Meta-analysis of lower perioperative blood glucose target levels for reduction of surgical-site infection.

BACKGROUND: There is a clear association between hyperglycaemia and surgical-site infection (SSI). Intensive glucose control may involve a risk of hypoglycaemia, which in turn results in potentially severe complications. A systematic review was undertaken of studies comparing intensive versus conventional glucose control protocols in relation to reduction of SSI and other outcomes, including hypoglycaemia, mortality and stroke. METHODS: PubMed, Embase, CENTRAL, CINAHL and WHO databases from 1 January 1990 to 1 August 2015 were searched. Inclusion criteria were RCTs comparing intensive with conventional glucose control protocols, and reporting on the incidence of SSI. Meta-analyses were performed with a random-effects model, and meta-regression was subsequently undertaken. Targeted blood glucose levels, achieved blood glucose levels, and important adverse events were summarized. RESULTS: Fifteen RCTs were included. The summary estimate showed a significant benefit for an intensive compared with a conventional glucose control protocol in reducing SSI (odds ratio (OR) 0·43, 95 per cent c.i. 0·29 to 0·64; P < 0·001). A significantly higher risk of hypoglycaemic events was found for the intensive group compared with the conventional group (OR 5·55, 2·58 to 11·96), with no increased risk of death (OR 0·74, 0·45 to 1·23) or stroke (OR 1·37, 0·26 to 7·20). These results were consistent both in patients with and those without diabetes, and in studies with moderately strict and very strict glucose control. CONCLUSION: Stricter and lower blood glucose target levels of less than 150 mg/dl (8·3 mmol/l), using an intensive protocol in the perioperative period, reduce SSI with an inherent risk of hypoglycaemic events but without a significant increase in serious adverse events.

Comparison of Imaging Strategies with Conditional versus Immediate Contrast-Enhanced Computed Tomography in Patients with Clinical Suspicion of Acute Appendicitis.

OBJECTIVES: To compare the diagnostic accuracy of conditional computed tomography (CT), i.e. CT when initial ultrasound findings are negative or inconclusive, and immediate CT for patients with suspected appendicitis. METHODS: Data were collected within a prospective diagnostic accuracy study on imaging in adults with acute abdominal pain. All patients underwent ultrasound and CT, read by different observers who were blinded from the other modality. Only patients with clinical suspicion of appendicitis were included. An expert panel assigned a final diagnosis to each patient after 6 months of follow-up (clinical reference standard). RESULTS: A total of 422 patients were included with final diagnosis appendicitis in 251 (60 %). For 199 patients (47 %), ultrasound findings were inconclusive or negative. Conditional CT imaging correctly identified 241 of 251 (96 %) appendicitis cases (95 %CI, 92 % to 98 %), versus 238 (95 %) with immediate CT (95 %CI, 91 % to 97 %). The specificity of conditional CT imaging was lower: 77 % (95 %CI, 70 % to 83 %) versus 87 % for immediate CT (95 %CI, 81 % to 91 %). CONCLUSION: A conditional CT strategy correctly identifies as many patients with appendicitis as an immediate CT strategy, and can halve the number of CTs needed. However, conditional CT imaging results in more false positives. KEY POINTS: • Conditional CT (CT after negative/inconclusive ultrasound findings) can be used for suspected appendicitis. • Half the number of CT examinations is needed with a conditional strategy. • Conditional CT correctly identifies as many patients with appendicitis as immediate CT. • Conditional imaging results in more false positive appendicitis cases.

Systematic review and meta-analysis of the open abdomen and temporary abdominal closure techniques in non-trauma patients.

BACKGROUND: Several challenging clinical situations in patients with peritonitis can result in an open abdomen (OA) and subsequent temporary abdominal closure (TAC). Indications and treatment choices differ among surgeons. The risk of fistula development and the possibility to achieve delayed fascial closure differ between techniques. The aim of this study was to review the literature on the OA and TAC in peritonitis patients, to analyze indications and to assess delayed fascial closure, enteroatmospheric fistula and mortality rate, overall and per TAC technique. METHODS: Electronic databases were searched for studies describing the OA in patients of whom 50% or more had peritonitis of a non-traumatic origin. RESULTS: The search identified 74 studies describing 78 patient series, comprising 4,358 patients of which 3,461 (79%) had peritonitis. The overall quality of the included studies was low and the indications for open abdominal management differed considerably. Negative pressure wound therapy (NPWT) was the most frequent described TAC technique (38 of 78 series). The highest weighted fascial closure rate was found in series describing NPWT with continuous mesh or suture mediated fascial traction (6 series, 463 patients: 73.1%, 95% confidence interval 63.3-81.0%) and dynamic retention sutures (5 series, 77 patients: 73.6%, 51.1-88.1%). Weighted rates of fistula varied from 5.7% after NPWT with fascial traction (2.2-14.1%), 14.6% (12.1-17.6%) for NPWT only, and 17.2% after mesh inlay (17.2-29.5%). CONCLUSION: Although the best results in terms of achieving delayed fascial closure and risk of enteroatmospheric fistula were shown for NPWT with continuous fascial traction, the overall quality of the available evidence was poor, and uniform recommendations cannot be made.

Systematic review and meta-analysis of somatostatin analogues for the treatment of pancreatic fistula.

BACKGROUND: Somatostatin analogues are used for the treatment of pancreatic fistula, with the aim of achieving fistula closure or reduction of output. METHOD: MEDLINE, Embase and Cochrane databases were searched systematically for relevant articles followed by hand-searching of reference lists. Data on patient recruitment, intervention and outcome were extracted and meta-analysis performed where reasonable. RESULTS: Seven randomized clinical trials met the inclusion criteria and included a total of 297 patients with fistulas of the gastrointestinal tract; of these, 102 patients had fistulas of pancreatic origin. Pooling of closure rates showed no significant difference between patients treated with somatostatin analogues compared with controls: odds ratio 1·52 (95 per cent confidence interval 0·88 to 2·61). Owing to inconsistent descriptions, pooling of results was not possible for other endpoints, such as time to fistula closure. CONCLUSION: There is no solid evidence that somatostatin analogues result in a higher closure rate of pancreatic fistula compared with other treatments.

Population preference for treatment of uncomplicated appendicitis.

BACKGROUND: Non-operative treatment of uncomplicated appendicitis is safe and increasing in popularity, but has other risks and benefits compared with appendicectomy. This study aimed to explore the preference of the general population regarding operative or antibiotic treatment of uncomplicated appendicitis. METHODS: In this prospective study, a clinical scenario and questionnaire were submitted to a panel comprising a sample of an average adult population. The survey was distributed by an independent, external research bureau, and included a comprehensive explanation of the risks and benefits of both treatment options. The primary outcome was the proportion of participants who would prefer antibiotics over surgery. Secondary outcomes were reasons for this preference and the accepted recurrence rate within 1 year when treated with antibiotics only. All outcomes were weighted for the average Dutch population. RESULTS: Of 254 participants, 49.2 per cent preferred antibiotic treatment for uncomplicated appendicitis, 44.5 per cent preferred surgery, and 6.3 per cent could not make a decision. About half of the participants preferring antibiotics would accept a recurrence risk of more than 50 per cent within 1 year. Avoiding surgery was their main reason. In participants preferring surgery, many tolerated a recurrence risk of no more than 10 per cent when treated with antibiotics. Removal of the cause of appendicitis was their main reason. CONCLUSION: Around half of the average population sample preferred antibiotics over surgical treatment of uncomplicated appendicitis and were willing to accept a high recurrence risk to avoid surgery initially. Participants who preferred surgery tolerated only a very low recurrence risk with antibiotic treatment.

Discriminating complicated from uncomplicated appendicitis by ultrasound imaging, computed tomography or magnetic resonance imaging: systematic review and meta-analysis of diagnostic accuracy.

BACKGROUND: Discriminating complicated from uncomplicated appendicitis is crucial. Patients with suspected complicated appendicitis are best treated by emergency surgery, whereas those with uncomplicated appendicitis may be treated with antibiotics alone. This study aimed to obtain summary estimates of the accuracy of ultrasound imaging, CT and MRI in discriminating complicated from uncomplicated appendicitis. METHODS: A systematic literature review was conducted by an electronic search in PubMed, Embase and the Cochrane Library for studies describing the diagnostic accuracy of complicated versus uncomplicated appendicitis. Studies were included if the population comprised adults, and surgery or pathology was used as a reference standard. Risk of bias and applicability were assessed with QUADAS-2. Bivariable logitnormal random-effect models were used to estimate mean sensitivity and specificity. RESULTS: Two studies reporting on ultrasound imaging, 11 studies on CT, one on MRI, and one on ultrasonography with conditional CT were included. Summary estimates for sensitivity and specificity in detecting complicated appendicitis could be calculated only for CT, because of lack of data for the other imaging modalities. For CT, mean sensitivity was 78 (95 per cent c.i. 64 to 88) per cent, and mean specificity was 91 (85 to 99) per cent. At a median prevalence of 25 per cent, the positive predictive value of CT for complicated appendicitis would be 74 per cent and its negative predictive value 93 per cent. CONCLUSION: Ultrasound imaging, CT and MRI have limitations in discriminating between complicated and uncomplicated appendicitis. Although CT has far from perfect sensitivity, its negative predictive value for complicated appendicitis is high.

Characterization of activating mutations of NOTCH3 in T-cell acute lymphoblastic leukemia and anti-leukemic activity of NOTCH3 inhibitory antibodies.

Notch receptors have been implicated as oncogenic drivers in several cancers, the most notable example being NOTCH1 in T-cell acute lymphoblastic leukemia (T-ALL). To characterize the role of activated NOTCH3 in cancer, we generated an antibody that detects the neo-epitope created upon gamma-secretase cleavage of NOTCH3 to release its intracellular domain (ICD3), and sequenced the negative regulatory region (NRR) and PEST (proline, glutamate, serine, threonine) domain coding regions of NOTCH3 in a panel of cell lines. We also characterize NOTCH3 tumor-associated mutations that result in activation of signaling and report new inhibitory antibodies. We determined the structural basis for receptor inhibition by obtaining the first co-crystal structure of a NOTCH3 antibody with the NRR protein and defined two distinct epitopes for NRR antibodies. The antibodies exhibit potent anti-leukemic activity in cell lines and tumor xenografts harboring NOTCH3 activating mutations. Screening of primary T-ALL samples reveals that 2 of 40 tumors examined show active NOTCH3 signaling. We also identified evidence of NOTCH3 activation in 12 of 24 patient-derived orthotopic xenograft models, 2 of which exhibit activation of NOTCH3 without activation of NOTCH1. Our studies provide additional insights into NOTCH3 activation and offer a path forward for identification of cancers that are likely to respond to therapy with NOTCH3 selective inhibitory antibodies.

Gemcitabine and cisplatin as induction regimen for patients with biopsy-proven stage IIIA N2 non-small-cell lung cancer: a phase II study of the European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group (EORTC 08955).

PURPOSE: Our objective was to better define the activity/feasibility of gemcitabine/cisplatin (GC) as induction chemotherapy in patients with stage IIIA N2 non-small-cell lung cancer (NSCLC) followed by surgery or radiotherapy within a large, ongoing comparative study (EORTC 08941). PATIENTS AND METHODS: Forty-seven chemotherapy-naive patients with NSCLC, median age of 58 years, stage IIIA N2 disease, World Health Organization performance status of 0 or 1, and the ability to tolerate a pneumonectomy received gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 and cisplatin 100 mg/m(2) on day 2, every 4 weeks. Patients received induction chemotherapy (three cycles) before re-evaluation and randomization to surgery or radiotherapy. RESULTS: Grade 3/4 thrombocytopenia, the main hematologic toxicity, occurred in 60% of patients but was not associated with bleeding. Full-dose gemcitabine was given in 48% of the courses. Severe nonhematologic toxicity was uncommon. Two patients with preexisting, autoimmune pulmonary fibrosis had deterioration of pulmonary function after radiotherapy. Thirty-three (70.2%; 95% confidence interval, 55.1% to 82.7%) of the 47 eligible patients had objective responses (three complete responses and 30 partial responses). Mediastinal nodes were tumor-free after induction therapy in 53% of cases. Resections were considered complete in 71% of the patients who underwent thoracotomy after induction therapy. Median survival for all recruited patients (N = 53) was 18.9 months, with an estimated 1-year survival rate of 69%. CONCLUSION: In patients with N2 stage IIIA NSCLC, GC is a highly active and well-tolerated induction regimen. GC should be explored in combination with surgery or radiotherapy in stage I and II patients.

Congenital gastric teratoma in Wiedemann-Beckwith syndrome.

Wiedemann-Beckwith syndrome (WBS) may be associated with abdominal tumors, including Wilms tumor, adrenocortical carcinoma, hepatoblastoma, gonadoblastoma, rhabdomyosarcoma, and neuroblastoma. We report on a newborn infant with WBS and a congenital teratoma of the stomach. This is the sole report of any teratoma being associated with WBS and also the first report of a tumor present at birth and visible prenatally in WBS. At birth this infant boy had the diagnostic findings of WBS with macroglossia, ear lobule creases and pits, nevus flammeus, and omphalocele, and an abdominal mass. Abnormalities were detected prenatally when ultrasound examination showed placental overgrowth, polyhydramnios, omphalocele, and posterior abdominal calcifications. Resection of the mass and partial gastrectomy were performed at age 10 days; histologic study showed an immature grade-II teratoma containing a mixture of mature and immature tissues from all germ layers. Results of cytogenetic studies of blood and teratoma were normal (46,XY). This congenital gastric teratoma in a newborn boy with classical WBS may represent either a tumor or an included twin. We discuss its implications for the association of WBS with neoplasia and monozygotic (MZ) twinning, review various neoplasias associated with WBS, and consider pathogenetic mechanisms.

Long term survival of a patient with malignant pleural mesothelioma as a late complication of radiotherapy for Hodgkin's disease treated with 90yttrium-silicate.

A case of malignant pleural mesothelioma (PM) 24 years after thoracic radiotherapy for Hodgkin's disease is presented. As primary treatment and to relieve symptoms of dyspnea secondary to pleural effusion a thoracic drain was installed, followed by intracavitary radiation therapy with 90yttrium-silicate. Minor complaints of fever and a dry cough as a side-effect of this treatment were effectively treated with prednisone during 2 weeks. The patient remains in a good clinical condition now 6 years after diagnosis. Considering the few therapeutic options the use of 90yttrium-silicate intrapleural installation could be propagated as a safe and effective antitumour treatment for a selected group of patients with malignant PM.

Infusions of lidocaine into the amygdala, but not the preoptic area, block pseudopregnancy in the rat.

In the rat, vaginocervical stimulation (VCS) received during mating is required for the subsequent expression of 10-12 days of twice-daily prolactin surges that are necessary for pregnancy or pseudopregnancy (PSP). This temporal separation of sensory stimulus and neuroendocrine response suggests that a mnemonic of the vaginocervical stimulation is created in the brain that triggers and sustains the daily prolactin surges. We investigated the possible involvement of the medial preoptic area (mPOA) and the medial amygdala (mAMYG) as potential neural sites involved in the processing of this neuroendocrine arc. Cycling female rats were bilaterally implanted with intracerebral cannulae in either the mPOA or mAMYG. On proestrus, females were manually palpated to confirm sexual receptivity and then received bilateral infusions of either the local anesthetic lidocaine, the Ca(++) channel blocker, verapamil, or phosphate-buffered saline (PBS) into either brain site before or both before and after receipt of 15 intromissions from an experienced male. Unmated control females received comparable infusions of lidocaine or verapamil, and were placed in the empty test arena for 10 min. Infusions consisted of either a single bilateral infusion 15 min before mating (Expt. 1), bilateral infusions both 15 min before and after mating (Expt. 2) or eight bilateral infusions separated by 30 min intervals spanning a period beginning 45 min before and ending 2 h 45 min after mating (Expt. 3). None of the lidocaine infusions into the mPOA prevented the establishment of PSP, and neither verapamil infusions into the mAMYG nor the shorter-term neural block (i.e. single or double lidocaine infusions) of the mAMYG prevented mating-induced PSP. However, the longer-term neural block (i.e. multiple lidocaine infusions) of the mAMYG significantly reduced the incidence of PSP. These data support previous findings that the mAMYG receives sensory input from VCS, and suggest that the mAMYG is a site at which a mnemonic of VCS is established.

Efficacy of HFA-beclomethasone dipropionate extra-fine aerosol (800 microg day(-1)) versus HFA-fluticasone propionate (1000 microg day(-1)) in patients with asthma.

Hydrofluoroalkane-134a beclomethasone dipropionate (HFA-BDP) extra-fine aerosol and HFA-fluticasone propionate (HFA-FP) are chlorofluorocarbon-free inhalers. We conducted an 8-week, open study to demonstrate the equivalence of HFA-BDP (800 microg day(-1)) and HFA-FP (1000 microg day(-1)) in moderate to severe asthma. Symptomatic patients on 500-1000 microg day(-1) CFC-BDP (or equivalent) and short-acting beta-agonist, were randomized to HFA-BDP (n = 101) or HFA-FP (n = 97) after 7-14 (+/-2) day run-in. In the intent-to-treat (ITT) population (n = 198), both treatments provided clinically and statistically significant improvements in asthma control, with increases in peak expiratory flow in the morning (AM PEF) and asthma symptoms (within treatment analysis P<0.05). Mean (SE) change in AM PEF from baseline at week 8 was equivalent (defined as 90% CI for the mean difference between treatments within +/-25 l min(-1)) in the two groups: 29.59 (5.19) l min(-1) for HFA-BDP vs. 17.3 (5.45) l min(-1) for HFA-FP (90% CI-0.02, 24.91). For the perprotocol population (n = 121), the mean (SE) change in AM PEF from baseline was not equivalent; AM PEF improved to a significantly greater extent in the HFA-BDP group than HFA-FP group [34.84 (7.08) vs. 20.63 (7.32) l min(-1) P<0.01; 90% CI; 2.66, 31.10]. At week 8 in the ITT population, there were no statistically significant differences in FEV1, beta-agonist use, asthma symptom/sleep disturbance scores, or percentage of days without asthma symptoms/sleep disturbance. There was a significantly greater reduction from baseline in mean eosinophil count for HFA-BDP compared with HFA-FP at weeks 3 and 8 (P<0.01), and eosinophil cationic protein value at week 8 (P<0.01). Both treatments were well tolerated and there were no statistically significant differences in urinary cortisol creatinine parameters. In conclusion, this study showed that, in patients with moderate-to-severe symptomatic asthma, HFA-BDP extra-fine aerosol 800 microg(-1) was at least as effective and equally well tolerated as 1000 microg day(-1) HFA-FP.

Treating problem-solving deficits on an acute care psychiatric inpatient unit.

Neuropsychological deficits in problem-solving are commonly found in patients with schizophrenia and severe affective disorders. However, in an acute care setting, treatment efforts do not typically target these deficits, even though they can impede recovery. This study aimed to evaluate the effectiveness of short-term problem-solving remediation in acutely ill psychiatric inpatients. Twenty-eight psychiatric inpatients identified as having a verbal problem-solving deficit received 6 h of either verbal problem-solving remediation or placebo instruction. Before and after treatment a nurse rated the patient's psychiatric status and the patient completed verbal and nonverbal problem-solving tests, and a self-report rating of symptoms and ability to cope with symptoms. Both groups of patients improved on the measure of verbal problem solving, but those receiving problem-solving remediation improved significantly more. Both groups made symptomatic improvement, but the patients receiving problem-solving remediation made significantly more improvement on the measure of coping ability and the nurses rated them as more improved, both psychiatrically and with regard to coping skills. Verbal problem-solving deficits are responsive to short-term remediation in an acute care setting, and treatment effects may generalize to improve ability to cope with psychiatric symptoms.

The use of lasers in pediatric surgery.

This report is a condensation of the Fred McLoed Lecture given at the Annual Meeting of the Canadian Association of Paediatric Surgeons. It briefly cites the basic fundamentals of lasers, the characteristics of those used in surgery, and their delivery systems. The advantages of laser surgery include the sealing of blood vessels, lymphatics, and nerve ends when used for cutting. This results in a relatively dry field of surgery and less postoperative pain. There is reduced opportunity for contaminants in a clean wound, and no spreading of infection in a contaminated one. Surgery can be carried out in confined areas in a drier field of view, and can be brought to small areas by fiberoptic cables. Highly precise and localized microsurgery is possible. The use of lasers is indicated in operations where significant blood loss is expected and in patients with bleeding tendencies. It is useful in surgery for malignant disease and through highly infected tissue. Other general indications are discussed. Specific surgical procedures where lasers have been useful include treatment of hemangiomas, surgery of the tongue, repair of pectus excavatum, partial splenectomy and splenic repair, hepatic lobectomy and hepatic repair, and resection of adrenal tumors. Lasers have also been useful in partial nephrectomy, excision biopsy, revision or closure of ileostomy or colostomy, endorectal mucosectomy, posterior sagittal anorectoplasty, treatment of condyloma acuminata, burn wound debridement, and infected tissue debridement. Anticipated uses include vascular, biliary tract, and intestinal repair and anastomoses, and photodynamic therapy (PDT) of neoplasms.

Diagnosis and surgical management of "H-type" tracheoesophageal fistula in infants and children.

By means of the new rod lens telescopic endoscopes, the diagnosis of H- or N-type tracheoesophageal fistula in infants and children can now be made definitively without the difficulties and complications previously described, and the numerous methods recommended in the literature, all of which have their inconsistensies, failures, errors, and dangers. Using these advanced endoscopes the fistula is demonstrated by bronchoscopy, a small Fogarty catheter is threaded through the opening in the trachea under direct view of the telescope and passed through the fistula into the esophagus. The balloon is inflated and the bronchoscope removed, leaving the catheter in place. A proper incision is then made in the neck or chest, depending on the location of the lesion, and the fistulous tract is quickly located by palpation of the balloon and catheter. Then with minimal and accurate dissection, correction is carried out.

Successful surgical repair of iatrogenic lung perforation in a neonate.

Iatrogenic lung perforation during closed tube thoracostomy for pneumothorax in neonates apparently occurs with disturbing frequency. This potentially lethal complication may be minimized by strict adherence to proper technique. In addition, an added margin of safety may be established by allowing some air to remain in the pleural space prior to placement of a chest tube. If iatrogenic perforation of the lung occurs despite appropriate precautions, surgical intervention may be indicated.

Hemangiomatosis of the pleura with hemorrhage and disseminated intravascular coagulation.

Hemangiomatosis involving the pleura is a rare cause of bloody pleural effusion in the neonate. When congestive heart failure and consumption coagulopathy are associated, the prognosis is particularly grave. Corticosteroids and radiation therapy have been reported to shrink hemangiomas. We present such a case in a 2.5-mo-old whose condition did not appear to respond to prednisone or radiation therapy but resolved quickly when cyclophosphamide was given. In this case cyclophosphamide appeared to be life saving.

The antepartum diagnosis of conjoined twins.

This is a case report in which the diagnosis of conjoined twins was made in a woman by ultrasonography in her eigth month of pregnancy. With this diagnosis, the mother-to-be was transported to a hospital with sophisticated obstetrical, neonatal, and pediatric surgical facilities. The twins were delivered by elective caesarian section and were seen to have anomalies requiring immediate surgery. Following stabilization and basic investigations, surgery was performed on the infants at 3 hr of age. This resulted in a condition that permitted a thorough postoperative work-up and elective separation several months later.

Mesenchymal hamartoma of the liver responsive to cyclophosphamide therapy: therapeutic approach.

A newborn infant is described with a highly vascular hepatic mesenchymal hamartoma causing hydrops fetalis, congestive heart failure, and consumption coagulopathy. There was a remarkable response of this life-threatening condition to cyclophosphamide therapy. A review of the various alternative therapeutic modalities is presented.

A new look at pediatric endoscopy.

As a result of recent developments in instrumentation, most endoscopic procedures can now be carried out safely in infants and children in less time and with less trauma than previously. In pediatric applications, laparoscopy is possible for the first time, bronchoscopy and esophagoscopy are greatly improved, and urethrocystoscopy can be done with accuracy and dispatch. Small flexible endoscopes have been evaluated for gastroduodenoscopy and colonoscopy.