When to consider electroconvulsive therapy (ECT).

OBJECTIVE: To familiarize the reader with the role of electroconvulsive therapy (ECT) in current psychiatric medicine. METHOD: We review clinical indications for ECT, patient selection, contemporary ECT practice, maintenance treatment and ECT in major treatment guidelines. RESULTS: ECT is underutilized largely due to persisting stigma and lack of knowledge about modern ECT technique. CONCLUSION: ECT remains a vital treatment for patients with severe mood disorders, psychotic illness and catatonia.

Optical coherence tomography of basal cell carcinoma: influence of location, subtype, observer variability and image quality on diagnostic performance.

BACKGROUND: We previously described the principal results from an observational, prospective, multicentre, clinical trial of the diagnostic value of optical coherence tomography (OCT) for basal cell carcinoma (BCC) in a clinical setting. In this trial, much additional useful information was gathered that warranted further analysis, presented here. OBJECTIVES: To investigate the influence of candidate diagnostic criteria, OCT image quality, lesion location, and observer confidence and interobserver variability on the diagnostic performance of OCT, and to assess its potential use for diagnosis of BCC subtypes. METHODS: A total of 234 clinically unclear 'pink lesions' were evaluated in three steps: after clinical examination, after adding dermoscopy and after adding OCT. In addition to the diagnoses (including lesion subtype), observers recorded which of 15 diagnostic criteria the OCT image contained, their confidence in the diagnoses, the OCT image quality and the anatomical location of the lesion. RESULTS: Diagnostic performance of OCT did not depend on the lesion's anatomical location. Good OCT image quality was correlated with improved diagnostic performance, but diagnostic performance for lesions with mediocre image quality was still better than by clinical and dermoscopic examination. The main reason for reduced image quality was superficial scales and crusting. Observer confidence in diagnosis was correlated with diagnostic performance. Interobserver diagnostic performance was consistently higher than clinical examination and dermoscopy across all sites. BCC subtype could be determined with moderate accuracy, but further independent image markers are required. CONCLUSION: OCT is useful in the diagnosis of BCC.

CD20-Specific Immunoligands Engaging NKG2D Enhance γδ T Cell-Mediated Lysis of Lymphoma Cells.

Human γδ T cells are innate-like T cells which are able to kill a broad range of tumour cells and thus may have potential for cancer immunotherapy. The activating receptor natural killer group 2 member D (NKG2D) plays a key role in regulating immune responses driven by γδ T cells. Here, we explored whether recombinant immunoligands consisting of a CD20 single-chain fragment variable (scFv) linked to a NKG2D ligand, either MHC class I chain-related protein A (MICA) or UL16 binding protein 2 (ULBP2), could be employed to engage γδ T cells for tumour cell killing. The two immunoligands, designated MICA:7D8 and ULBP2:7D8, respectively, enhanced cytotoxicity of ex vivo-expanded γδ T cells against CD20-positive lymphoma cells. Both Vδ1 and Vδ2 γδ T cells were triggered by MICA:7D8 or ULBP2:7D8. Killing of CD20-negative tumour cells was not induced by the immunoligands, indicating their antigen specificity. MICA:7D8 and ULBP2:7D8 acted in a dose-dependent manner and induced cytotoxicity at nanomolar concentrations. Importantly, chronic lymphocytic leukaemia (CLL) cells isolated from patients were sensitized by the two immunoligands for γδ T cell cytotoxicity. In a combination approach, the immunoligands were combined with bromohydrin pyrophosphate (BrHPP), an agonist for Vδ2 γδ T cells, which further enhanced the efficacy in target cell killing. Thus, employing tumour-directed recombinant immunoligands which engage NKG2D may represent an attractive strategy to enhance antitumour cytotoxicity of γδ T cells.

The mortality rate of electroconvulsive therapy: a systematic review and pooled analysis.

OBJECTIVE: Electroconvulsive therapy (ECT) remains underutilized because of fears of cognitive and medical risks, including the risk of death. In this study, we aimed to assess the mortality rate of ECT by means of a systematic review and pooled analysis. METHOD: The study was conducted in adherence with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The ECT-related mortality rate was calculated as the total number of ECT-related deaths reported in the included studies divided by the total number of ECT treatments. RESULTS: Fifteen studies with data from 32 countries reporting on a total of 766 180 ECT treatments met the inclusion criteria. Sixteen cases of ECT-related death were reported in the included studies yielding an ECT-related mortality rate of 2.1 per 100 000 treatments (95% CI: 1.2-3.4). In the nine studies that were published after 2001 (covering 414 747 treatments), there was only one reported ECT-related death. CONCLUSION: The ECT-related mortality rate was estimated at 2.1 per 100 000 treatments. In comparison, a recent analysis of the mortality of general anesthesia in relation to surgical procedures reported a mortality rate of 3.4 per 100 000. Our findings document that death caused by ECT is an extremely rare event.

A systematic review of left unilateral electroconvulsive therapy.

OBJECTIVE: To systematically review the published clinical trials, case series, and case reports on left unilateral (LUL) electrode placement for clinical electroconvulsive therapy (ECT). METHOD: PubMed, Ovid Medline, and the Cochrane Library were searched for articles concerning LUL ECT. Number of patients, efficacy, and cognitive outcomes were extracted from the papers that met our inclusion criteria. RESULTS: A total of 52 articles were included in this review, consisting of 33 clinical trials, seven case series, and 12 case reports. CONCLUSION: Overall, the efficacy of LUL electrode placement for the treatment of depression and psychosis is similar to that of right unilateral (RUL) and bilateral (BL) electrode placements. Patients receiving LUL ECT tend to experience more verbal memory impairment than patients receiving RUL ECT, but less verbal impairment than patients receiving BL ECT. In contrast, patients receiving LUL ECT tended to experience the least visual and nonverbal memory impairment, compared to patients receiving RUL or BL ECT.

The sensitivity and specificity of optical coherence tomography for the assisted diagnosis of nonpigmented basal cell carcinoma: an observational study.

BACKGROUND: The diagnostic criteria for basal cell carcinoma (BCC) using optical coherence tomography (OCT) have been described previously, but the clinical value of these findings remains unknown. OBJECTIVES: To investigate the diagnostic value of OCT for BCC in a typical clinical setting. The primary efficacy end point was a diagnosis of BCC for each lesion. Secondary end points were the diagnosis of other possible conditions. METHODS: This was an observational, prospective, multicentre study in which consecutive patients with nonpigmented pink lesions suspicious for BCC underwent clinical assessment, dermoscopy and OCT, with the diagnosis recorded at each stage. Once all diagnoses had been recorded, the histological results were disclosed. In total 164 patients with 256 lesions were recruited. Histology was missing for 21 lesions, leaving 235 lesions in 155 patients for analysis. RESULTS: Sixty per cent of lesions (141 of 235) were identified as BCC by histology. A slight increase of sensitivity was noted following OCT, which did not reach statistical significance. The specificity increased significantly from 28·6% by clinical assessment to 54·3% using dermoscopy and to 75·3% with the addition of OCT (P < 0·001). The positive predictive value for the diagnosis of BCC using OCT was 85·2% [95% confidence interval (CI) 78·6-90·4], and the negative predictive value was 92·1% (95% CI 83·6-97·0). The accuracy of diagnosis for all lesions increased from 65·8% with clinical evaluation to 76·2% following additional dermoscopy and to 87·4% with the addition of OCT. CONCLUSIONS: OCT significantly improved the diagnostic specificity for BCC compared with clinical assessment and dermoscopy alone.

[Modern diagnostic procedures in dermatological oncology]. / Moderne Diagnoseverfahren in der Dermatoonkologie.

BACKGROUND: New technologies, such as confocal laser scanning microscopy (CLSM), optical coherence tomography (OCT), electrical impedance spectroscopy (EIS) and multispectral analysis have greatly enriched the possibilities of diagnostics in dermatological oncology. They can be supplementary tools to dermatoscopy and histopathology to make a more precise diagnosis of skin lesions. OBJECTIVES: Increasing relevance of new systems for diagnosis and monitoring of dermatological therapy. Presentation of the technology and the diagnostic range of application for various skin lesions. MATERIAL AND METHODS: Presentation of scientifically relevant studies and statistical data, discussion of basic research and expert recommendations. RESULTS: The diagnostic spectrum of dermatological oncology has been significantly enriched in recent years. New technologies, such as CLSM, OCT, EIS and multispectral analysis are non-invasive and therefore painless for the patient. In only a few minutes these techniques deliver valid data and findings and provide dermatologists with more accurate diagnostic information about benign or malignant melanocytic skin lesions or the various forms of white skin cancer. CONCLUSION: In recent years, non-invasive diagnostic and analytical imaging procedures have been progressively established in dermatological oncology and supplement classical dermatoscopy and histopathology. With respect to the follow-up of different therapeutic modalities unnecessary tissue biopsies and scars can be reduced for patients.

Multivariate carbon and nitrogen stable isotope model for the reconstruction of prehistoric human diet.

Using a sample of published archaeological data, we expand on an earlier bivariate carbon model for diet reconstruction by adding bone collagen nitrogen stable isotope values (δ(15) N), which provide information on trophic level and consumption of terrestrial vs. marine protein. The bivariate carbon model (δ(13) C(apatite) vs. δ(13) C(collagen) ) provides detailed information on the isotopic signatures of whole diet and dietary protein, but is limited in its ability to distinguish between C(4) and marine protein. Here, using cluster analysis and discriminant function analysis, we generate a multivariate diet reconstruction model that incorporates δ(13) C(apatite) , δ(13) C(collagen) , and δ(15) N holistically. Inclusion of the δ(15) N data proves useful in resolving protein-related limitations of the bivariate carbon model, and splits the sample into five distinct dietary clusters. Two significant discriminant functions account for 98.8% of the sample variance, providing a multivariate model for diet reconstruction. Both carbon variables dominate the first function, while δ(15) N most strongly influences the second. Independent support for the functions' ability to accurately classify individuals according to diet comes from a small sample of experimental rats, which cluster as expected from their diets. The new model also provides a statistical basis for distinguishing between food sources with similar isotopic signatures, as in a previously analyzed archaeological population from Saipan (see Ambrose et al.: AJPA 104(1997) 343-361). Our model suggests that the Saipan islanders' (13) C-enriched signal derives mainly from sugarcane, not seaweed. Further development and application of this model can similarly improve dietary reconstructions in archaeological, paleontological, and primatological contexts.

Transradial Approach for Neuroendovascular Procedures: A Single-Center Review of Safety and Feasibility.

BACKGROUND AND PURPOSE: In recent years, the transradial approach has become more widely adopted for neuroendovascular procedures. The purpose of this study was to evaluate the safety and feasibility of a transradial approach and distal transradial access for neuroendovascular procedures in a single center. MATERIALS AND METHODS: Retrospective analysis was performed for all patients who underwent transradial approach or distal transradial access neuroendovascular procedures from January 2016 to August 2019 at a single center. Exclusion criteria included a Barbeau D waveform, a radial artery of <2 mm on sonographic evaluation, and known radial artery occlusion. Procedures were evaluated for technical success (defined as successful radial artery access and completion of the intended procedure without crossover to an auxiliary access site), complications, and adverse events during follow-up at 30 days. RESULTS: The transradial approach or distal transradial access was attempted in 279 consecutive patients (58.1% women; median age, 57.7 years) who underwent 328 standard or distal transradial approach procedures. Two-hundred seventy-nine transradial approach and 49 distal transradial approach procedures were performed (cerebral angiography [n = 213], intracranial intervention [n = 64], head and neck intervention [n = 30], and stroke intervention [n = 21]). Technical success was 92.1%. Immediate adverse events (2.1%) included radial access site hematoma (n = 5), radial artery occlusion (n = 1), and acute severe radial artery spasm (n = 1). Thirty-day adverse events (0.3%) included a radial artery pseudoaneurysm (n = 1). Twenty-six cases (7.9%) required crossover to transfemoral access. CONCLUSIONS: The transradial approach for neuroendovascular procedures is safe and feasible across a wide range of neuroendovascular interventions.

Racial and Socioeconomic Disparities in the Use and Outcomes of Endovascular Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Racial and socioeconomic disparities in the incidence, treatment, and outcomes of acute ischemic stroke exist and have been described. We aimed to characterize disparities in the use of endovascular thrombectomy in a nationally representative analysis. MATERIALS AND METHODS: Discharge data from the Nationwide Inpatient Sample between 2006 and 2016 were queried using validated International Classification of Disease codes. Patients admitted to US hospitals with acute ischemic stroke were included and stratified on the basis of race, income, and primary payer. Trends in endovascular thrombectomy use, good outcome (discharge to home/acute rehabilitation), and poor outcome (discharge to skilled nursing facility, hospice, in-hospital mortality) were studied using univariate and multivariable analyses. RESULTS: In this analysis of 1,322,162 patients, endovascular thrombectomy use increased from 53/111,829 (0.05%) to 3054/146,650 (2.08%) between 2006 and 2016, respectively. Less increase was observed in black patients from 4/12,733 (0.03%) to 401/23,836 (1.68%) and those in the lowest income quartile from 10/819 (0.03%) to 819/44,984 (1.49%). Greater increase was observed in the highest income quartile from 18/22,138 (0.08%) to 669/27,991 (2.39%). Black race predicted less endovascular thrombectomy use (OR = 0.79; 95% CI, 0.72-0.86). The highest income group predicted endovascular thrombectomy use (OR = 1.24; 95% CI, 1.13-1.36) as did private insurance (OR = 1.30; 95% CI, 1.23-1.38). High income predicted good outcome (OR = 1.10; 95% CI. 1.06-1.14), as did private insurance (OR = 1.36; 95% CI, 1.31-1.39). Black race predicted poor outcome (OR = 1.33; 95% CI, 1.30-1.36). All results were statistically significant (P < .01). CONCLUSIONS: Despite a widespread increase in endovascular thrombectomy use, black and low-income patients may be less likely to receive endovascular thrombectomy. Future effort should attempt to better understand the causes of these disparities and develop strategies to ensure equitable access to potentially life-saving treatment.

Electroconvulsive therapy is equally effective in unipolar and bipolar depression.

OBJECTIVE: To determine the relative efficacy of electroconvulsive therapy (ECT) in the treatment of bipolar (BP) and unipolar (UP) depressive illness and clarify its role in BP depression. METHOD: Patients referred for ECT with both UP and BP depressions. [classified by Structured Clinical Interview for DSM (SCID-I) criteria for history of mania] were included in a multi-site collaborative, double-masked, randomized controlled trial of three electrode placements - right unilateral, bifrontal or bitemporal - in a permutated block randomization scheme. RESULTS: Of 220 patients, 170 patients (77.3%) were classified as UP and 50 (22.7%) as BP depression in the intent-to-treat sample. The remission and response rates and numbers of ECT for both groups were equivalent. CONCLUSION: Both UP and BP depressions remit with ECT. Polarity is not a factor in the response rate. In this sample ECT did not precipitate mania in depressed patients. Treatment algorithms for UP and BP depression warrant re-evaluation.

Vessel Wall MRI Enhancement in Noninflammatory Cerebral Amyloid Angiopathy.

Cerebral amyloid angiopathy is characterized by deposition of amyloid-ß fibrils in the walls of small-to-medium-sized blood vessels. In this retrospective review of 5 patients with histologically confirmed noninflammatory cerebral amyloid angiopathy, high-resolution vessel wall MRI showed arterial wall enhancement in 2 patients (40%). Despite common consensus of equating vessel wall enhancement with inflammation, this report demonstrates that ß-amyloid accumulation alone without inflammation can be associated with arterial wall enhancement in a subset of patients.

A CD19-specific single-chain immunotoxin mediates potent apoptosis of B-lineage leukemic cells.

CD19 is a B-lineage-specific transmembrane signaling protein participating in the control of proliferation and differentiation. It is present at high surface density on chronic B-lymphocytic leukemia (B-CLL) cells and cells of other B-cell malignancies, and is a prime target for therapy with antibody-derived agents. Many attempts have been made to target malignant cells via CD19, but to date none of these agents have received drug approval. Here we report the design of a monovalent immunotoxin consisting of a CD19-specific single-chain Fv antibody fragment fused to a derivative of Pseudomonas Exotoxin A. This fusion protein induced efficient antigen-restricted apoptosis of several human leukemia- and lymphoma-derived cell lines including Nalm-6, which it eliminated at an effective concentration (EC(50)) of 2.5 nM. The agent displayed synergistic toxicity when used in combination with valproic acid and cyclosporin A in cell-culture assays. It induced apoptosis of primary malignant cells in 12/12 samples from B-CLL patients, including patients responding poorly to fludarabine, and of cells from one pediatric acute lymphoblastic leukemia patient. In NOD/SCID mice transplanted with Nalm-6 cells, the toxin prevented engraftment and significantly prolonged survival of treated mice. Owing to its efficient antigen-restricted antileukemic activity, the agent deserves further development towards clinical testing.