Epipericardial fat necrosis as cause of chest pain in patient after heart transplantation

Epipericardial fat necrosis is an uncommon clinical condition of unknown etiology. It typically presents as acute pleuritic chest pain and should be differentiated from acute pulmonary embolism and acute coronary syndrome. This condition is diagnosed by characteristic chest computed tomography findings of an ovoid mediastinal fatty lesion with intrinsic and surrounding soft‐tissue stranding. Treatment of epipericardial fat necrosis includes the administration of anti‐inflammatory agents, and symptoms usually resolve within a few days after treatment initiation. This disease entity has rarely been reported since it was first described in 1957. Most current knowledge of epipericardial fat necrosis is based on case reports that describe this condition in previously healthy individuals. We present the case of a 39‐year‐old woman with a history of heart transplant, who presented with chest pain secondary to epipericardial fat necrosis. Serial computed tomography revealed lesion resolution after appropriate treatment.     

Pancreatic islets engineered with a FasL protein induce systemic tolerance at the induction phase that evolves into long‐term graft‐localized immune privilege

We have previously shown that pancreatic islets engineered to transiently display a modified form of FasL protein (SA‐FasL) on their surface survive indefinitely in allogeneic recipients without a need for chronic immunosuppression. Mechanisms that confer long‐term protection to allograft are yet to be elucidated. We herein demonstrated that immune protection evolves in two distinct phases; induction and maintenance. SA‐FasL‐engineered allogeneic islets survived indefinitely and conferred protection to a second set of donor‐matched, but not third‐party, unmanipulated islet grafts simultaneously transplanted under the contralateral kidney capsule. Protection at the induction phase involved a reduction in the frequency of proliferating alloreactive T cells in the graft‐draining lymph nodes, and required phagocytes and TGF‐β. At the maintenance phase, immune protection evolved into graft site‐restricted immune privilege as the destruction of long‐surviving SA‐FasL‐islet grafts by streptozotocin followed by the transplantation of a second set of unmanipulated islet grafts into the same site from the donor, but not third party, resulted in indefinite survival. The induced immune privilege required both CD4⁺CD25⁺Foxp3⁺ Treg cells and persistent presence of donor antigens. Engineering cell and tissue surfaces with SA‐FasL protein provides a practical, efficient, and safe means of localized immunomodulation with important implications for autoimmunity and transplantation.     

Donor‐specific chimeric antigen receptor Tregs limit rejection in naive but not sensitized allograft recipients

Cell therapy with autologous donor‐specific regulatory T cells (Tregs) is a promising strategy to minimize immunosuppression in transplant recipients. Chimeric antigen receptor (CAR) technology has recently been used successfully to generate donor‐specific Tregs and overcome the limitations of enrichment protocols based on repetitive stimulations with alloantigens. However, the ability of CAR‐Treg therapy to control alloreactivity in immunocompetent recipients is unknown. We first analyzed the effect of donor‐specific CAR Tregs on alloreactivity in naive, immunocompetent mice receiving skin allografts. Tregs expressing an irrelevant or anti‐HLA‐A2‐specific CAR were administered to Bl/6 mice at the time of transplanting an HLA‐A2⁺ Bl/6 skin graft. Donor‐specific CAR‐Tregs, but not irrelevant‐CAR Tregs, significantly delayed skin rejection and diminished donor‐specific antibodies (DSAs) and frequencies of DSA‐secreting B cells. Donor‐specific CAR‐Treg–treated mice also had a weaker recall DSA response, but normal responses to an irrelevant antigen, demonstrating antigen‐specific suppression. When donor‐specific CAR Tregs were tested in HLA‐A2‐sensitized mice, they were unable to delay allograft rejection or diminish DSAs. The finding that donor‐specific CAR‐Tregs restrain de novo but not memory alloreactivity has important implications for their use as an adoptive cell therapy in transplantation.     

Quadritherapy vs standard tritherapy immunosuppressant regimen after heart transplantation: A propensity score–matched cohort analysis

After heart transplant, adding everolimus (EVL) to standard immunosuppressive regimen mostly relies on converting calcineurin inhibitors (CNIs) into EVL. The aim of this study was to describe the effects of combining low‐dose EVL and CNIs in maintenance immunosuppression regimen (quadritherapy) and compare it with standard tritherapy associating standard‐dose CNIs, mycophenolate mofetil, and corticosteroids. In the 3‐year registry cohort of heart transplanted patients, those who received quadritherapy were compared with those who received tritherapy. EVL was added after 3 months posttransplant. Three analyses were performed to control for confounders: propensity score matching, multivariable survival, and inverse probability score weighting analyses. Among 213 patients who were included (75 with quadritherapy), propensity score matching selected 64 unique pairs of patients with similar characteristics. In the matched cohort (n = 128), quadritherapy was associated with fewer deaths (3 [4.7%] vs 17 [21.9%], P = .007) and biopsy‐proven acute rejections (15 [23.4%] vs 31 [48.4%], P = .002). These results were confirmed in the overall cohort (n = 213), after multivariable and inverse probability score weighting analyses. Renal function and donor‐specific HLA‐antibodies remained similar in both groups. Low‐dose combination quadritherapy was associated with fewer deaths and rejections, compared with standard immunosuppression tritherapy.     

Description and function of a difficult airway service

The goal of the Pediatric Difficult Airway Service (DAS) is to improve the care of children with airway abnormalities primarily through identification of children at risk for failed airway management. The airway service encourages early recognition and provides consultation, a plan for airway management, expertise in airway management, and follow‐up care for children who have a difficult airway. The service has improved the education of healthcare professionals and heightened awareness about the consequences of failed airway management.     

Local and transient inhibition of p21 expression ameliorates age‐related delayed wound healing

Nonhealing chronic wounds in the constantly growing elderly population represent a major public health problem with high socioeconomic burden. Yet, the underlying mechanism of age‐related impairment of wound healing remains elusive. Here, we show that the number of dermal cells expressing cyclin‐dependent kinase inhibitor p21 was elevated upon skin injury, particularly in aged population, in both man and mouse. The nuclear expression of p21 in activated wound fibroblasts delayed the onset of the proliferation phase of wound healing in a p53‐independent manner. Further, the local and transient inhibition of p21 expression by in vivo delivered p21‐targeting siRNA ameliorated the delayed wound healing in aged mice. Our results suggest that the increased number of p21⁺ wound fibroblasts enforces the age‐related compromised healing, and targeting p21 creates potential clinical avenues to promote wound healing in aged population.     

Mastoid and epitympanic obliteration in canal wall up mastoidectomy for prevention of retraction pocket.

OBJECTIVE: To evaluate the surgical outcome in patients who have undergone mastoid and epitympanic obliteration technique. STUDY DESIGN:: Retrospective review. SETTING: Tertiary care referral center. PATIENTS: The study group included 151 patients with cholesteatoma who underwent mastoid and epitympanic obliteration technique. This technique was applied to cases who had a strong chance of recurrent retraction pocket and cholesteatoma formation, including those patients with an adhesive drum indicating poor eustachian tube function (n = 52) and patients with a destructive scutum (n = 68). Thirty-one patients had both an adhesive drum and a destructive scutum. INTERVENTION: The connection between the mastoid cavity and the middle ear was blocked by obliterating the epitympanum and antrum with bone pate and the remaining mastoid cavity with abdominal fat. MAIN OUTCOME MEASURES: The postoperative drum state, the incidence of retraction pocket formation and cholesteatoma recurrence, the surgical complications of obliteration, and the hearing outcome. RESULTS: In 114 of 151 patients (75.4%), the middle ear was well healed and well aerated. The retraction pocket formation or cholesteatoma recurrence did not develop in any subject. Postauricular skin depression was the most common complication of this technique (n = 31 [20.5%]). In three patients (2.0%), the bone pate used for obliteration was infected. Of the 56 cases who underwent a staged operation to regain their hearing, 37 resulted in a postoperative air-bone gap less than 20 dB hearing level. CONCLUSION: Mastoid and epitympanic obliteration is an effective option for preventing a retraction pocket and cholesteatoma recurrence in patients with a poorly functioning eustachian tube or a defective scutum, while preserving the same advantage of the canal wall up technique.     

How we do it: Modified Wehrs incus ossiculoplasty

• ? Ossiculoplasty is commonly performed as part of tympanoplasty. Hydroxyapatite is a favoured material for ossicular protheses.
• ? A modification to the Wehrs incus prosthesis^® is described.
• ? Twenty‐one procedures were performed on 20 patients and the results are reported.
• ? On average there was a 4–5 dB closure of the air–bone gap (ABG), with patients having a hearing gain procedure averaging 11 dB closure. Air–bone gap closure to ≤20 dB was achieved between 78% (0.5, 1, 2 kHz average) and 60% (0.5, 1, 2, 4 kHz average) of patients and this was stable during long‐term follow‐up of the ABG.
• ? Wehrs incus prosthesis^® ossiculoplasty provides a reliable result following ossiculoplasty when autograft incus is not available.