Single-cell Transcriptional Landscape of Temporal Neutrophil Response to Burn Wound in Larval Zebrafish.

Neutrophils accumulate early in tissue injury. However, the cellular and functional heterogeneity of neutrophils during homeostasis and in response to tissue damage remains unclear. In this study, we use larval zebrafish to understand neutrophil responses to thermal injury. Single-cell transcriptional mapping of myeloid cells during a 3-d time course in burn and control larvae revealed distinct neutrophil subsets and their cell-cell interactions with macrophages across time and conditions. The trajectory formed by three zebrafish neutrophil subsets resembles human neutrophil maturation, with varying transition patterns between conditions. Through ligand-receptor cell-cell interaction analysis, we found that neutrophils communicate more in burns in a pathway and temporal manner. Finally, we identified the correlation between zebrafish myeloid signatures and human burn severity, establishing GPR84+ neutrophils as a potential marker of early innate immune response in burns. This work builds a comparative single-cell transcriptomic framework to identify neutrophil markers of tissue damage using model organisms.

Tumor Pre-Targeting System Using Streptavidin-Expressing Bacteria.

PURPOSE: A major obstacle to targeted cancer therapy is identifying suitable targets that are specifically and abundantly expressed by solid tumors. Certain bacterial strains selectively colonize solid tumors and can deliver genetically encoded cargo molecules to the tumor cells. Here, we engineered bacteria to express monomeric streptavidin (mSA) in tumors, and developed a novel tumor pre-targeting system by visualizing the presence of tumor-associated mSA using a biotinylated imaging probe. PROCEDURES: We constructed a plasmid expressing mSA fused to maltose-binding protein and optimized the ribosome binding site sequence to increase solubility and expression levels. E. coli MG1655 was transformed with the recombinant plasmid, expression of which is driven by the pBAD promotor. Expression of mSA was induced by L-arabinose 4 days after injection of bacteria into mice bearing CT26 mouse colon carcinoma cells. Selective accumulation of mSA in tumor tissues was visualized by optical imaging after administration of a biotinylated fluorescent dye. Counting of viable bacterial cells was also performed. RESULTS: Compared with a conventional system, the novel expression system resulted in significantly higher expression of mSA and sustained binding to biotin. Imaging signals in tumor tissues were significantly stronger in the mSA-expressing group than in non-expressing group (P = 0.0005). Furthermore, the fluorescent signal in tumor tissues became detectable again after multiple inductions with L-arabinose. The bacterial counts in tumor tissues showed no significant differences between conditions with and without L-arabinose (P = 0.45). Western blot analysis of tumor tissues confirmed expression and binding of mSA to biotin. CONCLUSIONS: We successfully engineered tumor-targeting bacteria carrying a recombinant plasmid expressing mSA, which was targeted to, and expressed in, tumor tissues. These data demonstrate the potential of this novel tumor pre-targeting system when combined with biotinylated imaging probes or therapeutic agents.

The Hallmarks of Precancer.

Research on precancers, as defined as at-risk tissues and early lesions, is of high significance given the effectiveness of early intervention. We discuss the need for risk stratification to prevent overtreatment, an emphasis on the role of genetic and epigenetic aging when considering risk, and the importance of integrating macroenvironmental risk factors with molecules and cells in lesions and at-risk normal tissues for developing effective intervention and health policy strategies.

Single-cell transcriptional landscape of temporal neutrophil response to burn wound in larval zebrafish.

Neutrophils accumulate early in tissue injury. However, the cellular and functional heterogeneity of neutrophils during homeostasis and in response to tissue damage remains unclear. Here, we use larval zebrafish to understand neutrophil responses to thermal injury. Single-cell transcriptional mapping of myeloid cells during a 3-day time course in burn and control larvae revealed distinct neutrophil subsets and their cell-cell interactions with macrophages across time and conditions. The trajectory formed by three zebrafish neutrophil subsets resembles human neutrophil maturation, with varying transition patterns between conditions. Through ligand-receptor cell-cell interaction analysis, we found neutrophils communicate more in burns in a pathway and temporal manner. Finally, we identified the correlation between zebrafish myeloid signatures and human burn severity, establishing GPR84+ neutrophils as a potential marker of early innate immune response in burns. This work builds the molecular foundation and a comparative single-cell genomic framework to identify neutrophil markers of tissue damage using model organisms.

Fallopian tube single cell analysis reveals myeloid cell alterations in high-grade serous ovarian cancer.

Most high-grade serous ovarian cancers (HGSCs) likely initiate from fallopian tube (FT) epithelia. While epithelial subtypes have been characterized using single-cell RNA-sequencing (scRNA-Seq), heterogeneity of other compartments and their involvement in tumor progression are poorly defined. Integrated analysis of human FT scRNA-Seq and HGSC-related tissues, including tumors, revealed greater immune and stromal transcriptional diversity than previously reported. We identified abundant monocytes in FTs across two independent cohorts. The ratio of macrophages to monocytes is similar between benign FTs, ovaries, and adjacent normal tissues but significantly greater in tumors. FT-defined monocyte and macrophage signatures, cell-cell communication, and gene set enrichment analyses identified monocyte- and macrophage-specific interactions and functional pathways in paired tumors and adjacent normal tissues. Further reanalysis of HGSC scRNA-Seq identified monocyte and macrophage subsets associated with neoadjuvant chemotherapy. Taken together, our work provides data that an altered FT myeloid cell composition could inform the discovery of early detection markers for HGSC.

PTP1B phosphatase dampens iPSC-derived neutrophil motility and antimicrobial function.

Neutrophils are rapidly recruited to sites of infection and are critical for pathogen clearance. Therapeutic use of primary neutrophils has been limited as they have a short lifespan and are not amenable to genetic manipulation. Human induced pluripotent stem cells (iPSCs) can provide a robust source of neutrophils for infusion and are genetically tractable. However, current work has indicated that dampened intracellular signaling limits iPSC-derived neutrophil (iNeutrophil) cellular activation and antimicrobial response. Here, we show that protein tyrosine phosphatase 1B (PTP1B) inhibits intracellular signaling and dampens iNeutrophil effector function. Deletion of the PTP1B phosphatase increased PI3K and ERK signaling and was associated with increased F-actin polymerization, cell migration and phagocytosis. In contrast, other effector functions like NETosis and ROS production were reduced. PTP1B-deficient neutrophils were more responsive to A. fumigatus and displayed rapid recruitment and control of hyphal growth. Accordingly, depletion of PTP1B increased production of inflammatory factors including the neutrophil chemokine IL-8. Taken together, these findings suggest that PTP1B limits iNeutrophil motility and antimicrobial function.

Reprogramming a Doxycycline-Inducible Gene Switch System for Bacteria-Mediated Cancer Therapy.

PURPOSE: Attenuated Salmonella typhimurium is a potential biotherapeutic antitumor agent because it can colonize tumors and inhibit their growth. The present study aimed to develop a doxycycline (Doxy)-inducible gene switch system in attenuated S. typhimurium and assess its therapeutic efficacy in various tumor-bearing mice models. PROCEDURES: A Doxy-inducible gene switch system comprising two plasmids was engineered to trigger the expression of cargo genes (Rluc8 and clyA). Attenuated S. typhimurium carrying Rluc8 were injected intravenously into BALB/c mice bearing CT26 tumors, and bioluminescence images were captured at specified intervals post-administration of doxycycline. The tumor-suppressive effects of bacteria carrying clyA were evaluated in BALB/c mice bearing CT26 tumors and in C57BL/6 mice bearing MC38 tumors. RESULTS: Expression of the fimE gene, induced only in the presence of Doxy, triggered a unidirectional switch of the POXB20 promoter to induce expression of the cargo genes. The switch event was maintained over a long period of bacterial culture. After intravenous injection of transformed Salmonella into mice bearing CT26 tumors, the bacteria transformed with the Doxy-inducible gene switch system for Rluc8 targeted only tumor tissues and expressed the payloads 2 days after Doxy treatment. Notably, bacteria carrying the Doxy-inducible gene switch system for clyA effectively suppressed tumor growth and prolonged survival, even after just one Doxy induction. CONCLUSIONS: These results suggest that attenuated S. typhimurium carrying this novel gene switch system elicited significant therapeutic effects through a single induction triggering and were a potential biotherapeutic agent for tumor therapy.

Human CD79b+ neutrophils in the blood are associated with early-stage melanoma.

Purpose: Due to their abundance in the blood, low RNA content, and short lifespan, neutrophils have been classically considered to be one homogenous pool. However, recent work has found that mature neutrophils and neutrophil progenitors are composed of unique subsets exhibiting context-dependent functions. In this study, we ask if neutrophil heterogeneity is associated with melanoma incidence and/or disease stage. Experimental design: Using mass cytometry, we profiled melanoma patient blood for unique cell surface markers among neutrophils. Markers were tested for their predictiveness using flow cytometry data and random forest machine learning. Results: We identified CD79b+ neutrophils (CD3-CD56-CD19-Siglec8-CD203c-CD86LoCD66b+CD79b+) that are normally restricted to the bone marrow in healthy humans but appear in the blood of subjects with early-stage melanoma. Further, we found CD79b+ neutrophils present in tumors of subjects with head and neck cancer. AI-mediated machine learning analysis of neutrophils from subjects with melanoma confirmed that CD79b expression among peripheral blood neutrophils is highly important in identifying melanoma incidence. We noted that CD79b+ neutrophils possessed a neutrophilic appearance but have transcriptional and surface-marker phenotypes reminiscent of B cells. Compared to remaining blood neutrophils, CD79b+ neutrophils are primed for NETosis, express higher levels of antigen presentation-related proteins, and have an increased capacity for phagocytosis. Conclusion: Our work suggests that CD79b+ neutrophils are associated with early-stage melanoma.

Impact of In-house Candida auris Polymerase Chain Reaction Screening on Admission on the Incidence Rates of Surveillance and Blood Cultures With C. auris and Associated Cost Savings.

Background: The impact of strategies for rapid diagnostic screening of Candida auris on hospital operations has not been previously characterized. We describe the implementation of in-house polymerase chain reaction (PCR) testing on admission for screening of colonization with C. auris, associated process improvements, and financial impact. Methods: This study was conducted across an integrated health system. Patients were tested based on risk factors for C. auris carriage. Pre-intervention, the PCR was sent out to a reference laboratory, and postintervention was performed in-house. Changes in the incidence rates (IRs) of C. auris present on admission (CA-POA) and C. auris hospital-onset fungemia (CA-HOF) were assessed using interrupted time series analysis. The economic impact on isolation and testing costs was calculated. Results: Postintervention, the IR of CA-POA doubled (IRR, 2.57; 95% CI, 1.16-5.69; P = .02) compared with the pre-intervention period. The baseline rate of CA-HOF was increasing monthly by 14% (95% CI, 1.05-1.24; P = .002) pre-intervention, while during the postintervention period there was a change in slope with a monthly decrease in IR of 13% (95% CI, 0.80-0.99; P = .02). The median turnaround time (TAT) of the results (interquartile range) was reduced from 11 (8-14) days to 2 (1-3) days. Savings were estimated to be between $772 513.10 and $3 730 480.26. Conclusions: By performing in-house PCR for screening of C. auris colonization on admission, we found a doubling of CA-POA rates, a subsequent decrease in CA-HOF rates, reduced TAT for PCR results, and more efficient use of infection control measures. In-house testing was cost-effective in a setting of relatively high prevalence among individuals with known risk factors.

Lessons for the Next Generation of Scientists from the Second Annual Arthur and Sandra Irving Cancer Immunology Symposium.

The Arthur and Sandra Irving Cancer Immunology Symposium has been created as a platform for established cancer immunologists to mentor trainees and young investigators as they launch their research career in the field. By sharing their different paths to success, the senior faculty mentors provide an invaluable resource to support the development of the next generation of leaders in the cancer immunology community. This Commentary describes some of the key topics that were discussed during the 2022 symposium: scientific and career trajectory, leadership, mentoring, collaborations, and publishing. For each of these topics, established investigators discussed the elements that facilitate success in these areas as well as mistakes that can hinder progress. Herein, we outline the critical points raised in these discussions for establishing a successful independent research career. These points are highly relevant for the broader scientific community.

Stress Keratin 17 Is a Predictive Biomarker Inversely Associated with Response to Immune Check-Point Blockade in Head and Neck Squamous Cell Carcinomas and Beyond.

Low response rates in immune check-point blockade (ICB)-treated head and neck squamous cell carcinoma (HNSCC) drive a critical need for robust, clinically validated predictive biomarkers. Our group previously showed that stress keratin 17 (CK17) suppresses macrophage-mediated CXCL9/CXCL10 chemokine signaling involved in attracting activated CD8+ T cells into tumors, correlating with decreased response rate to pembrolizumab-based therapy in a pilot cohort of ICB-treated HNSCC (n = 26). Here, we performed an expanded analysis of the predictive value of CK17 in ICB-treated HNSCC according to the REMARK criteria and investigated the gene expression profiles associated with high CK17 expression. Pretreatment samples from pembrolizumab-treated HNSCC patients were stained via immunohistochemistry using a CK17 monoclonal antibody (n = 48) and subjected to spatial transcriptomic profiling (n = 8). Our findings were validated in an independent retrospective cohort (n = 22). CK17 RNA expression in pembrolizumab-treated patients with various cancer types was investigated for predictive significance. Of the 48 patients (60% male, median age of 61.5 years), 21 (44%) were CK17 high, and 27 (56%) were CK17 low. A total of 17 patients (35%, 77% CK17 low) had disease control, while 31 patients (65%, 45% CK17 low) had progressive disease. High CK17 expression was associated with a lack of disease control (p = 0.037), shorter time to treatment failure (p = 0.025), and progression-free survival (PFS, p = 0.004), but not overall survival (OS, p = 0.06). A high CK17 expression was associated with lack of disease control in an independent validation cohort (p = 0.011). PD-L1 expression did not correlate with CK17 expression or clinical outcome. CK17 RNA expression was predictive of PFS and OS in 552 pembrolizumab-treated cancer patients. Our findings indicate that high CK17 expression may predict resistance to ICB in HNSCC patients and beyond.

Nonclassical monocytes potentiate anti-tumoral CD8+ T cell responses in the lungs.

CD8+ T cells drive anti-cancer immunity in response to antigen-presenting cells such as dendritic cells and subpopulations of monocytes and macrophages. While CD14+ classical monocytes modulate CD8+ T cell responses, the contributions of CD16+ nonclassical monocytes to this process remain unclear. Herein we explored the role of nonclassical monocytes in CD8+ T cell activation by utilizing E2-deficient (E2-/-) mice that lack nonclassical monocytes. During early metastatic seeding, modeled by B16F10-OVA cancer cells injected into E2-/- mice, we noted lower CD8+ effector memory and effector T cell frequencies within the lungs as well as in lung-draining mediastinal lymph nodes in the E2-/- mice. Analysis of the myeloid compartment revealed that these changes were associated with depletion of MHC-IIloLy6Clo nonclassical monocytes within these tissues, with little change in other monocyte or macrophage populations. Additionally, nonclassical monocytes preferentially trafficked to primary tumor sites in the lungs, rather than to the lung-draining lymph nodes, and did not cross-present antigen to CD8+ T cells. Examination of the lung microenvironment in E2-/- mice revealed reduced CCL21 expression in endothelial cells, which is chemokine involved in T cell trafficking. Our results highlight the previously unappreciated importance of nonclassical monocytes in shaping the tumor microenvironment via CCL21 production and CD8+ T cell recruitment.

Cell-autonomous regulation of complement C3 by factor H limits macrophage efferocytosis and exacerbates atherosclerosis.

Complement factor H (CFH) negatively regulates consumption of complement component 3 (C3), thereby restricting complement activation. Genetic variants in CFH predispose to chronic inflammatory disease. Here, we examined the impact of CFH on atherosclerosis development. In a mouse model of atherosclerosis, CFH deficiency limited plaque necrosis in a C3-dependent manner. Deletion of CFH in monocyte-derived inflammatory macrophages propagated uncontrolled cell-autonomous C3 consumption without downstream C5 activation and heightened efferocytotic capacity. Among leukocytes, Cfh expression was restricted to monocytes and macrophages, increased during inflammation, and coincided with the accumulation of intracellular C3. Macrophage-derived CFH was sufficient to dampen resolution of inflammation, and hematopoietic deletion of CFH in atherosclerosis-prone mice promoted lesional efferocytosis and reduced plaque size. Furthermore, we identified monocyte-derived inflammatory macrophages expressing C3 and CFH in human atherosclerotic plaques. Our findings reveal a regulatory axis wherein CFH controls intracellular C3 levels of macrophages in a cell-autonomous manner, evidencing the importance of on-site complement regulation in the pathogenesis of inflammatory diseases.

A tessellated lymphoid network provides whole-body T cell surveillance in zebrafish.

Homeostatic trafficking to lymph nodes allows T cells to efficiently survey the host for cognate antigen. Nonmammalian jawed vertebrates lack lymph nodes but maintain diverse T cell pools. Here, we exploit in vivo imaging of transparent zebrafish to investigate how T cells organize and survey for antigen in an animal devoid of lymph nodes. We find that naïve-like T cells in zebrafish organize into a previously undescribed whole-body lymphoid network that supports streaming migration and coordinated trafficking through the host. This network has the cellular hallmarks of a mammalian lymph node, including naïve T cells and CCR7-ligand expressing nonhematopoietic cells, and facilitates rapid collective migration. During infection, T cells transition to a random walk that supports antigen-presenting cell interactions and subsequent activation. Our results reveal that T cells can toggle between collective migration and individual random walks to prioritize either large-scale trafficking or antigen search in situ. This lymphoid network thus facilitates whole-body T cell trafficking and antigen surveillance in the absence of a lymph node system.

Synergistic cancer immunotherapy utilizing programmed Salmonella typhimurium secreting heterologous flagellin B conjugated to interleukin-15 proteins.

The use of appropriately designed immunotherapeutic bacteria is an appealing approach to tumor therapy because the bacteria specifically target tumor tissue and deliver therapeutic payloads. The present study describes the engineering of an attenuated strain of Salmonella typhimurium deficient in ppGpp biosynthesis (SAM) that could secrete Vibrio vulnificus flagellin B (FlaB) conjugated to human (hIL15/FlaB) and mouse (mIL15/FlaB) interleukin-15 proteins in the presence of L-arabinose (L-ara). These strains, named SAMphIF and SAMpmIF, respectively, secreted fusion proteins that retained bioactivity of both FlaB and IL15. SAMphIF and SAMpmIF inhibited the growth of MC38 and CT26 subcutaneous (sc) tumors in mice and increased mouse survival rate more efficiently than SAM expressing FlaB alone (SAMpFlaB) or IL15 alone (SAMpmIL15 and SAMphIL15), although SAMpmIF had slightly greater antitumor activity than SAMphIF. The mice treated with these bacteria showed enhanced macrophage phenotype shift, from M2-like to M1-like, as well as greater proliferation and activation of CD4+ T, CD8+ T, NK, and NKT cells in tumor tissues. After tumor eradication by these bacteria, ≥50% of the mice show no evidence of tumor recurrence upon rechallenge with the same tumor cells, indicating that they had acquired long-term immune memory. Treatment of mice of 4T1 and B16F10 highly malignant sc tumors with a combination of these bacteria and an immune checkpoint inhibitor, anti-PD-L1 antibody, significantly suppressed tumor metastasis and increased mouse survival rate. Taken together, these findings suggest that SAM secreting IL15/FlaB is a novel therapeutic candidate for bacterial-mediated cancer immunotherapy and that its antitumor activity is enhanced by combination with anti-PD-L1 antibody.

Image-derived Metrics Quantifying Hemodynamic Instability Predicted Growth of Unruptured Intracranial Aneurysms.

Background: While image-derived predictors of intracranial aneurysm (IA) rupture have been well-explored, current understanding of IA growth is limited. Pulsatility index (PI) and wall shear stress pulsatility index (WSSPI) are important metrics measuring temporal hemodynamic instability. However, they have not been investigated in IA growth research. The present study seeks to verify reliable predictors of IA growth with comparative analyses of several important morphological and hemodynamic metrics between stable and growing cases among a group of unruptured IAs. Methods: Using 3D images, vascular models of 16 stable and 20 growing cases were constructed and verified using Geodesic techniques. With an overall mean follow-up period of 25 months, cases exhibiting a 10% or higher increase in diameter were considered growing. Patient-specific, pulsatile simulations were performed, and hemodynamic calculations were computed at 5 important regions of each aneurysm (inflow artery, aneurysm neck, body, dome, and outflow artery). Index values were compared between growing and stable IAs using ANCOVA controlling for aneurysm diameter. Stepwise multiple logistic regression and ROC analyses were conducted to investigate predictive models of IA growth. Results: Compared to stable IAs, growing IAs exhibited significantly higher intrasaccular PI, intrasaccular WSSPI, intrasaccular spatial flow rate deviation, and intrasaccular spatial wall shear stress (WSS) deviation. Stepwise logistic regression analysis revealed a significant predictive model involving PI at aneurysm body, WSSPI at inflow artery, and WSSPI at aneurysm body. Conclusions: Our results showed that high degree of hemodynamic variations within IAs is linked to growth, even after controlling for morphological parameters. Further, evaluation of PI in conjunction with WSSPI yielded a highly accurate predictive model of IA growth. Upon validation in future cohorts, these metrics may aid in early identification of IA growth and current understanding of IA remodeling mechanism.

A tessellated lymphoid network provides whole-body T cell surveillance in zebrafish.

Homeostatic trafficking to lymph nodes allows T cells to efficiently survey the host for cognate antigen. Non-mammalian jawed vertebrates lack lymph nodes but maintain similarly diverse T cell pools. Here, we exploit in vivo imaging of transparent zebrafish to investigate how T cells organize and survey for antigen in an animal devoid of lymph nodes. We find that naïve-like T cells in zebrafish organize into a previously undescribed whole-body lymphoid network that supports streaming migration and coordinated trafficking through the host. This network has the cellular hallmarks of a mammalian lymph node, including naïve T cells and CCR7-ligand expressing non-hematopoietic cells, and facilitates rapid collective migration. During infection, T cells transition to a random walk that supports antigen presenting cell interactions and subsequent activation. Our results reveal that T cells can toggle between collective migration and individual random walks to prioritize either large-scale trafficking or antigen search in situ . This novel lymphoid network thus facilitates whole-body T cell trafficking and antigen surveillance in the absence of a lymph node system. Significance Statement: In mammals, lymph nodes play a critical role in the initiation of adaptive immune responses by providing a dedicated place for T cells to scan antigen-presenting cells. Birds, reptiles, amphibians, and fish all maintain diverse repertoires of T cells but lack lymph nodes, raising questions about how adaptive immunity functions in lower jawed vertebrates. Here, we describe a novel network of lymphocytes in zebrafish that supports whole-body T cell trafficking and provides a site for antigen search, mirroring the function of mammalian lymph nodes. Within this network, T cells can prioritize large-scale trafficking or antigen scanning by toggling between two distinct modes of migration. This network provides valuable insights into the evolution of adaptive immunity.

Single-cell transcriptomic analysis of endometriosis.

Endometriosis is a common condition in women that causes chronic pain and infertility and is associated with an elevated risk of ovarian cancer. We profiled transcriptomes of >370,000 individual cells from endometriomas (n = 8), endometriosis (n = 28), eutopic endometrium (n = 10), unaffected ovary (n = 4) and endometriosis-free peritoneum (n = 4), generating a cellular atlas of endometrial-type epithelial cells, stromal cells and microenvironmental cell populations across tissue sites. Cellular and molecular signatures of endometrial-type epithelium and stroma differed across tissue types, suggesting a role for cellular restructuring and transcriptional reprogramming in the disease. Epithelium, stroma and proximal mesothelial cells of endometriomas showed dysregulation of pro-inflammatory pathways and upregulation of complement proteins. Somatic ARID1A mutation in epithelial cells was associated with upregulation of pro-angiogenic and pro-lymphangiogenic factors and remodeling of the endothelial cell compartment, with enrichment of lymphatic endothelial cells. Finally, signatures of ciliated epithelial cells were enriched in ovarian cancers, reinforcing epidemiologic associations between these two diseases.

[Ortho-geriatric rehabilitation: challenges and impact]. / Réadaptation ortho-gériatrique : enjeux et impact.

The risk of developing functional dependence rises with age. Following an acute event, a rehabilitation stay is often needed to restore functional capacities and consider home discharge. The geriatric rehabilitation process usually involves standardized multidisciplinary management, setting and frequent reviewing of the goals, and a discharge plan. In a retrospective observational study conducted in orthogeriatric rehabilitation conducted in Geneva, comorbidities, functional status at admission, and length of stay appear to have a significant impact on recovery potential and destination at discharge, whereas the intensity of the rehabilitation program (number of therapies per week) does not influence patient outcome.

Le risque de développer une dépendance fonctionnelle augmente avec l'âge. À la suite d'un événement aigu, un séjour en réadaptation est souvent nécessaire pour restaurer les capacités fonctionnelles et permettre un retour à domicile. Le processus de réadaptation gériatrique comporte une prise en charge standardisée pluridisciplinaire, la fixation et la révision régulière d'objectifs et la planification de la sortie. Dans une étude observationnelle rétrospective en réadaptation ortho-gériatrique menée à Genève, les comorbidités, l'état fonctionnel à l'admission et la durée de séjour prédisent les chances de récupération fonctionnelle et le retour à domicile, tandis que l'intensité du programme (nombre de thérapies par semaine) n'influence pas le devenir du patient.