Targeting the Complement Pathway in Kidney Transplantation.

The complement system is paramount in the clearance of pathogens and cell debris, yet is increasingly recognized as a key component in several pathways leading to allograft injury. There is thus a growing interest in new biomarkers to assess complement activation and guide tailored therapies after kidney transplantation (KTx). C5 blockade has revolutionized post-transplant management of atypical hemolytic uremic syndrome, a paradigm of complement-driven disease. Similarly, new drugs targeting the complement amplification loop hold much promise in the treatment and prevention of recurrence of C3 glomerulopathy. Although unduly activation of the complement pathway has been described after brain death and ischemia reperfusion, any clinical attempts to mitigate the ensuing renal insults have so far provided mixed results. However, the intervention timing, strategy, and type of complement blocker need to be optimized in these settings. Furthermore, the fast-moving field of ex vivo organ perfusion technology opens new avenues to deliver complement-targeted drugs to kidney allografts with limited iatrogenic risks. Complement plays also a key role in the pathogenesis of donor-specific ABO- and HLA-targeted alloantibodies. However, C5 blockade failed overall to improve outcomes in highly sensitized patients and prevent the progression to chronic antibody-mediated rejection (ABMR). Similarly, well-conducted studies with C1 inhibitors in sensitized recipients yielded disappointing results so far, in part, because of subtherapeutic dosage used in clinical studies. The emergence of new complement blockers raises hope to significantly reduce the negative effect of ischemia reperfusion, ABMR, and nephropathy recurrence on outcomes after KTx.

Mitochondrial transplantation in cardiac surgical patients: optimism, caveats, and outstanding questions.

PURPOSE OF REVIEW: Mitochondria satisfy the high metabolic demand of the heart, and also play major roles in reactive oxygen species signaling, calcium buffering, and regulation of cell death. Mitochondrial damage or dysfunction can drive diseases seen in cardiac surgical patients, including heart failure and ischemia/reperfusion injury. Exogenous transplantation of isolated mitochondria has been proposed as one way to augment mitochondrial function and mitigate a number of pathologic processes, with a heavy focus on ischemia/reperfusion injury. RECENT FINDINGS: Animal models of cardiac ischemia/reperfusion injury have shown functional benefits after mitochondrial transplantation. Many of the mechanisms underlying this therapy's effect; optimal dosing, delivery, and timing; and how it will translate to cardiac surgical patients are yet unknown. SUMMARY: Mitochondrial transplantation is a potential therapeutic strategy for cardiac ischemia/reperfusion injury. Effective application to selected cardiac surgical patients can be informed by further mechanistic investigations.

THE POTENTIAL RENOPROTECTIVE EFFECT OF TILIANIN IN RENAL ISCHEMIA REPERFUSION INJURY IN MALE RAT MODEL.

OBJECTIVE: The aim: To determine whether Tilianin (TIL) may have Nephroprotective effects on bilateral renal IRI in rats by analyzing kidney function biomarkers U and Cr, inflammatory cytokines like TNF α and IL-1ß, antioxidant marker total anti-oxidant Capacity (TAC), anti-apoptotic markers caspase-3, and histopathological scores. PATIENTS AND METHODS: Materials and methods: 20 rats divided into even 4 groups as: Sham group: Rats underwent median laparotomies without having their ischemia induced. Control group: Rats had bilateral renal ischemia for 30 minutes, followed by 2 hours of reperfusion. Vehicle group: 30 minutes prior to the onset of ischemia, rats were given a pretreatment of corn oil and DMSO. Tilianin treated group: Rats administered Tilianin 5 mg/kg for 30 min prior to ischemia induction, then IRI. RESULTS: Results: The study found that the serum levels of TNF, IL-1, caspase-3, urea and creatinine, as well as TNF and creatinine in the Tilianin group were significantly lower than those of the control and vehicle groups. On the other hand, it revealed that TAC levels are remarkably higher in the Tilianin group than they are in the control and vehicle groups. CONCLUSION: Conclusions: This study concluded that Tilianin have a Nephroprotective effect via multiple impacts as anti-inflammatory, anti-apoptotic, and anti-oxidant agents.

The evaluation of citral effects on experimental unilateral testicular ischemia/reperfusion injury.

This investigation aimed to evaluate the defensive impacts of citral on ischemia/reperfusion (I/R) injury induced by testicular torsion/detorsion (T/D) in rats in an experimental model. The grouping of subjects was as follows: (1) sham, (2) T/D, (3) and (4) T/D plus citral 150 and 300 mg/kg, respectively, and (5) intact (citral 300 mg/kg). T/D was performed by testicular 720° turning for 2 h and then detorsion for 24 h. Blood serum was obtained to assess testosterone and oxidative stress markers, epididymal sperms were collected for sperm staining and sperm analysis, and testicular tissues were examined for histopathology. T/D damage was associated with a remarkable decline in sperm total count, viability, and some velocity parameters in comparison to the sham group (p < 0.05), which could be reversed significantly by citral (p < 0.05). Histopathologically, T/D damage caused severe oedema, haemorrhage, inflammation, and seminiferous tubules disruption, while citral improved significantly the mean seminiferous tubular diameter, Cosentino's score, and Johnsen's score (p < 0.05). I/R injury was associated with significant increased malondialdehyde and oxidative stress index, and also significant reduced total antioxidant capacity and testosterone versus the sham group (p < 0.05), which all were prevented significantly by citral administration (p < 0.05). The outcomes greatly proved that testicular I/R injury could be significantly prevented by citral.

[COMPLEX TREATMENT OF PURULENT-NECROTIC COMPLICATIONS IN THE PATIENTS, SUFFERING DIABETIC FOOT SYNDROME, USING NEGATIVE TRESSURE AND CAPICOR PREPARATION].

The comparative analysis data were presented, concerning the results of complex treatment of 28 patients, suffering ischemic-gangrenous form of the diabetic foot syndrome, developing on background of chronic ischemia of the lower extremities stage IV. In 14 patients (main group) a routine complex of the treatment measures was added by application of an active pressure (negative pressure wound therapy - NPWT) and a capicor preparation; 14 patients (the comparison group) were treated in accordance to routine scheme. In accordance to the comparative analysis data, in patients of the main group the wound surface sarea have kept reducing in twice more rapid, than in a comparison group, the wounds healing was achieved in 94% patients, duration of the patients' stationary stay have reduced by (5.2 ± 1.4) days.

Ischemia of the glans penis following circumcision: case report and revision of the literature.

Ischemic complications of the glans penis are rare and commonly result from trauma, inadvertent administration of vasoconstrictive solutions, diabetes mellitus, circumcision and vasculitis; we refer about a young man with severe ischemia of the glans penis following circumcision. The patient had undergone circumcision 5 days before in a surgery department under local anesthesia (1% mepivacaine hydrochloride). The patient noticed a brownish color and edema of the glans penis at 24 h after he opened the wound dressing, but arrived to our hospital only 5 days after circumcision because these findings had progressed. Physical examination revealed the black color or necrotic appearance of the glans penis, and edema on the dorsal penile skin. The patient underwent antibiotic, antiplatatelet, corticosteroid and iperbaric therapy achieving a complete restitutio ad integrum.

[IMPROVEMENT OF A "DELAY" METHOD WHILE PREPARATION OF FLAPS FOR PLASTIC OPERATION].

The improved method "delay", providing preservation of a small bridge of tissues near the flap tip, which are compressed with ligature or the strip of the glove's rubber during 7 - 12 days, was proposed for prevention of critical ischemia in the flap tissues. It permits to avoid the flap tissues critical ischemia up to the moment of the vascular net and blood flow enhancement while a compelled division of the flap in conditions of the damaged tissues or the cases of the flap area bigger than the area of the nutrient vessels basin. The improved method "delay" was applied successfully while the flaps preparation, formatted on temporary and constant nutritive pedicle, to plastic operation in 7 injured persons, suffering trauma of extremities.

[Case of ischemic ileitis complicated by portal venous gas].

A 65-year-old woman was admitted with sudden-onset abdominal pain. Abdominal computed tomography revealed hepatic portal venous gas. Physical and laboratory examination suggested that a conservative approach was appropriate; however, 4 days later, the pain recurred and severe ischemic enteritis was diagnosed. A stenosis was identified 60 cm distal to the start of the ileum, and partial resection of the small intestine was performed. The diagnosis of ischemic enteritis was confirmed. Ischemic enteritis affecting the small intestine is uncommon, and enteritis causing intestinal stenosis with hepatic portal vein gas is even rarer.

Establishment and Validation of a Model for Fetal Neural Ischemia Using Necrotic Core-Free Human Spinal Cord Organoids.

Fetal spinal cord ischemia is a serious medical condition that can result in significant neurological damage and adverse outcomes for the fetus. However, the lack of an appropriate experimental model has hindered the understanding of the pathology and the development of effective treatments. In our study, we established a system for screening drugs that affect fetal spinal cord ischemia using spinal cord organoids. Importantly, we produced necrotic core-free human spinal cord organoids (nf-hSCOs) by reducing the organoid size to avoid potential complications of spontaneous necrosis in large organoids. Exposing nf-hSCOs to CoCl2 as a hypoxia mimetic and hypoglycemic conditions resulted in significant neuronal damage, as assessed by multiple assay batteries. By utilizing this model, we tested chemicals that have been reported to exhibit beneficial effects in brain organoid-based ischemia models. Surprisingly, these chemicals did not provide sufficient benefit, and we discovered that rapamycin is a mild neuroprotective reagent for both axon degeneration and neuronal survival. We propose that nf-hSCO is suitable for large-scale screening of fetal neural ischemia due to its scalability, ease of ischemic induction, implementation of quantifiable assay batteries, and the absence of spontaneous necrosis.

Biological implications of extracellular adenosine in hepatic ischemia and reperfusion injury.

The purine nucleoside adenosine is clinically employed in the treatment of supraventricular tachycardia. In addition, it has direct coronary vasodilatory effects, and may influence platelet aggregation. Experimental observations mechanistically link extracellular adenosine to cellular adaptation to hypoxia. Adenosine generation has been implicated in several pathophysiologic processes including angiogenesis, tumor defenses and neurodegeneration. In solid organ transplantation, prolonged tissue ischemia and subsequent reperfusion injury may lead to profound graft dysfunction. Importantly, conditions of limited oxygen availability are associated with increased production of extracellular adenosine and subsequent tissue protection. Within the rapidly expanding field of adenosine biology, several enzymatic steps in adenosine production have been characterized and multiple receptor subtypes have been identified. In this review, we briefly examine the biologic steps involved in adenosine generation and chronicle the current state of adenosine signaling in hepatic ischemia and reperfusion injury.

Anterior segment angiography in strabismus surgery.

BACKGROUND: Anterior ciliary arteries travelling along recti muscles provide anterior segment vascularization, which can be compromised by surgery involving more than 2 muscles. PATIENTS AND METHODS: We studied retrospectively the files of 10 patients in whom a fluorescein angiography of the iris had been performed as a pre-operative assessment prior to a second or third oculomotor surgery. RESULTS: The median age of the patients was 47.5 years (range 15 to 73 years). Relative iris ischemia was present in 4 patients following multiple surgeries, none of them presenting any general cardiovascular risk. The initial surgical protocol was modified according to angiographic results in these 4 patients. CONCLUSION: When further surgery has to be performed on previously multi-operated patients, anterior segment angiography can be useful in the planning of surgery in order to minimize the risks of anterior segment ischemia.

Ischemic necrosis with sigmoid perforation in a patient with Systemic Lupus Erythematosus (SLE): case report.

Systemic Lupus Erythematosus (SLE) is a chronic inflammatory rheumatic disease which affects the connective tissue. Its etiology is as yet unknown, while its pathogenesis involves the immune system. Both genetic and environmental and hormonal factors play a key role in the impaired immune regulation. A correlation with estrogens is demonstrated by the fact that the greatest incidence is found in young women, when estrogen secretion is at its highest. The disease is also reported to worsen in women taking oral contraceptives. It is therefore believed that the components of oral contraceptives, estrogens (ethinyl estradiol) and progestins, can affect the immune profile. Of the various complications attributed to systemic lupus erythematosus, gastrointestinal disorders are less common but potentially by far the most serious. We report a case of ischemic necrosis with sigma perforation in a patient with SLE. Signs and symptoms of acute abdomen in patients with SLE are rare (0.2%), but serious. Most patients require an exploratory laparotomy, as the causes are often linked with vasculitis.

Thoracic sympathectomy for digital ischemia: a summary of evidence.

BACKGROUND: Thoracic sympathectomy is used in the management of a variety of upper limb disorders. We have analyzed the evidence for thoracic sympathectomy in the management of digital ischemia. METHODS: We reviewed the English literature between 1980 and 2010. Our analysis included reports with the clinical end points of relief, recurrence of symptoms or healing of ulcers, or both. Primary Raynaud disease (PRD) and secondary Raynaud phenomenon (SRP) were analyzed separately. RESULTS: An initial postoperative positive effect was reported in 92% of PRD patients and in 89% of SRP patients. Long-term beneficial effect was 58% for PRD and 89% for SRP. Ulcer healing or improvement was achieved in 95%. CONCLUSIONS: The available evidence suggests that thoracic sympathectomy has a role in the treatment of severe PRD and SRP, albeit with better results in SRP patients than in PRD patients. In case of digital ulceration, thoracic sympathectomy may maximize tissue preservation or prevent amputation.

Inferior mesenteric artery aneurysm in the setting of chronic colonic vascular ectasia.

Colonic vascular ectasia is a condition characterized by dilated submucosal veins, venules, or capillaries found commonly in patients with lower gastrointestinal hemorrhage. We present a case of colorectal ectasia associated with ischemia and an inferior mesenteric artery aneurysm. These pathologic findings may be the result of the vascular ectasia and may add to the natural history of this condition.

Necrosis of the leg after intraarterial drug injection.

Inadvertent intraarterial injections in the context of drug abuse can cause damage to the vascular system. The clinical picture depends on the drug properties and ranges from partial ischemia to necrosis of the affected extremity. There are no current evidence-based guidelines regarding the management of intraarterial drug injections. In many cases the concept of solving vasospasm after injection is based on the use of intraarterial application of prostaglandins. We report a case in which a mixture of drugs was injected into the left femoral artery. The patient arrived 24 hours later with ischemia of the left leg at our emergency department. Angiography showed that there was no blood flowing in the leg. Despite intraarterial application of vasodilatators, regional neurolysis and thrombolyis with urokinase major amputation was unavoidable. The outcome after inadvertent injection depends on certain drug properties and the delay between injection and the beginning of therapy.

Abdominal angina due to obstruction of mesenteric artery treated with spinal cord stimulation: a clinical case.

INTRODUCTION: Abdominal angina occurs in patients affected by mesenteric artery obstruction, causing postprandial episodes of visceral pain. The conventional treatment consists of vessels revascularization, but sometimes this is not applicable. CASE REPORT: The authors report a case of a patient with severe abdominal angina caused by mesenteric ischemia, not treatable with surgery and few-responder to pharmacological therapy (opioids and epidural infusion of local anesthetics). After a successful screening test, the patient underwent implantation of a spinal cord stimulation (SCS) device. RESULTS: The stimulation provided a reduction in pain episodes (number and intensity) and in oral analgesics consumption. Results obtained support the clinical efficacy and durability of the SCS in the management of abdominal angina due to not treatable mesenteric ischemia. CONCLUSIONS: Spinal cord stimulation may be considered for abdominal angina, although there is still no evidence provided by controlled studies.

The plasma D-dimer trends and their value in acute lower limb ischemia patients treated by catheter directed thrombolysis.

To investigate the change trends of plasma D-dimer during catheter-directed thrombolysis (CDT) in acute lower limb ischemia (ALI) patients and their clinical value. A retrospective review of patients with ALI who received CDT was carried out. The repeated measurements of plasma D-dimer were analyzed by generalized estimating equations (GEEs) and the change trends of D-dimer were analyzed by spline regression approach. A total of 150 patients were included. Among them, 3 days of CDT was ineffective in 41 cases, effective in 33 cases and markedly effective in 76 cases. The results of GEEs analysis showed that serum D-dimer changed significantly with time (time effect, P < 0.001). Serum D-dimer levels of patients with different treatment outcomes were different after treatment (group effect, P < 0.001), and serum D-dimer levels in these three groups showed different trends over time (group*time effect, P < 0.001). The different trends in serum D-dimer level with time after treatment in the three groups could be directly seen in the spline regression curve (P < 0.001). The plasma D-dimer changes regularly during CDT for ALI. We can predict the efficacy of CDT and guide adjustments of the therapeutic regimen according to the trend of D-dimer changes during thrombolysis.

Gluteal compartment syndrome following abdominal aortic aneurysm repair: a case report.

Compartment syndromes occur when the elevated tissue pressure within a confined limb's myofascial compartment exceeds capillary pressure, with subsequent neurovascular compromise. In order to reduce disability and the consequences of ensuring ischemia, it is essential for early recognition and intervention. This is more commonly recognized in the calf. We report an unusual case of gluteal compartment syndrome after abdominal aortic aneurysm (AAA) repair.