Do preoperative oral antibiotics increase Clostridium difficile infection rates? An analysis of 13 959 colectomy patients.

AIM: The aim of this study was to determine whether or not preoperative oral antibiotic preparation (POAP) increases the rate of Clostridium difficile colitis (CDC) in patients undergoing colectomy. METHOD: In 2015, data for colectomies had been collected prospectively and recorded in the targeted colectomy option of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). This was available for retrospective analysis. Data available for analysis included elective and emergency status, POAP, surgical approach, primary anastomosis and CDC status. The effect of POAP on CDC was analysed and risk adjusted for 14 separate preoperative variables. RESULTS: In all, 13 959 adult patients underwent a colectomy in 2015 (POAP group 5311 and non- POAP group 8648). The overall rate of CDC in colectomy patients was 1.6% (227/13 959). On univariate analysis, CDC was significantly less common in the POAP group than in the non-POAP group (1.2% vs 1.9%, P = 0.003). Univariate analysis of a further 41 preoperative variables revealed 14 to be associated with CDC. However, after risk adjustment with these 14 variables, POAP lost its statistical significance (adjusted OR 0.902, 95% CI 0.584-1.486, P = 0.685). Only patients with pre-existing systemic inflammatory response syndrome appeared to be at increased risk of CDC (adjusted OR 2.154, 95% CI 1.139-4.074, P = 0.018). CONCLUSION: At the very least this study suggests it is safe to use POAP in colectomy patients without increasing the rate of CDC unless they have pre-existing systemic inflammatory response syndrome.

Risk factors for anastomotic leakage after colorectal resection: a retrospective analysis of 17 518 patients.

AIM: A large, prospectively collected, clinical database was analysed to determine the various pre- and intra-operative factors affecting anastomotic leakage (AL) in colorectal surgery. METHOD: Data on 17 518 patients having a colorectal resection with anastomosis, taken from the 2013 American College of Surgeons National Surgical Quality Improvement Program database, were included in the study. Multivariable logistic regression analysis was carried out to identify risk-adjusted predictive factors for AL. Statistical significance was set at P < 0.05 and confidence intervals were reported at the 95% level. RESULTS: The AL rate was 3.9% (687/17 518). Younger patients, male gender and an American Society of Anesthesiology (ASA) score of ≥ 3 (P < 0.001), smoking (P = 0.001), diabetes (P = 0.035), a preoperative serum albumin level of < 4 g/dl (P = 0.030), elective rectal cancer surgery (P = 0.024), emergency colectomy for bleeding (P = 0.013) and splenic flexure mobilization (P = 0.043) were associated with an increased risk of AL. Preoperative oral antibiotics (P < 0.001), right hemicolectomy (open or laparoscopic) and laparoscopic partial colectomy were associated with a reduced risk of AL compared with the entire group. Body mass index, preoperative chemotherapy, emergency surgery and mechanical bowel preparation were not related to AL. CONCLUSION: In contrast to most studies, younger age was found to be an independent risk factor for AL. The risk for AL was lower with laparoscopic partial colectomy and open or laparoscopic right hemicolectomy. Preoperative oral antibiotic preparation significantly reduces the risk of AL and should be incorporated as a standard protocol.

Pulmonary radiofrequency ablation in a district general hospital: is it a safe and effective treatment?

AIM: To analyse the technical success of ablation therapy and the incidence of complications in patients treated with pulmonary ablation and to assess factors affecting local disease control and patient survival in a subgroup with metastatic colorectal cancer. MATERIALS AND METHODS: Technical success and complications in all patients undergoing lung ablation between June 2009 and July 2015 were recorded. Overall survival and local disease control in a subgroup with metastases from a colorectal primary were calculated. Factors influencing outcome were explored. RESULTS: Two hundred and seven pulmonary ablations were performed in 86 patients at 156 attendances. Technical success was achieved in 207/207 (100%). Thirty and 90-day mortality was 0%. The major complication rate was 13/86 (15%). One hundred and one metastases were treated in 46 patients with a colorectal primary. This group had a mean ± standard error survival time of 53.58±3.47 months with a 1, 2, 3, 4, and 5-year survival rate of 97.4%, 91.3%, 81.5%, 59.8%, and 48%. There was no statistically significant difference in survival regarding time to development of metastatic disease, the total number of lesions ablated, the initial number of lesions ablated, the maximum size of lesion treated, or unilateral versus bilateral disease. Patients with extrapulmonary disease were found to have a shorter survival from the primary diagnosis. Seventy-eight (77.2%) of the 101 lesions were stable after first RFA. Local relapse was more likely when a metastasis was close to a large (>3 mm) vessel. CONCLUSION: RFA is a safe and effective procedure that can be performed without on-site cardiothoracic support. Good outcomes depend upon careful patient selection. This study supports its use in oligometastatic disease.

Patient-specific analysis of the relationship between the volume of tissue activated during DBS and verbal fluency.

Deep brain stimulation (DBS) for the treatment of advanced Parkinson's disease involves implantation of a lead with four small contacts usually within the subthalamic nucleus (STN) or globus pallidus internus (GPi). While generally safe from a cognitive standpoint, STN DBS has been commonly associated with a decrease in the speeded production of words, a skill referred to as verbal fluency. Virtually all studies comparing presurgical to postsurgical verbal fluency performance have detected a decrease with DBS. The decline may be attributable in part to the surgical procedures, yet the relative contributions of stimulation effects are not known. In the present study, we used patient-specific DBS computer models to investigate the effects of stimulation on verbal fluency performance. Specifically, we investigated relationships of the volume and locus of activated STN tissue to verbal fluency outcome. Stimulation of different electrode contacts within the STN did not affect total verbal fluency scores. However, models of activation revealed subtle relationships between the locus and volume of activated tissue and verbal fluency performance. At ventral contacts, more tissue activation inside the STN was associated with decreased letter fluency performance. At optimal contacts, more tissue activation within the STN was associated with improved letter fluency performance. These findings suggest subtle effects of stimulation on verbal fluency performance, consistent with the functional nonmotor subregions/somatotopy of the STN.

Cyclosporine versus tacrolimus treated liver transplant recipients with chronic hepatitis C: outcomes analysis of the UNOS/OPTN database.

Recurrent hepatitis C virus (HCV) remains a problematic cause of morbidity and mortality for liver transplant patients. Immunosuppression including calcineurin-inhibitors has been implicated in the acceleration of recurrent HCV. Recent studies suggest that outcomes may be better with cyclosporine (CSA-ME) compared to tacrolimus (TAC), but the data are inconclusive. We retrospectively analyzed data received from the United Network for Organ Sharing on 8809 chronic HCV liver transplant recipients receiving either cyclosporine microemulsion (CSA-ME) or tacrolimus (TAC) as maintenance immunosuppression prior to discharge. We analyzed patient death, graft failure, failure due recurrent disease and acute cellular rejection (ACR) for CSA-ME versus TAC treated patients. Three-year unadjusted patient and graft survival rates were 76.8% and 71.5%, respectively, in the CSA-ME group versus 79.9% and 75.0% in the TAC group. Propensity score-adjusted results suggest CSA-ME treated patients are at increased risk of patient death and graft failure [Hazards ratio (HR) = 1.17; 95% CI = 1.01-1.36 and HR = 1.19; 95% CI = 1.04-1.35, respectively] and biopsy-confirmed AR (HR = 2.03; 95% CI = 1.54-2.67) compared to TAC treated patients. These results provide evidence to reconsider the targeted administration of CSA-ME to HCV-infected liver transplant recipients.

Mood and motor effects of thalamic deep brain stimulation surgery for essential tremor.

PURPOSE: The aim of this study was to evaluate the effects of unilateral and bilateral ventralis intermedius (Vim) deep brain stimulation (DBS) on mood and motor function. METHODS: Thirty-one consecutive medication refractory patients with essential tremor who underwent unilateral or bilateral Vim DBS at University of Florida and returned for at least 6 -month follow-up completed the Visual Analog Mood (VAMS), the Beck Depression Inventory (BDI), and the Tremor Rating Scale (TRS) before and after surgery. We excluded all patients who were implanted at other institutions. RESULTS: The tense subscale of the VAMS improved significantly in both the unilateral and bilateral DBS groups (P < 0.001). On the VAMS afraid subscale, only the bilateral group trended toward improvement (P = 0.075). There were no significant changes for either group for the happy, confused, sad, angry, energetic or tired VAMS scores. TRS subscale scores all improved after unilateral and bilateral Vim DBS surgery (P < 0.001). CONCLUSIONS: Feelings of tenseness, tremor severity and ADLs improved following unilateral or bilateral Vim DBS for ET.

Entorhinal cortex volume in older adults: reliability and validity considerations for three published measurement protocols.

Measuring the entorhinal cortex (ERC) is challenging due to lateral border discrimination from the perirhinal cortex. From a sample of 39 nondemented older adults who completed volumetric image scans and verbal memory indices, we examined reliability and validity concerns for three ERC protocols with different lateral boundary guidelines (i.e., Goncharova, Dickerson, Stoub, & deToledo-Morrell, 2001; Honeycutt et al., 1998; Insausti et al., 1998). We used three novice raters to assess inter-rater reliability on a subset of scans (216 total ERCs), with the entire dataset measured by one rater with strong intra-rater reliability on each technique (234 total ERCs). We found moderate to strong inter-rater reliability for two techniques with consistent ERC lateral boundary endpoints (Goncharova, Honeycutt), with negligible to moderate reliability for the technique requiring consideration of collateral sulcal depth (Insausti). Left ERC and story memory associations were moderate and positive for two techniques designed to exclude the perirhinal cortex (Insausti, Goncharova), with the Insausti technique continuing to explain 10% of memory score variance after additionally controlling for depression symptom severity. Right ERC-story memory associations were nonexistent after excluding an outlier. Researchers are encouraged to consider challenges of rater training for ERC techniques and how lateral boundary endpoints may impact structure-function associations.

Preoperative oral antibiotic bowel preparation in elective resectional colorectal surgery reduces rates of surgical site infections: a single-centre experience with a cost-effectiveness analysis.

INTRODUCTION: Surgical site infections cause considerable postoperative morbidity and mortality. The aim of this study was to determine the effect on surgical site infection rates following introduction of a departmental oral antibiotic bowel preparation protocol. METHODS: A prospective single-centre study was performed for elective colorectal resections between May 2016-April 2018; with a control group with mechanical bowel preparation and treatment group with oral antibiotic bowel preparation (neomycin and metronidazole) and mechanical bowel preparation. The primary outcome of surgical site infection and secondary outcomes of anastomotic leak, length of stay and mortality rate were analysed using Fisher's exact test and independent samples t-tests. A cost-effectiveness analysis was also performed. RESULTS: A total of 311 patients were included; 156 in the mechanical bowel preparation group and 155 in the mechanical bowel preparation plus oral antibiotic bowel preparation group. The study included 180 (57.9%) men and 131 (42.1%) women with a mean age of 68 years. There was a significant reduction in surgical site infection rates (mechanical bowel preparation 16.0% vs mechanical bowel preparation plus oral antibiotic bowel preparation 4.5%; P = 0.001) and mean length of stay (mechanical bowel preparation 10.2 days vs mechanical bowel preparation plus oral antibiotic bowel preparation 8.2 days; P = 0.012). There was also a reduction in anastomotic leak and mortality rates. Subgroup analyses demonstrated significantly reduced surgical site infection rates in laparoscopic resections (P = 0.008). There was an estimated cost saving of £239.13 per patient and £37,065 for our institution over a one-year period. CONCLUSION: Oral antibiotic bowel preparation is a feasible and cost-effective intervention shown to significantly reduce the rates of surgical site infection and length of stay in elective colorectal surgery.

Fetal bovine bone cells synthesize bone-specific matrix proteins.

We isolated cells from both calvaria and the outer cortices of long bones from 3- to 5-mo bovine fetuses. The cells were identified as functional osteoblasts by indirect immunofluorescence using antibodies against three bone-specific, noncollagenous matrix proteins (osteonectin, the bone proteoglycan, and the bone sialoprotein) and against type 1 collagen. In separate experiments, confluent cultures of the cells were radiolabeled and shown to synthesize and secrete osteonectin, the bone proteoglycan and the bone sialoprotein by immunoprecipitation and fluorography of SDS polyacrylamide gels. Analysis of the radiolabeled collagens synthesized by the cultures showed that they produced predominantly (approximately 94%) type I collagen, with small amounts of types III and V collagens. In agreement with previous investigators who have employed the rodent bone cell system, we confirmed in bovine bone cells that (a) there was a typical cyclic AMP response to parathyroid hormone, (b) freshly isolated cells possessed high levels of alkaline phosphatase, which diminished during culture but returned to normal levels in mineralizing cultures, and (c) cells grown in the presence of ascorbic acid and beta-glycerophosphate rapidly produced and mineralized an extracellular matrix containing largely type I collagen. These results show that antibodies directed against bone-specific, noncollagenous proteins can be used to clearly identify bone cells in vitro.

Scatter factor/hepatocyte growth factor protects against cytotoxic death in human glioblastoma via phosphatidylinositol 3-kinase- and AKT-dependent pathways.

We have shown recently that the multifunctional growth factor, scatter factor/hepatocyte growth factor (SF/HGF), and its receptor c-met enhance the malignancy of human glioblastoma through an autocrine stimulatory loop (R. Abounader et al., J. Natl. Cancer Inst., 91: 1548-1556, 1999). This report examines the effects of SF/HGF:c-met signaling on human glioma cell responses to DNA-damaging agents. Pretreating U373 human glioblastoma cells with recombinant SF/HGF partially abrogated their cytotoxic responses to gamma irradiation, cisplatin, camptothecin, Adriamycin, and Taxol in vitro. This cytoprotective effect of SF/HGF occurred at least in part through an inhibition of apoptosis, as evidenced by diminished terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling index and reduced DNA laddering. Anti-c-met U1/ribozyme gene transfer inhibited the ability of SF/HGF to protect against single-strand DNA breakage, DNA fragmentation, and glioblastoma cell death caused by DNA-damaging agents, demonstrating a requirement for c-met receptor function. Phosphorylation of the cell survival-promoting kinase Akt (protein kinase B) resulted from SF/HGF treatment of U373 cells, and both Akt phosphorylation and cell survival induced by SF/HGF were inhibited by phosphatidylinositol 3-kinase inhibitors but not by inhibitors of mitogen-activated protein kinase kinase or protein kinase C. Cytoprotection by SF/HGF in vitro was also inhibited by transient expression of dominant-negative Akt. Transgenic SF/HGF expression by intracranial 9L gliosarcomas reduced tumor cell sensitivity to gamma irradiation, confirming the cytoprotective effect of SF/HGF in vivo. These findings demonstrate that c-met receptor activation by SF/HGF protects certain glioblastoma cells from DNA-damaging agents by activating phosphoinositol 3-kinase-dependent and Akt-dependent antiapoptotic pathways.

Motivational engagement in Parkinson's disease: Preparation for motivated action.

The current study investigated whether motivational dysfunction in Parkinson's patients is related to a deficit in preparing for motivated behavior. Based on previous studies, it was hypothesized that PD patients would show reduced preparation for action specifically when faced with threat (of loss) and that reduced action preparation would relate to self-report of apathy symptoms. The study measured an electrocortical correlate of preparation for action (CNV amplitude) in PD patients and healthy controls, as well as defensive and appetitive activation during emotional perception (LPP amplitude). The sample included 18 non-demented PD patients (tested on dopaminergic medications) and 15 healthy controls who responded as quickly as possible to cues signaling threat of loss or reward, in which the speed of the response determined the outcome. Results indicated that, whereas PD patients showed similar enhanced action preparation with the addition of incentives to controls, PD patients showed generally reduced action preparation, evidenced by reduced CNV amplitude overall. Results suggest that PD patients may have behavioral issues due to globally impaired action preparation but that this deficit is not emotion-specific, and movement preparation may be aided by incentive in PD patients.

Mood and cognitive changes with deep brain stimulation. What we know and where we should go.

AIM: The aim of this study was to completely review the literature on cognitive and mood changes resulting from deep brain stimulation (DBS), and to examine the factors that might lead to these changes. DBS has been shown to improve motor symptoms in many movement disorders. Despite the widespread use of this technique, there are relatively few well controlled studies describing the potential cognitive, mood and behavioral consequences that may result from DBS. Additionally, the factors that may influence these changes have not been carefully studied. METHODS: A complete survey of the articles exploring the effects of DBS on mood and cognition was performed. Each study identified was examined and categories of factors that may have influenced mood and cognition were noted. These factors included surgical target, number of patients studied, whether procedures were unilateral or bilateral, average age of patients, diagnosis, condition of the DBS during the study (on or off), pre-operative screening tests (e.g., dementia rating scale, mini mental state exam), and changes on mood and cognitive tests (categorized as no change, improved, or worsened). Studies were divided into evidence-based categories. RESULTS: There are many mood and cognitive changes that may result from DBS. Due to methodological limitations of existing studies there are important unanswered questions about cognitive and mood changes resulting from this type of surgery. The predominant amount of data regarding changes in mood and cognition with DBS is level 3 or case based evidence. CONCLUSIONS: There exists a paucity of well-controlled studies addressing the mood and cognitive changes that result from DBS. Carefully performed prospective studies may help us to understand the effects of DBS on mood and cognition.

Factors influencing synthesis and mineralization of bone matrix from fetal bovine bone cells grown in vitro.

This study of the in vitro synthesis and mineralization of bovine bone demonstrates that sheets of mineralized matrix can be produced consistently within 18-24 days of cell isolation. Mineralization surpasses that achieved by other systems with other species: The deposition of mineral extends beyond nodules to form branching trabeculae and then solid wafers of bone. Comparison of the fetal age of the bone source, enzyme digestion methods, seeding density, culture surface, nutritive media, and concentration of fetal calf serum and other additives, including insulin and ascorbic acid, has yielded a set of optimal culture conditions. In the presence of ascorbic acid and beta-glycerol phosphate, insulin has a dose-dependent effect on the morphology of the mineralized bone matrix produced. Quantitative analysis shows that in these cultures calcium accumulates most rapidly between days 6 and 10 after the introduction of mineralization medium but that mineral accretion continues throughout 14-16 days of culture. Alkaline phosphatase levels rise up to 200-fold, concomitant with a rapid increase in the number of cells per culture during the early mineralization phases; both fall as mineralization proceeds. This system has been used to study the induction of mRNA of type I collagen, alkaline phosphatase, and several noncollagenous bone proteins during the course of mineralization. Because of the degree of mineralization achieved with this system, it has many potential applications.

Aggressive phenotypic and genotypic features in pediatric and NF2-associated meningiomas: a clinicopathologic study of 53 cases.

Pediatric and NF2-associated meningiomas are uncommon and poorly characterized in comparison to sporadic adult cases. In order to elucidate their molecular features, we analyzed MIB-1, progesterone receptor (PR), NF2, merlin, DAL-1, DAL-1 protein, and chromosomal arms 1p and 14q in 53 meningiomas from 40 pediatric/NF2 patients using immunohistochemistry and dual-color fluorescence in situ hybridization (FISH). Fourteen pediatric (42%) patients, including 5 previously undiagnosed patients, had NF2. The remaining 19 (58%) did not qualify. All 7 of the adult patients had NF2. Meningioma grading revealed 21 benign (40%), 26 atypical (49%), and 6 anaplastic (11%) examples. Other aggressive findings included high mitotic index (32%), high MIB-1 LI (37%), aggressive variant histology (e.g. papillary, clear cell) (25%), brain invasion (17%), recurrence (39%), and patient death (17%). FISH analysis demonstrated deletions of NF2 in 82%, DAL-1 in 82%, 1p in 60%, and 14q in 66%. NF2-associated meningiomas did not differ from sporadic pediatric tumors except for a higher frequency of merlin loss in the former (p = 0.020) and a higher frequency of brain invasion in the latter (p = 0.007). Thus, although pediatric and NF2-associated meningiomas share the common molecular alterations of their adult, sporadic counterparts, a higher fraction are genotypically and phenotypically aggressive. Given the high frequency of undiagnosed NF2 in the pediatric cases, a careful search for other features of this disease is warranted in any child presenting with a meningioma.

Effects of left frontal transcranial magnetic stimulation on depressed mood, cognition, and corticomotor threshold.

BACKGROUND: The pathophysiology of depression may include synaptic hypoactivity of left prefrontal cortex. Several groups of investigators have described improved mood associated with rapid transcranial magnetic stimulation (rTMS) but have not looked for possible cognitive side effects associated with left prefrontal magnetic stimulation. METHODS: We measured the effects of left prefrontal rTMS on mood, cognition, and motor evoked potential threshold in 10 patients with medication-resistant major depression. RESULTS: In a 2-week open trial of left prefrontal rTMS off antidepressant medications, scores on the Hamilton Rating Scale for Depression and the Beck Depression Inventory decreased by 41% and 40%, respectively. After resuming pre-rTMS antidepressant medication, improvement in mood was still significant at 1 and 3 months later. rTMS had no adverse effects on neuropsychological performance. rTMS treatments were associated with significant decreases in motor evoked potential threshold in the 9 of 10 patients who remained off psychotropic medications during the 2-week treatment period. CONCLUSIONS: These preliminary data suggest that left prefrontal rTMS is safe and improves mood in patients with medication-resistant major depression. Changes in motor evoked potential threshold suggest that prefrontal rTMS may alter brain activity at sites remote from the stimulation. Double-blind, sham-controlled studies are needed.

Frontal verbal amnesia. Phonological amnesia.

Although aphasic patients with frontal lobe damage may demonstrate impaired retention of verbal material, significant anterograde memory disturbances have not, to our knowledge, been reported with a minor Broca's aphasia. We describe a patient with minor Broca's aphasia who exhibited an unusual and profound anterograde memory disturbance, especially for phonologically specified stimuli. We suggest that this disturbance is attributable to an impairment in the volitional, controlled search of stored phonological information.

Reaction times in Parkinson disease.

Ten hypokinetic parkinsonian patients and ten age- and sex-matched controls were tested, using reaction times with and without a warning signal. The time difference between each was used as a measure of phasic arousal. Both groups' reaction times improved with a warning signal, but there were no differences in reaction-time reduction between the parkinsonian and control groups. These results suggest either that hypokinesia in parkinsonism is not caused by an arousal defect or it is caused by a defect in the "autoevoked" arousal system.

Performance on hemispatial pointing task by patients with neglect syndrome.

Five patients with left hemispatial neglect and five aphasic control subjects were given a hemispatial pointing task. They were instructed to point to an imaginary point in space perpendicular to the midline of the chest. Right hemisphere-damaged subjects with neglect deviated more into the hemispace ipsilateral to the lesion than left hemisphere-damaged controls. This task did not require sensory input from left hemispace, and the defective performance cannot be attributed to sensory inattention or to impaired gaze or memory. The finding is compatible with hemispatial akinesia.