Heidi Bauer MD, MS, MPH

• Associate Adjunct Professor, Epidemiology

https://publichealth.berkeley.edu/people/heidi-bauer/

Primary endpoint is clinical benefit rate defined as complete/partial response + stable disease for $24 wks from randomization symptoms hypothyroidism order triamcinolone 4 mg with amex. Due to lack of targeted therapies treatment 1 degree av block purchase 4 mg triamcinolone with amex, there is no standard treatment of choice for triple negative breast cancer and chemotherapy remains the accepted standard medications qhs discount triamcinolone 4mg online. Many chemotherapeutic agents have been reported to have clinical activity either as single agent or in combination medicine engineering triamcinolone 4 mg low price. The primary objective is to compare progression-free survival in patients treated with carboplatin+everolimus to patients treated with carboplatin alone. The secondary objectives are to assess duration of response, disease control rate, progression-free survival, and overall survival. Secondary efficacy endpoints include clinical benefit rate, duration of response, progression-free, and overall survival. The trial will be terminated in stage I if 2 or less out of the first 15 participants respond. If the total number responding is less than or equal to 7, the combination is rejected. Eligible pts will have received 1-2 prior lines of chemotherapy for metastatic disease, including an anthracycline or taxane. Secondary endpoints are objective response rate, duration of response, change in tumor size, and overall survival for comparisons between combinations and for each combination vs Ola alone; drug exposure; and safety and tolerability. The first prespecified futility analysis in Stratum C has met the recruitment target and will be assessed by unblinded review April 2019. First Author: Leonel Fernando Hernandez-Aya, Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. T-cell responses to neoantigens are high in affinity and are not limited by central mechanisms of self-tolerance. Next-generation sequencing and epitope prediction algorithms are used to identify/prioritize neoantigens for vaccine design and development. Initially, all participants are treated with a run-in of gemcitabine + carboplatin (18-weeks; Part A). Subsequently, patients are treated with nab-paclitaxel + durvalumab + neoantigen vaccine vs. Secondary objectives include the safety and tolerability of the combination, progression-free survival, and overall survival. If there is at least one patient with objective response, accrual will continue to the second stage where an additional 16 patients will be enrolled. If there are at least 4 patients with an objective response among the 30 patients, the regimen will be considered worthy of further study. If the true response rate is 5%, the chance the regimen is declared worthy of further study is less than 5%. If the true response rate is 25%, the chance that the regimen is declared worthy of further study is. Tumor biopsies, peripheral blood, and stool collection are mandatory and will be obtained at baseline, on treatment (end of cycle 1), and at disease progression and will be assessed for potential biomarkers of treatment response. The trial was activated in February 2019, and accrual should be completed in 18 months. Enrollment was initiated Dec 2015 at 45 sites in Central and South America and enrollment has been completed. At final analysis, if there is an approximate difference of $10% favoring Oraxol, a p-value of 0. Secondary aims include local control in the metastatic site, new distant metastatic rate, and technical quality. Methods: Women with pathologically confirmed metastatic breast cancer to # 4 sites who have been diagnosed within 365 days with metastatic disease and the primary tumor site disease is controlled. Site radiation credentialing with a facility questionnaire and pretreatment review of first case is required. For the translational research assuming a two-sided probability of type I error of 0. Multivariable linear regression was performed to assess impact of baseline variables on change in intent to take medication. Here we report the results of exploratory analyses to assess whether the benefit of babytam varies among subgroups of patients defined by individual characteristics. Methods: Post-hoc subgroup analyses were performed according to a mixed approach based on the test for interaction and biological plausibility. Results: Age at menopause, smoking status and Ki-67 exhibited a significant interaction with treatment. Conclusions: Exploratory analyses showed a trend to a higher effect of babytam in women aged 50 or older, never smokers, women with hot flashes or abdominal obesity and tumors with Ki-67 above 10%. Our results provide insight into the efficacy of babytam towards a personalized preventive approach. Conclusions: Herein we report on the largest cohort of women with breast cancer treated with adjuvant radiotherapy at a single institution who have undergone germline testing. Further investigation to evaluate acute or late toxicities and secondary cancers as a result of radiotherapy is warranted. Risk of subsequent cancer diagnosis in patients treated with 3D conformal, intensity modulated, or proton beam radiation therapy. To analyze a more uniform population, cases were required to be non-metastatic and have at least 2 years of follow-up time. Diagnosis of a subsequent cancer was determined using a variable denoting the sequence of malignant neoplasms over the lifetime of the patient. Propensity score matching was additionally used to balance baseline characteristics. Associations of clinicopathologic features with toxicity were evaluated by multivariate regression. Median tangent dose was 50Gy; 62% included an additional boost (median 10Gy) and 48% used a bolus (median thickness 0. At last on-treatment visit, 31% had grade 2 dermatitis, 4% had other grade 2 events (fatigue, seroma, decreased range of motion, or pain), and 1% had grade 3 dermatitis. At 1 year, 13% had grade $2 toxicity: grade 2a lymphedema (n = 3), and grade 2 (n = 1) or 3 (n = 2) capsular contracture. Overall, no patients had significant (grade $2) telangiectasias, fibrosis, or fat necrosis; no grade 4 or 5 toxicities were seen. Methods: the Utah Population Database was used to identify 569,320 men, 40+ years with a pedigree that included at least three consecutive generations. These results are critically valuable in understanding and targeting high-risk populations that would benefit from genetic screening and enhanced surveillance. Results: In 2017, 77 patients were referred to genetics of which 45 underwent genetic counseling and testing. Since the study launched in 2018, 407 patients were referred and underwent testing through the study. This approach allows for more timely access to genetic information that may impact treatment strategies and medical management of family members. This excluded two pts with known primary hematological malignancies who were removed. To date, only the lung, breast, and colorectal cancer pts have been annotated (N = 372) since these cancers have an overall higher incidence and prevalence in society. Results: Annotation of lung cancer pts (155/880), breast (118/880), and colorectal cancer pts (99/880) is collected and represents about 40% of all pts. In the discovery phase, a total of 285 Spanish patients and 5,608 ancestry-matched controls were evaluated. In the validation stage, an independent cohort of 514 European patients and 27,173 ancestrymatched controls were analyzed. Results: Cases had a higher median age (56 years, range 30-82) than controls (48 years, range 5-72). Cases and controls were similar in solid tumor cancer history and known exposure to cancer cytotoxic therapy; 73. Of note, cases frequently had a concomitant second (n = 10; 29% of cases) or third (n = 4; 11. This study was censored on March 31, 2015 when all surviving patients had a minimum follow-up of 60 months. Results: the baseline clinical, laboratory, and tumor characteristics of the 2 groups were comparable. The 1-, 3-, and 5-year recurrence-free survival rates for the antiviral group and the control group were 85.

They withdraw from the main current of daily affairs as their thoughts and speech come to be dominated by the pain medicine misuse definition order triamcinolone 4 mg online. Once a person is subjected to the tyranny of chronic pain medicine vicodin purchase 4 mg triamcinolone visa, depressive symptoms are practically always added medications vaginal dryness cheap triamcinolone 4mg fast delivery. This is accomplished by a thorough interrogation of the patient medications that cause dry mouth purchase triamcinolone 4mg visa, with the physician carefully seeking out the main characteristics of the pain in terms of the following: 1. Location Mode of onset Provoking and relieving factors Quality and time-intensity attributes Duration Severity Knowledge of these factors in every common disease is the lore of medicine. Some physicians find it helpful, particularly in gauging the effects of analgesic agents, to use a "pain scale," i. Needless to say, this general approach is put to use every day in the practice of general medicine. Together with the physical examination, including maneuvers designed to reproduce and relieve the pain and ancillary diagnostic procedures, it enables the physician to identify the source of most pains and the diseases of which they are a part. Once the pains due to the more common and readily recognized diseases of each organ system are eliminated, there remain a significant number of chronic pains that fall into one of four categories: (1) pain from an obscure medical disease, the nature of which has not yet been disclosed by diagnostic procedures; (2) pain associated with disease of the central or peripheral nervous system. Every day, healthy persons of all ages have pains that must be taken as part of normal sensory experience. To mention a few, there are the "growing pains" of presumed bone and joint origin of children; the momentary hard pain over an eye or in the temporal or occipital regions, which strikes with such suddenness as to raise the suspicion of a ruptured intracranial aneurysm; inexplicable split-second jabs of pain elsewhere; the more persistent ache in the fleshy part of the shoulder, hip, or extremity that subsides spontaneously or in response to a change in position; the fluctuant precordial discomfort of gastrointestinal origin, which conjures up fear of cardiac disease; and the breathtaking "stitch in the side," due to intercostal or diaphragmatic cramp during exercise. These "normal pains," as they may be called, tend to be brief and to depart as obscurely as they came. Such pains come to notice only when elicited by an inquiring physician or when experienced by a patient given to worry and introspection. Whenever pain- by its intensity, duration, and the circumstances of its occurrence- appears to be abnormal or when it constitutes the chief complaint or one of the principal symptoms, the physician must attempt to reach a tentative decision as to its mech- Pain Due to Undiagnosed Medical Disease Here the source of the pain is usually in a bodily organ and is caused by a lesion that irritates and destroys nerve endings. It usually means an involvement of structures bearing the termination of pain fibers. Osseous metastases, tumors of the kidney, pancreas, or liver, peritoneal implants, invasion of retroperitoneal tissues or the hilum of the lung, and infiltration of nerves of the brachial or lumbosacral plexuses can be extremely painful, and the origin of the pain may remain obscure for a long time. Sometimes it is necessary to repeat all diagnostic procedures after an interval of a few months, even though at first they were negative. From experience one learns to be cautious about reaching a diagnosis from insufficient data. Treatment in the meantime is directed to the relief of pain, at the same time instilling in the patient a need to cooperate with a program of expectant observation. Neurogenic or Neuropathic Pain these terms are generally used interchangeably to designate pain that arises from direct stimulation of nervous tissue itself, central or peripheral, exclusive of pain due to stimulation of sensitized C fibers by lesions of other bodily structures. This category comprises a variety of disorders involving single and multiple nerves, notably trigeminal neuralgia and those due to herpes zoster, diabetes, and trauma (including causalgia, discussed further on); a number of polyneuropathies of diverse type; root irritation. As a rule, lesions of the cerebral cortex and white matter are associated not with pain but with hypalgesia. The clinical features that characterize central pain have been reviewed by Schott (1995). Particular diseases giving rise to neuropathic pain are considered in their appropriate chapters but the following remarks are of a general nature, applicable to all of the painful states that compose this group. The sensations that characterize neuropathic pain vary and are often multiple; burning, gnawing, aching, and shooting or lancinating qualities are described. There is an almost invariable association with one or more of the symptoms of hyperesthesia, hyperalgesia, allodynia, and hyperpathia (see above). The abnormal sensations coexist in many cases with a sensory deficit and local autonomic dysfunction. Furthermore, the pain may persist in the absence of a stimulus and generally responds poorly to treatment, including the administration of opioid medications. These pains are classified in clinical work by the mechanism that incited them or the anatomic distribution of the pain. Peripheral Nerve Pain Painful states that fall into this category are in most cases related to disease of the peripheral nerves, and it is to pain from this source that the term neuropathic is more strictly applicable. Pain states of peripheral nerve origin far outnumber those due to spinal cord, brainstem, thalamic, and cerebral disease. Although the pain is localized to a sensory territory supplied by a nerve plexus or nerve root, it often radiates to adjacent areas. Sometimes the onset of pain is immediate on receipt of injury; more often it appears at some point during the evolution or recession of the disorder. The disease of the nerve may be obvious, expressed by the usual sensory, motor, reflex, and autonomic changes, or these changes may be undetectable by standard tests. The postulated mechanisms of peripheral nerve pain are diverse and differ from those of central diseases. Some of the current ideas have been mentioned in the earlier section on chronic pain. He noted that when a group of neurons is deprived of its natural innervation, they become hyperactive. Others point to a reduced density of certain types of fibers in nerves supplying a causalgic zone as the basis of the burning pain, but the comparison of the density of nerves from painful and nonpainful neuropathies has not proved to be consistently different. For example, Dyck and colleagues, in a study of painful versus nonpainful axonal neuropathies, concluded that there was no difference between them in terms of the type of fiber degeneration. Also, the occurrence of ectopic impulse generation all along the surface of injured axons and the possibility of ephaptic activation of unsheathed axons seems applicable particularly to some causalgic states. Stimulation of the nervi nervorum of larger nerves by an expanding intraneural lesion or a vascular change was postulated by Asbury and Fields as the mechanism of nerve trunk pain. The sprouting of adrenergic sympathetic axons in response to nerve injury has already been mentioned and is an ostensible explanation for the abolition of causalgic pain by sympathetic blockade. This has given rise to the term sympathetically sustained pain for some cases of causalgia, as discussed below. Regenerating axonal sprouts, as in a neuroma, are also hypersensitive to mechanical stimuli. On a molecular level, it has been shown that sodium channels accumulate at the site of a neuroma and all along the axon after nerve injury, and that this gives rise to ectopic and spontaneous activity of the sensory nerve cell and its axon. Spontaneous activity in nociceptive C fibers is thought to give rise to burning pain; firing of large myelinated A fibers is believed to produce dysesthetic pain induced by tactile stimuli. The abnormal response to stimulation is also influenced by sensitization of central pain pathways, probably in the dorsal horns of the spinal cord, as outlined in the review by Woolf and Manion. Several observations have been made regarding the neurochemical mechanisms that might underlie these changes, but none provides a consistent explanation. Possibly more than one of these mechanisms is operative in a given peripheral nerve disease. Causalgia and Reflex Sympathetic Dystrophy (Complex Regional Pain Syndrome) Causalgia (see also pages 119 and 189) is the name that Weir Mitchell applied to a rare (except in time of war) type of peripheral neuralgia consequent upon trauma, with partial interruption of the median or ulnar nerve and, less often, the sciatic or peroneal nerve. It is characterized by persistent, severe pain in the hand or foot, most pronounced in the digits, palm of the hand, or sole. The pain has a burning quality and frequently radiates beyond the territory of the injured nerve. The painful parts are exquisitely sensitive to contactual stimuli, so the patient cannot bear the pressure of clothing or drafts of air; even ambient heat, cold, noise, or emotional stimuli intensify the causalgic symptoms. The affected extremity is kept protected and immobile, often wrapped in a cloth moistened with cool water. Sudomotor, vasomotor, and, later, trophic abnormalities are usual accompaniments of the pain. The skin of the affected part is moist and warm or cool and soon becomes shiny and smooth, at times scaly and discolored. For many years it was attributed to a short-circuiting of impulses, the result of an artificial connection between efferent sympathetic and somatic afferent pain fibers at the point of the nerve injury. The demonstration that the causalgic pain could be abolished by depletion of neurotransmitters at sympathetic adrenergic endings shifted the presumed site of sympathetic-afferent interaction to the nerve terminals and suggested that the abnormal cross-excitation is chemical rather than electrical in nature. An explanation favored in recent years is that an abnormal adrenergic sensitivity develops in injured nociceptors and that circulating or locally secreted sympathetic neurotransmitters trigger the painful afferent activity. Another theory holds that a sustained period of bombardment by sensory pain impulses from one region results in the sensitization of central sensory structures. Epidural infusions, particularly of analgesics or ketamine; intravenous infusion of bisphosphonates; and spinal cord stimulators are other forms of treatment (see Kemler). The roles of the central and sympathetic nervous systems in causalgic pain have been critically reviewed by Schott and by Schwartzman and McLellan.

In the rare cases of patients with a wedge compression fracture and neurological impairment treatment will depend on the degree of dysfunction and the risk of progression treatment depression generic 4 mg triamcinolone amex. More ominous than usual is a fracture of the transverse process of L5; this should alert one to the possibility of a vertical shear injury of the pelvis medications quetiapine fumarate discount 4mg triamcinolone. With severe bony injury medication 3 checks buy triamcinolone 4mg without a prescription, however medicine man lyrics discount triamcinolone 4mg without prescription, increasing kyphosis may occur and internal fixation should be considered. The posterior part of the vertebral body is shattered and fragments of bone and disc may be displaced into the spinal canal. Anteroposterior x-rays may show spreading of the vertebral body with an increase of the interpedicular distance. If there is minimal anterior wedging and the fracture is stable with no neurological damage, the patient (a) (b) 27. Severe ligamentous injuries are less predictable and posterior spinal fusion is advisable. Fracture-dislocation Segmental displacement may occur with various combinations of flexion, compression, rotation and shear. All three columns are disrupted and the spine is Jack-knife injury Combined flexion and posterior distraction may cause the mid-lumbar spine to jack-knife around an axis that is placed anterior to the vertebral column. This is seen most typically in lap seat-belt injuries, where the body is thrown forward against the restraining strap. There is little or no crushing of the vertebral body, but the posterior and middle columns fail in distraction; thus these fractures are unstable in flexion. The tear passes transversely through the bones or the ligament structures, or both. The most perfect example of tensile failure is the injury described by Chance in 1948, in which the split runs through the spinous process, the transverse processes, pedicles and the vertebral body. Xrays may show horizontal fractures in the pedicles or transverse processes, and in the anteroposterior view the apparent height of the vertebral body may be increased. These are the most dangerous injuries and are often associated with neurological damage to the lowermost part of the cord or the cauda equina. X-rays may show fractures through the vertebral body, pedicles, articular processes and laminae; there may be varying degrees of subluxation or even bilateral facet dislocation. In neurologically intact patients, most fracturedislocations will benefit from early surgery. In fracture-dislocation with a partial neurological deficit, there is also no evidence that surgical stabilization and decompression provides a better neurological outcome than conservative treatment. If surgical decompression and stabilization are performed, this may require a combined posterior and anterior approach. In fracture-dislocation without neurological deficit, surgical stabilization will prevent future neurological complications and allow earlier rehabilitation. When specialized surgery cannot be performed, these injuries can be managed non-operatively with postural reduction, bed rest and bracing. For patients with neurological impairment who have the benefit of being treated in a specialized spinal injuries unit, a strong case can be made for managing them also by non-operative methods. Three varieties of lesion occur: neurapraxia, cord transection and root transection. Neurapraxia Motor paralysis (flaccid), burning paraesthesia, sensory loss and visceral paralysis below the level of the cord lesion may be complete, but within minutes or a few hours recovery begins and soon becomes full. The condition is most likely to occur in patients who, for some reason other than injury, have a small-diameter anteroposterior canal; there is, however, no radiological evidence of recent bony damage. This is a temporary condition known as cord shock, but the injury is anatomical and irreparable. After a time the cord below the level of transection recovers from the shock and acts as an independent structure; that is, it manifests reflex activity. Within 4 weeks of injury tendon reflexes return and the flaccid paralysis becomes spastic, with increased tone, increased tendon reflexes and clonus; flexor spasms and contractures may develop with inadequate management. It is essential, when the bony injury is at the thoracolumbar junction, to distinguish between cord transection with root escape and cord transection with root transection. A patient with root escape is much better off than one with cord and root transection. Without detailed information, accurate diagnosis and prognosis are impossible; rectal examination is mandatory. Complete cord lesions Complete paralysis and anaesthesia below the level of injury suggest cord transection. During the stage of spinal shock when the anal reflex is absent (seldom longer than the first 24 hours) the diagnosis cannot be absolutely certain; if the anal reflex returns and the neural deficit (sensory and motor) persists, the cord lesion is complete. Complete lesions lasting more than 72 hours have only a small chance of neurological recovery. Incomplete cord lesions Root transection Motor paralysis, sensory loss and visceral paralysis occur in the distribution of the damaged roots. Root transection, however, differs from cord transection in two ways: recovery may occur and residual motor paralysis remains permanently flaccid. High cervical cord transection is fatal because all the respiratory muscles are paralysed. At the level of the C5 vertebra, cord transection isolates the lower cervical cord (with paralysis of the upper limbs), the thoracic cord (with paralysis of the trunk) and the lumbar and sacral cord (with paralysis of the lower limbs and viscera). With injury below the C5 vertebra, the upper limbs are partially spared and characteristic deformities result. Between T1 and T10 vertebrae the first lumbar cord segment in the adult is at the level of the T10 vertebra. Consequently, cord transection at that level spares the thoracic cord but isolates the entire lumbar and sacral cord, with paralysis of the lower limbs and viscera. The lower thoracic roots may also be transected but are of relatively little importance. Below T10 vertebra the cord forms a slight bulge (the conus medullaris) between the T10 and L1 vertebrae, and tapers to an end at the interspace between the L1 and L2 vertebrae. The L2 to S4 nerve roots arise from the conus medullaris and stream downwards in a bunch (the cauda equina) to emerge at successive levels of the lumbosacral spine. Therefore, spinal injuries above the T10 vertebra cause cord transection, those between the T10 and L1 vertebrae cause cord and nerve root lesions, and those below the L1 vertebra only root lesions. The commonest is the central cord syndrome where the initial flaccid weakness is followed by lower motor neuron paralysis of the upper limbs with upper motor neuron (spastic) paralysis of the lower limbs, and intact peri-anal sensation (sacral sparing). With the less common anterior cord syndrome there is complete paralysis and anaesthesia but deep pressure and position sense are retained in the lower limbs (dorsal column sparing). The posterior cord syndrome is rare; only deep pressure and proprioception are lost. There is loss of motor power on the side of the injury and loss of pain and temperature sensation on the opposite side. Most of these patients improve and regain bowel and bladder function and some walking ability. Below the T10 vertebra, discrepancies between neurological and skeletal levels are due to transection of roots descending from cord segments higher than the vertebral lesion. Frankel observed that 60 per cent of patients with partial cord lesions (Grades B, C or D) improved (spontaneously) by one grade regardless of the treatment type and a significant number are able to walk again. Although many of the patients who present in Frankel Grade A improve to B or C, only 5 per cent of these patients improve to Frankel D or E. Bladder and bowel For the first 24 hours the bladder distends only slowly, but, if the distension is allowed to progress, overflow incontinence occurs and infection is probable. In special centres it is usual to manage the patient from the outset by intermittent catheterization under sterile conditions.

Clinical features Patients are usually over 50 years old; they tend to be overweight and may have longstanding bow-leg deformity symptoms 4 months pregnant generic 4mg triamcinolone. Pain is the leading symptom medicine vile 4mg triamcinolone with amex, worse after use symptoms kidney pain discount 4 mg triamcinolone with visa, or (if the patello-femoral joint is affected) on stairs treatment action group discount 4 mg triamcinolone amex. On examination there may be an obvious deformity (usually varus) or the scar of a previous operation. Except during an exacerbation, there is little fluid and no warmth; nor is the synovial membrane thickened. Movement is somewhat limited and is often accompanied by patello-femoral crepitus. It is useful to test movement applying first a varus and then a valgus force to the knee; pain indicates which tibio-femoral compartment is involved. Patients may experience long periods of lesser discomfort and only moderate loss of function, followed by exacerbations of pain and stiffness (perhaps after unaccustomed activity). X-rays taken with the patient lying down (a,b) suggest only minor cartilage loss on the medial side of each knee. Supracondylar osteotomy Realignment osteotomy is unlikely to have any protective effect in a disease which is marked by generalized cartilage erosion. However, if the knee is stable and pain-free but troublesome because of valgus and flexion deformity, a corrective supracondylar osteotomy is useful. Arthroplasty Total joint replacement is useful when joint destruction is advanced. However, it is less successful if the knee has been allowed to become very unstable or very stiff; timing of the operation is important. Often there is a predisposing factor: injury to the articular surface, a torn meniscus, ligamentous instability or preexisting deformity of the hip or knee, to mention a few. Curiously, while the male:female distribution is more or less equal in white (Caucasian) peoples, black African women are affected far more frequently than their male counterparts. X-ray the anteroposterior x-ray must be obtained with the patient standing and bearing weight; only in this way can small degrees of articular cartilage thinning be revealed. The tibio-femoral joint space is diminished (often only in one compartment) and there is subchondral sclerosis. Osteophytes and subchondral cysts are usually present and sometimes there is soft-tissue calcification in the suprapatellar region or in the joint itself (chondrocalcinosis). If only the patello-femoral joint is affected, suspect a pyrophosphate arthropathy. Thus, with longstanding varus the Treatment If symptoms are not severe, treatment is conservative. A simple elastic support may do wonders, probably by improving proprioception in an unstable knee. Intra-articular corticosteroid injections will often relieve pain, but this is a stopgap, and not a very good one, because repeated injections may permit (or even predispose to) progressive cartilage and bone destruction. New forms of medication have been introduced in recent years, particularly the oral administration of glucosamine and intra-articular injection of hyalourans. Arthroscopic washouts, with trimming of degenerate meniscal tissue and osteophytes, may give temporary relief; this is a useful measure when there are contraindications to reconstructive surgery. Patellectomy is indicated only in those rare cases where osteoarthritis is strictly confined to the patellofemoral joint. However, bear in mind that extensor power will be reduced and if a total joint replacement is later needed pain relief will be less predictable than usual (Paletta and Laskin, 1995). The degree and accuracy of angular correction are the most important determinants of mid- and long-term clinical outcome. Replacement arthroplasty is indicated in older patients with progressive joint destruction. If the disease is largely confined to one compartment, a unicompartmental replacement can be done as an alternative to osteotomy. With modern techniques, and meticulous attention to anatomical alignment of the knee, the results of replacement arthroplasty are excellent. Arthrodesis is indicated only if there is a strong contraindication to arthroplasty. Two main categories are identified: (1) osteonecrosis associated with a definite background disorder [e. A third type, postmeniscectomy osteonecrosis, has been reported; its prevalence and pathophysiology are still unclear (Patel et al. Typically they give a history of sudden, acute pain on the medial side of the joint. On examination there is usually a small effusion, but the classic feature is tenderness on pressure upon the medial femoral or tibial condyle rather than along the joint line proper. Imaging X-ray the x-ray appearances are often unimpressive at the beginning, but a radionuclide scan may show increased activity on the medial side of the joint. On the femoral side, it is always the dome of the condyle that is affected, unlike the picture in osteochondritis dissecans. It shows the area of reactive bone surrounding the osteonecrotic lesion and can demonstrate the integrity of the overlying cortical shell of bone and articular cartilage. It is also helpful in determining prognosis concerning the natural course of the condition. The usual Special investigations Once the diagnosis is confirmed, investigations should be carried out to exclude generalized disorders known to be associated with osteonecrosis (see Chapter 6). Other conditions that have a sudden, painful onset and tenderness at the joint line are fracture of an osteoarthritic osteophyte, disruption of a degenerative meniscus, a stress fracture, pes anserinus bursitis and a local tendonitis. Resurfacing with osteochondral allografts has also been employed, with variable results. Because of loss of pain sensibility and proprioception, the articular surface breaks down and the underlying bone crumbles. Fragments of bone and cartilage are deposited in the hypertrophic synovium and may grow into large masses. Prognosis Symptoms and signs may stabilize and the patient be left with no more than slight distortion of the articular surface; or one of the condyles may collapse, leading to osteoarthritis of the affected compartment. The clinical progress depends on the radiographic size of the lesion, the ratio of size of the lesion to the size of the condyle (>40 per cent carries a worse prognosis) and the stage of the lesion (Patel et al. Clinical features the patient chiefly complains of instability; pain (other than tabetic lightning pains) is unusual. Radiologically the joint is subluxated, bone destruction is obvious and irregular calcified masses can be seen. Treatment Treatment is conservative in the first instance and consists of measures to reduce loading of the joint and analgesics for pain. Surgical options include arthroscopic debridement, Treatment Patients often seem to manage quite well despite the bizarre appearances. Clinical features Fresh bleeds cause pain and swelling of the knee, with the typical clinical signs of a haemarthrosis (see Chapter 5). There is a tendency to hold the knee in flexion and this may become a fixed deformity. X-rays Radiographic examination may show little abnormality, apart from local osteoporosis. In the elderly the injury is usually above the patella; in middle life the patella fractures; in young adults the patellar ligament can rupture. Tendon rupture sometimes occurs with minimal strain; this is seen in patients with connective tissue disorders. Treatment Both the haematologist and the orthopaedic surgeon should participate in treatment. Flexion deformity must be prevented by gentle physiotherapy and intermittent splintage. However, although replacement arthroplasty is feasible, this should be done only after the most searching discussion with the patient, where all the risks are considered, and only if a full haematological service is available. Avulsion of the quadriceps tendon from the upper pole of the patella is seen in the same group of people. The patient stumbles on a stair, catches his or her foot while walking or running, or may only be kicking a muddy football.

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