Assessing neurophysiological changes associated with combined transcranial direct current stimulation and cognitive‐emotional training for treatment‐resistant depression

Transcranial direct current stimulation (tDCS), a form of non‐invasive brain stimulation, is a promising treatment for depression. Recent research suggests that tDCS efficacy can be augmented using concurrent cognitive‐emotional training (CET). However, the neurophysiological changes associated with this combined intervention remain to be elucidated. We therefore examined the effects of tDCS combined with CET using electroencephalography (EEG). A total of 20 participants with treatment‐resistant depression took part in this open‐label study and received 18 sessions over 6 weeks of tDCS and concurrent CET. Resting‐state and task‐related EEG during a 3‐back working memory task were acquired at baseline and immediately following the treatment course. Results showed an improvement in mood and working memory accuracy, but not response time, following the intervention. We did not find significant effects of the intervention on resting‐state power spectral density (frontal theta and alpha asymmetry), time–frequency power (alpha event‐related desynchronisation and theta event‐related synchronisation) or event‐related potentials (P2 and P3 components). We therefore identified little evidence of neurophysiological changes associated with treatment using tDCS and concurrent CET, despite significant improvements in mood and near‐transfer effects of cognitive training to working memory accuracy. Further research incorporating a sham‐controlled group may be necessary to identify the neurophysiological effects of the intervention.     

Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications.

BACKGROUND AND AIMS: The role of clopidogrel in patients at risk for gastrointestinal complications is uncertain, although it has been recommended for patients who have gastrointestinal intolerance to aspirin. We tested the hypothesis that clopidogrel is as effective as esomeprazole and aspirin in preventing recurrences of ulcer complications. METHODS: This was a prospective, double-blind, randomized, controlled study of 170 patients who developed ulcer bleeding after the use of low-dose aspirin between November 2002 and January 2005. After healing of ulcers and eradication of Helicobacter pylori, if present, patients were assigned randomly to treatment with esomeprazole 20 mg/day and aspirin 100 mg/day (n = 86) or clopidogrel 75 mg/day (n = 84) for 52 weeks. The primary end point was recurrent ulcer complications. RESULTS: During a median follow-up period of 52 weeks, no patient in the esomeprazole group, as compared with 9 patients in the clopidogrel group, developed recurrent ulcer complications. The cumulative incidences of recurrent ulcer complications were 0% in patients receiving esomeprazole and aspirin and 13.6% in patients receiving clopidogrel (absolute difference, 13.6%; 95% confidence interval for the difference, 6.3-20.9; log-rank test, P = .0019). CONCLUSIONS: The combination of esomeprazole and aspirin is superior to clopidogrel in preventing ulcer complications in patients who have a past history of aspirin-related peptic ulcer bleeding.     

Antibody to cloned HSV glycoproteins B and D plus adult human leukocytes protect neonatal mice from lethal HSV infection

Antisera produced by HSV infection or following vaccination of guinea pigs with the cloned herpes simplex virus (HSV) glycoproteins gB and gD were compared for in vitro antibody-dependent cellular cytotoxicity (ADCC) activity and for in vivo protection. Antibody from guinea pigs was able to participate in ADCC with human mononuclear cells in vitro, anti-gBgD serum being equivalent to HSV convalescent sera. In vivo, each of the guinea pig sera was able to protect neonatal mice from a fatal HSV-1 infection when given with human mononuclear cells but not when given alone. The anti-gBgD serum was the most effective in vivo, protecting 15 of 17 (88%) neonatal mice when given at a 10⁻⁴ dilution with human mononuclear cells and was the only guinea pig serum protective at a 10⁻⁶ dilution (5 of 7 neonatal mice).     

Amelioration of established collagen-induced arthritis (CIA) with anti-IL-1

Inflammatory cytokines have been implicated in the pathogenesis of rheumatoid arthritis (RA). To investigate the role of interleukin-1 (IL-1) and tumor necrosis factor α (TNFα) in arthritic processes we studied the effect of neutralizing antibodies against murine IL-1 and TNFα in murine collagen-induced arthritis (CIA). Combined i.p. injection of anti-IL-1α and anti-IL-1β (anti-IL-1α,β), given before onset of the disease, completely prevented CIA. In contrast, treatment with anti-TNFα at this time point only delayed the onset of arthritis. Remarkably, a single injection of anti-IL-1α,β was also highly effective in suppressing established arthritis, reducing both inflammation and cartilage destruction. Suppression was most pronounced with the combination of anti-IL-1α and β, but anti-IL-1β alone also gave significant relief. Specific antibodies against TNFα had no effect on established CIA. Of interest, anti-IL-1α,β treatment started after onset of CIA completely normalized chondrocyte synthetic function, which was highly suppressed in the non-treated group. It is concluded that IL-1 and TNFα are important cytokines during the onset of CIA and that IL-1 is the key mediator of inflammation and cartilage damage in established CIA.     

Predicting discharge outcomes after total knee replacement using the Risk Assessment and Predictor Tool

Objective

To explore the use of the Risk Assessment and Predictor Tool (RAPT) as a pre-operative tool to predict postoperative discharge destination and length of stay for patients undergoing total knee replacement (TKR) in Singapore.

Participants and setting

A cohort of 569 patients undergoing primary TKR at the Singapore General Hospital were recruited prospectively from November 2009 to June 2010.

Intervention

All patients completed a modified RAPT questionnaire pre-operatively, and underwent standard clinical pathway guidelines for TKR throughout the study.

Main outcome measures

Actual discharge destination (ADDest) and length of stay (LOS).

Design

Total RAPT score and preferred discharge destination (PDD) were recorded pre-operatively, while ADDest and LOS were obtained immediately after discharge. Multivariable logistic regression and multivariable regression analysis were used to determine whether the RAPT items and score could predict the discharge outcomes.

Results

Total RAPT score was a significant predictor of LOS for patients following TKR (R = 0.24, P < 0.001); the higher the RAPT score, the longer the LOS. Total RAPT score was also a significant predictor of actual discharge to home [odds ratio (OR) 2.32, 95% confidence interval (CI) 1.11 to 4.85]. PDD was a significant predictor for LOS (R = 0.22, P < 0.001) and ADDest (R = 0.33, P < 0.001). Patients who chose to be discharged home were more likely to be directly discharged home (OR 9.79, 95% CI 5.07 to 18.89, P < 0.001).

Conclusion

Total RAPT score and PDD were significant predictors of ADDest and LOS for patients following TKR in Singapore. The ability to predict discharge outcomes following TKR could assist caregivers, healthcare professionals and administrators in optimising care and resource allocations for patients.     

Effects of E coli endotoxin on pancreatic hormones and blood flow

Studies were performed on anesthetized dogs to determine the relationship between endotoxin-induced alterations in pancreatic blood flow (PBF) and hormones that originate partially or completely from the pancreas. PBF was estimated in six dogs by radioactive microspheres (praeendoxin, 25 and 240 minutes postendotoxin). Insulin, glucagon, pancreatic polypeptide (PP), and somatostatin-like immunoreactivity (SLI) were assayed in arterial and portal venous blood. Cardiac output and mean arterial blood pressure (MABP) decreased 25 minutes after endotoxin administration (50% and 40%, respectively) and returned toward normal levels by four hours. However, there was 74% decrease in PBF at 25 minutes and a further drop four hours after endotoxin. Hormonal responses were characterized by a short-lived increase in arterial insulin, corresponding to a transient increase in blood glucose. Insulin release increased shortly after endotoxin. Arterial glucagon and PP increased two to five hours after endotoxin. There was a suggestion that the increase in PP was of nonpancreatic origin. Little change in plasma SLI was noted following endotoxin. Thus, it appears that endotoxin altered the release of different pancreatic hormones with a variable time courses.     

Resection of advanced stage neuroblastoma with the cavitron ultrasonic surgical aspirator

Current protocols for the treatment of neuroblastoma emphasize total or near total resection of tumor to improve survival. This is preferentially performed as a primary procedure, or is attempted at a second-look operation. Unfortunately, this tumor often grows to large size with invasion of the spinal canal, or encasement of major vascular or other retroperitoneal structures. A primary attempt at complete removal may result in difficult-to-control hemorrhage or injury to, or loss of, vital organs. A second-look procedure carries other intrinsic risks. It often must be performed during a period of chemotherapeutically induced hematologic and immunologic suppression. The presence of adhesions and dense scar tissue increases the complexity of the dissection. The Cavitron Ultrasonic Surgical Aspirator (CUSA) combines continuous fragmentation, irrigation, and aspiration in one instrument. Tissues high in water content are selectively fragmented and aspirated, while tissues high in collagen and elastin (such as blood vessels and pseudocapsular walls) are selectively spared. Five patients, two with large pelvic dumbell tumors, two with large intrathoracic tumors, and one with a seemingly unresectable large right adrenal tumor (crossing the midline with extensive aortocaval nodal involvement) had total or near-total resection accomplished using the CUSA. In these patients, initial resection of the relatively soft inner part of the tumor left a collapsed pseudocapsule, which was then removed under greatly improved exposure in a relatively small field. The constant aspiration virtually eliminated tumor spillage. Since most vessels were skeletonized without penetration, total blood loss was minimized. There were no intraoperative or postoperative complications.     

Sentinel Node Biopsy and Concomitant Probe-Guided Tumor Excision of Nonpalpable Breast Cancer

Background Preliminary data have shown encouraging results of a single intratumoral radiopharmaceutical injection that enables both sentinel node biopsy and probe-guided excision of the primary tumor in patients with nonpalpable breast cancer. The aim of the study was to evaluate this approach in a large group of patients. Methods Lymphoscintigraphy was performed in 368 patients with nonpalpable breast cancer after intratumoral injection of ^99mTc-nanocolloid (.2 mL, 123 MBq, 3.3 mCi) guided by ultrasound or stereotaxis. The sentinel node was pursued with the aid of vital blue dye (1.0 mL, intratumoral) and a gamma ray detection probe. In case of breast-conserving surgery, the probe was used to guide the excision. Results At least one sentinel node could be identified intraoperatively in 357 patients (97%), of whom 69 had involved nodes (19%). Age over 60 years was associated with less frequent nonaxillary lymphatic drainage and absence of internal mammary chain dissemination. Tumor-free margins were obtained in 262 (89%) of the 293 patients who underwent segmental excision. Re-excision of the primary tumor bed was performed in six patients (2%). During a median follow-up of 22 months, one breast recurrence and one axillary recurrence were observed. Conclusions Lymphatic mapping and probe-guided tumor excision of nonpalpable breast cancer by intralesional administration of a single dose of ^99mTc-nanocolloid and blue dye resulted in 97% identification of the sentinel node and in tumor-free margins in 89% of the patients who underwent breast-conserving surgery. Longer follow-up is needed to substantiate the accuracy and safety of this technique.     

Risk of invasion and axillary lymph node metastasis in ductal carcinoma in situ diagnosed by core-needle biopsy

BACKGROUND: The aim of the study was to assess the risk of invasion and axillary lymph node metastasis in patients with ductal carcinoma in situ (DCIS) diagnosed by preoperative core-needle biopsy. The data were used to select criteria for patients in whom sentinel node (SN) biopsy might be indicated. METHODS: One hundred and seventy-one women with 172 DCIS lesions diagnosed by core-needle biopsy were analysed. Axillary staging was performed by SN biopsy, axillary node sampling, or level 1-2 axillary lymph node dissection. RESULTS: Invasive breast cancer was found in the surgical specimens from 45 tumours (26.2 per cent). Risk factors for invasion were a palpable lesion (odds ratio (OR) 2.95 (95 per cent confidence interval 1.20 to 7.26); P = 0.019), presence of a mass on mammography (OR 3.06 (1.43 to 6.56); P = 0.004), and intermediate (OR 5.81 (1.18 to 28.57); P = 0.030) or poorly differentiated (OR 5.46 (1.17 to 25.64); P = 0.031) tumour grade. Lymph node metastases were found in ten women with DCIS and invasion on final pathology. Factors associated with metastases were age 55 years or less (P = 0.030), invasion of 1.0 cm or more (P < 0.001) and the presence of vascular invasion (P = 0.001). CONCLUSION: SN biopsy should be considered in women with an initial diagnosis of DCIS on core-needle biopsy who are at risk for invasion; this includes women with a palpable lump, a mass on mammography, and intermediate or poor tumour grade.