Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats.

Background: Chymase generates angiotensin II (ANG II) independently of angiotensin-converting enzyme in tissues and it contributes to vascular remodeling and development of hypertension, however the exact mechanism of its action is unclear. Methods: Hence, the effects of chymase inhibition were examined in anesthetized spontaneously hypertensive rats (SHR) in two stages of the disease development, ie. pre-hypertensive (SHR7) and with established hypertension (SHR16). Chymostatin, a commercial chymase inhibitor, was infused intravenously alone or in subsequent groups co-infused with captopril. Results: Mean blood pressure (MBP), total renal blood flow (RBF) and ANG II content (plasma and tissues) were measured. In SHR16 chymase blockade significantly decreased MBP (-6%) and plasma (-38%), kidney (-71%) and heart (-52%) ANG II levels. In SHR7 chymostatin did not influence MBP or RBF, but significantly decreased heart ANG II level. Conclusion: Jointly, functional studies and ANG II determinations support the evidence that in SHR chymase can raise plasma ANG II and contribute to blood pressure elevation. We propose that addition of chymase blockade to ACE inhibition could be a promising approach in the treatment of hypertensive patients resistant to therapy with ACE-inhibitors alone.

Differential osteopontin expression in human osteoblasts derived from iliac crest and alveolar bone and its role in early stages of angiogenesis.

In our previous study, we revealed significant differences of osteopontin (OPN) gene expression in primary human osteoblasts (HOBs) derived from iliac crest bone (iHOBs) and alveolar bone (aHOBs). The present study aims at assigning this discriminative expression to a possible biologic function. OPN is known to be involved in several pathologic and physiologic processes, among others angiogenesis. Therefore, we studied the reaction of human umbilical vein endothelial cells (HUVECs) to HOB-derived OPN regarding angiogenesis. To this end, human primary explant cultures of both bone entities from ten donors were established. Subsequent transcription analysis detected higher gene expression of OPN in iHOBs compared to aHOBs, thereby confirming the results of our previous study. This difference was particularly apparent when cultures were derived from female donors. Hence, OPN protein expression as well as the angiogenic potential of OPN was analyzed, originating from HOBs of one female donor. In accordance to the gene expression level, secreted OPN was more abundant in the supernatant of iHOBs than in aHOBs. Moreover, secreted OPN was found to stimulate migration of HUVECs, but not proliferation or tube formation. These results indicate an involvement in very early stages of angiogenesis and a functional distinction of OPN from HOBs derived from different bone entities.

Evaluation of long-term functional donor-site morbidity after deep circumflex iliac crest artery bone flap harvest.

PURPOSE: Free flap surgery can be associated with donor-site morbidity. The purpose of this study was to analyze long-term functional outcomes at the donor site after deep circumflex iliac artery (DCIA) bone flap harvesting. METHODS: Fourteen patients (8 men and 6 women, mean age 53.9 years; range 22-87 years) with mandible resection (8 carcinomas, 4 ameloblastomas, 1 osteonecrosis, and 1 myxofibroma) and DCIA flap reconstruction were included in an observational study. Ranges of motion in the hip and lumbar spine, Harris hip score (HHS), jumping mechanography, chair rising, and balance testing were performed on a ground force reaction plate (Leonardo Mechanograph, Novotec Medical GmbH, Germany). The primary outcome was the Esslinger fitness index (EFI, maximum peak power in W/kg normalized to age and gender). RESULTS: Functional assessment was performed preoperatively and 29.0 months postoperatively (range 12-51 months). Mean DCIA flap length was 6.3 cm (range 3.3-10.1 cm). Jaw reconstruction was successful in all cases. HHS (99.2 vs. 97.7 points, P = .004) and all ranges of motion in the lumbar spine and hip joint except for dorsal extension were significantly reduced postoperatively (range -4° to -11.0°). There was no significant difference between pre- and postoperative EFI (77.9% vs. 74.28%, P = .591) and body sway (1.25 cm2 vs. 2.01 cm2 , P = .806). Sensory deficits (n = 5), load dependent pain (n = 3), and limitations of daily activities (n = 3) were subjective complaints. CONCLUSION: Functional donor site morbidity after DCIA harvesting can be expected to be low in the long-term.

Anatomical variations of the principal nutrient pedicle for iliac crest graft: the ilio-lumbar artery.

PURPOSE: The purpose of this study is to observe the origin, course, length, diameter and termination of the ilio-lumbar artery (ILA) and its variations in south Indian population. MATERIALS AND METHODS: The study was carried out in 34 sides in 19 cadavers (R-18, L-16) used for routine dissection for undergraduate students during the period of 2017-2018 in Department of Anatomy, JIPMER, Puducherry. On each side of the pelvis, the origin, length, diameter, course of the ILA and its relations to the surrounding anatomical structures was observed and documented. RESULTS: Out of 34 formalin-fixed pelvis halves of human cadavers, the ILA originated from the common iliac artery (CIA), the trunk of the internal iliac artery (IIA) and posterior division of IIA in around 0%, 61.76%, and 38.23% of the cases, respectively. In all the cadavers, the ILA passes in between the obturator nerve anteriorly and the lumbosacral trunk posteriorly and ILA terminates by giving iliac and lumbar arteries medial to the psoas major muscle. CONCLUSIONS: In our study, we observed that the mean distance between the origin of ILA and the bifurcation of the CIA is significantly less than the study done previously. The knowledge about the variations in the origin, course, length, diameter, and termination of ILA is very important to the surgeon to avoid iatrogenic injury during surgeries in lumbosacral region and moreover, it will be easy to access the ILA for clamping or embolization. A similar study can be done with more sample size in different population to increase the knowledge base regarding ILA anatomy.

Iliopsoas hematoma in a patient with sickle cell disease.

Although musculoskeletal pain in patients with sickle cell disease (SCD) is most frequently the result of vaso-occlusive episodes, clinicians often consider other etiologies including osteomyelitis, avascular necrosis, and trauma. In this study, we report the case of a young female with SCD with hip and back pain secondary to a nontraumatic iliopsoas periosteal hematoma with evidence of adjacent bone infarction. The pathophysiology, diagnostic considerations, and management of periosteal hematomas in SCD are reviewed. This case highlights the need for recognition of unusual causes of musculoskeletal pain in SCD.

Translating Computer-Aided Design and Surgical Planning Into Successful Mandibular Reconstruction Using a Vascularized Iliac-Crest Flap.

PURPOSE: This study evaluated the computer-aided approach to the reconstruction of mandibular defects using a vascularized iliac-crest flap. MATERIALS AND METHODS: From December 2015 to October 2016, 14 patients (8 men and 6 women) 18 to 64 years old (median age, 29 yr) were treated at the Peking University School and Stomatology Hospital (Beijing, China). Biopsy specimens from all patients were subjected to histologic examination before segmental mandibulectomy. Computer-based surgical techniques, including virtual surgical planning, computer-aided design and manufacturing, rapid prototyping, and intraoperative navigation, were used to restore the anatomic continuity and configuration of the mandible using a vascularized iliac-crest flap. Two transverse dimensions and 1 anteroposterior (A-P) dimension were evaluated based on the virtual plan and postoperative computed tomogram. Lines from condylar head to condylar head and from gonial angle to gonial angle were defined as the transverse dimensions. A perpendicular line drawn from the mandibular midline to the center point on the condylar head to condylar head measurement was defined as the A-P dimension. Complications were evaluated during follow-up. RESULTS: The flap success rate was 92.9% (13 of 14), with 1 flap failure. After the operation, there were no other serious complications in 13 of the 14 patients, who exhibited a good mandibular configuration with good occlusion. Furthermore, the height of bone graft was sufficient for implants. Healing of the recipient and donor sites with no serious complication was uneventful. The average surgical errors in the A-P dimension and transverse dimensions were 1.8 ± 1.0 mm (range, 0.2 to 3.7 mm), 2.2 ± 1.1 mm (range, 0.9 to 5.0 mm), and 2.6 ± 1.6 mm (range, 0.3 to 7.2 mm), respectively. CONCLUSIONS: The use of these digital techniques was found to be a viable option for reconstruction of mandibular defects, but the results should be interpreted cautiously because of the small number of patients and the relatively short follow-up.

Correlation of CT imaging and histology to guide bone graft selection in scaphoid non-union surgery.

INTRODUCTION: For the treatment of scaphoid non-unions (SNU), different surgical techniques, including vascularized and non-vascularized bone grafts, are applied. Besides stability, vascularity, and the biological situation at the non-union site are important for healing and the appropriate choice of treatment. We assessed the healing potential of SNUs by histological parameters and compared it to CT parameters of bone structure and fracture location. Based on the results, we developed a CT classification and a treatment algorithm to impact graft selection in SNU surgery. PATIENTS AND METHODS: Preoperative 2D-CT reformations of 29 patients were analyzed for trabecular structure, sclerosis, and fragmentation of the proximal fragment. The fracture location was assessed on 3D-CT reconstructions and grouped in three zones depending on the potential blood supply. Samples were taken during surgery for histological evaluation. Histological parameters of bone healing were defined and a bone healing capacity score (BHC), reflecting histological bone viability, was calculated. CT findings were compared to BHC, age of SNU, and time to union. RESULTS: Cases with trabecular structure and without fragmentation showed a statistically significant higher BHC. Time to union was significantly faster if trabecular structure was present and sclerosis was absent. In intraarticular proximal pole non-unions, where no blood supply is assumed, the BHC was statistically significantly lower and time to union was longer compared to SNUs of the other locations. A statistically significant correlation between BHC and time to union was found in the proximal and distal fragment with higher BHC associated with faster healing. CONCLUSIONS: CT parameters of bone structure and fracture location can reflect histological healing capacity of SNUs. This can guide bone graft selection in SNU surgery.

An anatomical and histological study of the vascularized iliotibial tract graft.

BACKGROUND: An examination of the vascular anatomy of the iliotibial tract (IT) has not been previously reported. Because a flap resists infection better than an avascular graft, a vascularized IT graft is useful for reconstructive surgeries pertaining to infected wounds or wounds in contact with artificial material. The purpose of this study was to examine the vascular anatomy of the IT. MATERIALS AND METHODS: The study sample consisted of 39 limbs of freshly frozen cadavers. The study was divided into three parts. The ascending and transverse branches of the lateral circumflex femoral artery (LCFA) of all cadavers were injected with latex. Distance from the tensor fasciae latae muscle and the most distal point at which the vessel on the IT was stained by latex was recorded. A microscopic observation was performed for these limbs. The deep femoral artery (DFA) or superior lateral genicular artery (SLGA) was also observed. RESULTS: The length of the IT fed by the LCFA was 162.3 ± 36.2 mm. The IT vascularity was located between the layered structure of the fascia and there was a vascular source for the IT within 1 mm above the IT by optical microscopy. The vascularity derived from the DFA or SLGA was not confirmed in any specimens. CONCLUSIONS: Blood supply of the IT was derived from the LCFA and a vascularized IT graft could be elevated in length to approximately 16 cm. This knowledge may be useful for improving the safety of surgery when transferring an IT flap. © 2015 Wiley Periodicals, Inc. Microsurgery 36:325-329, 2016.

Biodegradable magnesium screws and vascularized iliac grafting for displaced femoral neck fracture in young adults.

OBJECTIVE: Avascular necrosis of femoral head and nonunion is a major complication after the treatment of displaced femoral neck fracture in young adults. The purpose of this study was to introduce a new technique using biodegradable magnesium screws and vascularised iliac grafting for displaced femoral neck fracture in young adults. METHODS: Totally 19 patients with displaced femoral neck fracture treated with this technique were retrospectively reviewed. The major steps of this technique included the harvesting of vascularized iliac graft, fixing of the fracture and biodegradable magnesium screws combined with vascularized iliac grafting implantation. RESULTS: All patients were followed for an average of 16 months (range: 8-24 months). Clinical and radiological outcomes were evaluated. In 18 cases (94.7 %), the hip union was achieved at an average duration of 4.1 months (range: 3.6-5 months). The nonunion was observed in 1 hip (5.3 %) and the revision to a hip replacement was conducted after twelve months of the operation. According to the Harris hip score (HHS) that was available for 17 hips with satisfactory union, excellent results were achieved in 14 cases (HHS ≥ 90), fair results in 3 cases (HHS: 80-90), and poor result in 1 hip (HHS < 80). No patient developed avascular necrosis of femoral head after operation. CONCLUSION: Biodegradable magnesium screws and vascularized iliac grafting based on the ascending branch of lateral femoral circumflex artery for displaced femoral neck fracture in young adults can provide the satisfactory results with a low rate of complications including avascular necrosis and nonunion. TRIAL REGISTRATION: This prospective and randomized controlled study was registered in the Chinese Clinical Trial Registry ( ChiCTR-TRC-13003238). Date of registration: 2013-3-21.

Operative treatment for scaphoid osteonecrosis (Preiser disease): salvage or excision? Report on two cases and a review of the literature.

Idiopathic avascular necrosis of the scaphoid, or Preiser disease, is a rare condition. Both the etiology and the pathology are still not well understood. We here present 2 cases with this disease and discuss the recommended treatment according to the stage of disease progression and by reference to previous studies in the literature. Similar to Kienböck disease, the recommended treatment should be selected according to the degree of disease progression. We believe that vascularized bone graft should be restricted to Herbert stage I or II cases with no evidence of radiocarpal arthritis or carpal instability. Our first case showed excellent revascularization following vascularized bone graft, as revealed by magnetic resonance image findings. The presence of arthrosis of the radiocarpal or mid-carpal joints is an indication for scaphoid excision with midcarpal fusion or proximal row carpectomy.

Nonvascularized bone grafts: how successful are they in reconstruction of segmental mandibular defects?

OBJECTIVE: Segmental mandibular defects can occur due to various etiologies, including trauma and tumor resection. Reconstruction should provide adequate support for subsequent dental rehabilitation and allow for proper occlusion. Nonvascularized bone grafts have been used for reconstructing mandibular defects in cases where vascularized grafts were not feasible. The objective of this study was to assess the success rate of these grafts in reconstruction of segmental defects of various sizes in the mandible. STUDY DESIGN: Fifty patients were included in this retrospective chart review. Length of the grafts varied from 3 to 20 cm and patients were followed up from 4 to 80 months. Fifteen grafts were harvested from anterior iliac crest, 23 from posterior iliac crest, 9 grafts were a combination of either with costochondral graft, and 3 were solely allografts. Bone morphogenetic protein was utilized in 41 cases as an adjunct. RESULTS: Success was defined as continuity of bone clinically and radiographically at a 4-month follow-up. Nonvascularized bone grafting was successful in 90% of cases. Complications were observed in 34% of cases, of which the most common were infection followed by wound dehiscence. CONCLUSIONS: Our study demonstrated substantial success rate with nonvascularized bone grafts in reconstruction of segmental mandibular defects.

Differential changes in vascular mRNA levels between rat iliac and renal arteries produced by cessation of voluntary running.

Early vascular changes at the molecular level caused by adoption of a sedentary lifestyle are incompletely characterized. Herein, we employed the rodent wheel-lock model to identify mRNAs in the arterial wall that are responsive to the acute transition from higher to lower levels of daily physical activity. Specifically, we evaluated whether short-term cessation of voluntary wheel running alters vascular mRNA levels in rat conduit arteries previously reported to have marked increases (i.e. iliac artery) versus marked decreases (i.e. renal artery) in blood flow during running. We used young female Wistar rats with free access to voluntary running wheels. Following 23 days of voluntary running (average distance of ∼15 km per night; ∼4.4 h per night), rats in one group were rapidly transitioned to a sedentary state by locking the wheels for 7 days (n = 9; wheel-lock 7 day rats) or remained active in a second group for an additional 7 days (n = 9; wheel-lock 0 day rats). Real-time PCR was conducted on total RNA isolated from iliac and renal arteries to evaluate expression of 25 pro-atherogenic and anti-atherogenic genes. Compared with the iliac arteries of wheel-lock 0 day rats, iliac arteries of wheel-lock 7 day rats exhibited increased expression of TNFR1 (+19%), ET1 (+59%) and LOX-1 (+31%; all P < 0.05). Moreover, compared with renal arteries of wheel-lock 0 day rats, renal arteries of wheel-lock 7 day rats exhibited decreased expression of ETb (-23%), p47phox (-32%) and p67phox (-19%; all P < 0.05). These data demonstrate that cessation of voluntary wheel running for 7 days produces modest, but differential changes in mRNA levels between the iliac and renal arteries of healthy rats. This heterogeneous influence of short-term physical inactivity could be attributed to the distinct alteration in haemodynamic forces between arteries.

Variants of the supplying vessels of the vascularized iliac bone graft and their relationship to important surgical landmarks.

The iliac bone crest is one of the most valuable regions for harvesting bone grafts, both vascularized and nonvascularized. Since the first commendable description of this region as a possible source for vascularized bone flaps by Taylor, little relevant information concerning the variations of the deep circumflex iliac vessels and their relationship to the neighboring structures has been published. The purpose of the current study was to examine this region clinically and anatomically, taking into consideration the former description by Taylor. We gathered all our findings on 216 iliac regions and proposed a new classification. In addition we measured the relationships between the deep circumflex iliac artery and important surgical landmarks. A comparison of our finding with other studies showed similarities and differences but was far more complete. Generally (92%) the deep circumflex iliac artery (DCIA) originated from external iliac artery (EIA) behind the inguinal ligament (IL) and passed cranio-laterally toward the anterior superior iliac spine, where it divided into two important branches. Four variations were observed of the DCIA. The deep circumflex iliac vein (DCIV) ran over (82.5%) or under (17.5%) the EIA. The superficial circumflex iliac vein (SCIV) was observed draining into the DCIV in some dissections. Three different variations of the superficial circumflex iliac artery (SCIA) were observed. The anatomical knowledge of these variations and their correlation to important surgical landmarks can help in harvesting the DCIA flap more safely and thus increasing the success rate while reducing donor site morbidity.

Management of scaphoid nonunion.

The primary risk factor for nonunion of the scaphoid is displacement/instability, but delayed or missed diagnosis, inadequate treatment, fracture location, and blood supply are also risk factors. Untreated nonunion leads to degenerative wrist arthritis-the so-called scaphoid nonunion advanced collapse wrist. However, the correlation of symptoms and disease is poor; the true "natural history" is debatable because we evaluate only symptomatic patients presenting for treatment. It is not clear that surgery can change the natural history, even if union is attained. The diagnosis of nonunion is made on radiographs, but computed tomography or magnetic resonance imaging scans can be useful to assess deformity and blood supply. Treatment options vary from percutaneous fixation to open reduction and internal fixation with vascularized or nonvascularized bone grafting to salvage procedures involving excision and/or arthrodesis of carpals.

Vascularized bone grafts for scaphoid nonunions.

Scaphoid fractures that fail to unite are at risk of developing avascular necrosis and progressive structural collapse, thereby complicating attempts at revision surgical treatment. Vascularized bone grafts have demonstrated utility in promoting consolidation in the treatment of scaphoid nonunions complicated by avascular necrosis. Numerous pedicled and free vascularized grafts have been described with variable, but generally favorable, outcomes. Understanding the indications for different grafts is critical to the successful application of these techniques and grafts in the treatment of challenging scaphoid nonunions.

Vascular iliac myofascial flap to repair compound defect of the jaw.

The vascular iliac myofascial flap is a compound flap with the deep circumflex iliac artery (DCIA) as the vascular pedicle, carrying the iliac bone and parts of the internal oblique, external oblique and muscle-fascial tissue that cover the surface of the iliac crest and inside the iliac bone. The aim of this study was to advocate a feasible surgical strategy for maxillofacial surgeons through our review of clinical applications and to improve the quality of life of patients after the operation. In recent years, Stomatology Hospital of Wuhan University has performed dozens of vascularized iliac myofascial flaps, not only to repair jaw defects but also to complete the repair of intraoral soft tissue defects. 20 patients were followed up. These patients with jaw tumors who received a vascular iliac myofascial flap to repair compound defects of the jaw from 2018 to 2020. The Quality of Life Questionnaire-Head and Neck Cancer-37 (QLQ-H&N37) was used to evaluate their speech function (Z=-0.061, P>0.05) and postoperative aesthetics (Z=-2.824, P<0.05). All patients obtained good surgical results and satisfaction in terms of aesthetics and function. The successful reconstruction of these cases prove that the vascularized iliac composite flap with myofascial tissue is a reliable flap for the reconstruction of maxillofacial defects.

Spatial gradients of blood vessels and hematopoietic stem and progenitor cells within the marrow cavities of the human skeleton.

This report evaluates the spatial profile of blood vessel fragments (BVFs) and CD34(+) and CD117(+) hematopoietic stem and progenitor cells (HSPCs) in human cancellous bone. Bone specimens were sectioned, immunostained (anti-CD34 and anti-CD117), and digitally imaged. Immunoreactive cells and vessels were then optically and morphometrically identified and labeled on the corresponding digital image. The distance of each BVF, or CD34(+) or CD117(+) HSPC to the nearest trabecular surface was measured and binned in 50-microm increments. The relative concentration of HSPCs and BVFs within cancellous marrow was observed to diminish with increasing distance in the marrow space. On average, 50% of the CD34(+) HSPC population, 60% of the CD117(+) HSPC population, and 72% of the BVFs were found within 100 microm of the bone surfaces. HSPCs were also found to exist in close proximity to BVFs, which supports the notion of a shared HSPC and vessel spatial niche.

Donor- and recipient-site morbidity of vascularized fibular and iliac flaps for mandibular reconstruction: A systematic review and meta-analysis.

The aim of this article is to evaluate the early and late morbidities of the donor- and recipient-site in patients undergoing mandibular reconstruction using either vascularized fibular flap (VFF) or vascularized iliac flap (VIF). Electronic databases, including PubMed, Web of Science, Cochrane Central and Embase, were explored for literature published until October 2020. A total of twenty-four articles reporting complications following mandibular reconstruction surgery with follow-up periods ranging from six to 63 months were selected based on the exclusion criteria. For each research, the JBI Critical Assessment Tool and the ROBINS-I Tool were used to analyze the methodological quality and the risk of bias. A single-arm meta-analysis was performed to have a synthesized analysis of the donor- and recipient-site early and late morbidities. Results showed that the early morbidities in VFF group ranged from 3% to 12%, and the late morbidities in VFF group ranged from 5% to 67%. In VIF group, the early morbidities ranged from 3% to 16%, and the donor-site late morbidities ranged from 6% to 43%. Complications with the top three morbidities in the VFF group were: chronic sensory disturbances at the donor-site (67%), malocclusion (22%) and chronic lower limb weakness (20%); and in the VIF group were: chronic sensory disturbances at the donor-site (43%), chronic pain at the donor-site (26%), chronic gait disturbance (20%). Further controlled clinical trials are needed to assess the long-term outcome of VFF or VIF grafting.