Effects of delayed repair of peripheral nerve injury on the spatial distribution of motor endplates in target muscle

Motor endplates(MEPs) are important sites of information exchange between motor neurons and skeletal muscle, and are distributed in an organized pattern of lamellae in the muscle. Delayed repair of peripheral nerve injury typically results in unsatisfactory functional recovery because of MEP degeneration. In this study, the mouse tibial nerve was transected and repaired with a biodegradable chitin conduit, immediately following or 1 or 3 months after the injury. Fluorescent α-bungarotoxin was injected to label MEPs. Tissue optical clearing combined with light-sheet microscopy revealed that MEPs were distributed in an organized pattern of lamellae in skeletal muscle after delayed repair for 1 and 3 months. However, the total number of MEPs, the number of MEPs per lamellar cluster, and the maturation of single MEPs in gastrocnemius muscle gradually decreased with increasing denervation time. These findings suggest that delayed repair can restore the spatial distribution of MEPs, but it has an adverse effect on the homogeneity of MEPs in the lamellar clusters and the total number of MEPs in the target muscle. The study procedures were approved by the Animal Ethics Committee of the Peking University People's Hospital(approval No. 2019 PHC015) on April 8, 2019.

The proteome of distal nerves: implication in delayed repair and poor functional recovery

Chronic denervation is one of the key factors that affect nerve regeneration.Chronic axotomy deteriorates the distal nerve stump,causes protein changes,and renders the microenvironment less permissive for regeneration.Some of these factors/proteins have been individually studied.To better delineate the comprehensive protein expression profiles and identify proteins that contribute to or are associated with this detrimental effect,we carried out a proteomic analysis of the distal nerve using an established delayed rat sciatic nerve repair model.Four rats that received immediate repair after sciatic nerve transection served as control,whereas four rats in the experimental group(chronic denervation)had their sciatic nerve repaired after a 12-week delay.All the rats were sacrificed after 16 weeks to harvest the distal nerves for extracting proteins.Twenty-five micrograms of protein from each sample were fractionated in SDS-PAGE gels.NanoLC-MS/MS analysis was applied to the gels.Protein expression levels of nerves on the surgery side were compared to those on the contralateral side.Any protein with a P value of less than 0.05 and a fold change of 4 or higher was deemed differentially expressed.All the differentially expressed proteins in both groups were further stratified according to the biological processes.A PubMed search was also conducted to identify the differentially expressed proteins that have been reported to be either beneficial or detrimental to nerve regeneration.Ingenuity Pathway Analysis(IPA)software was used for pathway analysis.The results showed that 709 differentially expressed proteins were identified in the delayed repair group,with a bigger proportion of immune and inflammatory process-related proteins and a smaller proportion of proteins related to axon regeneration and lipid metabolism in comparison to the control group where 478 differentially expressed proteins were identified.The experimental group also had more beneficial proteins that were downregulated and more detrimental proteins that were upregulated.IPA revealed that protective pathways such as LXR/RXR,acute phase response,RAC,ERK/MAPK,CNTF,IL-6,and FGF signaling were inhibited in the delayed repair group,whereas three detrimental pathways,including the complement system,PTEN,and apoptosis signaling,were activated.An available database of the adult rodent sciatic nerve was used to assign protein changes to specific cell types.The poor regeneration seen in the delayed repair group could be associated with the down-regulation of beneficial proteins and up-regulation of detrimental proteins.The proteins and pathways identified in this study may offer clues for future studies to identify therapeutic targets.

Delayed Management of Popliteal Artery Injury Following Knee Dislocation—A Case Report

Knee dislocations frequently involve vascular injuries that demand early diagnosis and timely intervention. Time of ischemia is pivotal in determining the outcome for the limb, delays in treatment beyond 8 hours significantly increase the risk of limb loss. Unfortunately, this critical window is often missed in resource-limited settings. Here we report a 25-year-old female sustained a left knee injury after falling into a trench. She was diagnosed with an open knee dislocation accompanied by a popliteal artery injury. However, revascularization was delayed for 18 hours due to limited resources, including the unavailability of a thrombectomy catheter. Postoperatively, the patient received anticoagulation therapy with serial limb assessments and after 3 weeks the laceration healed and the limb was still viable. Knee dislocations frequently result in vascular injury (popliteal artery most common), making prompt diagnosis and intervention essential for limb preservation. In settings with limited resources, like ours, delayed presentation and transfer to specialized centers contribute to prolonged ischemic times. Nonetheless, viable limbs should be revascularized in stable patients, even with prolonged ischemia. This case highlights the importance of limb revascularization despite delay. Efforts should be made to improve prompt diagnosis, timely referral, and availability of necessary equipment for vascular repair to optimize outcomes in similar cases.

Immediate versus delayed primary nerve repair in the rabbit sciatic nerve

It is well known that peripheral nerve injury should be treated immediately in the clinic, but in some instances, repair can be delayed. This study investigated the effects of immediate versus delayed （3 days after injury） neurorrhaphy on repair of transected sciatic nerve in New Zealand rabbits using stereological, histomorphological and biomechanical methods. At 8 weeks after immediate and delayed neurorrhaphy, axon number and area in the sciatic nerve, myelin sheath and epineurium thickness, Schwann cell morphology, and the mechanical property of nerve fibers did not differ obviously. These results indicate that delayed neurorrhaphy do not produce any deleterious effect on sciatic nerve repair.

Nerve function restoration following targeted muscle reinnervation after varying delayed periods

Targeted muscle reinnervation has been proposed for reconstruction of neuromuscular function in amputees.However,it is unknown whether performing delayed targeted muscle reinnervation after nerve injury will affect restoration of function.In this rat nerve injury study,the median and musculocutaneous nerves of the forelimb were transected.The proximal median nerve stump was sutured to the distal musculocutaneous nerve stump immediately and 2 and 4 weeks after surgery to reinnervate the biceps brachii.After targeted muscle reinnervation,intramuscular myoelectric signals from the biceps brachii were recorded.Signal amplitude gradually increased with time.Biceps brachii myoelectric signals and muscle fiber morphology and grooming behavior did not significantly differ among rats subjected to delayed target muscle innervation for different periods.Targeted muscle reinnervation delayed for 4 weeks can acquire the same nerve function restoration effect as that of immediate reinnervation.

Electrical stimulation does not enhance nerve regeneration if delayed after sciatic nerve injury: the role of fibrosis

Electrical stimulation has been shown to accelerate and enhance nerve regeneration in sensory and motor neurons after injury, but there is little evidence that focuses on the varying degrees of fibrosis in the delayed repair of peripheral nerve tissue. In this study, a rat model of sciatic nerve transec- tion injury was repaired with a biodegradable conduit at 1 day, 1 week, 1 month and 2 months after injury, when the rats were divided into two subgroups. In the experimental group, rats were treated with electrical stimuli of frequency of 20 Hz, pulse width 100 ms and direct current voltage of 3 V; while rats in the control group received no electrical stimulation after the conduit operation. His- tological results showed that stained collagen fibers comprised less than 20% of the total operated area in the two groups after delayed repair at both 1 day and 1 week but after longer delays, the collagen fiber area increased with the time after injury. Immunohistochemical staining revealed that the expression level of transforming growth factor ~ （an indicator of tissue fibrosis） decreased at both 1 day and 1 week after delayed repair but increased at both 1 and 2 months after delayed repair. These findings indicate that if the biodegradable conduit repair combined with electrical stimulation is delayed, it results in a poor outcome following sciatic nerve injury. One month after injury, tissue degeneration and distal fibrosis are apparent and are probably the main reason why electrical stimulation fails to promote nerve regeneration after delayed repair.

Timing of surgical repair of bile duct injuries after laparoscopic cholecystectomy: A systematic review

BACKGROUND The surgical management of bile duct injuries(BDIs)after laparoscopic cholecystectomy(LC)is challenging and the optimal timing of surgery remains unclear.The primary aim of this study was to systematically evaluate the evidence behind the timing of BDI repair after LC in the literature.AIM To assess timing of surgical repair of BDI and postoperative complications.METHODS The MEDLINE,EMBASE,and The Cochrane Library databases were systematically screened up to August 2021.Risk of bias was assessed via the Newcastle Ottawa scale.The primary outcomes of this review included the timing of BDI repair and postoperative complications.RESULTS A total of 439 abstracts were screened,and 24 studies were included with 15609 patients included in this review.Of the 5229 BDIs reported,4934(94%)were classified as major injury.Timing of bile duct repair was immediate(14%,n=705),early(28%,n=1367),delayed(28%,n=1367),or late(26%,n=1286).Standardization of definition for timing of repair was remarkably poor among studies.Definitions for immediate repair ranged from<24 h to 6 wk after LC while early repair ranged from<24 h to 12 wk.Likewise,delayed(>24 h to>12 wk after LC)and late repair(>6 wk after LC)showed a broad overlap.CONCLUSION The lack of standardization among studies precludes any conclusive recommendation on optimal timing of BDI repair after LC.This finding indicates an urgent need for a standardized reporting system of BDI repair.

A Two-Unit Cold Standby Repairable System with One Replaceable Repair Facility and Delay Repair: Some Reliability Problems

This paper considers a two–unit same cold standby repairable system with a replaceable repair facility and delay repair .The failure time of unit is assumed to follow exponential distribution , and the repair time and delay time of failed unit are assumed to follow arbitrary distributions , whereas the failure and replacement time distributions of the repair facility are exponential and arbitrary . By using the Markov renewal process theory, some primary reliability quantities of the system are obtained.

Analysis of imaging characteristics of blunt traumatic aortic dissection: an 8-year experience

BACKGROUND:Traumatic aortic dissection(TAD)has a low incidence but extremely high mortality.It always presents atypical clinical manifestations that are easily missed or misdiagnosed.This study mainly aims to describe the imaging characteristics and management of TAD patients.METHODS:A retrospective analysis of 27 blunt TAD patients was performed between 2013 and 2020.Demographic features,imaging characteristics,and management were analyzed.RESULTS:Twenty-seven patients with type B aortic dissection(age 56.04±16.07 years,20 men)were included.Aortic intimal tears were mostly initiated from the aortic isthmus.The sizes of the proximal intimal tears in the greater curvature were larger than those in the lesser curvature(1.78±0.56 cm vs.1.24±0.52 cm,P=0.031).Compared with those in the control group,the maximum diameters of the aortic arch,thoracic aorta,and abdominal aorta in the TAD patients were all significantly widened(all P<0.050).Multivariate logistic regression analysis showed that the maximum diameter of the thoracic aorta was an independent risk factor for TAD,with a predictive value with an area under the receiver operating characteristic curve(AUC)of 0.673.Finally,26 patients successfully underwent delayed thoracic endovascular aortic repair(TEVAR),and the remaining one patient was treated conservatively.No progression of aortic dissection or death occurred during the six-month follow-up period.CONCLUSIONS:In blunt trauma,the aortic isthmus is the most common site of proximal intimal tears.An accurate diagnosis of TAD requires an overall consideration of medical history and imaging characteristics.Delayed TEVAR might be an eff ective therapeutic option for TAD.

ANALYSIS OF BATCH ARRIVAL QUEUE WITH RANDOMIZED VACATION POLICY AND AN UN-RELIABLE SERVER

This paper examines an M[x]/G/1 queueing system with an unreliable server and a delayed repair, in which the server operates a randomized vacation policy with multiple vacations. Whenever the system is empty, the server immediately takes a,vacation. If there is at least one customer found waiting in the queue upon returning from a vacation, the server will be immediately activated for service. Otherwise, if no customers are waiting for service at the end of a vacation, the server either remains idle with probability p or leaves for another vacation with probability 1 -p. Whenever one or more customers arrive when the server is idle, the server immediately starts providing service for the arrivals. The server may also meet an unpredictable breakdown and the repair may be delayed. For such a system the authors derive the distributions of some important system characteristics, such as the system size distribution at a random epoch and at a departure epoch, the system size distribution at the busy period initiation epoch, and the distribution of the idle period and the busy period. The authors perform a numerical analysis for changes in the system characteristics, along with changes in specific values of the system parameters. A cost effectiveness maximization model is constructed to explain the benefits of such a queueing system.