ALVR109, an off-the-shelf partially HLA matched SARS-CoV-2-specific T cell therapy, to treat refractory severe COVID-19 pneumonia in a heart transplant patient: Case report.

An unvaccinated adult male heart transplant recipient patient with recalcitrant COVID-19 due to SARS-CoV-2 delta variant with rising nasopharyngeal quantitative viral load was successfully treated with ALVR109, an off-the-shelf SARS-CoV-2-specific T cell therapy. Background immunosuppression included 0.1 mg/kg prednisone, tacrolimus, and mycophenolate mofetil 1 gm twice daily for historical antibody-mediated rejection. Prior therapies included remdesivir, corticosteroids, and tocilizumab, with requirement for high-flow nasal oxygen. Lack of clinical improvement and acutely rising nasopharyngeal viral RNA more than 3 weeks into illness prompted the request of ALVR109 through an emergency IND. The day following the first ALVR109 infusion, the patient's nasopharyngeal SARS-CoV-2 RNA declined from 7.43 to 5.02 log10 RNA copies/ml. On post-infusion day 4, the patient transitioned to low-flow oxygen. Two subsequent infusions of ALVR109 were administered 10 and 26 days after the first; nasopharyngeal SARS-CoV-2 RNA became undetectable on Day 11, and he was discharged the following day on low-flow oxygen 5 weeks after the initial diagnosis of COVID-19. The clinical and virologic improvements observed in this patient following administration of ALVR109 suggest a potential benefit that warrants further exploration in clinical trials.

Efficacy of oral tofacitinib in refractory chronic spontaneous urticaria and urticarial vasculitis.

The treatment of chronic urticaria (CU) is difficult, currently, antihistamines (AH) are the mainstay of treatment, however, up to 40% of patients do not respond to even high (four-fold) daily doses of AH. Tofacitinib is, a small-molecule that blocks JAK1/3 and inhibits intracellular signaling of multiple key cytokines involved in the inflammatory cascade and its beneficial effects were reported in patients with mast cell activation disease but there is no report in patients with urticaria. Here, we present four cases of refractory CU and one case of urticarial vasculitis (UV) that were managed with tofacitinib. Despite the long-term unresponsiveness of various treatments in our patients, the addition of tofacitinib significantly improved the urticarial activity and ultimately led to tapering and discontinuation of cyclosporine or AH. In conclusion, tofacitinib appears to downregulate inflammatory phenomena associated with mast cells and might be a new therapeutic option for patients with refractory CU or UV.

The Immunogenetics of Lichen Planus.

Lichen planus (LP) is a multifaceted autoimmune disease affecting the skin, nails, hair, and mucous membranes, with several clinical subgroups. Cell-mediated immunity plays a key role in its progression. This chapter reviews the known genetic associations of lichen planus including HLA as well as non-HLA genes.

De novo tacrolimus extended-release tablets (LCPT) versus twice-daily tacrolimus in adult heart transplantation: Results of a single-center non-inferiority matched control trial.

Extended-release tacrolimus for prophylaxis of allograft rejection in orthotopic heart transplant (OHT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release tacrolimus (IR-tacrolimus). We compared the efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. Twenty-five prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 1 year was compared using non-inferiority analysis. LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 20% (90% CI: -40%, -.5%; non-inferiority P = .001). Tacrolimus trough levels peaked at 2-3 months and were higher in LCPT (median 14.5 vs. 12.7 ng/ml; P = .03) with similar dose levels (LCPT vs. IR-tacrolimus: .08 vs. .09 mg/kg/day; P = .33). Cardiovascular-related readmissions were reduced by 62% (P = .046) in LCPT patients. The complication rate per transplant admission and all-cause readmission rate did not differ significantly. These results suggest that LCPT is non-inferior in efficacy to IR-tacrolimus with a similar safety profile and improved bioavailability in OHT.

Distal Versus Proximal Radial Artery Access for Cardiac Catheterization and Intervention: Design and Rationale of the DIPRA Trial.

BACKGROUND: Radial artery (RA) catheterization is the access of choice over femoral artery access for most interventional vascular procedures given its safety and faster patient recovery. There has been growing interest in distal radial artery (dRA) access as an alternative to the conventional proximal radial artery (pRA) access. Preserving the RA is important which serves as a potential conduit for future coronary artery bypass surgery, dialysis conduit or preserve the artery for future cardiovascular procedures. The dRA runs in close proximity to the radial nerve, which raises the concern of potential detrimental effects on hand function. STUDY DESIGN: The Distal versus Proximal Radial Artery Access for cardiac catheterization and intervention (DIPRA) trial is a prospective, randomized, parallel-controlled, open-label, single center study evaluating the outcomes of hand function and effectiveness of dRA compared to pRA access in patients undergoing cardiac catheterization. The eligible subjects will be randomized to dRA and pRA access in a (1:1) fashion. The primary end point is an evaluation of hand function at one and twelve months follow-up. Secondary end points include rates of access site hematoma, access site bleeding, other vascular access complications, arterial access success rate, and RA occlusion at one and twelve months follow up. CONCLUSION: Effects of dRA on hand function remains unknown and it's use questionable in the presence of a widely accepted pRA. DIPRA trial is designed to determine the safety and effectiveness of dRA for diagnostic and interventional cardiovascular procedures compared to the standard of care pRA.

Stevens-Johnson Syndrome due to COVID-19 vaccination.

As public COVID-19 vaccination programs are being implemented, it is possible that more rare and serious adverse effects such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrosis (TEN) may occur.

Genital Lesions Masquerading as Condyloma Acuminata: A Case Series Report.

Herein we report three married women referred to Dermatology Clinic of Loghman Hakim Hospital, Tehran, Iran in 2017 for evaluation and treatment of genital warts. Two patients were complaining of flat-topped papules on their labia major and the third one was presented with asymptomatic papillary projections on her vestibule and inner aspect of both labia minora. Histological examination revealed the diagnosis of syringoma, lymphangioma circumscriptum (LC) and vestibular papillomatosis respectively. Familiarity with these uncommon conditions which clinically mimic genital warts helps to prevent labeling a patient with sexually transmitted disease before histological confirmation and prevent unnecessary treatment.

Salvage of severe primary graft dysfunction following heart transplantation using extracorporeal life support.

Primary graft dysfunction (PGD) is the leading cause of early mortality after heart transplantation. Typically, mechanical circulatory support is necessary to provide hemodynamic support and to enable graft recovery. However, both the reported incidence of PGD and the reported salvage rates with extracorporeal membrane oxygenation (ECMO) vary widely. This may partly be due to variations in the definition of PGD and its levels of severity. We analyzed a prospectively maintained database of 255 transplant recipients at our institution to determine the effectiveness of ECMO support in those who develop severe PGD as defined by the International Society for Heart and Lung Transplantation consensus guidelines. Nineteen (7.5%) patients (aged 32-69 years) developed severe PGD and were treated with veno-arterial (VA) ECMO, which was initiated in the operating room at the time of transplant in most patients. The majority received VA ECMO through femoral cannulation. Two patients required veno-venous ECMO for respiratory support after VA ECMO separation. The 30-day in-hospital survival rate following transplantation was 63% (n = 12). In conclusion, ECMO proved to be a viable option for early hemodynamic support in patients with severe PGD and has become our preferred modality for mechanical circulatory support in these patients.

Pulsed dye laser in treatment of steroid-induced atrophy.

BACKGROUND: One of the important and distressing cutaneous side effects of steroid therapy is skin atrophy, which has no definite and effective treatment. To the best of our knowledge, laser therapy for steroid-induced atrophic scars has not been investigated to date. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of pulsed dye laser in the treatment of steroid-induced atrophic scars. METHODS: In this pilot study, 15 patients with at least one atrophic patch were treated with the 585-nm pulsed dye laser at 4-week interval sessions until achieving complete improvement or until patient were lost to follow-up. Clinical outcome was assessed via standard photographic method before each treatment session and after the final visit. An independent dermatologist evaluated the photographs. RESULT: All of the patients (13 females and two males) with 25-59 years of age experienced some degree of improvement, except one patient who withdrew from the treatment after three sessions. The treatment was well tolerated. CONCLUSION: The results of our study indicated that pulsed dye laser therapy could be employed as a new method in the treatment of steroid-induced atrophic scars. Pulsed dye laser might affect the lesions through inducing collagen deposition and production of more superficial dermal elastin as well as less unidirectional collagen in clusters.