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The use of retrievable stents and suction through a balloon guide catheter during thrombus retrieval was also recommended. Of the 165 participants randomized to endovascular intervention, retrievable stents were used in 130 of the 151 (86. Midway through the trial, the inclusion criteria were modified to accommodate sites with limited perfusion imaging capability. Sites with perfusion imaging were encouraged to continue to use the target mismatch criteria. A total of 71 patients were enrolled under the initial imaging entry criteria and 125 patients under the revised imaging entry criteria. Stroke October 2015 Selected Clinical Outcomes for Recent Randomized, Clinical Trials of Endovascular Treatments for Acute Ischemic Stroke Outcomes Primary End Point Death (90 d/3 mo) Comparison 0. Groin puncture had to be within 6 hours, and endovascular treatment had to be completed within 8 hours after stroke onset. The results of the interim analysis showed that the stopping criteria for efficacy were met, and the trial was halted. Endovascular therapy, initiated at a median of 210 minutes (interquartile range, 166­251 minutes) after the onset of stroke, increased early neurological improvement at 3 days (80% versus 37%; P=0. These data do not establish the benefit of intra-arterial fibrinolytic salvage, nor can they establish lack of benefit. Three of the 5 stent retriever studies specified a 6-hour window after stroke onset (2 specified 6 hours to groin puncture; the third specified 6 hours to start treatment). How much the overall positivity in these 2 trials was completely driven by those treated at shorter times is unknown at this time. On the basis of these data, a waiting period is not necessary to achieve beneficial outcome in these patients. Participants were randomized 1:1 to receive either medical therapy alone or thrombectomy with a stent retriever. When results of other similar trials became known, the Data Safety Monitoring Board recommended the recruitment be stopped because the emerging results showed that equipoise was lost, although the interim results did not reach the prespecified stopping boundaries. The subsequent trials using stent retrievers almost exclusively demonstrated improved results for both recanalization rates and outcome. Studies have Powers et al Focused Update on Acute Ischemic Stroke and Endovascular Treatment 3029 All of these studies enrolled participants 18 years of age. There are no randomized trials of endovascular therapy in patients <18 years of age. Ischemic stroke resulting from large-vessel occlusion is rare in children and young adults relative to older individuals, posing challenges to rigorous study of this clinical scenario. Case reports and case series have documented that high rates of recanalization and favorable outcomes in young patients can be achieved with endovascular therapy. Studies in the United States, the United Kingdom, Australia, and Canada have shown median times from onset of symptoms to initial brain imaging for pediatric stroke of 8. Four of the 5 stent retriever trials used a prestroke function eligibility criterion. The concomitant use of distal-access suction catheters during stent retriever mechanical thrombectomy has been described in retrospective case series. There are several potential advantages and disadvantages for angioplasty and stenting at the time of thrombectomy. Although immediate revascularization may reduce the risk of recurrent stroke, urgent stenting generally requires antiplatelet prophylaxis, which has been associated with intracranial hemorrhage in this setting. Carotid stenting and intracranial thrombectomy for the treatment of acute stroke resulting from tandem occlusions with aggressive antiplatelet therapy may be associated with a high incidence of intracranial hemorrhage. General anesthesia with intubation and conscious sedation are the 2 most frequently used anesthetic approaches for patients with an acute ischemic stroke receiving endovascular therapy. For the first 71 patients enrolled, an additional inclusion criterion was the presence of target mismatch defined as infarct core 50 mL (as assessed by specialized software19) and ischemic penumbra 15 mL with a mismatch ratio >1. To date, subgroup analyses with the various imaging criteria have not been published. In these trials, the use of advanced imaging selection criteria had the potential advantage of increasing the likelihood of showing treatment benefit by enhancing the study population with patients most likely to respond to therapy. However, the inherent disadvantage of this study design is the possibility that patients who may have responded to therapy were excluded.

Recognition and attachment of the particle to be ingested by the leukocytes: Phagocytosis is enhanced if the material to be phagocytosed is coated with certain plasma proteins called opsonins. The three major opsonins are: the Fc fragment of the immunoglobulin, components of the complement system C3b and C3bi, and the carbohydrate-binding proteins ­ lectins. Engulfment: During engulfment, extension of the cytoplasm (pseudopods) flow around the object to be engulfed, eventually resulting in complete enclosure of the particle within the phagosome created by the cytoplasmic membrane of the phagocytic cell. As a result of fusion between the phagosome and lysosome, a phagolysosome is formed and the engulfed particle is exposed to the degradative lysosomal enzymes. Oxygen-independent mechanism: this is mediate by some of the constituents of the primary and secondary granules of polymorphonuclear leukocytes. The lysosomal enzymes are, however, essential for the degradation of dead organisms within phagosomes. These species have single unpaired electrons in their outer orbits that react with molecules in cell membrane or nucleus to cause damages. The destructive effects of H2O2 in the body are gauged by the action of the glutathione peroxidase and catalase. This H2O2 ­ halide - myecloperoxidease system is the most efficient bactericidal system in neutrophils. A similar mechanism is also effective against fungi, viruses, protozoa and helminths. Chemical mediators of inflammation Chemical mediators account for the events of inflammation. Inflammation has the following sequence: Cell injury Chemical mediators Acute inflammation. Sources of mediators: the chemical meditors of inflammation can be derived from plasma or cells. Once activated and released from the cells, most of these mediators are short lived. Morphology of acute inflammation Characteristically, the acute inflammatory response involves production of exudates. An exudate is an edema fluid with high protein concentration, which frequently contains inflammatory cells. A transudate is simply a non-inflammatory edema caused by cardiac, renal, undernutritional, & other disorders. There are different morphologic types of acute inflammation: 1) Serous inflammation this is characterized by an outpouring of a thin fluid that is derived from either the blood serum or secretion of mesothelial cells lining the peritoneal, pleural, and pericardial cavities. It resolves without reactions 31 2) Fibrinous inflammation More severe injuries result in greater vascular permeability that ultimately leads to exudation of larger molecules such as fibrinogens through the vascular barrier. Fibrinous exudate is characteristic of inflammation in serous body cavities such as the pericardium (butter and bread appearance) and pleura. Course of fibrinous inflammation include: Resolution by fibrinolysis Scar formation between perietal and visceral surfaces i. Pus is a thick creamy liquid, yellowish or blood stained in colour and composed of A large number of living or dead leukocytes (pus cells) Necrotic tissue debris Living and dead bacteria Edema fluid There are two types of suppurative inflammation: A) Abscess formation: An abscess is a circumscribed accumulation of pus in a living tissue. It is encapsulated by a so-called pyogenic membrane, which consists of layers of fibrin, inflammatory cells and granulation tissue. B) Acute diffuse (phlegmonous) inflammation this is characterized by diffuse spread of the exudate through tissue spaces. And the fibrinogen, the necrotic epithelium, the neutrophilic polymorphs, red blood cells, bacteria and tissue debris form a false (pseudo) membrane which forms a white or colored layer over the surface of inflamed mucosa. Pseudomembranous inflammation is exemplified by Dipthetric infection of the pharynx or larynx and Clostridium difficille infection in the large bowel following certain antibiotic use. Beneficial effects Dilution of toxins: the concentration of chemical and bacterial toxins at the site of inflammation is reduced by dilution in the exudate and its removal from the site by the flow of exudates from the venules through the tissue to the lymphatics. Protective antibodies: Exudation results in the presence of plasma proteins including antibodies at the site of inflammation. Thus, antibodies directed against the causative organisms will react and promote microbial destruction by phagocytosis or complement-mediated cell lysis. Fibrin formation: this prevents bacterial spread and enhances phagocytosis by leukocytes. Plasma mediator systems provisions: the complement, coagulation, fibrinolytic, & kinin systems are provided to the area of injury by the process of inflammation.

A7 parasagittal hypoperfusion injury with cortical and subcortical damage in the parasagittal area (arrow); A8 acute severe term asphyxial insult of basal ganglia and thalamus lesions (left) with typical involvement of thalamus, globus pallidus and putamen (arrows), and lesions of the central region (arrows, right). B5 middle cerebral artery infarction with cortical, subcortical and thalamic involvement. The clinical patterns and molecular genetics of lissencephaly and subcortical band heterotopia. These can cause anxiety to inexperienced clinicians, radiologists, and of course, families. Minimize the risk of unearthing incidentalomas by resisting the temptation to perform non-indicated examinations! If the site of the incidentaloma is distant from the likely site of pathology, given the examination findings, then it is easier to be reassuring about its non-significance. The large majority of these spontaneously close in early infancy, but may persist into adulthood. Also known as Virchow­Robin spaces, they are associated with some neurological diseases (such as mucopolysaccharidoses), but are more commonly normal variants. Small cysts, such as that shown, are commonly asymptomatic (the location at the anterior pole of the temporal lobe is typical). Haemorrhage into very large cysts is also recognized; however, a cyst as small as that illustrated is very benign and should be ignored. In situations of greater tonsillar descent, radiological evidence of foramen magnum crowding, and symptoms of headache, the findings may be significant. In unclear situations a follow-up study after an interval of 12 mths may clarify its non-progressive nature. Recall that testing spinothalamic sensation in relevant dermatomes is the most sensitive clinical indicator of a syrinx (see b p. If appearances are striking, and head circumference is large, consider benign external hydrocephalus (see Figure 3. Approach the first step is to distinguish hypomyelination or delayed myelination from dysmyelination. This is done by comparison of the T1 and T2 characteristics of the white matter in relation the appearance of grey matter structures. Because of physiological changes in white matter signal appearance in the first 2 yrs of life reflecting myelination (see b p. After this time, white matter should be normally be dark (reflecting completed myelination) on T2 (Figure 3. Further characterization is based on a combination of radiological features (particularly the anatomical location of abnormal white matter) and associated clinical features. Please note that variant and atypical forms make this a more complex process than the flowchart necessarily suggests (Schiffmann and van der Knaap, 20091)! Cortex White matter Basal ganglia T1 T2 Normal (after ~ 18m) or or T1 T2 Leukoencephalopathy or Leukodystrophy T1 T2 T1 T2 T1 T2 Hypomyelination. Specific scenarios · Unilateral hemi-syndrome: consider migraine or epilepsy (the duration of disturbed sensation will help differentiate). Proximal arm/shoulder pain or dysaesthesia often precedes the weakness of neuralgic amyotrophy. Much more commonly a child with developmental disability will show indifference to pain: he feels (and withdraws automatically from) painful stimuli but shows little emotional distress. Such disturbances will typically be reported in patchy distributions that do not correspond to anatomical segmental or peripheral nerve territory distributions. Paroxysmal extreme pain disorder · the preferred name for what was previously known as familial rectal pain syndrome. Difficulties raising head from pillow, combing hair, brushing teeth, shaving, raising arms above head, getting up from chair, stairs and use of banisters, running, hopping, jumping. Difficulties opening screw cap or door knob, turning key, buttoning clothes, writing, falling on uneven ground, tripping, hitting curb, difficulty in heel walking, toe walking, foot drop. Distal weakness is usually due to neuropathy (any), but also some muscle diseases (Emery­Dreifuss, myotonic dystrophy, dysferlinopathy, Miyoshi myopathy). Difficulties bending forward, lifting head off the bed, respiratory involvement, nocturnal hypoventilation, and diaphragmatic weakness; seen in congenital myopathies and glycogen storage disorders. Antenatal onset suggested by polyhydramnios, reduced foetal movements, unusual foetal presentation in labour, contractures (arthrogryposis including foot deformity), congenital dysplasia of the hip. Associated features/system enquiry · Toe walking: Duchenne, Becker, Emery­Dreifuss, Charcot­Marie Tooth.

Chronic cholecystitis is ongoing chronic inflammation of the gallbladder, usually caused by gallstones. Well-developed examples show stromal and mural lymphocytic and plasmacytic infiltrates. Ascending cholangitis is a bacterial infection of the bile ducts ascending up to the liver, usually associated with obstruction of bile flow oftentimes from bile duct stones. Gross examination shows yellow speckling of the red-tan mucosa ("strawberry gallbladder"). Hydrops of the gallbladder (mucocele) occurs when chronic obstruction of the cystic duct leads to the resorption of the normal gallbladder contents and enlargement of the gallbladder by the production of large amounts of clear fluid (hydrops) or mucous secretions (mucocele). When the tumor does present, it may be with cholecystitis, enlarged palpable gallbladder, or biliary tract obstruction (uncommon). Klatskin tumor is a carcinoma of the bifurcation of the right and left hepatic bile ducts. Risk factors for bile duct cancer include Clonorchis (Opisthorchis) sinensis (liver fluke) in Asia and primary sclerosing cholangitis. Microscopic examination shows adenocarcinoma arising from the bile duct epithelium. Bile duct carcinoma is carcinoma of the extrahepatic bile ducts, Adenocarcinoma of the ampulla of Vater may exhibit duodenal, biliary, or pancreatic epithelium. Causes of jaundice include overproduction of bilirubin, defective hepatic bilirubin uptake, defective conjugation, and defective excretion. Jaundice related to overproduction of bilirubin can be seen in hemolytic anemia and ineffective erythropoiesis (thalassemia, megaloblastic anemia, etc. Chronic hemolytic anemia patients often develop pigmented bilirubinate gallstones. Risk factors include prematurity and hemolytic disease of the newborn (erythroblastosis fetalis). Physiologic jaundice of the newborn can be complicated by kernicterus; treatment is phototherapy. Hereditary hyperbilirubinemias When hyperbilirubinemia is prolonged in the newborn, a mutation affecting bilirubin conjugation enters the differential diagnosis. It produces conjugated hyperbilirubinemia and a distinctive black pigmentation of the liver, but has no clinical consequences. Biliary tract obstruction may have multiple etiologies, including gallstones; tumors (pancreatic, gallbladder, and bile duct); stricture; and parasites (liver flukes-Clonorchis [Opisthorchis] sinensis). The presentation can include jaundice and icterus; pruritus due to increased plasma levels of bile acids; abdominal pain, fever, and chills; dark urine (bilirubinuria); and pale clay-colored stools. Lab studies show elevated conjugated bilirubin, elevated alkaline phosphatase, and elevated 5ґ-nucleotidase. Females have 10 times the incidence of primary biliary cirrhosis compared to males; the peak incidence is age 40­50. Presentation includes obstructive jaundice and pruritus; xanthomas, xanthelasmas, and elevated serum cholesterol; fatigue; and cirrhosis (late complication). Most patients have another autoimmune disease (scleroderma, rheumatoid arthritis or systemic lupus erythematosus). Microscopically, lymphocytic and granulomatous inflammation involves interlobular bile ducts. The exact etiologic mechanism is not known but growing evidence supports an immunologic basis. Microscopically, there is periductal chronic inflammation with concentric fibrosis around bile ducts and segmental stenosis of bile ducts. Clinical Correlate Prothrombin time, not partial thromboplastin time, is used to assess the coagulopathy due to liver disease. Causes of cirrhosis include alcohol, viral hepatitis, biliary tract disease, hemochromatosis, cryptogenic/idiopathic, Wilson disease, and -1-antitrypsin deficiency. On gross Pathology, micronodular cirrhosis has nodules <3 mm, while macronodular cirrhosis has nodules >3 mm; mixed micronodular and macronodular cirrhosis can also occur. At the end stage, most diseases result in a mixed pattern, and the etiology may not be distinguished based on the appearance. Cirrhosis has a multitude of consequences, including portal hypertension, ascites, splenomegaly/hypersplenism, esophageal varices, hemorrhoids, caput medusa, decreased detoxification, hepatic encephalopathy, spider angiomata, palmar erythema, gynecomastia, decreased synthetic function, hepatorenal syndrome and coagulopathy. Microscopically, the liver initially shows centrilobular macrovesicular steatosis (reversible) that can eventually progress to fibrosis around the central vein (irreversible).

Endometrial adenocarcinoma is the most common malignant tumor of the lower female genital tract. It most commonly affects postmenopausal women who present with abnormal uterine bleeding. Endometrial Carcinoma Invading the Myometrium Less common types of uterine malignancy include leiomyosarcoma, a malignant, smooth muscle tumor, and carcinosarcoma, which contains both malignant stromal cells and endometrial adenocarcinoma. Adenomyosis is an invagination of the deeper layers of the endometrium into the myometrium, which causes menorrhagia and dysmenorrhea. Anovulation can cause abnormal uterine bleeding, especially in women near menarche and menopause. Biopsy shows glandular and stromal breakdown in a background of proliferative phase endometrium. Accurate diagnosis requires exclusion of other endocrine disorders that might affect reproduction. Patients are usually young women of reproductive age who present with oligomenorrhea or secondary amenorrhea, hirsutism, infertility, or obesity. Gross examination is notable for bilaterally enlarged ovaries with multiple cysts; microscopic examination shows multiple cystic follicles. Previously, epithelial tumors were characterized by histology into the categories cystadenoma (benign), borderline, and cystadenocarcinoma. Now, serous tumors are classified as low grade and high grade for prognostic significance. Note · the Pap test has reduced the incidence of cervical cancer in the United States. Psammoma Bodies (Concentric Calcifications) in a Serous Tumor Ovarian Germ Cell Tumors · Teratoma (dermoid cyst) ° Vast majority (>95%) of ovarian (but not testicular) teratomas are benign; commonly occurs in early reproductive years ° Include elements from all 3 germ cell layers: ectoderm (skin, hair, adnexa, neural tissue), mesoderm (bone, cartilage), and endoderm (thyroid, bronchial tissue) ° Complications include torsion, rupture, and malignant transformation ° Can contain hair, teeth, and sebaceous material 204 Chapter 22 · Female Genital Pathology ° the term struma ovarii is used when there is a preponderance of thyroid tissue ° Immature teratoma is characterized by histologically immature tissue · Dysgerminoma ° Malignant; commonly occurs in children and young adults ° Risk factors include Turner syndrome and disorders of sexual development ° Gross and microscopic features are similar to seminomas ° Are radiosensitive; prognosis is good Ovarian Sex Cord­Stromal Tumors · Ovarian fibroma ° Most common stromal tumor; forms a firm, white mass ° Meigs syndrome refers to the combination of fibroma, ascites, and pleural effusion. Primary sites for metastatic tumor to the ovary include breast cancer, colon cancer, endometrial cancer, and gastric "signet-ring cell" cancer (Krukenberg tumor). Incidence in the United States is 1 per 1,000 pregnancies, with an even higher incidence in Asia. Choriocarcinoma is a malignant germ cell tumor derived from the trophoblast that forms a necrotic and hemorrhagic mass. Placental site trophoblastic tumor is a tumor of intermediate trophoblast which usually presents <2 years after pregnancy with bleeding and an enlarged uterus. In ectopic pregnancy, the fetus implants outside the normal location, most often in the fallopian tube, and less often in the ovaries or abdominal cavity. Enlarged placenta is common with maternal diabetes mellitus, Rh hemolytic disease, and congenital syphilis. Succenturiate lobes are accessory lobes of the placenta which may cause hemor- rhage if torn away from the main part of the placenta during delivery. Placental abruption is partial premature separation of the placenta away from the endometrium, with resulting hemorrhage and clot formation. Risk factors include hypertension, cigarette use, cocaine, and older maternal age. Vaginal delivery can cause the placenta to tear, with potentially fatal maternal or fetal hemorrhage. In placenta accreta, the placenta implants directly in the myometrium rather than in endometrium. Twin placentation · Fraternal twins always have 2 amnions and 2 chorions; placental discs are usually separate, but can grow together to appear to be a single placental disc. Acute mastitis causes an area of erythema and firmness in the breast, commonly during lactation. The breast is often biopsied to differentiate the condition from inflammatory carcinoma, another painful breast condition. Microscopically there is acute and chronic inflammation with abscess formation in some cases. Fat necrosis is often related to trauma or prior surgery, and it may produce a palpable mass or a discrete lesion with calcifications on mammography. Microscopic changes include fat necrosis, chronic inflammation, hemosiderin deposits and fibrosis with calcification. Because they carry varying degrees of risk for breast cancer, it is important to identify each type histologically. The changes most often involve the upper outer quadrant and may produce a palpable mass or nodularity.