In few patients with highly aggressive disease, the scanning can be repeated after 6 months. They are monitored by biannual neck examinations and serum thyroglobulin determinations. Radioiodine wholebody scan to detect any recurrence should be done in patients whose serum thyroglobulin levels rise above 5ng/ml during suppressive thyroid replacement or above 10 ng/ml when hypothyroid. Bone metastasis resistant to radioiodine may be treated by localized radiotherapy for palliation. Measurement of serum calcitonin levels is performed at 3-month intervals for the first 3 years after operation and biannually thereafter. Postoperatively, plasma levels of calcitonin can be used as a marker to detect recurrent disease. Whole body somastotatin (octreotide) scanning may be more useful in these patients. Prior to reoperation, venous sampling for calcitonin should be used to indicate which side of the neck has disease. Laparoscopy of the liver may be considered to exclude small liver metastases that may be present and undetectable on imaging studies. Resection of recurrent tumour may be helpful occasionally but is rarely feasible technically. When near total or total thyroidectomy can be done with minimal complications, it is believed that this is the treatment of choice for most thyroid cancers. The use of radioiodine in the treatment of functioning distant metastases has been well accepted, however, its use in remnant ablation for welldifferentiated thyroid cancer is still controversial [11. As the incidence of the disease is very low and the nature of the malignancy is indolent, a large number of cases to establish good statistical data are required. Most published reports deal with a small series of cases and hence are not statistically significant. In order to overcome these deficiencies, reports are now being published on collated data obtained from several centres [11. Here again the problems encountered are the differing protocols for treatment with radioiodine, the indications for treatment which may include or exclude ablation of residual thyroid tissue, cervical nodal metastases and distal metastases. The doses of radioiodine given for ablation of residual thyroid tissue and metastatic disease also vary. The most reliable conclusions regarding treatment protocol encountered in radioiodine treatment are obtained from retrospective studies reported on a large series of patients followed over a period of several decades from single institutions with a more or less unchanged protocol of treatment. These reports from a handful of centres around the world are the most referred and cited studies [11. The growing awareness of subtle short- and long term consequences of this therapy and its ineffectiveness in advanced metastatic thyroid carcinoma have led to a more cautious and conservative approach to its use. This review is intended to highlight the areas in which 131I therapy has had its greatest achievements as well as those clinical situations in which its use is not supported by clinical experience or retrospective studies. If the radioiodine uptake is above 15% and a neck scan shows a significant amount of thyroid remnant tissue then a revision or completion thyroidectomy may be considered. Those patients who have large palpable nodes in the neck which may have been noticed after the primary thyroidectomy are advised nodal clearance. Following revision surgery, another diagnostic radioiodine scan and uptake study is undertaken which will determine the necessity of radioiodine treatment. Surgery of the primary thyroid is performed in many small hospitals all over the country and as a result of the lack of adequate experience and confidence of the surgeons the extent of the thyroid removal ranges from a nodulectomy to a subtotal thyroidectomy to a near total thyroidectomy. Hence the need for diagnostic large dose radioiodine for the further management is indicated. At the centre, patients are given radioiodine therapy depending on the neck uptake and extent of metastases as evident from whole body scan findings. Such patients are not treated with radioiodine and are started on thyroxine suppression. This results in a higher uptake and better chance for successful ablation of the thyroid with 131I therapy. Hence, post-surgery, T4 is not administered and diagnostic studies are performed 4-6 weeks after the surgery.
Children should have supplemental steroids before surgery and prior to treating hypothyroidism. Endovascular procedures (intra-arterial embolization) may aid subsequent resection. Five-year survival rates are around 25%, with the extent of surgical resection being important for prognosis. Myeloablative chemotherapy or chemoradiotherapy followed by autologous bone marrow transplantation is under investigation for the high risk group. Peripheral nerve tumours Schwannoma, neurofibroma, perineuroma, malignant peripheral nerve sheath tumour. Staging evaluation this is required for posterior fossa medulloblastoma, ependymoma and for pineal lesions. Cerebellar mutism (posterior fossa syndrome) this is a complication of posterior fossa surgery, particularly resection of midline posterior fossa tumours, such as medulloblastoma (therefore more common in children than adults). This section, however, deals mainly with inborn errors of metabolism that may be thought of as treatable early epileptic encephalopathies. Although rare, these disorders are potentially treatable, and prompt diagnosis and treatment may have marked impact on outcome. Outcome Life-long treatment; likely learning difficulties, particularly language delay; more severe motor disorder and developmental delay if treatment is delayed. Pyridoxine and pyridoxal-responsive seizures There is a group of children with severe symptomatic epilepsy, often infantile spasms, who respond to vitamin B6, but in whom subsequent withdrawal is possible. In such cases withdrawal of pyridoxine to confirm dependency is no longer recommended. Vitamin B12 (cobalamin) this is an essential water-soluble vitamin from meat and dairy products. Expect to see improvement in haematological and biochemical indices, mood and well-being within 1 week; in contrast, neurological improvement takes months to years, and indeed in the remethylation defects, progression continues. Acquired B12 deficiency and subacute combined degeneration of the cord Acquired B12 deficiency occurs in pernicious anaemia, an autoimmune condition resulting in destruction of the gastric parietal cells responsible for secretion of intrinsic factor. Pre-symptomatic diagnosis of B12 deficiency following identification of a megaloblastic anaemia is typical, however late diagnosis can result in neurological damage. Many effects of B12 deficiency are secondary to folate deficiency (as folate regeneration is B12 dependent) and will be ameliorated by folate supplementation. There are, however, some specifically B12 dependent processes including myelination that are not folate-responsive. This has led to debate about the wisdom of introduction of folate fortification of flour as a public-health measure to prevent neural tube defects (by ensuring adequate folate levels in women in the early days of pregnancy during neural tube formation); as folate supplementation will treat megaloblastic anaemia. The syndrome of late neurological damage due to B12 deficiency comprises non-specific psychiatric features with a characteristic pattern of spinal cord involvement known as subacute combined degeneration of the cord. Folate Folates are water-soluble vitamins, essential from dietary sources (leafy vegetables, nuts, beans). As folate metabolism is closely linked to B12 metabolism, not surprisingly clinical features are similar. Folinic acid-responsive seizures Neonates with intractable seizure picture resembling pyridoxinedependent epilepsy (see b p. Vitamin E this is a generic term for a group of related compounds (tocopherols and tocotrienols). An antioxidant, particularly protecting membrane phospholipids from radical oxygen species. Neurological conditions responsive to vitamin E can be considered as two groups: conditions of vitamin E deficiency and conditions of increased stress on antioxidant protection. Studies have indicated that vitamin E supplementation decreases the incidence of intraventricular haemorrhage and of retinopathy of prematurity in pre-terms, but may increase the risk of sepsis and necrotizing enterocolitis by impairing normal oxygendependent antimicrobial defences.
Diseases
Nonetheless, as an initial primary treatment we recommend that total/near total thyroidectomy should be done. Surgery for nodal metastases As to the management of cervical nodal metastases, surgical removal of these nodes is generally advocated. However, the extent of the neck dissection for nodal clearance appears controversial. Restricted surgery for removal of the neck nodes has been suggested by some as the residual nodal disease left after conservative surgery can be effectively treated by 131I, primarily because nodal disease in children concentrates 131I avidly [9. They advise that the surgery in children and adolescents should be similar to that in adults. In the absence of clinically palpable disease (about 33% of the patients have occult microscopic nodal involvement) a prophylactic neck nodal dissection had been recommended in the past. However, prophylactic neck nodal dissection has failed to prevent relapse in 22% of the cases [9. If these nodes become palpable later, removal of nodal metastases at relapse has been considered as adequate salvage treatment. Surgical morbidity Radical neck dissection and total thyroidectomy are bound to lead to several complications. The major complications are permanent hypocalcemia due to hypoparathyroidism which occurs in 7-46% of children (Table 9. This variable incidence is due to improved surgical techniques and experiences gained by surgeons in procedures of total thyroidectomy [9. Another major complication is permanent recurrent laryngeal nerve paralysis which is reported to be as high as 14% by La Quagila and associates [9. Some less important complications include minor bleeding, facial oedema, transient hypocalcemia, hypertrophied scar and transient recurrent laryngeal nerve paralysis. Radioiodine treatment Differentiated thyroid carcinoma in childhood has been considered to have a favourable prognosis. Radioiodine treatment has been therefore considered unnecessary by many investigators. Radioiodine is therefore being advocated in cases where the tumour is invasive and unresectable and/or there are distant metastases. Moreover, 131I therapy for ablating residual thyroid tissue is a subject of considerable controversy. Residual thyroid tissue Low incidence of recurrences in children who have undergone total/near total thyroidectomy followed by 131I therapy has been observed. In order to facilitate the 131 I concentration by pulmonary metastases it is mandatory to ablate the competing residual thyroid tissue left behind after surgery. As the primary tumour is invasive and the incidence of 85 metastases to nodes and lungs is high, the recurrence at a later stage could be avoided if the remnant tissue is ablated. In most of the cases 131I treatment for residual thyroid tissue is effective with only a single therapy [9. Nodal metastases the non-palpable cervical nodal metastases, if present after surgery, are responsive to 131I and a complete response is seen in almost 66-100% of the cases [9. Incidence of nodal recurrence in 131I treated patients is lower than the reported range of 24-34% in patients not given 131I [9. Pulmonary metastases There is a greater consensus regarding the need to give 131I for lung metastases in comparison with that of treating remnant thyroid tissue. It is known that 131I concentration in clinically stable lung metastases may persist for many years [9. Although 131I treatment for ablating residual tissue as well as pulmonary metastases has been found to be safe, several treatments over a number of years can rarely result in radiationinduced fibrosis leading to pulmonary insufficiency. Retrospectively, it appears that patients who have radiographically stable pulmonary metastases or minimal 131I concentration may be monitored conservatively with thyroglobulin (Tg) measurement, chest X ray and pulmonary function tests without further 131I therapy, albeit in children X ray is not a good modality to detect early disease in lungs. Tumour response to radioiodine therapy and possible adverse effect Overall, the radioiodine therapy in children is effective and gives long term disease-free survival.
Therefore, blood glucose levels should be monitored hourly (as needed) for 4 to 6 hours following insulin administration, and dextrose should be administered as necessary. Bicarbonate therapy can also be used to correct severe hyperkalemia because increased blood pH causes intracellular hydrogen ions to exit cells in exchange for potassium, which shifts intracellularly. Use of calcium, insulin, and bicarbonate is reserved for life-threatening hyperkalemia; appropriate fluid therapy is the cornerstone of treating hypoadrenocorticism and hyperkalemia. This is only an adjunctive treatment: It does not lower potassium levels and is merely cardioprotective. Therefore, primary therapy aimed at volume expansion and lowering blood potassium levels should be instituted in conjunction with calcium gluconate administration. Others recommend correction to 14 mEq/L, which can be achieved by changing "12" to "14" in the above equation. Glucocorticoid deficiency can independently cause or contribute to dehydration and shock because lack of cortisol decreases vascular sensitivity to catecholamines. Thus glucocorticoid therapy should be instituted in combination with fluid therapy. Because hypoadrenocorticism manifests in many ways, other symptomatic therapies may be indicated in patients with acute disease. Mental status, pulse rate and quality, heart rate, and capillary refill time should be evaluated. Fluid rates should be adjusted to correct dehydration and azotemia and keep up with maintenance requirements and ongoing losses. Electrolyte concentrations should be measured before fluid therapy is initiated (if possible), following initial fluid resuscitation and then every 1 to 2 hours as needed until the patient is hemodynamically stable and potassium levels are out of the life-threatening range. Electrocardiography should also be used to monitor hyperkalemic patients with arrhythmias until the electrocardiogram normalizes. The electrocardiogram and blood urea nitrogen concentrations should also begin to return to normal. If potassium levels are high and sodium levels low at this point, the dose should be increased by 5% to 10% at its next administration. If the potassium level is low and sodium level is high, the dose should be decreased. February 2005 Dose changes affect peak activity of the drug but do not affect duration of activity. Electrolyte levels should be checked again after 25 days to monitor the duration of efficacy. High potassium and/or low sodium concentrations indicate that the interval must be decreased by 1 day. Following initial stabilization, the frequency of administration may sometimes be slowly lengthened to 26 to 30 days. Furthermore, Feldman and Nelson1 warn that using lower doses may be risky and may precipitate an addisonian crisis. The dog should be rechecked weekly after the initial crisis until electrolyte levels stabilize and then two to three times annually. Therefore, only 50% of dogs that receive fludrocortisone require additional prednisone supplementation. The glucocorticoid property of fludrocortisone is often responsible for the most common side effects associated with the drug-polyuria and polydipsia. If a dog develops polyuria and polydipsia while receiving fludrocortisone, salt supplementation should first be eliminated and additional prednisone should be tapered and discontinued without causing signs of hypocortisolism (if possible). In addition to occasionally causing polyuria and polydipsia, the glucocorticoid activity of fludrocortisone can also cause mild to moderate asymptomatic elevations in liver enzymes. Prices for both the starting and median maintenance doses of fludrocortisone have been calculated, although the dose may actually be greater for an individual patient. Owners should be instructed on how much to give during these periods (including hospitalization for another ailment or surgery), and administration of parenteral steroids by clients during an emergency is an option. Because dogs with secondary or atypical hypoadrenocorticism are only corticosteroid deficient, only prednisone must be administered. The same protocol as that for corticosteroid administration in primary hypoadrenocorticism should be used.
Stabilize extremity then rotate catheter & syringe clockwise while pulling straight back. Don sterile protective equipment (technically only need gloves, mask, bouffant cap) and clean skin vigorously with chlorhexidine. A sterile field is not technically required but may drape the area w/ a sterile sheet or towels. May attach a 2nd 30cc syringe to drain additional fluid for sx relief pending size of effusion. Make lidocaine wheal w/ 25G, then inject track (aspiration before injecting, goal is not spinal anesthesia). If flow slows, try rotating needle or minimally advancing or withdrawing with stylet in place. Identify: Height of effusion determined by auscultation & percussion of chest wall. Prep & drape: thoracentesis kit, put on sterile gown and gloves, sterilize patient w/ chlorhexidine, then drape 4. Using 22G needle, walk the needle over superior aspect of the rib while intermittently aspirating and injecting perpendicular to the pleural space 6. When aspirated pleural fluid, withdraw slightly then anesthetize the parietal pleura (highly sensitize) with 2-3cc of lidocaine. Attach 18G over-the-needle catheter to syringe & advance over superior aspect of the rib, pulling back while advancing 8. When fluid aspirated, stop advancing & guide plastic catheter over needle Catheter has valve preventing fluid or air from entering the pleural space, so may use both hands to prepare for your next step 9. Attach 60 cc syringe to 3-way stopcock connected to catheter, withdraw full syringe of fluid, and put in appropriate tubes for lab & micro studies 10. Aspirate fluid slowly into the syringe and inject back into bag, never fully empty the syringe as it can lead to difficulty on repeat aspiration. When done, withdraw catheter while patient is humming (to avoid air entry into pleural space); cover site with occlusive dressing 13. Hemothorax/intercostal vessel injury: risk if inferior approach to rib or elderly (tortuous vessels). Vasovagal Syncope/Pleural Shock: Caused by needle penetrating parietal pleura; supportive care 4. A pericardial pigtail catheter is often left in for 24-72h to allow for serial drainage, preventing re-accumulation and repeated procedures. Recommendations are often found in the report from the cath lab when the drain was initially placed. Holding the sterilized area, take catheter from nursing and sterilize remaining portion 3. Place sterile towels around and underneath distal catheter and stopcock, and lay catheter down 4. Hold up flush port; nursing will connect heparin syringe (syringe itself is not sterile) to open/sterilized tip, turn stopcock to the remaining capped valve, and infuse 2cc heparin.
Syndromes
Many day-to-day complaints are also unknowingly caused by delayed food sensitivities: cloudy thinking, inability to concentrate, lethargy, headaches, migraine, joint pain, muscle weakness, depression, chronic sinus issues, plugged ears or chronic ear infections, weight gain, dark circles under your eyes, rosy cheeks, acne, and oddly, cravings for the food you are allergic or sensitive to , are all common food allergy reactions. Leaky Gut Syndrome and Adrenal Fatigue When you have multiple food sensitivities, the lining of your stomach and intestines becomes irritated and inflamed, and if you are continually eating something or other that is irritating, it never has a chance to rest and heal, leading to stomach pain, or heartburn, or gas, or other digestive discomfort. You may even develop "Leaky Gut Syndrome", which is an increased permeability of the intestinal wall (or holes) that allows undigested proteins, fats, toxins and Dr. This irritation triggers increased cortisol secretion as your adrenal glands are alerted to an increase in histamine levels (the histamine causes the inflammation, the cortisol is an anti-inflammatory). Mucosal barriers line the surfaces of your eyes, ears, nose, sinuses, mouth, throat, gastrointestinal tract (from mouth to anus), respiratory tract, urogenital tract, and the vaginal tract. The ozone layer lets the right amount of sunlight through, sustaining life on earth; your mucosal barriers allow nutrients through, sustaining your health. However, just as the earth has a damaged ozone layer, many of us have compromised mucosal barriers that fail to protect us from infectious agents, allergens, and other harmful substances. Commonly, those who get sick, their mucosal barriers were unable to encapsulate the offending organism and eliminate them. The structures of the mucosal barriers vary in appearance depending on their locations in the body. Perhaps the most important one is the barrier lining your intestines, given its sheer enormity and its role in digestion and immunity. What is important is that you appreciate their significance and vulnerability when exposed to chronic stress, especially in regards to the gastrointestinal tract. A structurally sound mucosal barrier is vital to preventing infection and illness-and not just, because it acts as a border through which harmful substances are denied access. A healthy mucosal barrier contains adequate amounts of secretory antibodies, which are proteins released to neutralize foreign substances, like undigested food, infectious organisms, chemicals that have entered the body. These mucosal antibodies are known as immunoglobulins, with the most abundant being secretory immunoglobulin A, or secretory IgA. All of these antibodies recognize and neutralize commonly encountered pathogens such as bacteria, fungi, parasites, viruses, and yeast. When secretory IgA levels are adequate, food proteins are efficiently processed and the potential for adverse reactions, including allergies and food sensitivities, are reduced. The longer you remain in fight-or- flight while under chronic stress, the longer it takes for the immunocytes to recover and stabilize secretory IgA production. Simply put, prolonged stress results in adrenal exhaustion and depressed first line immune defense opening the door for opportunistic infections. Jerry Jerry, a 40-year-old single male, suffered from chronic fatigue, fibromyalgia, chronic intestinal yeast infections, and depression. He had gone for extensive laboratory testing and had seen numerous doctors, all to no avail. Although his growth hormone profile was at the low end of the reference range for a man his age, it was recommended to him that taking human growth hormone supplements would not address the root cause of his complex health problems. Having struggled with no relief for almost 10 years, Jerry felt helpless and had lost hope; he seemed on the verge of a mental, emotional, and physical breakdown. A complete review was done looking at his complete medical history: physical examinations, laboratory tests, current and past symptoms, family history, home environment, hobbies, and so on. While many doctors had run many laboratory tests, there was no rationale to the testing. The resulting data was incomplete and, as a result, none of his previous doctors had formed a meaningful diagnosis. Lacking integrated data, the pieces of the puzzle could not be put together, and the source of his problems had remained a mystery for many years. Because none of the laboratory testing ordered by other doctors pointed conclusively to the cause of his chronic fatigue, Jerry was simply told that he was "too stressed out. The psychiatrist emphatically stated that his problems were not psychologically based. As seen numerous times, the results provided the missing links to his health crisis. Jerry had advanced adrenal exhaustion and associated low thyroid output, which explained his chronic fatigue. The hyper motility was caused by gluten intolerance and two parasitic infections, Giardia lamella and Cryptosporidium parvum.
Endometriosis is often clinically silent, however, and can only be excluded definitively by laparoscopy. However, the etiology is not ascertained in up to half of men with suspected male factor infertility. Testosterone levels should be measured if the sperm count is low on repeated examination or if there is clinical evidence of hypogonadism. In many situations, including unexplained infertility, mild to moderate endometriosis, and/or borderline semen parameters, a stepwise approach to infertility is optimal, beginning with low-risk interventions and moving to more invasive, higher-risk interventions only if necessary. Dopamine agonists, for example, may be indicated in patients with hyperprolactinemia (Chap. The efficacy of clomiphene for ovulation induction is highly dependent on patient selection. Clomiphene citrate is less successful in patients with hypogonadotropic hypogonadism. Aromatase inhibitors have also been investigated for the treatment of infertility. Initial studies are promising, but these medications have not been approved for this indication. Disadvantages include a significant risk of multiple gestation and the risk of ovarian hyperstimulation, but careful monitoring and a conservative approach to ovarian stimulation reduce these risks. Pregnancy rates are similar to those following the use of gonadotropins, but rates of multiple gestation are lower and there is virtually no risk of ovarian hyperstimulation. None of these methods are effective in women with premature ovarian failure in whom donor oocyte or adoption are the methods of choice. Medical management of advanced stages of endometriosis is widely used for symptom control but has not been shown to enhance fertility. In moderate to severe endometriosis, conservative surgery is associated with pregnancy rates of 50 and 39%, respectively, compared with rates of 25 and 5% with expectant management alone. Teenage pregnancies continue to represent a serious public health problem in the United States, with >1 million unintended pregnancies each year-a significantly greater incidence than in other industrialized nations. Only 15% of couples report having unprotected sexual intercourse in the past 3 months. A reversible form of contraception is used by >50% of couples, while sterilization (in either the male or female) has been employed as a permanent form of contraception by over a third of couples. Pregnancy termination is relatively safe when directed by health care professionals but is rarely the option of choice. No single contraceptive method is ideal, although all are safer than carrying a pregnancy to term. The effectiveness of a given method of contraception depends not only on the efficacy of the method itself. Discrepancies between theoretical and actual effectiveness emphasize the importance of patient education and compliance when considering various forms of contraception (Table 10-5). Knowledge of the advantages and disadvantages of each contraceptive is essential for counseling an individual about the methods that are safest and most consistent with his or her lifestyle. However, their effectiveness is highly dependent on adherence and proper use (Table 10-5). Sterilization refers to a procedure that prevents fertilization by surgical interruption of the fallopian tubes in women or the vas deferens in men. Although tubal ligation and vasectomy are potentially reversible, these procedures should be considered permanent and should not be undertaken without patient counseling. Several methods of tubal ligation have been developed, all of which are highly effective with a 10-year cumulative pregnancy rate of 1. However, when pregnancy does occur, the risk of ectopic pregnancy may be as high as 30%. The success rate of tubal reanastomosis depends on the method used, but even after successful reversal, the risk of ectopic pregnancy remains high.
Thyroid Cancer There have been multiple studies, prospective and retrospective, for the commercially available molecular classifiers for indeterminate and suspected malignant thyroid nodules, such as the Afirma Gene Expression Classifier, and next generation sequencing test panels, such as ThyGenX/ThyraMir and ThyroSeq v3. The samples were categorized using the Bethesda System for reporting thyroid cytology into B3 and B4 nodules. Molecular Oncology Testing for Cancer Diagnosis, Prognosis, and Treatment Decisions UnitedHealthcare Commercial Medical Policy Proprietary Information of UnitedHealthcare. The reference standard for determination of benign or malignant nodules was the histopathology of the thyroidectomy specimen. Outside this range it is unlikely the test can provide information that would alter management. In addition, the Afirma 167 gene classifier appears to be less accurate in nodules with that contain benign Hurthle cells. In several studies that examined the cytology population percentage of Hurthle cells, the test was more likely to report a suspicious for malignancy result for which the patient was sent for surgery, and therefore limited the clinical utility of the test (Harrell and Bimston, 2014, Brauner et al. Compared to a 74% previous historical rate of surgery for cytologically indeterminate nodules, the operative rate fell to 7. According to the authors, these reasons are concordant with those typically given for operation on cytologically benign nodules. Similar findings also were obtained for suspicious for follicular neoplasm-follicular neoplasm lesions. After adding a cohort of tissue samples, the authors found 38/76 (50%) of histopathology malignant samples and 15/75 (20%) of benign samples to harbor a genetic alterations. During 36 months of Molecular Oncology Testing for Cancer Diagnosis, Prognosis, and Treatment Decisions UnitedHealthcare Commercial Medical Policy Proprietary Information of UnitedHealthcare. Limitations of this study are small patient population and non-randomization of patients. The samples consisted of an initial set of 235 aspirates representing 118 nodules with benign cytology, including 13 with surgical outcome (12 benign, 1 malignant), 73 with malignant cytology, including 51 with surgical outcome (1 benign, 50 malignant), and 44 with indeterminate cytology, all with available surgical outcome. The second set of aspirates consisted of 42 distinct nodules with indeterminate cytology and surgical outcome. The authors found that standard mutation testing alone had a sensitivity of 61%, consistent with the literature. The authors reported the diagnostic sensitivity and specificity of the combined algorithm was 89% and 85%, respectively. If molecular testing is being considered, patients should be counseled regarding the potential benefits and limitations of testing and about the possible uncertainties in the therapeutic and long-term clinical implications of results. Informed patient preference and feasibility should be considered in clinical decision-making. They conclude that there is currently no single optimal molecular test that can definitively rule in or rule out malignancy in all cases of indeterminate cytology. They state that molecular profiling should be considered in nodules with indeterminate cytology, and not in those who are found to be clearly benign or malignant. They find that there is insufficient evidence either for, or against, gene expression classifiers. There is insufficient evidence to use molecular profiling to determine the extent of surgical interventions, or for use with low risk indeterminate cytology cases. Hematological Malignancies Leukemias Peterson et al (2015) conducted a study to determine the clinical utility and diagnostic yield, plus examine the rationale, of including microarray analysis in the diagnosis of hematological neoplasias. Nearly 90% of chromosome abnormalities found in the patients were also identified by microarray. Balanced rearrangements were not found by microarray, but of 19 rearrangements that appeared "balanced" by routine cytogenetics, 7 had alterations found by microarray at the breakpoints. Overall, 9 patients were found to have abnormalities not detected by routine cytogenetics. Arrays missed small deletions at 11q and 17p due to their limited sensitivity in Molecular Oncology Testing for Cancer Diagnosis, Prognosis, and Treatment Decisions UnitedHealthcare Commercial Medical Policy Proprietary Information of UnitedHealthcare. Ultimately the medium density array was validated for clinical use and was found in 98. The experts reviewed the literature and using an evidence-based methodology intended to meet recommendations from the Institute of Medicine, a set of guidelines was developed. The guidelines were reviewed by an independent panel and were made available for public comment.
When reduced to near-normal weight and maintained there for a while, (some) obese individuals have lower energy expenditure than (some) lean individuals. There is also a tendency for those who will develop obesity as infants or children to have lower resting energy expenditure rates than those who remain lean. The physiologic basis for variable rates of energy expenditure (at a given body weight and level of energy intake) is essentially unknown. A mutation in the human 3-adrenergic receptor may be associated with increased risk of obesity and/or insulin resistance in certain (but not all) populations. It is the thermogenesis that accompanies physical activities other than volitional exercise, such as the activities of daily living, fidgeting, spontaneous muscle contraction, and maintaining posture. Leptin in Typical Obesity the vast majority of obese persons have increased leptin levels but do not have mutations of either leptin or its receptor. The mechanism for leptin resistance, and whether it can be overcome by raising leptin levels, is not yet established. Some data suggest that leptin may not effectively cross the blood-brain barrier as levels rise. It is also apparent that the degree to which obesity affects particular organ systems is influenced by susceptibility genes that vary in the population. Insulin Resistance and Type 2 Diabetes Mellitus Hyperinsulinemia and insulin resistance are pervasive features of obesity, increasing with weight gain and diminishing with weight loss (Chap. Insulin resistance is more strongly linked to intraabdominal fat than to fat in other depots. The molecular link between obesity and insulin resistance in tissues such as fat, muscle, and liver has been sought for many years. Despite nearly universal insulin resistance, most obese individuals do not develop diabetes, suggesting that the onset of diabetes requires an interaction between obesity-induced insulin resistance and other factors that predispose to diabetes, such as impaired insulin secretion (Chap. Obesity, however, is a major risk factor for diabetes, and as many as 80% of patients with type 2 diabetes mellitus are obese. Weight loss and exercise, even of modest degree, are associated with increased insulin sensitivity and often improve glucose control in diabetes. Reproductive Disorders Disorders that affect the reproductive axis are associated with obesity in both men and women. Male hypogonadism is associated with increased adipose tissue, often distributed in a pattern more typical of females. However, masculinization, libido, potency, and spermatogenesis are preserved in most of these individuals. Free testosterone may be decreased in morbidly obese men whose weight is >200% ideal body weight. Obesity has long been associated with menstrual abnormalities in women, particularly in women with upper body obesity (Chap. Obesity and overweight together are the second leading cause of preventable death in the United States, accounting for 300,000 deaths per year. The increased conversion of androstenedione to estrogen, which occurs to a greater degree in women with lower body obesity, may contribute to the increased incidence of uterine cancer in postmenopausal women with obesity. When the additional effects of hypertension and glucose intolerance associated with obesity are included, the adverse impact of obesity is even more evident. Measurement of blood pressure in the obese requires use of a larger cuff size to avoid artifactual increases. Obesity-induced hypertension is associated with increased peripheral resistance and cardiac output, increased sympathetic nervous system tone, increased salt sensitivity, and insulin-mediated salt retention; it is often responsive to modest weight loss. Pulmonary Disease Obesity may be associated with a number of pulmonary abnormalities. These include reduced chest wall compliance, increased work of breathing, increased minute ventilation due to increased metabolic rate, and decreased functional residual capacity and expiratory reserve volume. Severe obesity may be associated with obstructive sleep apnea and the "obesity hypoventilation syndrome" with attenuated hypoxic and hypercapnic ventilatory responses. Sleep apnea can be obstructive (most common), central, or mixed and is associated with hypertension. Gallstones Obesity is associated with enhanced biliary secretion of cholesterol, supersaturation of bile, and a higher incidence of gallstones, particularly cholesterol gallstones.
The progression of retinopathy in individuals in the Diabetes Control and Complications Trial is graphed as a function of the length of follow-up with different curves for different A1C values. This study utilized multiple treatment regimens and monitored the effect of intensive glycemic control and risk factor treatment on the development of diabetic complications. In addition, individuals were randomly assigned to different antihypertensive regimens. In fact, the beneficial effects of blood pressure control were greater than the beneficial effects of glycemic control. Blindness is primarily the result of progressive diabetic retinopathy and clinically significant macular edema. Diabetic retinopathy is classified into two stages: nonproliferative and proliferative. Nonproliferative diabetic retinopathy usually appears late in the first decade or early in the second decade of the disease and is marked by retinal vascular microaneurysms, blot hemorrhages, and cotton wool spots. Mild nonproliferative retinopathy progresses to more extensive disease, characterized by changes in venous vessel caliber, intraretinal microvascular abnormalities, and more numerous microaneurysms and hemorrhages. The pathophysiologic mechanisms invoked in nonproliferative retinopathy include loss of retinal pericytes, increased retinal vascular permeability, alterations in retinal blood flow, and abnormal retinal microvasculature, all of which lead to retinal ischemia. The appearance of neovascularization in response to retinal hypoxia is the hallmark of proliferative diabetic retinopathy. These newly formed vessels appear near the optic nerve and/or macula and rupture easily, leading to vitreous hemorrhage, fibrosis, and ultimately retinal detachment. Not all individuals with nonproliferative retinopathy develop proliferative retinopathy, but the more severe the nonproliferative disease, the greater the chance of evolution to proliferative retinopathy within 5 years. This creates an important opportunity for early detection and treatment of diabetic retinopathy. Clinically significant macular edema can occur when only nonproliferative retinopathy is present. Fluorescein angiography is useful to detect macular edema, which is associated with a 25% chance of moderate visual loss over the next 3 years. This patient has neovascular vessels proliferating from the optic disc, requiring urgent panretinal laser photocoagulation. Fortunately, this progression is temporary, and in the long term, improved glycemic control is associated with less diabetic retinopathy. Individuals with known retinopathy are candidates for prophylactic photocoagulation when initiating intensive therapy. Once advanced retinopathy is present, improved glycemic control imparts less benefit, though adequate ophthalmologic care can prevent most blindness. Routine, 286 nondilated eye examinations by the primary care provider or diabetes specialist are inadequate to detect diabetic eye disease, which requires an ophthalmologist for optimal care of these disorders. Proliferative retinopathy is usually treated with panretinal laser photocoagulation, whereas macular edema is treated with focal laser photocoagulation. Although exercise has not been conclusively shown to worsen proliferative diabetic retinopathy, most ophthalmologists advise individuals with advanced diabetic eye disease to limit physical activities associated with repeated Valsalva maneuvers. Aspirin therapy (650 mg/d) does not appear to influence the natural history of diabetic retinopathy. Like other microvascular complications, the pathogenesis of diabetic nephropathy is related to chronic hyperglycemia. In some individuals with type 1 diabetes and microalbuminuria of short duration, the microalbuminuria regresses. Once macroalbuminuria develops, blood pressure rises slightly and the pathologic changes are likely irreversible. Risk factors for radiocontrast-induced nephrotoxicity are preexisting nephropathy and volume depletion. As part of comprehensive diabetes care, microalbuminuria should be detected at an early stage when effective therapies can be instituted. Non-diabetes-related conditions that might increase microalbuminuria are urinary tract infection, hematuria, heart failure, febrile illness, severe hyperglycemia, severe hypertension, and vigorous exercise.
References:
