Acute kidney injury due to bilateral malignant ureteral obstruction:Is there an optimal mode of drainage?

There is a well-known relationship between malignancy and impairment of kidney functions,either in the form of acute kidney injury or chronic kidney disease.In the former,however,bilateral malignant ureteral obstruction is a surgically correctable factor of this complex pathology.It warrants urgent drainage of the kidneys in emergency settings.However,there are multiple controversies and debates about the optimal mode of drainage of the bilaterally obstructed kidneys in these patients.This review addressed most of the concerns and provided a comprehensive presentation of this topic from the recent literature.Also,we provided different perspectives on the management of the bilateral obstructed kidneys due to malignancy.Despite the frequent trials for improving the success rates and functions of ureteral stents,placement of a percutaneous nephrostomy tube remains the most recommended tool of drainage due to bilateral ureteral obstruction,especially in patients with advanced malignancy.However,the disturbance of the quality of life of those patients remains a major unresolved concern.Beside the unfavorable prognostic potential of the underlying malignancy and the various risk stratification models that have been proposed,the response of the kidney to initial drainage can be anticipated and evaluated by multiple renal prognostic factors,including increased urine output,serum creatinine trajectory,and time-to-nadir serum creatinine after drainage.

Acute kidney injury due to bilateral ureteral obstruction in children

Bilateral ureteral obstruction in children is a rare condition arising from several medical or surgical pictures.It needs to be promptly suspected in order to attempt a quick renal function recovery.In this paper we concentrated on uncommon causes of obstruction,with the aim of giving a summary of such multiple,rare and heterogeneous conditions joint together by the common denominator of sudden bilateral ureteral obstruction,difficult to be suspected at times.Conversely,typical and well-known diseases have been just run over.We considered pediatric cases of ureteral obstruction presenting as bilateral,along with some cases which truly appeared as single-sided,because of their potential bilateral presentation.We performed a review of the literature by a search on Pub Med,Cross Ref Metadata Search,internet and reference lists of single articles updated to May 2014,with no time limits in the past.Given that we deal with rare conditions,we decided to include also papers in non-English languages,published with an English abstract.For the sake of clearness,we divided our research results into 8 categories:(1) urolithiasis;(2) congenital urinary tract malformations;(3) immuno-rheumatologic causes of ureteral obstruction;(4) ureteral localization of infections;(5) other systemic infective causes of ureteral obstructions;(6) neoplastic intrinsic ureteral obstructions;(7) extrinsic ureteralobstructions; and(8) iatrogenic trigonal obstruction or inflammation.Of course,different pathogenic mechanisms underlay those clinical pictures,partly wellknown and partly not completely understood.

Adult iatrogenic ureteral injury and strictureeincidence and treatment strategies

Iatrogenic ureteral injuries and strictures are relatively common complication of pelvic surgery and radiation treatment.Left untreated they are associated with severe shortand long-term complications such as urinoma,septic state,renal failure,and loss of a renal unit.Treatment depends on timing of diagnosis,as well as extent of injury,and ranges from simple endoscopic management to complex surgical reconstruction under usage of pedicled grafts.While recent advances in ureteral tissue engineering are promising the topic is still underreported.Historically a domain of open surgery,laparoscopic and robotic-assisted approaches have proven their feasibility in small case series,and are increasingly being utilized as means of reconstructive surgery.This review aims to give an outline of incidence and treatment of ureteral injuries and strictures in light of the latest advances.

URETERAL INJURY DURING GYNECOLOGICAL LAPAROSCOPIC SURGERIES: REPORT OF TWELVE CASES

Objective To investigate ureteral injury during gynecological laparoscopic surgeries.Methods From January 1990 to December 2005, 12868 gynecological laparoscopic surgeries were conducted in Peking Union Medical College Hospital with 12 ureteral injuries reported. The present study investigated several aspects, including surgical indications, uterine size, pelvic adhesion, operative procedures, symptoms, diagnostic time and methods, injury site and type, subsequent treatment, and prognosis. Results The incidence of ureteral injury was 0.093% (12/12868) in all cases, 0.42% (11/2586) in laparoscopic hysterectomy [laparoscopically assisted vaginal hysterectomy (LAVH) or total laparoscopic hysterectomy (TLH)], and 0.01% (1/10282) in non-LAVH surgeries. Enlarged uterus, pelvic adhesion, and endometrosis were risk factors associated with ureteral injury. Only one injury was found intraoperatively while others were found postoperatively. The injury sites were at the pelvic brim (2 cases) or the lower part of ureter (10 cases). Patients were treated with ureteral stenting (effective in 2 cases) or laparotomy and open repair. Prognoses were favorable in most cases. Conclusions Most laparoscopic ureteral injuries occur during laparoscopic hysterectomy. Further evaluation is required when ureteral injury is suspected, and surgical repair is the major treatment for ureteral injury.

A method for reducing thermal injury during the ureteroscopic holmium laser lithotripsy

Objective:Many studies have demonstrated the heat effect from the holmium laser lithotripsy can cause persistent thermal injury to the ureter.The purpose of this study was to elucidate the use of a modified ureteral catheter with appropriate firing and irrigation to reduce the thermal injury to the“ureter”during the ureteroscopic holmium laser lithotripsy in vitro.Methods:An in vitro lithotripsy was performed using a modified catheter(5 Fr)as the entrance for the irrigation and the holmium laser fiber while using the remaining space in the ureteroscopic channel as an outlet.Different laser power settings(10 W,20 W,and 30 W)with various firing times(3 s,5 s,and 10 s)and rates of irrigation(15 mL/min,20 mL/min,and 30 mL/min)were applied in the experiment.Temperature changes in the“ureter”were recorded with a thermometer during and after the lithotripsy.Results:During the lithotripsy,the local highest mean temperature was 60.3℃ and the lowest mean temperature was 26.7℃.When the power was set to 10 w,the temperature was maintained below 43℃ regardless of laser firing time or irrigation flow.Regardless of the power or firing time selected,the temperature was below 43℃ at the rate of 30 mL/min.There was a significant difference in temperature decrease when continuous 3 s drainage after continuous firing(3 s,5 s,or 10 s)compared to with not drainage(p<0.05)except for two conditions of 0.5 J×20 Hz,30 mL/min,firing 5 s,and 1.0 J×10 Hz,30 mL/min,firing 5 s.Conclusion:Our modified catheter with timely drainage reducing hot irrigation may significantly reduce the local thermal injury effect,especially along with the special interrupted-time firing setting during the simulated holmium laser procedure.

Sex-dependent alterations in extracellular vesicles linking chronic spinal cord injury to brain neuroinflammation and neurodegeneration

Traumatic spinal cord injury(SCI)is a devastating exogenous injury with long-lasting consequences and a leading cause of death and disability worldwide.Advances in assistive technology,rehabilitative interventions,and the ability to identify and intervene in secondary conditions have significantly increased the long-term survival rate of SCI patients,with some people even living well into their seventh or eighth decade.These survival changes have led neurotrauma researchers to examine how SCI interacts with brain aging.Public health and epidemiological data showed that patients with long-term SCI can have a lower life expectancy and quality of life,along with a higher risk of comorbidities and complications.

Spinal cord injury regenerative therapy development:integration of design of experiments

Spinal cord injury(SCI)can cause motor and sensory paralysis,and autonomic nervous system disorders including malfunction of urination and defecation,thereby significantly impairing the quality of life.Researchers continue to explo re new stem cell strategies for the treatment of paralysis by transpla nting human induced pluripotent stem cell-derived neural ste m/progenitor cells(hiPSCNS/PCs)into spinal cord injured tissues.

Deciphering the mechanobiology of microglia in traumatic brain injury with advanced microsystems

Advanced microsystems in traumatic brain injury research:Traumatic brain injury(TBI)results from a mechanical insult to the brain,leading to neuronal and axonal damage and subsequently causing a secondary injury.Within minutes of TBI,a neuroinflammatory response is triggered,driven by intricate molecular and cellular inflammatory processes.

Visualizing traumatic brain injury:ocular clues for diagnosis and assessment

Traumatic brain injury (TBI) is defined as damage to the brain resulting from an external sudden physical force or shock to the head.It is considered a silent public health epidemic causing significant death and disability globally.There were 64,000 TBI related deaths reported in the USA in 2020,with about US$76 billion in direct and indirect medical costs annually.

A lead role for a“secondary”axonal injury response

Stress signaling following axon injury stimulates a transcriptional program for regeneration that might be exploited to promote central nervous system repair.However,this stress response drives neuronal apoptosis in non-regenerative environments.This duality presents a quandary for the development of therapeutic interventions:manipulating stress signaling to enhance recovery of damaged neurons risks accelerating neurodegeneration or restricting regenerative potential.This dichotomy is well illustrated by the fates of retinal ganglion cells(RGCs)following optic nerve crush.In this central nervous system injury model,disruption of a stress-activated MAP kinase(MAPK)cascade blocks the extensive apoptosis of RGCs that occurs in wild-type mice(Watkins et al.,2013;Welsbie et al.,2017).

Secretome of polarized macrophages:potential for targeting inflammatory dynamics in spinal cord injury

Spinal cord injury(SCI)involves an initial traumatic phase,followed by secondary events such as ischemia,increased blood-spinal cord barrier permeability,ionic disruption,glutamate excitotoxicity,and metabolic alterations.A pe rsistent and exagge rated inflammato ry response within the spinal cord accompanies these events(Lima et al.,2022).The complexity and interplay of these mechanisms exacerbate the initial injury,leading to a degenerative process at the injury site.While the initial trauma is unavoidable,the secondary injury begins within minutes and can last for months,creating an optimal window for therapeutic intervention.

Remaking a connection:molecular players involved in post-injury synapse formation

Functional recovery from central nervous system(CNS)trauma depends not only on axon regeneration or compensatory sprouting of uninjured fibers but also on the ability of newly grown axons to establish functional synapses with appropriate targets.Although several studies have successfully promoted long-distance axonal regeneration in distinct CNS injury models,none of them have resulted in a viable therapeutic approach for patient recovery.A possible reason may be the lack of new synaptogenesis for reestablishing the circuitry lost after injury.Herein,we discuss how our understanding of the mechanisms that instruct synapse formation in the injured nervous system may contribute to the design of new strategies to promote functional restoration in traumatic CNS disorders.

New insights on the role of chondroitin sulfate proteoglycans in neural stem cell–mediated repair in spinal cord injury

Extensive neurodegeneration is a hallmark of traumatic spinal cord injury (SCI) that underlies permanent sensorimotor and autonomic impairments (Alizadeh et al.,2019).Following the primary impact,the spinal cord undergoes a cascade of secondary injury mechanisms that are driven by disruption of the blood-spinal cord ba rrier,vascula r inju ry,glial reactivity,neu roinfla mmation,oxidative stress,lipid peroxidation,and glutamate excitotoxicity that culminate in neuronal and oligodendroglial cell death,demyelination,and axonal damage(Alizadeh et al.,2019).To achieve a meaningful functional recovery after SCI,regeneration of new neurons and oligodendrocytes and their successful growth and integration within the neural network are critical steps for reconstructing the damaged spinal cord tissue (Fischer et al.,2020).

Stepping up after spinal cord injury:negotiating an obstacle during walking

Every day walking consists of frequent voluntary modifications in the gait pattern to negotiate obstacles.After spinal cord injury,stepping over an obstacle becomes challenging.Stepping over an obstacle requires sensorimotor transformations in several structures of the brain,including the parietal cortex,premotor cortex,and motor cortex.Sensory information and planning are transformed into motor commands,which are sent from the motor cortex to spinal neuronal circuits to alter limb trajectory,coordinate the limbs,and maintain balance.After spinal cord injury,bidirectional communication between the brain and spinal cord is disrupted and animals,including humans,fail to voluntarily modify limb trajectory to step over an obstacle.Therefore,in this review,we discuss the neuromechanical control of stepping over an obstacle,why it fails after spinal cord injury,and how it recovers to a certain extent.

Hypidone hydrochloride(YL-0919)ameliorates functional deficits after traumatic brain injury in mice by activating the sigma-1 receptor for antioxidation

Traumatic brain injury involves complex pathophysiological mechanisms,among which oxidative stress significantly contributes to the occurrence of secondary injury.In this study,we evaluated hypidone hydrochloride(YL-0919),a self-developed antidepressant with selective sigma-1 receptor agonist properties,and its associated mechanisms and targets in traumatic brain injury.Behavioral experiments to assess functional deficits were followed by assessment of neuronal damage through histological analyses and examination of blood-brain barrier permeability and brain edema.Next,we investigated the antioxidative effects of YL-0919 by assessing the levels of traditional markers of oxidative stress in vivo in mice and in vitro in HT22 cells.Finally,the targeted action of YL-0919 was verified by employing a sigma-1 receptor antagonist(BD-1047).Our findings demonstrated that YL-0919 markedly improved deficits in motor function and spatial cognition on day 3 post traumatic brain injury,while also decreasing neuronal mortality and reversing blood-brain barrier disruption and brain edema.Furthermore,YL-0919 effectively combated oxidative stress both in vivo and in vitro.The protective effects of YL-0919 were partially inhibited by BD-1047.These results indicated that YL-0919 relieved impairments in motor and spatial cognition by restraining oxidative stress,a neuroprotective effect that was partially reversed by the sigma-1 receptor antagonist BD-1047.YL-0919 may have potential as a new treatment for traumatic brain injury.

Complement-dependent neuroinflammation in spinal cord injury:from pathology to therapeutic implications

Spinal cord injury remains a major cause of disability in young adults,and beyond acute decompression and rehabilitation,there are no pharmacological treatments to limit the progression of injury and optimize recovery in this population.Following the thorough investigation of the complement system in triggering and propagating cerebral neuroinflammation,a similar role for complement in spinal neuroinflammation is a focus of ongoing research.In this work,we survey the current literature investigating the role of complement in spinal cord injury including the sources of complement proteins,triggers of complement activation,and role of effector functions in the pathology.We study relevant data demonstrating the different triggers of complement activation after spinal cord injury including direct binding to cellular debris,and or activation via antibody binding to damage-associated molecular patterns.Several effector functions of complement have been implicated in spinal cord injury,and we critically evaluate recent studies on the dual role of complement anaphylatoxins in spinal cord injury while emphasizing the lack of pathophysiological understanding of the role of opsonins in spinal cord injury.Following this pathophysiological review,we systematically review the different translational approaches used in preclinical models of spinal cord injury and discuss the challenges for future translation into human subjects.This review emphasizes the need for future studies to dissect the roles of different complement pathways in the pathology of spinal cord injury,to evaluate the phases of involvement of opsonins and anaphylatoxins,and to study the role of complement in white matter degeneration and regeneration using translational strategies to supplement genetic models.

Astrocytes, reactive astrogliosis, and glial scar formation in traumatic brain injury

Traumatic brain injury is a global health crisis,causing significant death and disability worldwide.Neuroinflammation that follows traumatic brain injury has serious consequences for neuronal survival and cognitive impairments,with astrocytes involved in this response.Following traumatic brain injury,astrocytes rapidly become reactive,and astrogliosis propagates from the injury core to distant brain regions.Homeostatic astroglial proteins are downregulated near the traumatic brain injury core,while pro-inflammatory astroglial genes are overexpressed.This altered gene expression is considered a pathological remodeling of astrocytes that produces serious consequences for neuronal survival and cognitive recovery.In addition,glial scar formed by reactive astrocytes is initially necessary to limit immune cell infiltration,but in the long term impedes axonal reconnection and functional recovery.Current therapeutic strategies for traumatic brain injury are focused on preventing acute complications.Statins,cannabinoids,progesterone,beta-blockers,and cerebrolysin demonstrate neuroprotective benefits but most of them have not been studied in the context of astrocytes.In this review,we discuss the cell signaling pathways activated in reactive astrocytes following traumatic brain injury and we discuss some of the potential new strategies aimed to modulate astroglial responses in traumatic brain injury,especially using cell-targeted strategies with miRNAs or lncRNA,viral vectors,and repurposed drugs.

Combinatorial therapies for spinal cord injury repair

Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

Pharmacological intervention for chronic phase of spinal cord injury

Spinal cord injury is an intractable traumatic injury. The most common hurdles faced during spinal cord injury are failure of axonal regrowth and reconnection to target sites. These also tend to be the most challenging issues in spinal cord injury. As spinal cord injury progresses to the chronic phase, lost motor and sensory functions are not recovered. Several reasons may be attributed to the failure of recovery from chronic spinal cord injury. These include factors that inhibit axonal growth such as activated astrocytes, chondroitin sulfate proteoglycan, myelin-associated proteins, inflammatory microglia, and fibroblasts that accumulate at lesion sites. Skeletal muscle atrophy due to denervation is another chronic and detrimental spinal cord injury–specific condition. Although several intervention strategies based on multiple outlooks have been attempted for treating spinal cord injury, few approaches have been successful. To treat chronic spinal cord injury, neural cells or tissue substitutes may need to be supplied in the cavity area to enable possible axonal growth. Additionally, stimulating axonal growth activity by extrinsic factors is extremely important and essential for maintaining the remaining host neurons and transplanted neurons. This review focuses on pharmacotherapeutic approaches using small compounds and proteins to enable axonal growth in chronic spinal cord injury. This review presents some of these candidates that have shown promising outcomes in basic research(in vivo animal studies) and clinical trials: AA-NgR(310)ecto-Fc(AXER-204), fasudil, phosphatase and tensin homolog protein antagonist peptide 4, chondroitinase ABC, intracellular sigma peptide,(-)-epigallocatechin gallate, matrine, acteoside, pyrvate kinase M2, diosgenin, granulocyte-colony stimulating factor, and fampridine-sustained release. Although the current situation suggests that drug-based therapies to recover function in chronic spinal cord injury are limited, potential candidates have been identified through basic research, and these candidates may be subjects of clinical studies in the future. Moreover, cocktail therapy comprising drugs with varied underlying mechanisms may be effective in treating the refractory status of chronic spinal cord injury.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.