Liver resident macrophages Kupffer cells (KCs) and infiltrating Ly6Chi monocytes both contribute to liver tissue regeneration in various pathologies, but also to disease progression upon disruption of orderly consecutive regeneration cascades. Little is known about molecular pathways that regulate their differentiation, maintenance, or their inflammatory behavior during injury. Here we show that COMMD10-deficient KCs adopt liver-specific identity. Strikingly, COMMD10-deficiency in KCs and in other tissue resident macrophages impedes their homeostatic survival, leading to their continuous replacement by Ly6Chi monocytes. While COMMD10-deficiency in KCs mildly worsens acetaminophen-induced liver injury (AILI), its deficiency in Ly6Chi monocytes results in exacerbated and sustained hepatic damage. Monocytes display unleashed inflammasome activation and reduced type I interferon response and acquire ‘neutrophil-like’ and lipid associated macrophage differentiation fates. Collectively, COMMD10 appears indispensable for KC and other tissue resident macrophage survival and is an important regulator of Ly6Chi monocyte fate decisions and reparative behavior in the diseased liver.
9 November 2023 in The International Journal of Lower Extremity Wounds
Diabetic foot ulcer represents the primary cause of hospital admissions, amputations, and mortality in diabetic patients. The development of diabetic foot ulcers is influenced by peripheral neuropathy, infection, and ischemia, with diabetes contributing to peripheral artery disease. Free tissue transfer combined with revascularisation of the lower extremity provides the potential opportunity for limb salvage in individuals with lower extremity defects due to critical limb ischemia and diabetic foot.
Effective cryopreservation of large tissues, limbs, and organs has the potential to revolutionize medical post-trauma reconstruction options and organ preservation and transplantation procedures. To date, vitrification and directional freezing are the only viable methods for long-term organ or tissue preservation, but are of limited clinical relevance. This work aimed to develop a vitrification-based approach that will enable the long-term survival and functional recovery of large tissues and limbs following transplantation. The presented novel two-stage cooling process involves rapid specimen cooling to subzero temperatures, followed by gradual cooling to the vitrification solution (VS) and tissue glass transition temperature. Flap cooling and storage were only feasible at temperatures equal to or slightly lower than the VS Tg ( i.e. , −135°C). Vascularized rat groin flaps and below-the-knee (BTK) hind limb transplants cryopreserved using this approach exhibited long-term survival (>30 days) following transplantation to rats. BTK-limb recovery included hair regrowth, normal peripheral blood flow, and normal skin, fat, and muscle histology. Above all, BTK limbs were reinnervated, enabling rats to sense pain in the cryopreserved limb. These findings provide a strong foundation for the development of a long-term large-tissue, limb and organ preservation protocol for clinical use.
Background/Objectives: Breast cancer-related lymphedema (BCRL) is a chronic complication of breast cancer treatment, leading to physical and psychological morbidity. While widely studied globally, the prevalence and risk factors for BCRL in Israeli patients remain unexplored. This study’s objectives were to determine the prevalence of BCRL in Israeli women treated for breast cancer, validate the Hebrew-translated Norman Questionnaire (NQ) for BCRL screening, and identify risk factors associated with the condition. Methods: A single-center study was conducted at Tel Aviv Sourasky Medical Center, including 181 patients who underwent unilateral axillary lymph node interventions between 2015 and 2018. Participants completed the Hebrew-translated NQ, which was validated through clinical evaluation and circumference-based volume measurements in a subset of 20 patients. Prevalence rates and risk factors were analyzed using multivariate modeling. Results: The prevalence of BCRL was 20%, with rates varying by procedure: 8.9% for sentinel lymph node biopsy, 19.6% for lymph node sampling, and 37.5% for axillary lymph node dissection (ALND). Of the 35 patients with BCRL, only 14% had been previously diagnosed. Risk factors included ALND (OR = 97.31), a higher lymph node excision count (OR = 0.81), and referral to physiotherapy (OR = 133.50). The Hebrew NQ demonstrated strong validity (rs = 0.852; p < 0.001). Conclusions: This is the first study to estimate BCRL prevalence in Israeli women, highlighting underdiagnosis and the need for improved early detection. The Hebrew NQ is a reliable screening tool, enabling timely referral and intervention. Early diagnosis is crucial for optimizing treatment outcomes and improving the quality of life of BCRL patients.
1 August 2025 in Plastic and Reconstructive Surgery - Global Open
Background: Peripheral nerve injuries often lead to inconsistent outcomes due to the complexity of nerve regeneration. Hyperbaric oxygen therapy (HBOT) has been proposed to enhance regeneration by improving oxygenation, promoting angiogenesis, and facilitating cellular repair processes. This study evaluated the effects of long-term HBOT on axonal regeneration, remyelination, and functional recovery in a rat model of sciatic nerve injury repaired with autologous nerve grafts. Methods: Forty-two adult male Wistar rats were divided into control (surgery only) and treatment (surgery plus HBOT) groups. HBOT (2 atmospheres absolute, 100% oxygen, 1 h/d, 5 d/wk) was administered for 8 weeks. Functional recovery was assessed using the sciatic functional index, whereas regeneration was evaluated with electrophysiological tests, histological analysis, and immunohistochemistry at postoperative days (PODs) 14, 35, and 90. Results: HBOT enhanced axonal regeneration and remyelination in the middle and distal segments of the graft by POD 35. Motor neuron preservation was significantly higher in the treatment group, approaching levels of uninjured nerves by POD 90. Electrophysiological analyses revealed earlier and more consistent reinnervation in the HBOT group, with improved normalized compound muscle action potential amplitudes at POD 60. However, functional recovery assessed by the sciatic functional index showed no significant differences between groups, likely due to autotomy and the lack of physiotherapy. Conclusions: Long-term HBOT accelerates axonal regeneration and remyelination in a rat model of peripheral nerve injury and grafting. These findings suggest that HBOT is a promising adjunctive therapy for complex nerve injuries, with potential clinical applications in reconstructive nerve surgery.