University Hospital Cologne

Familial hypocalciuric hypercalcemia (FHH) is a rare genetic disorder of calcium regulation. FHH type 3 (FHH3), caused by pathogenic variants in AP2S1, may present with clinically significant complications. Data on the treatment of this rare disorder is limited. CASE DESCRIPTION: We report an 11-year-old girl with a de novo heterozygous pathogenic variant in AP2S1 (NM_004069.6): c.44G>T p.(Arg15Leu). At the age of seven, our patient presented with hypercalcemia, hypocalciuria, and elevated parathyroid hormone (PTH), which were accompanied by low bone mineral density and persistent neurodevelopmental difficulties. Primary hyperparathyroidism and causative variants in the CASR gene were excluded, and cinacalcet was initiated. After a dose titration and vitamin D3 dose adjustments, a normalization of serum calcium and PTH was achieved, and symptoms improved substantially, although lumbar bone mineral density declined further, and neurological symptoms remained. CONCLUSIONS: This case demonstrates cinacalcet as an effective and well-tolerated therapy in FHH3, with unresolved questions regarding skeletal and neurocognitive outcomes.

Summary The role of the peripheral immune system in Alzheimer’s Disease (AD) remains insufficiently resolved, limiting the understanding of systemic disease effects and mechanisms. Here, we employed three high-resolution single-cell techniques, including flow cytometry, single-cell RNA- and ATAC-sequencing, to investigate peripheral immunity in AD dementia and earlier stages of the AD trajectory in over 100 patients. We identified reduced humoral immune responses in AD, characterized by a diminished B cell compartment displaying an impaired activation phenotype. Classical monocytes expanded in mild cognitive impairment and early AD dementia, acquiring a NF- k B/AP-1-mediated low-grade inflammation phenotype. Our findings link peripheral dysregulation in innate and adaptive immunity at cell frequency, transcriptional and epigenetic levels to the AD trajectory and provide insights into distinct phenotypes that define AD progression in contrast to healthy aging across cohorts.

Phytoextracts are safer, more affordable, and more readily available than conventional medications, making them promising anti-parasitic treatment options. Cryptosporidium species (spp.) and Giardia duodenalis are protozoan parasites responsible for cryptosporidiosis and giardiasis, respectively, primarily affecting immunocompromised individuals, children, and populations in developing countries. Although treatment options exist, many of them have significant side effects. The current review aims to evaluate the efficacy of phytoextracts tested against Cryptosporidium spp. and G. duodenalis infections. The current review indicated that the Asteraceae and Rutaceae families were the most extensively investigated sources of phytoextracts. Additionally, Zingiber officinale is the only extract to demonstrate efficacy against both parasites in in vivo studies. Furthermore, Curcuma longa and Morinda royoc showed the highest in vitro efficacy against Cryptosporidium spp. and G. duodenalis, respectively. These results underscore the potential of phytoextracts as alternative therapeutic modalities for the treatment of cryptosporidiosis and giardiasis.

Proximal femur fractures are the most common fractures in older people. Despite existing guidelines, post-operative care remains challenging. The integration of an app into rehabilitation presents a promising solution for older patients recovering from such fractures. This study aimed to develop an app-assisted rehabilitation concept for older adults after a proximal femur fracture, define the requirements for the app, and identify the prerequisites for the implementation of the concept. The study was conducted in two phases. In the first phase, online surveys and a focus group explored key aspects of the concept’s development, structured by the Consolidated Framework for Implementation Research (CFIR). In the second phase, a think-aloud approach assessed user perspectives and interactions, with data analysed using the framework approach. This study included patients (n = 11) with and without prior experience using health apps, an informal caregiver (n = 1), as well as physical therapists (n = 9) and physicians with expertise in managing patients after a proximal femur fracture (n = 5). The proposed concept builds on inpatient rehabilitation and integrates an app offering educational content, personalized training programs, questionnaires, and tests to assess relevant treatment factors, supplemented by personal therapy sessions. Autonomy for patients in deciding whether and to what extent informal caregivers are involved in their rehabilitation was emphasized. Training for both patients and stakeholders to use the app effectively is essential. The concept primarily aims to promote patients’ independence. The app requirements include adaptability to geriatric patients’ physical abilities, user-friendly navigation, motivational design, compatibility with various operating systems, and credibility of content. Prerequisites for implementation include the cognitive and physical abilities of patients and the willingness of both patients and stakeholders to acquire skills needed for the adoption of an app-assisted concept. Organizational structures must support the concept, accompanied by a feasible remuneration framework. The study resulted in the development of the PROGRES(S) concept. Successful design and implementation of this app-assisted rehabilitation concept require consideration of all CFIR dimensions. If proven feasible, acceptable, and effective, PROGRES(S) could complement existing rehabilitation programs and support patients who otherwise lack or have limited access to rehabilitation services.

Lymphocele formation is a frequent complication after kidney transplantation, occurring in up to 26% of recipients. It results mainly from lymphatic injury during dissection of the iliac vessels and can impair graft function by compressing the renal graft, vascular structures, or ureter. Improved intraoperative visualization of lymphatic vessels may reduce this risk. Indocyanine green (ICG) fluorescence technology enables real-time lymphatic mapping. This study evaluated the feasibility and clinical utility of ICG fluorescence-guided lymphography during kidney transplantation. In a prospective single-center study, ICG lymphography was performed in 21 consecutive living-donor kidney transplantations. Under ultrasound guidance, ICG was injected into the subcutaneous tissue of the ipsilateral femoral triangle one hour before surgery. Lymphatic structures were visualized intraoperatively using a handheld fluorescence imaging system (Spy-Phi, Stryker) at four procedural time points. Identified lymphatic vessels were preserved, and any visualized lymphatic leakage was clipped. Postoperative surveillance included weekly ultrasonography in the early postoperative phase and MRI at 6 months. ICG injection enabled clear visualization of retroperitoneal lymphatic vessels in all 21 cases. Lymphatic structures were successfully preserved during dissection. In two cases, intraoperative lymphatic leakage was detected and controlled. Postoperative ultrasound showed no perirenal fluid collections in any patient. MRI performed in 15/21 patients at 6 months confirmed absence of lymphocele formation. ICG-guided lymphography is a safe, feasible technique for intraoperative visualization of lymphatic vessels during kidney transplantation and may help prevent lymphocele formation.