Parenting Adolescents

The period of adolescence is often thought to be one of intense stress and turmoil. Yet many parents and teens negotiate this developmental stage without extreme family conflict and without sacrificing close relationships. This review summarizes a portion of the literature on parent-adolescent relationships, focusing on monitoring and control of adolescent behavior and parenting style. Basic principles to emphasize when working with adolescents and parents are also included

Parenting Adolescents

The period of adolescence is often thought to be one of intense stress and turmoil. Yet many parents and teens negotiate this developmental stage without extreme family conflict and without sacrificing close relationships. This review summarizes a portion of the literature on parent-adolescent relationships, focusing on monitoring and control of adolescent behavior and parenting style. Basic principles to emphasize when working with adolescents and parents are also included

The StO2 non-invasive tissue hypoperfusion monitor as a screening tool for early sepsis detection in the emergency department

Background: Early Recognition of patients with sepsis induced tissue hypoperfusion (SITH) Remains a significant clinical challenge. Non--‐invasive Tissue oxygenation saturation (StO2) Monitors have been developed to provide rapid, low--‐cost, and non--‐invasive bedside assessments of tissue oxygen extraction; they have not been well validated as an initial screening tool for sepsis in the ED. Objectives: To Assess the efficacy of initial bedside StO2 Readings in the early identification of patients with SITH And to compare StO2 Readings with lactate levels. Methods: IRB approved, prospective, observational pilot study of a convenience sample of ED Patients presenting with a sepsis continuum diagnosis. Setting: Urban Tertiary care center with 90k visits/yr. Inclusion criteria: Suspicion Of new infection plus 2 SIRS criteria. Exclusion criteria: \u3c18 Or no suspicion of infection. Study procedures: Demographics, co--‐morbidities, clinical data, treatment, disposition, and mortality were collected. A Portable In--‐Spectra ‘Spot Check’ StO2 Monitor was used totake a StO2 Reading at the thenar eminence; a second reading was taken three hours later. All Investigators were trained with the device to record data with a high degree of accuracy and reliability. Abnormal StO2 Was defined as \u3c80% or\u3e91%. The Study was observational and there were no clinical interventions. Descriptive Statistics were employed and Sensitivity/Specificity, Likelihood ratios, andNPV/PPV Were calculated with 95% Confidence intervals (in parenthesis) where appropriate. Results: 79 Patients were enrolled into the study. Mean Age 63 (range 21--‐96). 61 Were admitted to the hospital, 5 To ICU (100% With St02\u3c74%). 3 Mortalities (100% With St02\u3c72%). 75% (9/12) Of patients with an ED Lactate \u3e2.3 Had an abnormal St02. 80% (4/5) For lactate \u3e3, And 100%(3/3) For Lactate \u3e4. For Any initial SITH (MAP\u3c65 Or Lactate \u3e2.3): Sensitivity: 92% (77.5--‐98.2), Specificity: 82.2% (67.9--‐92), +LR: 5.2 (2.7--‐9.7), --‐LR: 0.1 (0.03--‐0.3), PPV: 80.5% (65.1--‐91.2), NPV: 92.5% (80--‐98.3). Conclusions: StO2 May be a useful, rapid, low--‐cost, and non--‐invasive bedside screening tool for SITH In the ED, Particularly for severely ill patients. Further Studies are needed to determine StO2’s Ability to predict mortality and assess response to therapy

Parenting adolescents.

The period of adolescence is often thought to be one of intense stress and turmoil. Yet many parents and teens negotiate this developmental stage without extreme family conflict and without sacrificing close relationships. This review summarizes a portion of the literature on parent-adolescent relationships, focusing on monitoring and control of adolescent behavior and parenting style. Basic principles to emphasize when working with adolescents and parents are also included

368 REVEAL: Phase 1 dose-escalation study of NKTR-262, a novel TLR7/8 agonist, plus bempegaldesleukin: local innate immune activation and systemic adaptive immune expansion for treating solid tumors

Background NKTR-262 is a small-molecule agonist of toll-like receptors (TLR) 7/8. Given by intratumoral (IT) injection, NKTR-262 is retained within the tumor microenvironment (TME) and promotes an immunostimulatory milieu and tumor antigen release. Bempegaldesleukin (BEMPEG) is a CD122-preferential IL-2 pathway agonist, which increases proliferation and tumor infiltration of CD8+ T cells and natural killer (NK) cells. Preclinically, NKTR-262 plus BEMPEG combined innate immune signaling and enhanced antigen presentation, with sustained T-cell activation, resulting in tumor growth inhibition of treated and abscopal lesions. Methods This phase 1 dose-escalation study enrolled patients with relapsed/refractory, advanced/metastatic solid tumors (REVEAL; NCT03435640). Patients received escalating doses of NKTR-262 (0.03 mg to 3.84 mg IT) followed 3 weeks‘ later by BEMPEG (0.006 mg/kg IV) q3wk utilizing a 3+3 design. The primary endpoint was safety and tolerability, including definition of the recommended phase 2 dose (RP2D). Other endpoints included antitumor activity, pharmacodynamics, and pharmacokinetics. Results As of June 15, 2020, 36 patients were enrolled. One dose-limiting toxicity, transient transaminase elevation, was observed at the highest NKTR-262 dose (3.84 mg). The most frequent treatment-related adverse events were flu-like symptoms, fatigue, nausea, and pruritus, consistent with the known profile of BEMPEG. Early evidence of clinical activity was observed in patients with metastatic melanoma, with a disease control rate (partial response [PR] + stable disease) of 41.2% (7/17 patients), including two patients with PRs after progression on two prior immunotherapy regimens. Preliminary analyses showed dose-dependent induction of CXCL10 and type 1 interferon genes, consistent with TLR7/8 engagement. CD11c+ target cells were significantly more abundant in baseline melanoma biopsies than other tumor types (p\u3c0.001). Induction of TLR7/8-responsive genes correlated with CD11c+ baseline density (p\u3c0.05). Minimal TLR7/8-dependent changes in immune cell subsets or inflammatory cytokines were observed in peripheral blood, reflecting favorable TME modifications driven by retention of NKTR-262. Increased activation of CD4+, CD8+, and NK cells in blood were observed, consistent with BEMPEG mechanism of action. Conclusions NKTR-262 plus BEMPEG led to engagement of the entire immune activation cascade required for systemic tumor clearance. Robust TLR7/8 engagement supported the NKTR-262 mechanism of action, while the minimal toxicity profile underscored the benefit of local delivery of NKTR-262, and the BEMPEG combination induced systemic activation of T and NK cells. These data support the RP2D of NKTR-262 (3.84 mg IT) plus BEMPEG (0.006 mg IV) q3w, and the initiation of the phase 1b dose-expansion phase, which is exploring concurrent dosing, with or without nivolumab, in relapsed/refractory metastatic melanoma patients. Trial Registration NCT03435640 Ethics Approval The study was approved by the institutional review board of each participating site. http://dx.doi.org/10.1136/jitc-2020-SITC2020.036

Genetic modifiers of respiratory function in Duchenne muscular dystrophy.

Respiratory insufficiency is a major complication of Duchenne muscular dystrophy (DMD). Its progression shows considerable interindividual variability, which has been less thoroughly characterized and understood than in skeletal muscle. We collected pulmonary function testing (PFT) data from a large retrospective cohort followed at Centers collaborating in the Italian DMD Network. Furthermore, we analyzed PFT associations with different DMD mutation types, and with genetic variants in SPP1, LTBP4, CD40, and ACTN3, known to modify skeletal muscle weakness in DMD. Genetic association findings were independently validated in the Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG-DNHS)