Recurrent Treatment of Refractory Acute Cellular Rejection with Alemtuzumab after Lung Transplantation.

We present an exceptional case of a lung transplant recipient successfully treated by multiple courses of alemtuzumab for refractory acute cellular rejection. The patient experienced multiple episodes of acute cellular rejection following the transplantation procedure. Alemtuzumab was initiated as third-line rejection treatment and was repeated six times. Each treatment course resulted in complete recovery of the pulmonary function and depletion of T- and B-lymphocytes and NK cells. The onset of rejection was consistently preceded by the recovery of NK cells, while T- and B-lymphocytes remained depleted. This suggests a rejection process mediated by NK cells. This case contributes to recent research findings suggesting that NK cells play a significant role in acute cellular rejection in lung transplant recipients and stresses the importance to further investigate the role of NK cells in rejection. Furthermore, it demonstrates that acute cellular rejection following lung transplantation can be repeatedly managed by treatment with alemtuzumab. DATA AVAILABILITY STATEMENT: The authors confirm that the data supporting the findings of this study are available within the article.

Improving Patient Access to Hospital Pharmacists Using eConsults: Retrospective Descriptive Study.

BACKGROUND: eConsults are increasingly used worldwide to reduce specialist referrals and increase access to medical care. An additional benefit of using an eConsult tool is a reduction of health care costs while improving the quality of health care and patient participation. Currently, shared decision making is increasingly implemented and preferred by patients. eConsults are also a promising tool to improve access to the hospital pharmacist. Patients often have questions about their medication. When medication is started during a hospital admission or outpatient visit, community pharmacists are not always sufficiently informed to answer patient questions. Direct contact with hospital pharmacists may be more appropriate and efficient. This contact is facilitated through the eConsult feature in the hospital's patient portal. OBJECTIVE: This study aims to evaluate the prevalence and contents of the eConsults sent by patients to hospital pharmacists. METHODS: A first retrospective descriptive study was conducted at the Leiden University Medical Center in the Netherlands. Patients who sent at least one eConsult to a hospital pharmacist between March 2017 and December 2021 were included. Patient characteristics and the number of medications taken were extracted from electronic health records. The content of eConsults was analyzed and grouped into different subjects. Time of sending of the eConsults was analyzed. A comparison was made between the number of eConsults sent to the hospital pharmacy and the number sent to the medical center. Finally, the appropriateness for evaluation by the hospital pharmacist was assessed in all eConsults. RESULTS: During the study period, 983 eConsults (from 808 patients) were sent to the hospital pharmacist. The average patient age was 56 (SD 15.9) years, and 51.4% (415/808) were male; 47.8% (386/808) of the patients used 0 to 4 medications, 33.0% (267/808) used 5 to 9 medications, and 19.2% (155/808) used ≥10 medications. Of the eConsults, 10.9% (107/983) were excluded due to not being medication-related or not intended for the hospital pharmacist. Patients being treated in 31 medical specialties sent eConsults to the hospital pharmacist. The most common medical specialty was cardiology with 22.5% (197/876) of the eConsults. Most eConsults were sent during office hours (614/876, 70.2%). eConsult subjects were medication verification (372/876, 42.5%), logistics (243/876, 27.7%), therapeutic effect and adverse events (100/876, 11.4%), use of medication (87/876, 9.9%), and other subjects (74/876, 8.4%). CONCLUSIONS: Introducing eConsults allows patients to ask medication-related questions directly to hospital pharmacists. Our study shows that patients send medication reconciliation-related eConsults most often. Use of the eConsult tool leads to fast, direct, and documented communication between patient and hospital pharmacist. This can reduce medication-related errors, improve patient empowerment, and increase access to the hospital pharmacist.

Durability of Immune Responses After Boosting in Ad26.COV2.S-Primed Healthcare Workers.

The emergence of SARS-CoV-2 variants raised questions regarding the durability of immune responses after homologous or heterologous boosters after Ad26.COV2.S-priming. We found that SARS-CoV-2-specific binding antibodies, neutralizing antibodies, and T cells are detectable 5 months after boosting, although waning of antibodies and limited cross-reactivity with Omicron BA.1 was observed.

Ad26.COV2.S priming provided a solid immunological base for mRNA-based COVID-19 booster vaccination.

The emergence of novel SARS-CoV-2 variants led to the recommendation of booster vaccinations after Ad26.COV2.S priming. It was previously shown that heterologous booster vaccination induces high antibody levels, but how heterologous boosters affect other functional aspects of the immune response remained unknown. Here, we performed immunological profiling of Ad26.COV2.S-primed individuals before and after homologous or heterologous (mRNA-1273 or BNT162b2) booster. Booster vaccinations increased functional antibodies targeting ancestral SARS-CoV-2 and emerging variants. Especially heterologous booster vaccinations induced high levels of functional antibodies. In contrast, T-cell responses were similar in magnitude following homologous or heterologous booster vaccination and retained cross-reactivity towards variants. Booster vaccination led to a minimal expansion of SARS-CoV-2-specific T-cell clones and no increase in the breadth of the T-cell repertoire. In conclusion, we show that Ad26.COV2.S priming vaccination provided a solid immunological base for heterologous boosting, increasing humoral and cellular responses targeting emerging variants of concern.

Internal wave turbulence near a Texel beach.

A summer bather entering a calm sea from the beach may sense alternating warm and cold water. This can be felt when moving forward into the sea ('vertically homogeneous' and 'horizontally different'), but also when standing still between one's feet and body ('vertically different'). On a calm summer-day, an array of high-precision sensors has measured fast temperature-changes up to 1 °C near a Texel-island (NL) beach. The measurements show that sensed variations are in fact internal waves, fronts and turbulence, supported in part by vertical stable stratification in density (temperature). Such motions are common in the deep ocean, but generally not in shallow seas where turbulent mixing is expected strong enough to homogenize. The internal beach-waves have amplitudes ten-times larger than those of the small surface wind waves. Quantifying their turbulent mixing gives diffusivity estimates of 10(-4)-10(-3) m(2) s(-1), which are larger than found in open-ocean but smaller than wave breaking above deep sloping topography.