Neuropathic pain induced by spinal cord injury (SCI) is clinically challenging with inadequate long-term treatment options. Partial pain relief offered by pharmacologic treatment is often counterbalanced by adverse effects after prolonged use in chronic pain patients. Cell-based therapy for neuropathic pain using GABAergic neuronal progenitor cells (NPC) has the potential to overcome untoward effects of systemic pharmacotherapy while enhancing analgesic potency due to local activation of GABAergic signaling in the spinal cord. However, multifactorial anomalies underlying chronic pain will likely require simultaneous targeting of multiple mechanisms. Here we explore the analgesic potential of genetically modified rat embryonic GABAergic NPCs releasing a peptidergic NMDA receptor antagonist, Serine1-histogranin (SHG), thus targeting both spinal hyperexcitability and reduced inhibitory processes. Recombinant NPCs were designed using either lentiviral or adeno-associated-viral vectors (AAV2/8) encoding single and multimeric (6 copies of SHG) cDNA. Intraspinal injection of recombinant cells elicited enhanced analgesic effects compared to nonrecombinant NPCs in spinal cord injury-induced pain in rats. Moreover, potent and sustained antinociception was achieved, even following a 5 weeks post-injury delay, using recombinant multimeric NPCs. Intrathecal injection of SHG antibody attenuated analgesic effects of the recombinant grafts suggesting active participation of SHG in these antinociceptive effects. Immunoblots and immunocytochemical assays indicated ongoing recombinant peptide production and secretion in the grafted host spinal cords. These results support the potential for engineered NPCs grafted into the spinal dorsal horn to alleviate chronic neuropathic pain.
Acquired hemophilia A or acquired factor VIII deficiency is a rare bleeding disorder due to the presence of autoantibodies to factor VIII. It has been associated with autoimmune conditions, certain medications, and malignancy. It has a high morbidity and mortality, and early diagnosis and treatment is critically important. Acquired hemophilia A usually manifests with soft tissue bleeding, such as epistaxis, genitourinary, or gastrointestinal bleeding and rarely with hemarthrosis. In this case report, we present the management of an uncommon case of acquired hemophilia A in a patient with metastatic prostate adenocarcinoma who presented with both hemarthrosis and soft tissue bleeding. Bleeding was controlled with recombinant factor VIIa, factor VIII bypassing agent, and immunosuppressive therapy with prednisone and rituximab. Chemotherapy with docetaxel was also promptly initiated to address the underlying condition and achieve long-term remission, which is currently ongoing for 10 months.
A 16-year-old girl presented with bilateral back pain caused by bilateral upper pole ureteropelvic junction obstructions; an extremely rare phenomenon. Bilateral robotically assisted upper pole pyeloplasties were preformed at the same setting with an excellent clinical response. Although rare, upper pole ureteropelvic junction obstruction is a defined entity that urologists should be aware of.
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