectasis causes fever at all. Large studies are needed to precisely evaluate the contribution of atelectasis in EPF.