Use of Near-Infrared Spectroscopy to Monitor Lower Extremity Perfusion in Pediatric Patients Undergoing Cardiac Catheterization.

Acute femoral artery occlusion is common in pediatric patients following cardiac catheterization. A variety of means are utilized to assess lower extremity (LE) perfusion and arterial patency following cardiac catheterization including palpation of pulses, pulse oximetry, subjective assessment of lower extremity color and temperature, and ultrasound. We sought to evaluate the utility of Near-Infrared Spectroscopy (NIRS) to monitor LE perfusion in pediatric patients undergoing cardiac catheterization. INVOS pediatric sensors were placed on bilateral LE in all pediatric patients ≤ 40 kg undergoing cardiac catheterization. Data were recorded continuously from the start of the procedure until 4-6 h after completion of the procedure. NIRS readings were compared between the accessed versus non-accessed LE at baseline before start of case, time of vascular access, arterial sheath exchange when applicable, sheath withdrawal, and Safeguard application, deflation, and removal. 133 patients underwent 152 catheterizations with mean age 2.4 ± 2.3 years and mean weight 12.4 ± 13.2 kg. NIRS oximetry readings were significantly decreased in the LE with arterial access compared to non-accessed LE from time of sheath insertion until removal of the pressure assist device post procedure. A greater difference was noted in smaller patients. NIRS oximetry readings did not correlate with subjective assessment of lower extremity perfusion after arterial sheaths were removed. One patient had pulse loss 4 h post procedure with a decrease in oximetry readings noted at this point on review. Weight-based heparin protocol was initiated, and a gradual improvement in oximetry readings was noted over the next 5 h. Vascular ultrasound 12 h later showed no evidence of arterial thrombus. NIRS may be helpful in identifying patients who are risk for developing arterial thrombus post cardiac catheterization and for monitoring response to therapy; however, further study in these patients is warranted.

Biomarkers on melanoma patient T cells associated with ipilimumab treatment.

BACKGROUND: Ipilimumab induces long-lasting clinical responses in a minority of patients with metastatic melanoma. To better understand the mechanism(s) of action and to identify novel biomarkers associated with the clinical benefit and toxicity of ipilimumab, baseline characteristics and changes in CD4(+) and CD8(+) T cells from melanoma patients receiving ipilimumab were characterized by gene profiling and flow cytometry. METHODS: Microarray analysis of flow-cytometry purified CD4(+) and CD8(+) T cells was employed to assess gene profiling changes induced by ipilimumab. Selected molecules were further investigated by flow cytometry on pre, 3-month and 6-month post-treatment specimens. RESULTS: Ipilimumab up-regulated Ki67 and ICOS on CD4(+) and CD8(+) cells at both 3- and 6-month post ipilimumab (p ≤ 0.001), decreased CCR7 and CD25 on CD8(+) at 3-month post ipilimumab (p ≤ 0.02), and increased Gata3 in CD4(+) and CD8(+) cells at 6-month post ipilimumab (p ≤ 0.001). Increased EOMES(+)CD8(+), GranzymeB(+)EOMES(+)CD8(+) and decreased Ki67(+)EOMES(+)CD4(+) T cells at 6 months were significantly associated with relapse (all p ≤ 0.03). Decreased Ki67(+)CD8(+) T cells were significantly associated with the development of irAE (p = 0.02). At baseline, low Ki67(+)EOMES(+)CD8(+) T cells were associated with relapse (p ≤ 0.001), and low Ki67(+)EOMES(+)CD4(+) T cells were associated with irAE (p ≤ 0.008). CONCLUSIONS: Up-regulation of proliferation and activation signals in CD4(+) and CD8(+) T cells were pharmacodynamic markers for ipilimumab. Ki67(+)EOMES(+)CD8(+) and Ki67(+)EOMES(+)CD4(+)T cells at baseline merit further testing as biomarkers associated with outcome and irAEs, respectively.

Group cognitive-behavioral therapy versus selective serotonin reuptake inhibitors for obsessive-compulsive disorder: a practical clinical trial.

Clinical effectiveness of group cognitive-behavioral therapy (GCBT) versus fluoxetine in obsessive-compulsive disorder outpatients that could present additional psychiatric comorbidities was assessed. Patients (18-65 years; baseline Yale-Brown Obsessive-Compulsive-Scale [Y-BOCS] scores ≥ 16; potentially presenting additional psychiatric comorbidities) were sequentially allocated for treatment with GCBT (n=70) or fluoxetine (n=88). Mean Y-BOCS scores decreased by 23.13% in the GCBT and 21.54% in the SSRI groups (p=0.875). Patients presented a mean of 2.7 psychiatric comorbidities, and 81.4% showed at least one additional disorder. A reduction of at least 35% in baseline Y-BOCS scores and CGI ratings of 1 (much better) or 2 (better) was achieved by 33.3% of GCBT patients and 27.7% in the SSRI group (p=0.463). The Y-BOCS reduction was significantly lower in patients with one or more psychiatric comorbidities (21.15%, and 18.73%, respectively) than in those with pure OCD (34.62%; p=0.034). Being male, having comorbidity of Major Depression, Social Phobia, or Dysthymia predicted a worse response to both treatments. Response rates to both treatments were similar and lower than reported in the literature, probably due to the broad inclusion criteria and the resulting sample more similar to the real world population.

Extended dose ipilimumab with a peptide vaccine: immune correlates associated with clinical benefit in patients with resected high-risk stage IIIc/IV melanoma.

PURPOSE: To determine safety and feasibility of adjuvant ipilimumab following resection of high-risk melanoma and to identify surrogate markers for benefit. EXPERIMENTAL DESIGN: In this phase II trial, 75 patients with resected stage IIIc/IV melanoma received the CTLA-4 antibody ipilimumab every 6 to 8 weeks for 1 year. Eligible patients received further maintenance treatments. The first 25 patients received 3 mg/kg of ipilimumab, and an additional 50 patients received 10 mg/kg. HLA-A*0201+ patients received multipeptide immunizations in combination with ipilimumab. Leukapheresis was performed prior to and 6 months after initiation of treatment. RESULTS: Median overall and relapse-free survivals were not reached after a median follow-up of 29.5 months. Significant immune-related adverse events were observed in 28 of 75 patients and were positively associated with longer relapse-free survival. Antigen-specific T cell responses to vaccine were variable, and vaccine combination was not associated with additional benefit. No effects on T regulatory cells were observed. Higher changes in Th-17 inducible frequency were a surrogate marker of freedom from relapse (P = 0.047), and higher baseline C-reactive protein (CRP) levels were associated with freedom from relapse (P = 0.035). CONCLUSIONS: Adjuvant ipilimumab following resection of melanoma at high risk for relapse appeared to be associated with improved outcome compared to historical reports. Significant immune-related adverse events were generally reversible and appeared to be associated with improved relapse-free survival. Although vaccination failed to induce a consistent in vitro measurable response, a higher change in Th-17 inducible cells and higher baseline CRP levels were positively associated with freedom from relapse.

Are psychiatric residents still interested in psychoanalysis? A brief report.

In spite of the efficacy of the psychodynamic psychotherapies, the number of young psychiatric residents interested in psychodynamic therapies is decreasing. Our psychoanalytical group, Genden (Genève-Denver), explored the possible reasons for psychiatric residents' hesitation to get psychoanalytic training. Five psychoanalytical psychotherapists met weekly for a year in order to debate that question, focusing on personal feedbacks from all of our 100 residents in psychiatry working with us for at least 4 years. Following the residents' responses, our focus group proposed ten commonsense feedbacks for psychoanalysts regarding stimulating young psychiatric residents' interest in psychoanalytic approaches.

Effects of prior augmentation and reduction mammoplasty to sentinel node lymphatic mapping in breast cancer.

Previous plastic surgery procedures such as breast augmentation or reduction mammoplasty can potentially alter the lymphatic drainage of the breast. The purpose of this study is to determine the success rates of sentinel node lymphatic mapping in patients with previous plastic surgical procedures of the breast. A total of 83 patients with a history of plastic surgery of the breast that underwent subsequent sentinel node mapping between 1996 and 2008 were retrospectively analyzed. Eight-three patients that underwent a total of 108 sentinel node biopsies. Hundred cases (93%) previously underwent breast augmentation and eight cases (7%) previously underwent reduction mammoplasty. The mean time between the previous plastic surgical procedures and the sentinel node biopsy was 10.3 years (range: 2 months-32 years). Indications for the mapping procedure were invasive cancer (n = 64), ductal carcinoma in situ (n = 17), and prophylactic mastectomy (n = 27). The identification rate of the sentinel node was 95.3% (103/108). The success rate based on type of procedure was 96% (96/100) for augmentation and 87.5% (7/8) for reduction mammoplasty. With a mean follow-up of 3.4 years, there has been only one local axillary recurrence that occurred at the time of an ipsilateral breast recurrence following lumpectomy. Lymphatic mapping can be successfully performed in patients who have previously undergone plastic surgery operations.

HDAC2 regulates chromatin plasticity and enhances DNA vulnerability.

Histone deacetylases (HDAC) may have a prominent role in the development of cancer and the response to anticancer therapy. However, the therapeutic relevance and tissue specificity of individual HDAC enzymes remain largely unknown. HDAC inhibitors may function as sensitizing agents to chemotherapies that target DNA through their effects on chromatin structure and plasticity. Here, we report a new role for HDAC2 as a regulator of chromatin compaction status and the mediator of HDAC inhibitor-induced sensitization to chemotherapy. The selective depletion of HDAC2 by small interfering RNA led to reduced expression of heterochromatin maintenance proteins and morphologic changes indicative of chromatin decondensation. Furthermore, depletion of HDAC2 but not HDAC1 or HDAC6 was sufficient to sensitize breast cancer cells to topoisomerase inhibitor-induced apoptosis. The levels of HDAC2 expression appear to correlate with the degree of HDAC inhibitor-induced histone acetylation in a surrogate tissue in patients. These data suggest that HDAC2 may be a relevant pharmacologic and biological target for combination therapy involving drugs that target DNA.