A practical guide to real-world implementation of pre-emptive therapy for Cytomegalovirus disease prevention in high-risk seronegative liver transplant recipients with seropositive donors.

The Comparison of Antiviral Preventative Strategies In Liver Transplant (CAPSIL) study showed pre-emptive therapy (PET) to be superior to antiviral prophylaxis for Cytomegalovirus (CMV) disease prevention in high-risk CMV seronegative liver transplant recipients (LTRs) with seropositive donors (D+R-). Despite the statistical superiority of PET over prophylaxis in research settings, PET is perceived as a logistically more complex strategy that requires careful coordination of weekly CMV PCR testing, prompt initiation of CMV antivirals upon viremia detection, and timely cessation of antivirals following viremia resolution. Transplant centers may be hesitant to use PET for CMV disease prevention in D+R- LTRs out of concern that PET coordination is not feasible in clinical practice. We recently described our experience using PET in CMV D+R- LTRs in a real-world setting, and found it to be as effective for CMV disease prevention as PET performed as part of a clinical trial. Here, we describe a systematic approach for PET implementation in real-world settings and provide practical tools to address anticipated challenges. This framework can support transplant programs in overcoming logistical barriers to PET and incorporating an evidence-based and cost-effective CMV prevention strategy into routine care for high-risk CMV D+R- LTRs.

Subtle Changes in Tacrolimus Levels Have an Impact on Early Donor-Specific Antibodies in Kidney Transplantation.

Introduction: The impact of each immunosuppressive agent on de novo donor-specific antibodies in kidney transplant recipients varies among extant literature. Project aims: Patterns in immunosuppression and the effects on incidence of de novo donor-specific antibodies were evaluated. Design: Adult kidney transplant recipients from 2017 to 2019 without preformed antibodies were sampled. Allograft function, de novo donor-specific antibodies, tacrolimus concentrations, duration of goal-dose antiproliferatives, and steroid doses were recorded. Outcomes included incidence of de novo donor-specific antibodies, and their relation to tacrolimus concentrations, time at goal-dose antiproliferatives, and steroid doses. Results: Recipients (N = 153) were followed for 1 year; all were crossmatch negative and received rabbit antithymocyte globulin induction. Sixteen (10%) recipients developed de novo donor-specific antibodies in a median of 31 days [interquartile range, IQR: 12-67 days], most were Class II antibodies (87.5%). Incidence of de novo donor-specific antibodies did not differ based on induction dosing. Tacrolimus levels in the first month were lower for patients with de novo donor-specific antibodies (8.8 ng/mL vs 10.4 ng/mL, P < .01). There was no difference in time on goal antiproliferative doses, but higher steroid doses (0.4 vs 0.3 mg/kg/d; P = .02) were noted in patients with antibodies. Steroid dosing was likely impacted by baseline risk factors. Conclusion: A significant association was found between lower tacrolimus concentrations early post-transplant and incidence of de novo donor-specific antibodies. This highlighted the importance of clinician attention to subtle changes in tacrolimus and the impact it can have on antibody risk in the early post-transplant period.

Effect of a Lifestyle Intervention on Cardiometabolic Health Among Emerging Adults: A Randomized Clinical Trial.

Importance: The prevalence of obesity has increased substantially among emerging adults, yet no previous large-scale behavioral weight loss trials have been conducted among this age group. Objective: To test the effect of 2 theory-based motivational enhancements on weight loss within a primarily digital lifestyle intervention designed for emerging adults. Design, Setting, and Participants: In this randomized clinical trial conducted at an academic medical research center, 382 participants aged 18 to 25 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 25 to 45 were enrolled between February 2, 2016, and February 6, 2019. Data collection was completed February 8, 2020. Analysis was performed on an intention-to-treat basis. Interventions: Participants were randomized to 1 of 3 groups: developmentally adapted behavioral weight loss (aBWL), aBWL plus behavioral economics (aBWL + BE), or aBWL plus self-determination theory (aBWL + SDT). All groups received a 6-month intervention with 1 group session, 1 individual session, and a digital platform (digital tools for self-monitoring, weekly lessons, tailored feedback, text messages, and optional social media). The aBWL + BE group received modest financial incentives for self-monitoring and weight loss; the aBWL + SDT group received optional experiential classes. Coaching and message framing varied by group. Main Outcomes and Measures: The primary outcome was mean (SE) weight change (in kilograms) at 6 months. Secondary outcomes included proportion of participants achieving weight loss of 5% or more, percentage weight change, waist circumference, body composition, and blood pressure. Results: Among the 382 participants (mean [SD] age, 21.9 [2.2] years), 316 (82.7%) were female, mean (SD) BMI was 33.5 (4.9), 222 (58.1%) were of underrepresented race and/or ethnicity, and 320 (83.8%) were retained at the primary end point. There was a significant time effect for mean (SE) weight loss (-3.22 [0.55] kg in the aBWL group; -3.47 [0.55] kg in the aBWL + BE group; and -3.40 [0.53] kg in the aBWL + SDT group; all P < .001), but no between-group differences were observed (aBWL vs aBWL + BE: difference, -0.25 kg [95% CI, -1.79 to 1.29 kg]; P = .75; aBWL vs aBWL + SDT: difference, -0.18 kg [95% CI, -1.67 to 1.31 kg]; P = .81; and aBWL + SDT vs aBWL + BE: difference, 0.07 kg [95% CI, -1.45 to 1.59 kg]; P = .93). The proportion of participants achieving a weight loss of 5% or more was 40.0% in the aBWL group (50 of 125), 39.8% in the aBWL + BE group (51 of 128), and 44.2% in the aBWL + SDT group (57 of 129), which was not statistically different across groups (aBWL vs aBWL + BE, P = .89; aBWL vs aBWL + SDT, P = .45; aBWL + SDT vs aBWL + BE, P = .54). Parallel findings were observed for all secondary outcomes-clinically and statistically significant improvements with no differences between groups. Conclusions and Relevance: In this randomized clinical trial, all interventions produced clinically significant benefit, but neither of the motivational enhancements promoted greater reductions in adiposity compared with the developmentally adapted standard group. Continued efforts are needed to optimize lifestyle interventions for this high-risk population and determine which intervention works best for specific individuals based on sociodemographic and/or psychosocial characteristics. Trial Registration: ClinicalTrials.gov Identifier: NCT02736981.

Behavioral weight loss in emerging adults: Design and rationale for the Richmond Emerging Adults Choosing Health (REACH) randomized clinical trial.

BACKGROUND: In the U.S., over 40% of 18-25 year olds meet criteria for overweight or obesity. Yet, no large-scale trials have targeted this age group for behavioral weight loss (BWL). Formative data revealed that existing BWL programs do not meet their unique needs and identified motivation as a fundamental barrier for weight management. The goal of the Richmond Emerging Adults Choosing Health (REACH) trial was to test the efficacy of two mHealth lifestyle interventions specifically focused on enhancing motivation, relative to adapted standard. METHODS: Participants (N = 381, 18-25 years, body mass index 25-45 kg/m2) will be randomized to 1) adapted BWL (aBWL), 2) aBWL + self-determination theory (aBWL+SDT), or 3) aBWL + behavioral economics (aBWL+BE). All arms will receive a 6-month intervention, delivered via one group session and one individual session, followed by an mHealth platform. Assessments will occur at baseline, 3-months, 6-months (post-treatment) and 12-months (following a no-contact period). The primary aim is to compare weight loss outcomes at 6 months. Secondary aims include changes at 6-months in physical and behavioral cardiometabolic risk factors, as well as psychosocial measures. We will also explore weight loss maintenance, change in hypothesized mediators, and moderators of treatment response. DISCUSSION: REACH is the first large-scale BWL trial designed specifically for emerging adults. Further, it will be the first trial to compare a lifestyle intervention grounded in self-determination theory to one rooted in behavioral economics. If clinically significant reductions in adiposity are achieved, findings could inform a scalable treatment model to meet the needs of this vulnerable population. TRIAL REGISTRATION: NCT02736981.

Hand tumors: II. Benign and malignant bone tumors of the hand.

The incidence of both benign and malignant bone tumors arising in the hand is relatively low in comparison with other locations. Although the overwhelming majority of these tumors are benign, even benign tumors can be locally destructive and compromise hand function. Intralesional tumor excision is the most appropriate surgical intervention for many benign bone tumors of the hand; however, destructive or malignant tumors may require wide local excision or even amputation to achieve complete tumor eradication. The purpose of this review article is to provide an overview of the pertinent benign and malignant bone tumors that may be encountered by hand surgeons. Clinical presentation, radiographic features, recommended workup, and available treatment options are all reviewed.

Hand tumors: I. skin and soft-tissue tumors of the hand.

SUMMARY: Hand tumors of the skin and soft tissue are frequently encountered by plastic surgeons. Although similar to lesions affecting other parts of the body, the presentation, workup, and treatment options often differ in the hand secondary to its complex anatomy and functional significance. The purpose of this article is to provide an overview of those lesions that commonly arise in the hand-including epidermal inclusion cysts, ganglion cysts, and glomus tumors-in addition to tumors such as soft-tissue sarcomas that are rare but nonetheless require astute diagnosis and expedient initiation of treatment. Presenting symptoms and clinical features, recommended workup, and appropriate treatment options are reviewed.

Supraclavicular artery island flap innervation: anatomical studies and clinical implications.

BACKGROUND: Recently, the supraclavicular artery island flap has gained popularity as a regional flap for head and neck reconstruction. During clinical follow-up, some patients report referred sensation to the shoulder when there is contact with the flap skin island surface. The authors examine the anatomical origin/characteristics of the supraclavicular nerves (C3-4) to this flap and its relationship to the flap pedicle and anatomical boundaries. METHODS: SAI flap harvest and nerve dissection was performed in seven fresh frozen cadavers (n = 10) using loupe magnification in order to further elucidate the sensory nerve branches in a typical SAI flap. RESULTS: Branches of the supraclavicular nerve innervating the SAI flap were found to emerge from the deep fascia at a separate location from the vascular pedicle with the major nerve root exiting underneath the sternocleidomastoid muscle near the midpoint of the muscle belly. The nerve branches proximal to the pedicle with one branch exiting anterior to the flap and another running axially along the length of the flap. The majority (9/10) flaps had a major cutaneous nerves located 1-2 cm anterior to the pedicle. One (1/10) of the flaps had a major cutaneous nerve located 1-2 cm posterior to the pedicle toward the trapezius muscle. In 3 of the 10 flaps, smaller cutaneous nerves were also found posterior to the pedicle in a more distal location of the flap. CONCLUSIONS: The supraclavicular nerves innervating the SAI flap are easily identifiable and can be preserved or ligated, depending on the desired flap function, when present close to the pedicle. Further clinical investigation is warranted to confirm the potential benefit of using the SAI flap as a neurotized regional flap for head/neck reconstruction.

Scar contractures of the hand.

This article discusses scar contracture of the hand. It contains a brief outline of the anatomy of the hand and upper extremities and the types of injuries involved. Hand reconstruction, including examination, nonoperative treatment, surgery, excision and skin grafting, flaps, postoperative management, and complications, are covered.

Tyramine receptor (SER-2) isoforms are involved in the regulation of pharyngeal pumping and foraging behavior in Caenorhabditis elegans.

Octopamine regulates essential processes in nematodes; however, little is known about the physiological role of its precursor, tyramine. In the present study, we have characterized alternatively spliced Caenorhabditis elegans tyramine receptor isoforms (SER-2 and SER-2A) that differ by 23 amino acids within the mid-region of the third intracellular loop. Membranes prepared from cells expressing either SER-2 or SER-2A bind [3H]lysergic acid diethylamide (LSD) in the low nanomolar range and exhibit highest affinity for tyramine. Similarly, both isoforms exhibit nearly identical Ki values for a number of antagonists. In contrast, SER-2A exhibits a significantly lower affinity than SER-2 for other physiologically relevant biogenic amines, including octopamine. Pertussis toxin treatment reduces affinity for both tyramine and octopamine, especially for octopamine in membranes from cells expressing SER-2, suggesting that the conformation of the mid-region of the third intracellular loop is dictated by G-protein interactions and is responsible for the differential tyramine/octopamine affinities of the two isoforms. Tyramine reduces forskolin-stimulated cAMP levels in HEK293 cells expressing either isoform with nearly identical IC50 values. Tyramine, but not octopamine, also elevates Ca2+ levels in cells expressing SER-2 and to a lesser extent SER-2A. Most importantly, ser-2 null mutants (pk1357) fail to suppress head movements while reversing in response to nose-touch, suggesting a role for SER-2 in the regulation of foraging behavior, and fail to respond to tyramine in assays measuring serotonin-dependent pharyngeal pumping. These are the first reported functions for SER-2. These results suggest that C. elegans contains tyramine receptors, that individual SER-2 isoforms may differ significantly in their sensitivity to other physiologically relevant biogenic amines, such as octopamine (OA), and that tyraminergic signaling may be important in the regulation of key processes in nematodes.