Prospective validation of classification of intraoperative adverse events (ClassIntra): international, multicentre cohort study.

OBJECTIVE: To prospectively assess the construct and criterion validity of ClassIntra version 1.0, a newly developed classification for assessing intraoperative adverse events. DESIGN: International, multicentre cohort study. SETTING: 18 secondary and tertiary centres from 12 countries in Europe, Oceania, and North America. PARTICIPANTS: The cohort study included a representative sample of 2520 patients in hospital having any type of surgery, followed up until discharge. A follow-up to assess mortality at 30 days was performed in 2372 patients (94%). A survey was sent to a representative sample of 163 surgeons and anaesthetists from participating centres. MAIN OUTCOME MEASURES: Intraoperative complications were assessed according to ClassIntra. Postoperative complications were assessed daily until discharge from hospital with the Clavien-Dindo classification. The primary endpoint was construct validity by investigating the risk adjusted association between the most severe intraoperative and postoperative complications, measured in a multivariable hierarchical proportional odds model. For criterion validity, inter-rater reliability was evaluated in a survey of 10 fictitious case scenarios describing intraoperative complications. RESULTS: Of 2520 patients enrolled, 610 (24%) experienced at least one intraoperative adverse event and 838 (33%) at least one postoperative complication. Multivariable analysis showed a gradual increase in risk for a more severe postoperative complication with increasing grade of ClassIntra: ClassIntra grade I versus grade 0, odds ratio 0.99 (95% confidence interval 0.69 to 1.42); grade II versus grade 0, 1.39 (0.97 to 2.00); grade III versus grade 0, 2.62 (1.31 to 5.26); and grade IV versus grade 0, 3.81 (1.19 to 12.2). ClassIntra showed high criterion validity with an intraclass correlation coefficient of 0.76 (95% confidence interval 0.59 to 0.91) in the survey (response rate 83%). CONCLUSIONS: ClassIntra is the first prospectively validated classification for assessing intraoperative adverse events in a standardised way, linking them to postoperative complications with the well established Clavien-Dindo classification. ClassIntra can be incorporated into routine practice in perioperative surgical safety checklists, or used as a monitoring and outcome reporting tool for different surgical disciplines. Future studies should investigate whether the tool is useful to stratify patients to the appropriate postoperative care, to enhance the quality of surgical interventions, and to improve long term outcomes of surgical patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03009929.

Preliminary evidence for an increased likelihood of a stable trajectory in mild cognitive impairment in individuals with higher motivational abilities.

BACKGROUND: Motivational abilities (MA), that describe skills in relation to goal-oriented behavior, have recently been found to be associated with neuropathological aging. Here we examine the impact of MA on the long-term course of mild cognitive impairment (MCI). METHODS: We followed-up N = 64 individuals diagnosed with MCI (Mage = 73 years, 44% female) for 3 years. MA were assessed by long-term informants of the participants using two scales: motivation and decision regulation [Volitional Components Questionnaires, VCQ, (Kuhl and Fuhrmann, Decomposing self-regulation and self-control: the volitional components inventory, 1998)]. Cognitive abilities were assessed with the Mini Mental State Examination (J Psychiatr Res 12:189-98, 1975). Survival analyses and multilevel modeling (MLM) were applied to determine the predicting effect of informant-rated MA at baseline on the likelihood of MCI stability and on the trajectory of cognitive abilities. RESULTS: Fifty percent (n = 32) of the MCI participants remained stable, while 32.8% (n = 21) and 17.2% (n = 11) converted to Alzheimer's disease (AD) or dropped-out, respectively. Survival analyses revealed that MCI cases with higher-rated MA at baseline were more likely to exert a stable course in MCI over 3 years (p = 0.036) when controlling for demographic characteristics and executive function. MLM analyses indicated that higher informant-rated MA at baseline were significantly related to higher cognitive abilities, even when controlling for MCI subtype (p = 0.030). CONCLUSIONS: This study provides preliminary longitudinal evidence for a lower risk of conversion to AD and higher cognitive abilities by higher rated MA at an early stage of MCI.

Spontaneous right whole-lung torsion secondary to bronchial carcinoma: a case report.

BACKGROUND: Spontaneous whole lung torsion is an absolut rarity and most cases occur after previous surgery. CASE PRESENTATION: We present the case of a spontaneous whole-lung torsion in a 82-year old man. The patient was referred to our thoracic surgery department from the emergency department of a referring hospital with rapidly progressive dyspnea. CT-scan revealed a 180° degree counterclockwise torsion of the entire right lung with complete atelectasis and congestion of the upper lobe as well as pleural effusion. Thoracoscopy confirmed lung torsion and revealed hemorrhagic infarction of the upper lobe. Subsequently thoracotomy and upper lobectomy were performed. Most likely the lung torsion occurred due to a combination of pleural effusion and venous congestion with complete atelectasis of the upper lobe as a result of adenocarcinoma of the upper lobe. CONCLUSIONS: To our knowledge this is the first reported case of a patient presenting with lung torsion as the first symptom of lung cancer. When lung torsion is suspected rapid diagnosis is crucial in order to prevent hemorrhagic lung infarction.

SWR1 and INO80 chromatin remodelers contribute to DNA double-strand break perinuclear anchorage site choice.

Persistent DNA double-strand breaks (DSBs) are recruited to the nuclear periphery in budding yeast. Both the Nup84 pore subcomplex and Mps3, an inner nuclear membrane (INM) SUN domain protein, have been implicated in DSB binding. It was unclear what, if anything, distinguishes the two potential sites of repair. Here, we characterize and distinguish the two binding sites. First, DSB-pore interaction occurs independently of cell-cycle phase and requires neither the chromatin remodeler INO80 nor recombinase Rad51 activity. In contrast, Mps3 binding is S and G2 phase specific and requires both factors. SWR1-dependent incorporation of Htz1 (H2A.Z) is necessary for break relocation to either site in both G1- and S-phase cells. Importantly, functional assays indicate that mutations in the two sites have additive repair defects, arguing that the two perinuclear anchorage sites define distinct survival pathways.

Targeted INO80 enhances subnuclear chromatin movement and ectopic homologous recombination.

Chromatin in the interphase nucleus moves in a constrained random walk. Despite extensive study, the molecular causes of such movement and its impact on DNA-based reactions are unclear. Using high-precision live fluorescence microscopy in budding yeast, we quantified the movement of tagged chromosomal loci to which transcriptional activators or nucleosome remodeling complexes were targeted. We found that local binding of the transcriptional activator VP16, but not of the Gal4 acidic domain, enhances chromatin mobility. The increase in movement did not correlate strictly with RNA polymerase II (PolII) elongation, but could be phenocopied by targeting the INO80 remodeler to the locus. Enhanced chromatin mobility required Ino80's ATPase activity. Consistently, the INO80-dependent remodeling of nucleosomes upon transcriptional activation of the endogenous PHO5 promoter enhanced chromatin movement locally. Finally, increased mobility at a double-strand break was also shown to depend in part on the INO80 complex. This correlated with increased rates of spontaneous gene conversion. We propose that local chromatin remodeling and nucleosome eviction increase large-scale chromatin movements by enhancing the flexibility of the chromatin fiber.

Instruments for comprehensive needs assessment in individuals with cognitive complaints, mild cognitive impairment or dementia: a systematic review.

OBJECTIVE: In recent years, it has become more common to complement the objective assessment of symptoms with an assessment of individual needs patterns that are created by the individual pattern of symptoms. However, little is known on needs patterns in individuals with subjective cognitive impairment, mild cognitive impairment and dementia. Thus, on the basis of an analysis of the development of needs in the course of cognitive decline, we provide an overview of the existing needs assessment instruments with respect to feasibility, validity and reliability. METHOD: We conducted a literature search in PsycINFO and PubMed including all publications up to September 2009. We included needs assessment instruments for use in older individuals with mental or cognitive disorders and dementia. RESULTS: We identified 17 needs assessment instruments for individuals with mental disorders, cognitive impairment or dementia. The analysis of selected articles demonstrated a wide range of needs indicators within different subgroups. Validity and reliability range between moderate and good. CONCLUSIONS: Even though a wide range of needs assessment instruments is available, most instruments assess the needs of individuals with subjective cognitive impairment, mild cognitive impairment and dementia on a general level rather than on a more concrete level that may serve better to inform interventions for this growing population. In addition, we suggest basing the development of instruments firmly on an adequate theoretical framework and standardised procedural guidelines.

Perioperative management of Glanzmann's syndrome: how we did it!

Thrombasthenia Glanzmann, named after the Swiss paediatrician Eduard Glanzmann (1887-1959), is a rare disease of platelet dysfunction. This disease is characterized by a deficiency or defect of the fibrinogen receptor (GPIIb-IIIa) on the platelet surface. The GPIIb-IIIa receptor has an essential function in the adhesion and aggregation of the platelets. The platelets of these patients cannot bind fibrinogen and aggregation does not occur. Patients have a severe lifelong risk of bleeding, especially during surgical procedures. These patients require a special perioperative regimen for an adequate function of the coagulation system to prevent intraoperative and postoperative bleeding. In this study, we present the perioperative management of a patient with thrombasthenia Glanzmann during elective inguinal hernia repair.

Blunt injury to the thyroid gland: proposed classification and treatment algorithm.

BACKGROUND: Traumatic hemorrhage of the thyroid gland is a rare injury with few published case reports. Surgical and nonsurgical management have been advocated but there is no consensus of opinion. METHODS: This study is a retrospective review of published case reports including two own cases. A classification and an algorithm for diagnosis and treatment of thyroid gland injuries is proposed. RESULTS: A literature review reveals 16 case reports. Of these, 11 patients underwent neck exploration for control of hemorrhage and resection of the associated thyroid abnormality while 5 patients were conservatively managed. Of note is the fact that 10 of the 16 patients (63%) had pre-existing thyroid disease. These 10 patients constituted (91%) of the group requiring surgical treatment. CONCLUSION: Our proposed classification and algorithm offers management guidelines for this rather rare injury. Conservative treatment may be successful in selected patients with lower grade injuries and without concomitant thyroid disease.

Pre-emptive analgesia using intravenous fentanyl plus low-dose ketamine for radical prostatectomy under general anesthesia does not produce short-term or long-term reductions in pain or analgesic use.

The aim of the study was to evaluate post-operative pain and analgesic use after pre-operative or post-incisional i.v. fentanyl plus low dose i.v. ketamine vs. a standard treatment receiving i.v. fentanyl but not ketamine. Men undergoing radical prostatectomy under general anesthesia were randomly assigned in a double-blinded manner to one of three groups. Patients received i.v. fentanyl before incision followed by an i.v. bolus dose (0.2 ml kg(-1)) and an i.v. infusion (0.0025 ml kg(-1)min(-1)) of 1 mg ml(-1) ketamine (group 1) or normal saline (groups 2 and 3). Seventy minutes after incision, patients received i.v. fentanyl followed by an i.v. bolus dose (0.2 ml kg(-1)) and an i.v. infusion (0.0025 ml kg(-1)min(-1)) of saline (groups 1 and 3) or ketamine (group 2). Pain, von Frey pain thresholds, and cumulative morphine consumption using patient-controlled analgesia (PCA) were assessed up to 72 h after surgery. 143 patients completed the study (group 1, n = 47, group 2, n = 50, group 3, n = 46). Cumulative PCA morphine (mean+/-SD) did not differ significantly among groups (group 1, 92.3+/-45.9 mg; group 2, 107.2+/-58.4 mg; group 3, 103.6+/-50.4 mg; P = 0.08 for groups 1 vs. 2, and groups 1 vs. 3). On day 3, the hourly rate (mean+/-SEM) of morphine consumption was significantly lower (p < 0.0009) in group 1 (0.61+/-0.013 mg h(-1)) than group 2 (0.86+/-0.011 mg h(-1)) and group 3 (0.89+/-0.008 mg h(-1)). Pain scores and von Frey pain thresholds did not differ significantly among groups. Two-week and 6-month follow-ups did not reveal significant group differences in pain incidence, intensity, disability or mental health. Pre-operative, low-dose administration of i.v. ketamine did not result in a clinically meaningful reduction in pain or morphine consumption when compared with post-incisional administration of ketamine or a saline control condition.

Postoperative morphine use and hyperalgesia are reduced by preoperative but not intraoperative epidural analgesia: implications for preemptive analgesia and the prevention of central sensitization.

BACKGROUND: The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control. METHODS: Patients undergoing major gynecologic surgery by laparotomy were randomly assigned to three groups and studied in a double-blinded manner. Group 1 received epidural lidocaine and fentanyl before incision and epidural saline 40 min after incision. Group 2 received epidural saline before incision and epidural lidocaine and fentanyl 40 min after incision. Group 3 received a sham epidural control (with saline injected into a catheter taped to the back) before and 40 min after incision. All patients underwent surgery with general anesthesia. RESULTS: One hundred forty-one patients completed the study (group 1, n = 45; group 2, n = 49; group 3, n = 47). Cumulative patient-controlled analgesia morphine consumption at 48 h was significantly lower (P = 0.04) in group 1 (89.8 +/- 43.3 mg) than group 3 (112.5 +/- 71.5 mg) but not group 2 (95.4 +/- 60.2 mg), although the hourly rate of morphine consumption between 24 and 48 h after surgery was significantly lower (P < 0.0009) in group 1 (1.25 +/- 0.02 mg/h) than group 2 (1.41 +/- 0.02 mg/h). Twenty-four hours after surgery, the visual analog scale pain score on movement was significantly less intense (P = 0.005) in group 1 (4.9 +/- 2.2 cm) than group 3 (6.0 +/- 2.6 cm) but not group 2 (5.3 +/- 2.5 cm), and the von Frey pain threshold near the wound was significantly higher (P = 0.03) in group 1 (6.4 +/- 0.6 log mg) than in group 3 (6.1 +/- 0.8 log mg) but not group 2 (6.2 +/- 0.7 log mg). CONCLUSIONS: Preincisional administration of epidural lidocaine and fentanyl was associated with a significantly lower rate of morphine use, lower cumulative morphine consumption, and reduced hyperalgesia compared with a sham epidural condition. These results highlight the importance of including a standard treatment control group to avoid the problems of interpretation that arise when two-group studies of preemptive analgesia (preincisional vs. postsurgery) fail to find the anticipated effects.

CT-guided percutaneous embolization of a lumbar artery maintaining a type II endoleak.

PURPOSE: To demonstrate the possibility of percutaneous embolization of a type II endoleak guided by computed tomographic (CT) fluoroscopy. CASE REPORT: A type II endoleak maintained by a hypertrophic fourth lumbar artery failed to occlude spontaneously 7 months after stent-graft deployment for endovascular repair of an infrarenal abdominal aortic aneurysm. A percutaneous procedure was performed to eliminate the endoleak using needle puncture and embolization under CT fluoroscopic guidance. The sagittal diameter of the aneurysm sac, which had remained constant after initial endovascular exclusion, shrank from 5.2 to 4.8 cm in the 3 months following embolization. CONCLUSIONS: Percutaneous embolization of lumbar branches guided by CT fluoroscopy may be an alternative to other therapies for type II endoleaks.

The stability of a ketamine-morphine solution.

UNLABELLED: Recent advances in acute pain mechanisms and management have implicated the N-methyl D-aspartate receptor-ion channel complex in the development of postoperative hyperalgesia and acute opioid tolerance. N-methyl D-aspartate receptor antagonists such as ketamine have been used increasingly in clinical studies in an effort to minimize acute postoperative pain and reduce opioid requirements. A mixture of ketamine and an opioid administered in the same solution and syringe would be a practical and useful technique for postoperative epidural analgesia, continuous IV infusion, or patient-controlled IV analgesia. We investigated the stability of a morphine sulfate and racemic ketamine solution in saline at pH 5.5-7.5 over a period of 4 days. Our study demonstrates that the ketamine-morphine mixture at a clinically relevant concentration seems to be stable at room temperature, at a wide range of pH values, for at least 4 days. IMPLICATIONS: Small-dose ketamine is used with increasing frequency in the acute postoperative setting as an adjunct to traditional opioid analgesics. We show that a racemic ketamine and morphine solution at a clinically relevant concentration seems to be stable at room temperature at a wide range of pH values for at least 4 days.

Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes.

Ketamine hydrochloride is a well known general anesthetic and short acting analgesic in use for almost 3 decades. The role of the NMDA receptor in the processing of nociceptive input has led naturally to renewed clinical interest in N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine. This paper reviews the use and efficacy of low-dose ketamine in the management of acute postoperative pain. The literature was obtained from a computer search of the MEDLINE database from 1966 through December 1998. Studies were included for review if they were randomized, prospective, controlled, double-blind and reported pain scores. We evaluate the clinical literature and discuss the efficacy of low-dose ketamine in the management of acute postoperative pain when administered alone or in conjunction with other agents via the oral, intramuscular, subcutaneous, intravenous and intraspinal routes. Low-dose ketamine is defined as a bolus dose of less than 2 mg/g when given intramuscularly or less than 1 mg/kg when administered via the intravenous or epidural route. For continuous i.v. administration low-dose ketamine is defined as a rate of < or =20 microg/kg per min. We conclude that ketamine may provide clinicians with a tool to improve postoperative pain management and to reduce opioid related adverse effects. The evidence suggests that low-dose ketamine may play an important role in postoperative pain management when used as an adjunct to local anesthetics, opioids, or other analgesic agents. Further research is required in the following areas: (a) dose-finding studies for ketamine as an adjunct to opioids and local anesthetics (b) efficacy and optimal route of administration (c) the role of S(+)-ketamine; (d) the influence of ketamine on long-term outcome such as chronic pain (e) long-term physical and chemical stability of mixtures containing ketamine (f) spinal toxicity of ketamine and (g) effects of low-dose ketamine on cognitive and memory functioning after surgery.