Forxiga

Mike Zevitz, M.D.

• Assistant Professor
• Chicago Medical School
• Chicago, IL

Systemic corticosteroids in association and C3 deposition in epidermal intercellular with the treatment of underlying neoplasm diabetes insipidus neurosurgery effective forxiga 10mg. Cicatricial Pemphigoid involving the gingiva diabetes zyprexa cheap forxiga online, although ultimately other sites in the oral cavity may be involved blood sugar solution buy 10mg forxiga with amex. The Cicatricial pemphigoid diabetes knowledge questionnaire order cheapest forxiga, or benign mucous mem- mucosal lesions are recurrent vesicles or small brane pemphigoid diabetes mellitus for nursing students discount forxiga 5mg online, is a chronic bullous disease of bullae that rupture diabete alta sintomas forxiga 10mg online, leaving a raw eroded surface autoimmune origin that preferentially affects mu- that finally heals by scar formation (Fig. Frequently, occurs more frequently in women than in men the disease affects exclusively the gingiva in the (1. The oral mucosa is invariably affected and, in 95% of ocular lesions consist of conjunctivitis, symble- the cases, the mouth is the initial site of involve- pharon, trichiasis, dryness, and opacity of the ment. The most consistent oral lesions are those cornea frequently leading to complete blindness 208 22. Less commonly, other mucosae the differential diagnosis includes pemphigus vul- (genitals, anus, nose, pharynx, esophagus, larynx) garis, bullous pemphigoid, linear IgA disease, are involved (Fig. Skin lesions occur in bullous and erosive lichen planus, dermatitis her- about 10 to 20% of the cases and consist of bullae petiformis, erythema multiforme, Stevens-John- that usually appear on the scalp, face, and neck son syndrome, and lupus erythematosus. Helpful laboratory tests include histopathologic examination and direct immuno- fluorescence of oral mucosa biopsy specimens. Skin Diseases Childhood Cicatricial Pemphigoid Laboratory tests to confirm the diagnosis are direct and indirect immunofluorescence and his- Cicatricial pemphigoid is a chronic autoimmune topathologic examination. However, at least eight well-documented cases of cicatricial pem- phigoid of childhood have been recorded so far. Five of the patients were girls and three were Bullous Pemphigoid boys, aged 4 to 18 years. All patients except one Bullous pemphigoid is a chronic autoimmune had oral lesions, and in four, desquamative ging- mucocutaneous bullous disease that affects ivitis was the cardinal manifestation of the disease women more frequently than men (1. However, well- mucosa, eyes, genitalia, anus, and skin are identi- documented cases have been described in child- cal to those seen in cicatricial pemphigoid of adult- hood. Clinically, the cutaneous lesions begin as a the differential diagnosis includes juvenile bul- nonspecific generalized rash and ultimately large, lous pemphigoid, juvenile pemphigus, childhood tense bullae develop that rupture, leaving dermatitis herpetiformis, childhood linear IgA denuded areas without a tendency to extend disease, childhood chronic bullous disease, and peripherally. The oral well as direct and indirect immunofluorescent mucosa is affected in about 40% of the cases, tests confirm the diagnosis. Other mucous mem- branes, such as the conjunctiva, esophagus, va- gina, and anus, may also be affected. Linear Immunoglobulin A Disease the disease has a chronic course with remis- Linear IgA disease has been recognized as a new sions and exacerbations and generally a good nosologic entity in the spectrum of chronic bullous prognosis. Linear IgA disease is rare and charac- the differential diagnosis includes pemphigus terized by spontaneous bullous eruption on the vulgaris, cicatricial pemphigoid, dermatitis her- skin and mucous membranes, and homogeneous petiformis, linear IgA disease, erosive lichen IgA deposits along the dermoepidermal junction planus, and discoid lupus erythematosus. The disease is more common Laboratory tests helpful for the final diagnosis in women than men, with an average age of onset between 40 and 50 years and has been described include histopathologic examination, as well as both in adults and children. Generally, the clinical manifestations of the disease are indistinguishable from those seen in cicatricial pemphigoid. The differential diagnosis includes cicatricial pem- phigoid, dermatitis herpetiformis, bullous pem- phigoid, and chronic bullous disease of childhood. Childhood cicatricial pemphigoid, small hemorrhagic bulla on the gingiva in a 14-year-old girl. Linear immunoglobulin A disease, erosion on the tongue covered by a whitish pseudo- membrane. Dermatitis Herpetiformis mucosa are more frequently involved than the gingiva, lips, and tonsils. Dermatitis herpetiformis, or Duhring-Brocq dis- the disease runs a very prolonged course with ease, is a chronic recurrent skin disease charac- remissions and exacerbations. In 60 to 70% of the terized by pruritus and a symmetrical papulo- cases gluten-sensitive enteropathy coexists. The disease occurs at any age, including includes minor aphthous ulcers, herpetiform childhood, but is more common between 20 and ulcers, erythema multiforme, pemphigus vulgaris, 50 years of age and males are more frequently cicatricial pemphigoid, linear IgA disease, and affected than females. The cause remains unknown, although the oc- currence of IgA and C3 deposits in the upper Laboratory tests supporting the diagnosis are his- dermis and at the dermoepidermal junction sug- topathologic examination and direct immuno- gests that immunologic mechanisms may play a fluorescence. Sulfones and sulfapyridines and, in severe burning and pruritus, and small vesicles, certain cases, corticosteroids. Gluten-free diet which group in a herpes-like pattern, involving the may check disease activity. Clinically, the maculopapular lesions are considered as one of the main types of oral lesions (Fig. In addition, erythematous, purpuric, vesicular, and erosive types have been described (Fig. The vesicles appear in a cyclic pattern, rupture rapidly, leaving superficial painful erosions resembling aphthous ulcers. Dermatitis herpetiformis, papules and small vesicles on the skin, grouped in a herpeslike pattern. Dermatitis herpetiformis, intact bulla on the lower lip mucosa and small erosions on the gingiva. Epidermolysis Bullosa Acquisita Lichen Planus Epidermolysis bullosa acquisita is a rare, non- Lichen planus is a common, chronic inflammatory inherited, chronic mechanobullous disease with disease of the skin and mucous membranes. Clinically, the disease cause of lichen planus remains unknown, although is characterized by the formation of bullae, mainly recent evidence suggests that immunologic on the skin overlying joints, which are frequently mechanisms may play a role in the pathogenesis. The bullae are the association of lichen planus with autoimmune tense, may contain blood, and heal with scarring. Involvement of the oral mucosa is not equally members of all races and has a cosmopoli- frequent. The following diagnostic criteria what more often than men, and the majority of of epidermolysis bullosa acquisita have been pro- the patients (about 70%) are between 30 and 60 posed: no family history; adult onset; bullae for- years of age. Clinically, the cutaneous lesions mation after mechanical trauma, which heal with appear as small, flat, polygonal, shiny papules scarring, milia, and nail dystrophy; exclusion of all (Fig. Early papules are red, whereas older other bullous diseases; histopathologic, direct and lesions display the characteristic violaceous color. They are distributed in a the differential diagnosis includes pemphigus, symmetrical pattern, more frequently over the cicatricial pemphigoid, bullous pemphigoid, der- flexor surfaces of the forearms and wrists, the matitis herpetiformis, linear IgA disease, and por- sacral area, the back, and the lateral sides of the phyria cutanea tarda. Clinically, the following forms of oral lichen periphery, papules or lines may be seen (Fig. The reticular form is Frequently, the atrophic and erosive forms, when the most common variant and is characterized by located on the gingiva, may be manifested as small white papules, which may be discrete but desquamative gingivitis (Fig. The second most frequent variant and is characterized bullous form is rare and is characterized by bullae by small or extensive painful erosions with iso- formation of variable size, which rupture rapidly lated papules or lines at the periphery (Fig. The bullae the atrophic form is less common and usually the usually arise on a background of papules or striae. The lesions have a smooth red characterized by pigmented papules arranged in a surface and poorly defined borders, and, at the reticular pattern interspersed with whitish lesions 22. This form is due to local melanin Psoriasis overproduction during the acute phase of the dis- Psoriasis is a common, chronic, recurrent skin ease. It is most frequent on the skin and should disease of unknown cause, which is characterized not be confused with pigmentation that may by the presence of erythematous, scaly plaques. Oral lichen planus may follow a course of re- There is no sex predilection, and the age of onset is usually beyond 25 years, although the disease missions and exacerbations. The disease most fre- quently affects the buccal mucosa, tongue, gin- may also affect children. Cutaneous lesions are usually located on the extensor surfaces of the giva, and rarely the lips, palate, and floor of the extremities, particularly the elbows and knees, the mouth. The lesions are usually symmetrical and asymptomatic or cause mild discomfort, such as a lumbar area, the scalp, and nails (Fig. Depending on the morphology of the skin lesions, burning sensation, irritation after contact with certain varieties of psoriasis have been recog- certain foods, and an unpleasant feeling of rough- nized, such as annular, circinate, guttate, nummu- ness in the mouth. Rarely, when xerostomia coexists, erythematosus, erythroplakia, erythema mul- erythematous and scaly lesions may appear on the tiforme, cicatricial pemphigoid, bullous pem- dorsal surface of the tongue. The oral lesions are phigoid, pemphigus, dermatitis herpetiformis, predominantly located on the tongue, followed by secondary syphilis and syphilitic glossitis, can- the gingiva, buccal mucosa, floor of the mouth, didosis, and leukoplakia. Histopathologic examination pathognomonic and pose diagnostic problems that and direct immunofluorescent examinations help may be solved with histologic examination. No therapy is needed when the lesions geographic tongue, geographic stomatitis, leuko- are asymptomatic. Aromatic retinoids (etretinate) and cy- Laboratory test to confirm the diagnosis is his- closporine mouthwashes have also been used with topathologic examination. Topical steroids, coal tar, y-methoxy- psoralen and ultraviolet A irradiation, methotrex- ate, hydroxyurea, cyclosporine, and aromatic retinoids (etretinate) have been used for treat- ment of skin lesions. Psoriasis, circular and semicircular whitish lesions on the tongue similar to geographic tongue. Skin Diseases Mucocutaneous Malignant Acanthosis Nigricans Lymph Node Syndrome Malignant acanthosis nigricans is a form of acan- M ucocutaneous lymph node syndrome, or thosis nigricans that occurs in adults and is invari- Kawasaki disease, is an acute febrile illness that ably associated with internal cancers, usually predominantly affects children and rarely young adenocarcinoma of the stomach or other internal adults. Although the dis- mucosa is involved in about 30 to 40% of the order is known to be a systemic vasculitis, the cases. Clinically, it is lomatous lesions, usually of normal color, are characterized by the following diagnostic criteria: noted, which grow and occupy large areas. Similar lesions have been usually of the tips of the fingers and toes, poly- described in other mucosae (conjunctiva, anus, morphous nonvesicular skin rash, cervical lymph vagina, pharynx, esophagus, intestine, etc. The node enlargement, and oropharyngeal manifesta- skin is rough, hyperpigmented, and multiple tions. Mucocutaneous lymph node syndrome, enlarged, red tongue, and conjuctival injection. Malignant acanthosis nigricans, marked pigmentation and papillary hyperplasia of the skin. Skin Diseases Acrodermatitis Enteropathica Perioral Dermatitis Acrodermatitis enteropathica is a rare hereditary Perioral dermatitis is a characteristic persistent disease transmitted as an autosomal recessive eruption around the mouth that is composed of trait. The disease is related to zinc deficiency due micropapular and papulopustular lesions on an to an inability to absorb dietary zinc from the inflamed base. It is fatal during infancy or early child- quently in young women who have been using hood if left untreated. Other factors, like cosmetics, sist of areas of erythema associated with vesicles fluorinated toothpastes, and contraceptive pills and pustules in crops that in a few days become have also been blamed. Some of these lesions prove to be due to region affecting mainly the chin, upper lip, and secondary infection, especially by Candida albi- the sides of the nose, with small papules and cans. Characteristically, the lesions are located papulopustules, usually occurring in clusters. The typical location is the the eyelids and in the glabella, there is a typical perioral area, where angular cheilitis may appear, clear zone between the affected skin and the ver- but rarely areas of erythema with white macules of milion border of the lips (Fig. Oral tetracycline 250 mg 2-3 Laboratory test confirming the diagnosis is the times daily for 3 weeks and then once a day for measurement of serum zinc concentration. Treatment consists of the administration of zinc salts and a diet rich in zinc salts. Lip-Licking Dermatitis Lip-licking dermatitis is a condition that most commonly occurs in children and is characterized by an inflammation involving the lips and the adjacent skin area. Clinically, the lips and the perioral skin mani- fest erythema associated with scaling, crusting, and fissuring of variable severity (Fig. Lip-licking dermatitis is an irritant contact der- matitis, secondary to the habit of licking the lips. The elimination of the habit of licking the lips is often sufficient to cure this condition. In severe cases, topical corticosteroids in medium- low potency for a short time are usually of help. Acrodermatitis entero- pathica, characteristic lesions on the perioral area, commissures, and skin of the face. Vitiligo although radiation, mechanical and immune fac- usually appears before the age of 20 years and is tors, and viruses have been implicated in the due to the absence of melanocytes and melanin in pathogenesis. Clinically, white asymptomatic Warty dyskeratoma appears usually in middle- macules varying in size from several millimeters to age, and men are more frequently affected than several centimeters in diameter appear, which are women (ratio 2. The rarely affected, and only 20 oral dyskeratomas lesions are more frequently located on the dorsal were found in the literature in a review by me in aspect of the hands, the neck, periorificial regions 1985. Rarely, lesions may appear on the less nodular or papular elevation, with a small lips, whereas the oral mucosa usually remains central crater and smooth or papillomatous sur- unaffected (Fig. It is sessile with whitish or normal color and a diameter ranging from a few millime- ters to 1 cm. Almost all intraoral lesions occur on keratinized areas (alveolar ridge, hard palate, gin- giva) exposed to friction and mechanical irrita- tion. Laboaratory test important to establish the diag- nosis is the histopathologic examination. Hematologic Disorders Iron Deficiency Anemia Plummer-Vinson Syndrome Iron deficiency anemia represents an advanced Plummer-Vinson syndrome is characterized by a stage of iron deficiency. It may result from inade- combination of iron deficiency anemia, dysphagia, quate dietary iron intake, malabsorption, blood and, oral lesions, and it usually appears in middle- loss, or rarely intravascular hemolysis with aged women. Iron deficiency anemia is wide- to those seen in iron deficiency anemia, with a spread throughout the world and is more common characteristic smooth atrophic and red tongue among children, persons on a poor diet, and (Fig. The dysphagia is due to painful erosions and the clinical manifestations of chronic iron de- strictures of the esophagus. Leukoplakia and oral ficiency anemia include fatigue, anorexia, and oropharyngeal squamous cell carcinoma may headache, lassitude, tachycardia, neurologic dis- develop. The oral manifestations include a burning sensation of the tongue, pallor of the oral Pernicious Anemia mucosa, and gradual atrophy of the filiform and Pernicious anemia is a megaloblastic anemia due fungiform papillae of the tongue. Progressively, to vitamin B12 deficiency, usually caused by a the dorsal surface of the tongue becomes smooth gastric mucosal defect that decreases intrinsic fac- and glistening (Fig. Other less frequent causes are total gastrec- Rarely, leukoplakia or superficial erosions may tomy, pancreatic dysfunction, parasitic diseases develop, and angular cheilitis and oral candidosis are common findings.

Med J Aust 2003;178(12):621–623 for heavy menstrual bleeding: a randomized controlled trial diabetes prevention conference purchase forxiga master card. Hormonalcontraceptionastreatmentforheavy Obstet Gynecol 2010;116(04):865–875 menstrual bleeding: a systematic review diabetes mellitus definition medical buy forxiga 10 mg with mastercard. Hysterectomy diabetes type 2 fatigue forxiga 5mg free shipping, endometrial ablation and 47 Gupta B blood sugar after meal purchase forxiga 5mg with visa, Mittal S managing diabetes with exercise discount 10mg forxiga amex, Misra R diabetes dukan diet buy forxiga 5mg without a prescription, Deka D, Dadhwal V. Levonorgestrel- Mirena for heavy menstrual bleeding: a systematic review of releasing intrauterine system vs. Clinical Am J Obstet Gynecol 1996;175(06):1432–1436, discussion trial of the uterine thermal balloon for treatment of menorrhagia. Cost-utility of levonorgestrel tives for acute uterine bleeding: a randomized controlled trial. This review emphasizes intended use, chemical composition, degradative mechanisms, and pre-clinical safety, efficacy, and performance, while summarizing the key advantages and disadvantages for each degradable technology that is currently under development for transarterial embolization. This review is intended to provide an inclusive reference for clinicians that may facilitate an understanding of clinical and technical concepts related to this field of interventional radiology. For materials scientists, this review highlights innovative devices and current evaluation methodologies. Degradable microspheres are intended to provide effective embolization on a transient basis. Ideally, after achieving their clinical outcome, they are removed from the body without interfering with the functionality of other organs. Unlike conventional permanent agents, degradable microspheres should be designed to optimize the window of therapeutic intent (e. A significant driver for the development and utilization of degradable microspheres is that patients commonly express worries about foreign materials remaining in the body, and while this may not be a physiological problem, it is certainly an important consideration for patients, and may provide competitive marketing advantages for next generation technologies [1]. Although the safety, efficacy, and performance of permanent embolic agents are well established in the clinical literature, degradable microspheres may present new safety concerns. Fortunately, when developing new biomaterials for clinical applications, researchers benefit from the existence of international standards and guidance documents to help address potential risks. With respect to vascular embolization devices, specific guidance documents have been published by regulatory agencies. This document emphasizes (i) ease of deliverability (from a friction and tortuosity standpoint), (ii) acute complications, (iii) local and systemic foreign body reactions, (iv) recanalization, (v) embolization effectiveness, and (vi) device migration. Given the potential new safety risks that may arise from the use of degradable microspheres, these considerations are critical in the design and evaluation of new microsphere technologies. Further to such guidance documents, it is also instructive to consider the ideal characteristics of degradable microspheres. These innovative technologies must provide predictable and effective occlusion while also providing: 1. Tailored degradation timeframes—to provide adequate infarction to the target tissues in a variety of indications, subsequently allowing return of flow (e. A variety of tightly calibrated particle size distributions—to optimize particle delivery according to target artery anatomy [3] 3. Ease of delivery through conventional microcatheters—to facilitate adoption of the novel technology into established embolization techniques 4. While most of the above points are reasonably self-evident, the last point of multi-modal imageability raises an important and additional design consideration. Specifically, an understanding of the temporal and spatial distribution of embolic microspheres is clinically beneficial [5], with the assurance that degradation byproducts should not, for instance, generate artifacts arising from degradation. It is also important to clarify the definitions and terms utilized in the literature related to degradable microspheres. However, it must be acknowledged that these terms, which are often used as synonyms for one another, are poorly defined and that despite significant efforts to find consensus about such terms, no agreed consensus in the interventional radiology or broader biomaterials literature exists [6]. Broadly, degradation refers to a deleterious change in the chemical structure, physical properties and appearance of materials [7]. This format was deliberately chosen to provide a robust framework for discussing the current state of the art technologies with respect to potential risks that may need to be considered as part of a design control process for the development of new degradable microsphere technologies. Finally, a review of the preclinical models utilized by the identified papers will be provided to further highlight the current understanding of the safety, efficacy, and performance of degradable microspheres. A summary of the materials identified from this formative analysis is provided in Table 1. Subsequently, each material type was cross-referenced with the peer-reviewed literature using the standard search parameters outlined (Table 1). Materials reviewed and generalized search strategy parameters for PubMed and Web of Science. Eligibility of the papers was established in line with the objectives of this work; specifically, the inclusion criteria adhered strictly to (1) preclinical studies with established control articles. Papers not meeting these criteria were excluded from the review, along with papers associated with in vitro studies, degradable microspheres for chemoembolization, and opinion-based articles. Initial Returned Searches based on Table 1, with Articles Meeting Inclusion Criteria. Current State of the Art Based on the search methods, five materials were identified as candidates for review in this paper. Although Chitin was the search term originally entered, its derivative in microsphere form (Chitosan microspheres) warranted inclusion within the assessment, as the chitin agents were all irregular particles. Finally, the paper provides a brief commentary on preclinical investigation methodologies utilized by those articles included for review. It is a linear co-polymer that can be synthesized with different ratios of lactic and glycolic acids [9]. Only one of these papers met the inclusion criteria, the remainder of the articles were substantially focused on in vitro studies and materials for chemoembolization. This paper utilized a uterine artery sheep model over a period of 12 months, with animals divided into four cohorts (1, 3, 6, and 12 months). However, it is reasonable to assume this small particle size represents a higher risk with respect to biological response. The authors note, similar to other published literature that no significant difference in (i) the volume of test and control materials delivered or (ii) the fluoroscopic times required to achieve effective stasis for either product [20]. Authors and Study Model Test Material Time to Complete Acute Complications Local and Systemic Foreign Embolization Year of & Duration Information. Ease of Use Degradation of Test Recanalization (Vessel Body Reactions Effectiveness. No 12 (100%) treated uterine (Mean weight distribution was observed, but Recanalized vessels differences reported between arteries and in 1 untreated ca. Microspheres of both types were embedded in a thin collagen matrix with small numbers of macrophages and occasional giant cells present. Yet inflammation was not a significant feature of the reaction to either type of microsphere. Initially, occlusion was mechanical in nature due to aggregation of microspheres within the target vessel. In this study, the term appears to refer to the reopening of the vessel that has been embolized) [18]. Acute complications, such as vessel rupture and perforation, were not assessed in this paper. Nevertheless, the authors state that inflammation was not a significant feature of the reaction to either type of microsphere [18] and no significant systemic foreign body reactions were reported on hematological and clinical chemistry analyses. Although the risk of migration did not appear to be directly assessed by Owen et al. This difference may be explained by the compressibility of the control microspheres [24], which likely facilitated passage of the material through small diameter anastomoses joining the uterine artery with the vaginal and ovarian arteries [25]. Furthermore, and perhaps more concerning, was the presence of particles in the vesicle artery, as this was likely a result of reflux out of the uterine artery back into the umbilical artery, resulting in possible non-target embolization [25]. These observations are of import with respect to designing degradable microspheres. Firstly, inherent to the design, the degradation must be predictable and proceed in a manner that avoids complications associated with non-targeted embolization due passage of smaller particles through the target vascular bed. This may raise safety concerns with respect to the clinical utility of materials designed to degrade in a timeframe shorter than that associated with the development of a sufficient foreign body response (encapsulation of material at the target area), which may mitigate the risk of migration. For example, it is considered in the literature that degradation timeframes of ca. Dichotomously, engineering microspheres that degrade over time periods sufficient to cause biological responses, suitable to mitigating migration risk. Only two of these papers met the inclusion criteria, the remainder of articles were substantially focused on in vitro studies and drug eluting materials. With respect to the former, the study utilized a uterine artery sheep model for a duration of seven days, with tris-acryl gelatin microspheres (500–700 µm) as a control. The latter study used a porcine kidney model for a period of up to seven days with gelatin sponge particles as a control. Authors and Year Study Model & Test Material Time to Complete AcuteComplications Local and Systemic Foreign Embolization Device of Publication Duration Information. Ease of Use Degradation of Test Recanalization (Vessel Body Reactions Effectiveness. Large variations due to including myointimal Hematoxylin-eosin-saffron angiography Study duration: 500–700 µm the mean volume of At day 7 the test methodology proliferation, medial stain used. Test article abnormal behavior (macrophages, lymphocytes (Mean weight article injected was at day 7, though showed fully patent vessel reported and fibrocytes). At day 7, test 700–900 µm demonstrated material was not visible, no complete recanalization fragments of materials were 300–500 µm and 500–700 observed in histological µm demonstrated partial slides/analysis. At day 7 the test absence of vascular lumen endometrium and endometrium and Sheep. The authors suggest Study duration: distribution histological For test article complete that for the test 7 days. Control material parenchymal defects 500–700 µm test material and volume of control was showed evidence of were associated with 4:5 ratio for control 1. No data confirming actual particle size distribution was listed in either study, thus it may be assumed that the size classifications were based on sieve aperture utilized to produce the microspheres. It is worth noting sieve aperture tolerances allow for a degree of error and the actual particle size distributions may be as low as 286 µm and as high as 585 µm for the 300–500 µm range, 480 µm to 815 µm for the 500–700 µm range, and 670 µm to 970 µm for the 700–900 µm range [29]. With respect to injectability and ease of use, no substantial differences between the test and control articles were reported in either study [2,28]. The reported mean volume of particles delivered by both groups showed variability, suggesting different volumes may have been utilized from one animal to next. These discrepancies may be due to variability in animal vasculature—both between and within species but are worthy of note since they may confound the observations. Both papers angiographically monitored the animals at three time points, as follows: before delivery of microspheres, 10 min after embolization was achieved, and after seven days. It was observed that decreased particle size distributions resulted in more distal occlusion, greater necrosis, and lower recanalization rates [28]. However, given the encouraging results, future work will likely buttress and substantiate this early data; it would be of benefit to develop methodologies that make it possible to definitively determine the in vivo degradation timeframes of degradable microspheres. Such methodologies would be of immense benefit since it is widely accepted that initial host-material responses, including (but not limited to) protein deposition and cellular interactions, may accelerate or impede the degradation rates of biomaterials [30]. This group did not comment on degradation time as a factor, rather stated the level of necrosis correlated with the distribution of the microspheres, with those positioned distal to the arcuate artery yielding significantly more necrosis. Given the variability in the size distribution of gelatin sponge, it is likely the control agent was present both proximal and distal to this anatomical location, resulting in a higher level of necrosis [28]. As discussed previously, the absence of this biological occlusion may increase the risk of migration and non-target embolization, as small microsphere fragments may break off and travel forward through small anastomoses, or reflux retrograde into neighboring vasculature [2,28]. This two-part system avoids small molecular cross-linking agents, which are usually considered to have higher cytotoxic potential [34]. Chitosan is a naturally occurring polysaccharide derived from the exoskeleton of crustaceans that is commonly used in medicine and pharmaceuticals [38]. Chitosan is not one chemical entity but varies in composition depending on manufacturing; during alkaline hydrolysis of chitin to form chitosan, N-deacetylation and depolymerization occur to varying extents. Structurally, chitosan is considered a polymer of glucosamine and N-acetylglucosamine, linked by 1,4-glucosidic bonds [39]. Glucosamine then goes on to produce glycosaminoglycans, proteoglycans, and glycolipids in the body. The rate of degradation is historically believed to depend on the acetylation of chitosan, with more acetylated and thus more crystalline chitosans (like chitin) showing faster rates of degradation [38–41]. Only one of these papers met the inclusion criteria, the remainder of articles were substantially focused on drug-carrying materials and neuroprotective effects in ischemic brain injury. Angiography was performed before, immediately after, and 15 min after the embolization procedure. The control article was deemed significantly more difficult to use as it tended to stick to both the syringe and the microcatheter, substantially reducing the percentage of particles delivered per syringe. In the present study, the timeframe of 15 min did not allow for assessment of in vivo degradation or recanalization. Nonetheless from a performance standpoint, the authors stated that more cross-linking can provide for a slower rate of degradation [42,43]. The key focus of this paper was related to the acute phase of embolization, focusing on initial particle distribution and level of occlusion. Comparisons regarding material performance were made when total occlusion (effective stasis) was used as an end point (versus a pre-determined dose). Despite these observations, the authors reported no statistical differences in the diameter of occluded vessels or the magnitude of particle deformation between any of the materials [42].

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References

• Warach S, Gaa J, Siewert B, et al. Acute human stroke studied by whole brain echo planar diffusion-weighted magnetic resonance imaging. Ann Neurol 1995;37(2):231-41.
• Fuster V, Moreno PR, Fayad ZA, Corti R, Badimon JJ. Atherothrombosis and high-risk plaque: part I: evolving concepts. J Am Coll Cardiol. 2005;46:937-954.
• Badjatia N. Hyperthermia and fever control in brain injury. Crit Care Med. 2009;37(7 Suppl): S250-S257.
• Hadjiliadis D, Howell DN, Davis RD, et al. Anastomotic infections in lung transplant recipients. Ann Transplant. 2000; 5:13-19.
• Mayer SA, Brun NC, Begtrup K, et al: Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage, N Engl J Med 358:2127-2138, 2008.
• White HD. GISSI-2 and the heparin controversy. Lancet. 1990;336:297-298.