Fever at Time of Leukemia Diagnosis in Children: Predictor of Bloodstream Infection or Catheter Removal?

PURPOSE: To assess the incidence of fever at diagnosis in children with leukemia and determine if fever at diagnosis is a predictor of bloodstream infection (BSI) or central venous access device (CVAD) removal for infection either within the first 30 days or between 30 and 90 days after CVAD insertion. MATERIALS AND METHODS: One hundred fifty-one patients with acute leukemia (July 1, 2018, to December 31, 2020) who underwent a CVAD insertion within 2 weeks of diagnosis were included. Patient data included demographic characteristics, fever at diagnosis, CVAD type, antibiotics before and/or on the day of CVAD insertion, BSI incidence, BSI rates per 1,000 catheter days, and need for catheter removal after CVAD insertion within 30 days and between 30 and 90 days. RESULTS: Patients with fever at diagnosis had a significantly higher incidence of BSI within the first 30 days after CVAD insertion (17/23) than that among patients without fever (6/23) (P = .046) at diagnosis. No statistically significant difference was observed in the incidence of BSI between 30 and 90 days after CVAD insertion between patients with fever (5/11) and those without fever at diagnosis (6/11) (P = .519). Fever at diagnosis was not a predictor of CVAD removal within 30 days (9 patients required CVAD removal; 7/9 had fever and 2/9 had no fever) (P = .181) or between 30 and 90 days (4 patients required CVAD removal; 1/4 had fever and 3/4 had no fever at diagnosis) (P = .343) after insertion. CONCLUSIONS: Fever at diagnosis in patients with leukemia is not a predictor of CVAD removal for infection.

Sirolimus for vascular anomalies associated with PTEN hamartoma tumor syndrome.

Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a rare condition associated with vascular anomalies and increased tumor risk. Sirolimus, an mTOR inhibitor used for managing vascular anomalies is underexplored in PHTS. A single-institution retrospective review of children with PHTS and vascular anomalies treated with sirolimus identified seven patients. Median age at sirolimus initiation was 10 years. After a median 2.5-year follow-up, six of seven patients (86%) showed significant clinical improvement. No significant adverse effects were observed, except mild buccal ulcers and acne. This study supports sirolimus as an effective and safe treatment for vascular anomalies in a small group of children with PHTS.

Complications of pediatric macrocystic lymphatic malformations of the head and neck: a survival analysis of treated and untreated patients.

OBJECTIVE: To compare events of recurrent swelling between treated and untreated patients with macrocystic lymphatic malformations of the head and neck not involving the airway. The frequency and timing of emergency department (ED) visits related to the event were analysed to provide data on efficacy and ideal timing of treatment. METHODS: A 5-year retrospective review of a hospital database was conducted reviewing 35 patients (15 female, 20 male; mean age 3.9 years) with macrocystic lymphatic malformations of the head and neck not involving the airway. Patients treated with oral medications were excluded. A survival analysis was performed comparing the incidence of recurrent swelling of the malformation. A Cox regression analysis was conducted using age, gender, diameter of lymphatic malformation at presentation, and echogenicity on US as covariates. Fisher's test and mean comparisons were performed to correlate the populations baselines and the number and frequency of ED visits between the 2 groups. RESULTS: Thirteen patients underwent sclerotherapy soon after initial presentation and 22 elected for observation. The two baseline populations differed at presentation with the treatment group being younger (1.4 ± 2.4 vs. 5.4 ± 6.3 years, p = 0.03) and with larger lesions (5.7 ± 2.7 vs. 4.0 ± 1.7 cm p = 0.03). Mean follow-up time was 2.7 years. Survival analysis showed 1 or multiple recurrences affected 16 patients in the untreated group and 3 patients in the treated group. (p = 0.04). Age, gender, diameter of the lesion at presentation and increased echogenicity on US were not predictive factors of recurrence. Although the probability of visiting the ED at least once did not differ between the two groups (p = 0.42), patients from the non-treatment group were more likely to visit the ED more than once (p = 0.03). CONCLUSIONS: Sclerotherapy treatment may reduce the chance of recurrent swelling or an event after initial presentation to the ED.

Safety and Effectiveness of Sclerotherapy for Nonparasitic Splenic Cysts: A Systematic Review and Meta-Analysis.

PURPOSE: To assess the reported safety and effectiveness of sclerotherapy for the treatment of nonparasitic splenic cysts through a systematic review and meta-analysis. MATERIALS AND METHODS: A systematic search of PubMed MEDLINE, Embase, Web of Science, and the Cochrane Library through July 2023 was performed. Studies including at least 5 patients reporting percutaneous sclerotherapy of nonparasitic splenic cysts, initial and posttreatment cyst size, clinical symptoms as well as adverse events (AEs), and recurrence rates were included. A 0-8-point scale for case reports and case series was used to assess bias. Data were analyzed using random-effects meta-analysis. RESULTS: Twenty-three of 833 citations were selected for full-text assessment, and 7 studies were included for a total of 99 patients. The methodological quality of the studies included scored 3-7. Composite analysis demonstrated 38% (95% CI, 23%-55%) rate of recurrence after treatment with significant heterogeneity; however, when assessed for a cyst size of <8 cm, recurrence dropped to 7% (95% CI, 2%-20%). Residual symptoms after treatment completion were present in 17% (95% CI, 7%-33%). Intraprocedural and postprocedural AE rates were 6% (95% CI, 3%-13%) and 6% (95% CI, 3%-12%) respectively. CONCLUSIONS: Sclerotherapy of splenic cysts seemed to be safe, with a high rate of recurrence for cysts ≥8 cm.

Splenic embolization in trauma: results of a survey from an international cohort.

PURPOSE: A questionnaire regarding splenic embolization in trauma was submitted to an international sample of IR faculty members, to compare their practice to the available recommendations. METHODS: A 21 multiple-choice questionnaire was sent to an international cohort of 96 IR faculty. Questions included the initial patient evaluation, embolization materials and techniques, post-procedure management, availability of an institutional protocol, and use of guidelines. RESULTS: For each question, there were from a minimum of 45 to a maximum of 52 responders: 94% require a CT with contrast prior to embolization, and 87% use the American Association for the Surgery of Trauma (AAST) scale to grade the splenic injuries. Embolization is performed across all values of the AAST scale. Of the patients with injuries of grade III or greater, embolization is primarily done for those patients who are hemodynamically stable. Unstable patients are embolized less frequently and primarily in cases in which the injuries are of a lower grade. Coils are the preferred material for proximal embolization (69%). Particles/Gelfoam is the preferred material for distal embolization (38%). In total, 63% administer intravenous antibiotics before the procedure and 15% administer intra-arterial antibiotics during the procedure. After embolization, follow-up imaging is recommended by 87%, antibiotics are administered regularly by 33%, clinical follow-up is recommended by 73%, and vaccination against encapsulated organisms is routinely recommended by 39%. CONCLUSIONS: There is significant variability among a heterogeneous cohort of respondents. Available recommendations may not be sufficiently addressing the practice of splenic embolization.

Three-Year Efficacy and Safety of the Misago Peripheral Stent for Superficial Femoral Artery Disease: Final Results from the OSPREY Trial.

PURPOSE: This study evaluated the long-term outcomes of the Misago peripheral stent trial (Terumo) for atherosclerotic lesions in the superficial femoral artery (SFA) in patients with claudication. MATERIALS AND METHODS: This was a prospective multicenter, single-arm, clinical trial of primary stent placement for de novo cases of SFA disease conducted in the United States and Asia. The primary endpoint was freedom from clinically driven target lesion revascularization (CD-TLR) at 36 months. Secondary outcomes were ankle-brachial index (ABI), Rutherford score, Walking Impairment Questionnaire (WIQ), a quality of life survey, and rate of device fracture. RESULTS: A total of 276 patients (64.4% male; mean age, 69.3 ± 10.1 years) were enrolled. Freedom from CD-TLR was 78.5% (95% confidence interval [CI], 73.0%-83.0%) at 24 months and 75.4% (95% CI, 69.6%-80.2%) at 36 months. Baseline ABI was 0.7 ± 0.1 and 0.98 ± 0.20 (P < .001) at 30 days after the procedure. Baseline Rutherford score was 3.6 ± 0.6 and 1.6 ± 1.0 30 at 30 days after the procedure (P < .001). Mean (and changed) ABI and Rutherford score at 36 months compared to day 30 after the procedure were, respectively, 0.91 (-0.1 ± 0.2) and 1.5 (-0.2 ± 1.1). WIQ score at baseline was 21.49 ± 26.30 and 50.51 ± 38.49 at 30 days after the procedure ( P < .001). The mean WIQ score at 2 years was 46.65 ± 37.31 (P = .12). Stent fracture rate at 36 months was 2.0% (4 of 202 patients). CONCLUSIONS: OSPREY (Occlusive-Stenotic Peripheral Artery Revascularization Study) 36-month data demonstrated persistent freedom from CD-TLR and sustained improvement in ABI and Rutherford score with primary stent placement for SFA lesions.

Factors Related to Late False Lumen Enlargement after Thoracic Stent-Graft Placement for Type B Aortic Dissection.

PURPOSE: To evaluate significant factors related to delayed aortic false lumen (FL) enlargement in patients who have undergone thoracic stent-graft placement for type B aortic dissection. MATERIALS AND METHODS: The study included 62 patients (45 male, 17 female) aged 26-80 years (mean age, 58.1 y) who underwent thoracic endovascular aortic repair for type B aortic dissection at a single institution between January 2005 and May 2015. Mean age of aortic dissections was 5.3 months (range, 0.1-73.3 mo). Maximum aortic diameter at presentation was 41.7 mm ± 8.3. The follow-up period ranged from 3 to 104 months (mean, 27.1 mo). Computed tomographic (CT) angiography studies were reviewed to identify FL diameter enlargements > 5 mm at different levels along and distal to the stent graft. Imaging findings and clinical variables were investigated to determine their correlation with FL enlargement. RESULTS: No significant difference was found between the ages of aortic dissections in patients with and without FL enlargement (P = .26). On follow-up CT angiography, 16 patients had 2 or more communication channels between the FL and the systemic circulation, 7 of whom showed FL enlargement > 5 mm (P = .007). Twenty-seven patients showed complete FL thrombosis, none of whom had FL enlargement (P < .001). CONCLUSIONS: Two or more communication channels between the FL and the systemic circulation represent a risk factor for FL enlargement regardless of the age of the dissection. Patients with thrombosis of the FL are less likely to experience FL enlargement.

Comparative analysis of Bcl-2 family protein overexpression in CAR T cells alone and in combination with BH3 mimetics.

Approximately 50% of patients with hematologic malignancies relapse after chimeric antigen receptor (CAR) T cell treatment; mechanisms of failure include loss of CAR T persistence and tumor resistance to apoptosis. We hypothesized that both of these challenges could potentially be overcome by overexpressing one or more of the Bcl-2 family proteins in CAR T cells to reduce their susceptibility to apoptosis, both alone and in the presence of BH3 mimetics, which can be used to activate apoptotic machinery in malignant cells. We comprehensively investigated overexpression of different Bcl-2 family proteins in CAR T cells with different signaling domains as well as in different tumor types. We found that Bcl-xL and Bcl-2 overexpression in CAR T cells bearing a 4-1BB costimulatory domain resulted in increased expansion and antitumor activity, reduced exhaustion, and decreased apoptotic priming. In addition, CAR T cells expressing either Bcl-xL or a venetoclax-resistant Bcl-2 variant led to enhanced antitumor efficacy and survival in murine xenograft models of lymphoma and leukemia in the presence or absence of the BH3 mimetic venetoclax, a clinically approved BH3 mimetic. In this setting, Bcl-xL overexpression had stronger effects than overexpression of Bcl-2 or the Bcl-2(G101V) variant. These findings suggest that CAR T cells could be optimally engineered by overexpressing Bcl-xL to enhance their persistence while opening a therapeutic window for combination with BH3 mimetics to prime tumors for apoptosis.

Immunotherapy against the Cystine/Glutamate Antiporter xCT Improves the Efficacy of APR-246 in Preclinical Breast Cancer Models.

Breast cancer is the most frequent cancer in women. Despite recent clinical advances, new therapeutic approaches are still required. The cystine-glutamate antiporter xCT, encoded by the SLC7A11 gene, which imports cystine in exchange with glutamate, is a potentially new target for breast cancer therapy, being involved in tumor cell redox balance and resistance to therapies. xCT expression is regulated by the oncosuppressor p53, which is mutated in many breast cancers. Indeed, mutant p53 (mut-p53) can induce xCT post-transcriptional down modulation, rendering mut-p53 tumors susceptible to oxidative damage. Interestingly, the drug APR-246, developed to restore the wild-type function of p53 in tumors harboring its mutation, alters the cell redox balance in a p53-independent way, possibly rendering the cells more sensitive to xCT inhibition. Here, we propose a combinatorial treatment based on xCT immunetargeting and APR-246 treatment as a strategy for tackling breast cancer. We demonstrate that combining the inhibition of xCT with the APR-246 drug significantly decreased breast cancer cell viability in vitro and induced apoptosis and affected cancer stem cells' self-renewal compared to the single treatments. Moreover, the immunetargeting of xCT through DNA vaccination in combination with APR-246 treatment synergistically hinders tumor progression and prevents lung metastasis formation in vivo. These effects can be mediated by the production of anti-xCT antibodies that are able to induce the antibody dependent cellular cytotoxicity of tumor cells. Overall, we demonstrate that DNA vaccination against xCT can synergize with APR-246 treatment and enhance its therapeutic effect. Thus, APR-246 treatment in combination with xCT immunetargeting may open new perspectives in the management of breast cancer.

Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies.

The cystine/glutamate antiporter xCT is a tumor-associated antigen that has been newly identified in many cancer types. By participating in glutathione biosynthesis, xCT protects cancer cells from oxidative stress conditions and ferroptosis, and contributes to metabolic reprogramming, thus promoting tumor progression and chemoresistance. Moreover, xCT is overexpressed in cancer stem cells. These features render xCT a promising target for cancer therapy, as has been widely reported in the literature and in our work on its immunotargeting. Interestingly, studies on the TP53 gene have revealed that both wild-type and mutant p53 induce the post-transcriptional down modulation of xCT, contributing to ferroptosis. Moreover, APR-246, a small molecule drug that can restore wild-type p53 function in cancer cells, has been described as an indirect modulator of xCT expression in tumors with mutant p53 accumulation, and is thus a promising drug to use in combination with xCT inhibition. This review summarizes the current knowledge of xCT and its regulation by p53, with a focus on the crosstalk of these two molecules in ferroptosis, and also considers some possible combinatorial strategies that can make use of APR-246 treatment in combination with anti-xCT immunotargeting.

Biomarkers in the setting of benign prostatic hyperplasia-induced lower urinary tract symptoms: what an interventional radiologist needs to know.

With increasing evidence to support prostate artery embolization (PAE) in the treatment of benign prostatic hyperplasia (BPH)-induced lower urinary tract symptoms (LUTS), Interventional Radiologists have begun to play an important role in the management of these patients. One area of knowledge needed when developing a PAE practice is knowledge of prostate-specific antigen (PSA) and other biomarkers utilized to detect prostate cancer in this population and what role they should play in the work up and follow-up of patients presenting with presumed BPH-induced LUTS. Furthermore, understanding how to evaluate presumed BPH-induced LUTS and stratify the risk of prostate cancer is an important skill to develop. The goal of this review is to provide Interventional Radiologists who have begun or aim to begin a PAE practice with the information they need to know regarding PSA levels and prostate cancer risk stratification for this patient population.

An experimental setup to test dual-joystick directional responses to vibrotactile stimuli.

In this paper we investigate the influence of the location of vibrotactile stimulation in triggering the response made using two handheld joysticks. In particular, we compare performance with stimuli delivered either using tactors placed on the palm or on the back of the hand and with attractive (move toward the vibration) or repulsive prompts (move away from the vibration). The experimental set-up comprised two joysticks and two gloves, each equipped with four pager motors along the cardinal directions. In different blocks, fifty-three volunteers were asked to move the joysticks as fast as possible either towards or away with respect to the direction specified by a set of vibrating motors. Results indicate that participants performed better with attractive prompts (i.e. responses were faster and with fewer errors in conditions where participants were asked to move the joysticks in the direction of the felt vibration) and that the stimulation delivered on the back of the hand from the gloves gives better results than the stimulation on the palm delivered by the joysticks. Finally, we analyse the laterality, the relation between correct responses and reaction times, the direction patterns for wrong responses and we perform an analysis on the Stimulus-Response Compatibility and on the training effect.

Clinical impact of strict criteria for selectivity and lateralization in adrenal vein sampling.

INTRODUCTION: Selectivity index (SI) and lateralization index (LI) thresholds determine the adequacy of adrenal vein sampling (AVS) and the degree of lateralization. The purpose of this study was investigate the clinical outcome of patients whose adrenal vein sampling was interpreted using "strict criteria" (SC) (SIpre-stimuli≥3, SIpost-stimuli≥5 and LIpre-stimuli≥4, LIpost-stimuli≥4). MATERIALS AND METHODS: A retrospective review of 73 consecutive AVS procedures was performed and 67 were technically successful. Forty-three patients showed lateralization and underwent surgery, while 24 did not lateralize and were managed conservatively. Systolic blood pressure (SBP), diastolic blood pressure (DBP), kalemia (K(+)), and the change in number of blood pressure (BP) medications were recorded for each patient before and after AVS and potential surgery were performed. RESULTS: In the surgery group, BP and K(+) changed respectively from 160±5.3/100±2.0 mmHg to 127±3.3/80±1.9 (p <0.001) and from 3.00±0.10 to 4.4±0.09 (p <0.001). In the medically managed group, BP and K(+) changed respectively from 148±7.3/93±4.3 to 135±3.3/86±1.9 (p <0.001) and from 2.68±0.10 to 4.3±0.09. After surgery or AVS, the patients who took ≥3 blood pressure medications were six (14.0%) in the lateralized group and 22 (91.7%) in the non-lateralized group (p <0.001). CONCLUSIONS: AVS interpretation with SC leads to significant clinical improvement in both patients who underwent surgery and those managed conservatively.

Ondansetron inhibits the analgesic effects of tramadol: a possible 5-HT(3) spinal receptor involvement in acute pain in humans.

UNLABELLED: To investigate a possible antinociceptive role of serotonin receptor subtype 3 (5-HT(3)), we evaluated the effects of a coadministration of ondansetron, a 5-HT(3) selective antagonist, and tramadol, a central analgesic dependent on enhanced serotonergic transmission. Fifty-nine patients undergoing ear, throat, and nose surgery, using tramadol for 24-h postoperative patient-controlled analgesia (bolus = 30 mg; lockout interval = 10 min) were randomly allocated either to a group receiving ondansetron continuous infusion (1 mg. mL(-1). h(-1)) for postoperative nausea and vomiting (Group O) or to a control group receiving saline (Group T). Pain and vomiting scores and tramadol consumption were evaluated at 4, 8, 12, and 24 h. Pain scores were never >4, according to a 0-10 numerical rating scale, in both groups. Group O required significantly larger doses of tramadol at 4 h (213 versus 71 mg, P < 0.001), 8 h (285 versus 128 mg, P < 0.002), and 12 h (406 versus 190 mg, P < 0.002). Vomiting scores were higher in Group O at 4 h (P < 0.05) and 8 h (P = 0.05). We conclude that ondansetron reduced the overall analgesic effect of tramadol, probably blocking spinal 5-HT(3) receptors. IMPLICATIONS: Serotonin is an important neurotransmitter of the descending pathways that down-modulate spinal nociception. In postoperative pain, ondansetron, a selective 5-HT(3) receptor antagonist, increased the analgesic dose of tramadol. We suggest that, when antagonized for antiemetic purpose, 5-HT(3) receptors foster nociception, because of their site-dependent action.