The reconstituted preparation results in a colourless to pale yellow transparent solution cardiovascular system blood vessels quizlet order procardia 30mg online. Parenteral drug products should be inspected visually for particulates and discolouration prior to administration cardiovascular jobs cheap procardia 30 mg without prescription. Patients should be observed for fever and chills or other infusion associated symptoms arteries right lateral view discount 30mg procardia overnight delivery. For management of a suspected drug overdose coronary heart improvement program buy 30mg procardia otc, contact your regional Poison Control Centre cardiovascular fitness examples discount 30mg procardia otc. Pharmacokinetics Page 76 of 126 the pharmacokinetics of trastuzumab have been studied in breast cancer patients with metastatic disease cardiovascular system diagnosis purchase 30 mg procardia. In phase I studies, short duration intravenous infusions of 10, 50, 100, 250 and 500 mg once weekly in patients demonstrated dose-dependent pharmacokinetics at doses below 100 mg. The inter-patient variability in clearance and volume of distribution was 43% and 29% (co-efficient of variation), respectively. It should be noted that these values represent free and dimer complexes of trastuzumab as the assay utilized was unable to detect the trimer complex. Patients with higher baseline shed antigen levels were more likely to have lower serum trough concentrations of trastuzumab, however, with weekly dosing, most patients with elevated shed antigen levels achieved target serum concentrations by week 6. Data suggest that the disposition of trastuzumab is not altered based on age or serum creatinine (up to 2. Steady state concentrations should be reached by 49 days, (four equilibrium half lives) or approximately 7 weeks. Special Populations and Conditions Detailed pharmacokinetic studies in geriatric patients and those with renal or hepatic impairment have not been carried out. The product is not intended to be stored after dilution unless the dilution has taken place under controlled and validated aseptic conditions. Disposal of unused/expired medicines the release of pharmaceuticals in the environment should be minimized. Medicines should not be disposed of via wastewater and disposal through household waste should be avoided. Local requirements should be followed for the disposal process of unused/expired medicines. Prior radiotherapy required for nodal (axillary, internal mammary) or pT4 disease. Whole breast irradiation required during study; partial breast or internal mammary radiation prohibited. The efficacy results from the interim efficacy analysis crossed the protocol pre-specified statistical boundary of 0. This translates into an absolute benefit in terms of an 8 year disease free survival rate of 6. The rate of secondary cardiac endpoints was increased in the 2-year treatment arm (8. More patients experienced at least one grade 3 or 4 adverse event in the 2-year treatment arm (20. The benefit in disease-free survival was seen in all subgroups analysed (Please see Figure 2). Disease-free survival was the pre-specified primary endpoint of the combined efficacy analysis of these studies. A total of 3752 patients were evaluable for analysis of efficacy at the time of the definitive disease-free survival analysis. Disease-free survival was defined as the time from randomization to recurrence, contralateral breast cancer or other second primary cancer, or death, whichever occurred first. Patients were eligible if they had 2+ or 3+ levels of overexpression (based on a 0 to 3+ scale) by immunohistochemical assessment of tumour tissue performed by a central testing lab. Of 222 patients enrolled, 68% had received prior adjuvant chemotherapy, 32% had one and 68% had received two prior chemotherapy regimens for metastatic disease, and 26% had received prior myeloablative treatment with hematopoietic rescue. Complete responses were observed only in patients with disease limited to skin and lymph nodes. The primary endpoint was overall survival which was defined as the time from the date of randomization to the date of death from any cause. At the time of the analysis a total of 349 randomized patients had died: 182 patients (62. Page 98 of 126 One year after the clinical cutoff date of the definitive efficacy and safety second interim analysis, updated overall survival analysis demonstrated that 446 patients had died: 225 patients (78%) in the control arm and 221 patients (75%) in the treatment arm. A total of 351 patients [60%] did not receive previous treatments for gastric cancer. Within a given tissue, these receptors are rarely if ever expressed individually, but are found in various combinations. Trastuzumab significantly reduced the percentage of cells undergoing S-phase and increased the percentage of cells in G0/G1. Moreover, a similar induction of the retinoblastoma-related protein, p130, was also observed. These data are consistent with the notion that the cytostatic effects of trastuzumab result from an inhibition of cell cycle progression. Molecules involved in cell adhesion are thought to play a critical role in malignant progression. One of these molecules, E-cadherin, plays a central role in maintaining epithelial cell morphology. Trastuzumab - Mediated Receptor Down Modulation: Downregulation of receptor-ligand complexes is thought to be a major attenuation mechanism for receptor-induced signaling. Interaction with this low affinity Fc receptor is avidity driven; opsonization of tumour cell targets with trastuzumab was required for activity. Statistically superior antitumour efficacy was observed in vivo with trastuzumab in combination with cisplatin, doxorubicin, paclitaxel, cyclophosphamide, methotrexate, etoposide, and vinblastine. For the drug 5fluorouracil, which was antagonistic with trastuzumab in vitro, the combination in vivo was superior to trastuzumab alone but not to 5-fluorouracil alone. The combination of paclitaxel and trastuzumab resulted in the highest tumour growth inhibition and had a significantly superior complete tumour regression rate when compared to paclitaxel or trastuzumab alone. Nonclinical Pharmacokinetics: Nonclinical pharmacokinetic data collected in mice and monkeys indicate that trastuzumab is eliminated slowly from the serum. In mice, trastuzumab displayed dose-independent pharmacokinetics following single doses. Single-dose data in monkeys demonstrated evidence of dose-dependent kinetics, in that half-life increased and clearance decreased at higher single doses. Monkeys also showed non-linear kinetics between single- and multiple-dose administration. Multiple doses between approximately 2-25 mg/kg resulted in similar kinetics in monkeys. The initial volume of distribution approximates plasma volume, and in monkeys the estimated steady-state volume is not more than approximately 60% greater. Disposition of trastuzumab is comprised of both clearance and distribution processes. It is difficult to label a particular disposition process as a clearance or distribution process because one involves irreversible binding leading to trastuzumab degradation and the other involves reversible binding, which permits trastuzumab survival. Determination of shed antigen in baseline serum samples revealed that 64% (286/447) of patients had detectable shed antigen, which ranged as high as 1880 ng/mL (median = 11 ng/mL). Patients with higher baseline shed antigen levels were more likely to have lower serum trough concentrations. However, with weekly dosing, most patients with elevated shed antigen levels achieved target serum concentrations of trastuzumab by week 6. In one study, mean serum trough concentrations of trastuzumab, when administered in combination with paclitaxel, were consistently elevated approximately 1. Mean trough and peak trastuzumab serum concentrations at week 20 in patients in the combination study H0648g were 85. However, the estimates of the pharmacokinetic parameters in the selected population pharmacokinetic model were insensitive to concomitant chemotherapy (paclitaxel or anthracycline/cyclophosphamide). In primate studies, administration of trastuzumab with paclitaxel resulted in a reduction in trastuzumab clearance. Serum levels of trastuzumab in combination with cisplatin, doxorubicin or epirubicin plus cyclophosphamide did not suggest any interactions; no formal drug interaction studies were performed. The in vitro tissue binding profile of trastuzumab to monkey tissues demonstrated that the monkey was an appropriate model for comprehensive toxicity testing. Acute Toxicity Studies: In acute dose studies, trastuzumab was well tolerated and produced no evidence of systemic toxicity at any dose tested, including the highest dose that could be delivered of a 5 mg/mL formulation. Intravenous administration of trastuzumab as a single dose of 94 mg/kg (mice), or 47-50 mg/kg (monkeys), produced no findings of toxicologic significance in any parameter evaluated. Bridging studies conducted in monkeys to evaluate the safety and pharmacokinetics of trastuzumab, produced by optimization of the manufacturing process including a cell line change (from H2 to H13), revealed no evidence of acute toxicity or changes in pharmacokinetic disposition in monkeys. Trastuzumab produced from a subsequent manufacturing scale up and formulation change (lyophilization) resulted in comparable pharmacokinetic profiles in monkeys and had no effect on safety endpoints. The findings from the acute toxicity studies with trastuzumab are summarized in Error! Multidose Toxicity Studies: In multiple-dose studies, trastuzumab was well tolerated and produced no evidence of systemic toxicity at any dose tested, including the highest dose that could be delivered of 25 mg/kg. Intravenous administration of trastuzumab as multiple intravenous doses in monkeys of up to 25 mg/kg given weekly for 26 weeks, or twice-weekly for up to 12 weeks, produced no findings of toxicologic significance in any parameter evaluated. The following is a summary of the electrocardiographic findings that were statistically significant in this study from control. In female monkeys, at weeks 5 and 21, the Q-T interval for the 5 mg/kg dose was 0. The heart rate, at week 17, for the 5 and 25 mg/kg dose, was 145 and 160 beats/minute, respectively (Vehicle 183 beats/minute). There were no statistically significant electrocardiographic findings in female monkeys at weeks 9, 13, 17 and 26, and in male monkeys at weeks 5, 13, 21 and 26. In male monkeys during the recovery phase (weeks 30 and 34), the heart rate for the 25 mg/kg dose was 190 beats/minute (Vehicle 160 beats/minute) and 180 beats/minute (Vehicle 200 beats/minute), respectively; while the Q-T interval was 0. In female monkeys, at weeks 30 and 34, the heart rate was 190 beats/minute (Vehicle 210 beats/minute) and 140 beats/minute (Vehicle 180 beats/minute), respectively; while the Q-T interval was 0. Although, administration of trastuzumab was associated with a mild reduction in heart rate in some male monkeys receiving 5 or 25 mg/kg, this was not considered toxicologically significant since bradycardia was not present in these monkeys. There was no toxicological significance of the aberrant ventricular complexes seen in monkeys treated with trastuzumab since these were not seen broadly in all treated monkeys. The findings from the multidose toxicity studies with trastuzumab are summarized in Error! Special Toxicity Studies: Specific toxicity studies performed with trastuzumab included: issue cross-reactivity studies in human and monkey tissue, immunogenicity, drug interaction, and local tolerance studies, in vitro hemolytic potential/blood compatibility studies, and a systemic toxicity study in mice with the formulation component trehalose. No gross or histopathologic changes were observed in tissues which demonstrated trastuzumab binding in the tissue cross-reactivity studies. Page 106 of 126 In addition, trehalose, a component of the lyophilized formulation, produced no evidence of clinical or anatomical toxicity when given daily to mice at intravenous doses of up to 1 g/kg. In local tolerance studies conducted in rabbits, no gross or histopathologic evidence of irritative potential was noted following intravenous administration of the liquid or lyophilized trastuzumab formulations at a concentration of 5 mg/mL. Both the liquid and lyophilized formulations are compatible with whole blood, serum, and plasma obtained from humans and monkeys. Page 107 of 126 Table 38: Overall Summary of Nonclinical Acute Toxicity Studies with Trastuzumab Study No. Page 108 of 126 Table 39: Overall Summary of Nonclinical Acute Toxicity Studies with Trastuzumab Study No. All animals survived the study, and no test material-related overt clinical signs of toxicity were observed. Furthermore, there were no statistically significant or otherwise notable differences between the two groups that might be attributed to the different formulations. This study was conducted to support the clinical use of trastuzumab produced by a scaled-up manufacturing process, trastuzumab (H13-12K) this study was conducted to support the clinical use of lyophilized trastuzumab. Page 110 of 126 Table 41: Overall Summary of Nonclinical Special Toxicity Studies with Trastuzumab Study No. Murine antibody muMab 4D5 reacts in normal tissues paralleling the patterns observed for trastuzumab. Differences in staining may reflect methodological conditions employed to detect these two antibodies. The patterns of immunoreactivities observed in human tumours are almost identical for these two antibodies. The pattern of staining observed with humanized trastuzumab was similar in distribution, but inconsistent and less intense. The differences in staining observed between trastuzumab and muMab 4D5 may be attributed to methodological differences in detection of the two antibodies. Trastuzumab, trastuzumab (high glutamine variant), trastuzumab (low glutamine variant), and trastuzumab (arginine variant) were not immunogenic based on expected pharmacokinetics and a lack of antibody response, whereas muMab 4D5 was considered immunogenic in the cynomolgus monkey. Page 111 of 126 Table 42: Overall Summary of Nonclinical Special Toxicity Studies with Trastuzumab Study No. Taxol is a registered Trade-Mark of Bristol-Myers Squibb Company Cytoxan is a registered Trade-Mark of Mead Johnson & Company Page 112 of 126 Table 43: Overall Summary of Nonclinical Special Toxicity Studies with Trastuzumab Study No. A single challenge dose was administered to those monkeys (in Study 92-458-1450) that had received 6 months of weekly injections of the high or low glutamine variant-containing trastuzumab (H2) preparations. When trastuzumab was administered during the period of organogenesis, fetal serum trastuzumab concentrations ranged from 10%-19% of maternal values. Administration during the last trimester was associated with trastuzumab fetal serum concentrations of approximately 33% of maternal concentrations. The difference in fetal serum trastuzumab concentrations obtained in the early and late gestational periods may be attributable to the time between trastuzumab administration and maternal/fetal blood sampling. However, an increase in fetal/maternal serum concentration ratio is consistent with an increase in immunoglobulin transfer rate observed as gestation progresses in both humans and in nonhuman primates.
Relevant prior and concomitant medications included the use of simvastatin capillaries under nose generic procardia 30mg, lisinopril heart disease medicine discount procardia 30mg fast delivery, furosemide capillaries of the heart best procardia 30mg, aspirin arteries known resistance vessels cheap 30mg procardia, cilostazol cardiovascular test discount 30mg procardia visa, metformin capillaries leaking blood buy discount procardia 30 mg on line, and glimepiride. Due to the presence of comorbidities, including peripheral vascular disease, concomitant loop diuretic use, and a reported Hgb concentration of 14. However, in the Placebo Pool, no subjects had Hct concentrations 65% (considered a critical value). For the cases occurring following at least a six-month of treatment exposure, malignancy was reported in 0. Based on my review of all the malignancy data (including premalignant conditions; Table 31), there did not appear to be any obvious trends or imbalances in the types of malignancies between treatment arms, and no new safety signals were identified. However, these data were limited in terms of assessing causal associations or tumor promoting properties for individual malignancies. Similarly, the abdominal ultrasound showed an enlarged pancreatic head along with gallstones. A cholecystectomy and two liver biopsies were performed on Day 245, and the subject was discharged on Day 246. The liver biopsy results showed a morphological and immunological profile consistent with adenocarcinoma of the liver (samples were positive for carcinoembryonic antigen, caudal type homeobox 2, keratin 18, keratin 17, and had isolated positive cells for keratin 20). Subject 0502213: a 47-year-old white male with T2D for approximately 11 years was randomized to the ertugliflozin15 mg/sitagliptin 100 mg. On Day 108 he was hospitalized for abdominal bloating/discomfort with nausea and vomiting, and discharged on this same day. On Day 115 he was readmitted with abdominal pain and obstructive jaundice (scleral icterus and abdominal tenderness). The subject did not have a history of alcohol abuse, chronic pancreatitis, or liver cirrhosis, and prior medication use was not relevant. The subject was scheduled to be transferred to another facility for further evaluation and management as well as surgical intervention as needed. An endoscopic ultrasound showed a round hypoechoic and heterogeneous mass (50x40 mm in diameter) in the pancreatic head, and fine needle biopsy confirmed adenocarcinoma. The subject underwent a rendezvous procedure (Day 123) with stenting of the common bile duct from liver to intestine. The subject was discharged on Day 125, with plans for follow-up discussion regarding therapeutic options. Due to the relatively short latency periods between the diagnosis of pancreatic carcinoma and treatment exposure. In the three trials that included ertugliflozin plus sitagliptin treatment arms, subjects were exposed to ertugliflozin plus sitagliptin combination therapy for a mean duration of approximately 173 days. Additionally, in ertugliflozin-treated male subjects, events of genital mycotic infection were more frequent in uncircumcised men (5. It is noted that four of eight male ertugliflozin-treated subjects with phimosis required circumcision. Thus, there is limited hypoglycemia data on the use of ertugliflozin in combination with these drugs in the entire patient population that may be exposed to ertugliflozin-containing products. Nevertheless, it is expected that ertugliflozin in combination with either of these would increase the risk for hypoglycemia. Except for the ertugliflozin plus sitagliptin factorial trial (P005/1019), in which hypoglycemia was observed in 9% (22/244) of subjects in the ertugliflozin 15 mg/sitagliptin 100 mg arm compared to 5. Adjudicated Hepatic Events the Applicant acknowledges that hepatic safety is a significant issue in drug development. One case (Subject 0502519) involved a 54-year-old male who presented with a pancreatic carcinoma on Day 242 (previously described in Section 8. None of these cases were adjudicated as confirmed pancreatitis (acute or chronic). Brief narrative summaries of the three ertugliflozin-treated subjects are as follows: Ertugliflozin 5 mg Arm: Subject 0502509: 55-year-old white female with T2D for approximately 14 years, randomized to ertugliflozin 5 mg in Trial P005/1019, was hospitalized on Day 98 for possible pancreatitis associated with a 3-week history of right upper abdominal quadrant pain (worse after meals) and progressive nausea, vomiting, diarrhea, dehydration and weight loss (approximately 5. Imaging (ultrasound and computed tomography scan) showed evidence of gallbladder stones/sludge consistent with acute on chronic cholecystitis. The urinalysis was significant for glucose, trace ketones, 1+ occult blood, leukocytes, and >100,000 cfu/mL of E. She underwent a laparoscopic cholecystectomy on Day 101, and was discharged on Day 103. Ertugliflozin 15 mg Arm: Subject 0200171: 64-year-old white male with T2D for approximately 24 years, receiving metformin 2000 mg daily, was randomized to ertugliflozin 15 mg arm in Trial P002/1013. The subject reported nausea and vomiting for 3 weeks, along with bilateral pedal edema, managed with promethazine and furosemide, respectively. I agree that there is insufficient information for this subject with long-standing T2D to determine a diagnosis of pancreatitis. Further, both promethazine167 and furosemide168,169 have both been associated with cholestatic jaundice. None of the events in the ertugliflozin-treated subjects appeared to be related to volume depletion and/or hemoconcentration. At the time of randomization his concomitant medications included indapamide/perindopril, atorvastatin, carvedilol, aspirin/bisoprolol, piracetam, pentoxifylline, and acenocoumarol. Predisposing and precipitating risk factors of ketoacidosis have not been well characterized, but may include known precipitating events of ketoacidosis. Determination as to whether a case met the prespecified case definition of ketoacidosis was based on independent review by each member, and majority (2/3) or complete (3/3) agreement. All three cases involved intercurrent illnesses (n=2 sepsis; and n=1 viral illness). She was subsequently hospitalized (Day 325) with a diagnosis of metabolic acidosis secondary to this event. She did not have a recent history of dietary changes or prior history of alcohol abuse, diabetic ketoacidosis, or ingestion of ethylene-glycol, salicylates, or methanol. There was no evidence of T1D or secondary causes of diabetes resulting in insulin deficiency. Relevant labs included blood ketones large amount (reference range: negative), sodium 125 and 128 mmol/L (136145 mmol/L), potassium 5. The urine cultures did not show any significant growth, and the urinalysis showed protein 0. The subject was diagnosed with diabetic ketoacidosis as a result of a bacterial infection. The study medication was interrupted from Day 329 to Day 365 due to the event of Klebsiella sepsis, and then permanently discontinued on Day 365 due to the event of metabolic acidosis. The investigator felt that the event of ketoacidosis was precipitated by a viral infection. Symptoms included acute high fever, right hypochondrium pain, and a poor appetite. Venous blood gas showed a mild metabolic acidosis, and an abdominal ultrasound showed an enlarged gallbladder with a thickened wall. She was diagnosed with acute cholecystitis, Streptococcus pneumonia sepsis, and diabetic ketoacidosis, and treated with intravenous fluids, insulin, and antibiotics. The investigator felt that the Streptococcus pneumoniae septicemia was the precipitating factor for the other associated events. However, it is noted that all three cases of ketoacidosis involved ertugliflozin in combination with metformin. Considering that these events occurred in the setting of intercurrent illness, of which one subject had normal serum lactate concentrations, and a second had possible autoimmune diabetes, it is unclear whether concomitant use of metformin with ertugliflozin may have contributed to the risk of ketoacidosis/metabolic acidosis in these cases. Lower-limb infections, gangrene, diabetic foot ulcers, and ischemia were the more common precipitating factors for amputations in these trials. On May 16, 2017, the Drug Safety Communication was updated, stating that a Boxed Warning would be added to canagliflozin product labeling. A summary table and clinical narratives with graphical patient profiles of these subjects are presented in Appendix 13. The median duration of exposure at the time of the first surgical procedure was 228 days (mean 271; range 36-577 days), with a risk of approximately 3 amputations per 1000 patient-years of exposure for ertugliflozin-treated subjects compared to approximately 0. The Applicant noted that the number of cases was limited, involved subjects with baseline risk factors for these events. I concur that there were few amputations in the study population, and that these events occurred in at-risk subjects. However, the observed numeric imbalance favoring the non-ertugliflozin comparator arm. On October 12, 2017, the Applicant provided the requested amputation data for Trial P004/1021 (presented in Table 38 below). Based on these data, higher event rates on treatment were observed in the ertugliflozin treatment arms (6. In addition to amputations, the Applicant also searched the narratives and datasets of the Phase 3 ertugliflozin program for the occurrence of peripheral revascularization procedures. Only three subjects had revascularization procedures (two in the non-ertugliflozin arm and one in the ertugliflozin 15 mg arm). Eland Baro conducted the statistical review (dated August 15, 2017) of the cardiovascular safety of ertugliflozin. In the 2-year rat carcinogenicity study, ertugliflozin was administered at doses up to 15 mg/kg/day. Ertugliflozinrelated neoplastic findings included an increased incidence of benign and combined benign and malignant adrenal medullary pheochromocytoma in male rats at 15 mg/kg/day. This finding was attributed to carbohydrate malabsorption leading to altered calcium homeostasis, which has been associated with pheochromocytoma development in rats and has unclear relevancy to human risk. Based on the nonclinical data, ertugliflozin was not mutagenic or clastogenic (microbial reverse mutation, in vitro cytogenetic, and in vivo rat micronucleus assays). Human Reproduction and Pregnancy In the rat fertility and embryonic development study, male and female rats were administered ertugliflozin at 5, 25, and 250 mg/kg/day. In their clinical program, there have been two pregnancies; one in a 39-year-old female (Subject 0200629) in the ertugliflozin 5 mg arm (positive pregnancy testing on Days 247 and 251) that ended in an elective abortion on Day 254, and the other in a 34-year-old white female (Subject 0311794) in the placebo arm that resulted in a spontaneous abortion on Day 205. Currently, there is limited clinical experience with the use of ertugliflozin as monotherapy or in combination with sitagliptin or metformin in pregnant or lactating women, and therefore the (b) (4) I concur that the available data are insufficient to inform the use of ertugliflozin during pregnancy. It is noted that postmarketing enhanced pharmacovigilance for pregnancy outcomes was required for dapagliflozin and canagliflozin approval. Additionally, current prescribing practices would likely result in patients being switched to insulin therapy, thus exposure in the later part of pregnancy is unlikely. As such, it was decided that this would not be a post-marketing requirement for empagliflozin. The Applicant includes contact information for their sitagliptin surveillance program. Similar information is not included in proposed labeling for the other two products. However, she acknowledged that poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications and the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Although metformin (immediate-release) is approved for use in children with T2D, pediatric clinical trials and/or assessments on growth and development for either ertugliflozin or sitagliptin have not been completed. For additional information, please refer to: \cdsesub1evsprod
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eq-pediatric-waiver. For this product, the Applicant stated that conduct of appropriate studies in all pediatric populations would be impossible or highly impracticable to conduct. The Applicant states that there are concerns with the potential effects of ertugliflozin on bone (b) (4) metabolism and bone health. Markers of bone health should be monitored in the planned pediatric trial regardless of findings in adults. Overdose, Drug Abuse Potential, Withdrawal, and Rebound the Applicant states that there is no data available related to overdose of ertugliflozin as monotherapy or in combination sitagliptin or metformin. Expectations on Safety in the Postmarket Setting Ertugliflozin is intended to be prescribed as an adjunct to diet and exercise to improve glycemic control in adults with T2D. The main safety concern was an imbalance in the number of subjects who experienced lower limb amputations (11 ertugliflozin-treated subjects vs. Both cases were coded as mild in severity, and resolved without discontinuation in study medication (please refer to Section 8. Relevant medical history included morbid obesity, asthma and sleep apnea syndrome; but there was no prior history of genital infections. An ultrasound scan of the scrotum showed wall thickening, but no soft tissue gas, abscess or fluid collection; both urine and blood cultures were negative. The subject received fluconazole and broad spectrum intravenous antibiotics (cefepime, vancomycin, and metronidazole) for the cellulitis and supportive therapy for all other events. Relevant medical history included fasciectomy (right leg wound), debridement (right leg wound), myositis, necrotizing myositis, arthritis bacterial, carbuncle, cellulitis, sepsis, two soft tissue flap operations of the right leg, synovectomy, and soft tissue necrosis. The subject had been experiencing soft tissue defect with muscle pain prior to study. Since the soft tissue defect and wound muscle pain persisted but had not worsened, the subject came to the outpatient department on Day 70. On examination, it was noted that upper 1/3 of the wound was healing well and lower third of the wound had poor granulation. No X-ray of the affected limb was performed, and there was no surgical removal of necrotic tissue. Administration of study medication was not interrupted (ertugliflozin was continued to Week 104). The most common adverse reactions, reported in 2% of subjects and more frequently in ertugliflozin-treated subjects than placebo-treated subjects, included female and male genital mycotic infections, urinary tract infections, headache, vaginal symptoms, increased urination, nasopharyngitis, back pain, weight decreased, and thirst.
Pragmatic management of Panton-Valentine leukocidin-associated staphylococcal diseases cardiovascular board certification order procardia 30 mg on-line. Successful treatment of staphylococcal toxic shock syndrome with linezolid: a case report and in vitro evaluation of the production of toxic shock syndrome toxin type 1 in the presence of antibiotics coronary heart pain buy 30mg procardia free shipping. The microbiology of chronic osteomyelitis: prevalence of resistance to common empirical anti-microbial regimens capillaries in small intestine cheap procardia 30 mg on-line. Outcomes of osteomyelitis among patients treated with outpatient parenteral antimicrobial therapy heart disease hypertension order procardia 30 mg line. The epidemiology of hematogenous vertebral osteomyelitis: a cohort study in a tertiary care hospital cardiovascular disease nursing journal articles order procardia 30 mg with visa. Epidemiology of acute vertebral osteomyelitis in Denmark: 137 cases in Denmark 1978-1982 blood vessels genital area 30 mg procardia, compared to cases reported to the National Patient Register 1991-1993. Vertebral osteomyelitis: longterm outcome for 253 patients from 7 Cleveland-area hospitals. Bacteraemia and subsequent vertebral osteomyelitis: a retrospective review of 125 patients. Vertebral osteomyelitis in Goteborg, Sweden: a retrospective study of patients during 1990-95. Comparison of clinical features and outcomes of Staphylococcus aureus vertebral osteomyelitis caused by methicillin-resistant and methicillin-sensitive strains. Vertebral osteomyelitis at a Norwegian university hospital 1987-97: clinical features, laboratory findings and outcome. Adult native septic arthritis: a review of 10 years of experience and lessons for empirical antibiotic therapy. Recent trends in adult-onset septic arthritis of the knee and hip: retrospective analysis of patients treated during the past 50 years. Prospective comparative study of patients with culture proven and high suspicion of adult onset septic arthritis. Characteristics of patients with definite septic arthritis at Hamad General Hospital, Qatar: a hospital-based study from 2006 to 2011. Acute haematogenous prosthetic joint infection: prospective evaluation of medical and surgical management. Osteomyelitis: a review of clinical features, therapeutic considerations and unusual aspects. Changing pattern of bone and joint infections due to Staphylococcus aureus: study of cases of bacteremia in Denmark, 1959-1988. Increasing incidence of pyogenic spondylodiscitis: a 14-year population-based study. Incidence and risk factors for mortality of vertebral osteomyelitis: a retrospective analysis using the Japanese diagnosis procedure combination database. Pyogenic vertebral osteomyelitis: a systematic review of clinical characteristics. Diagnosis and management of primary pyogenic spinal infections in intravenous recreational drug users. Clinical and molecular aspects of the pathogenesis of Staphylococcus aureus bone and joint infections. Role of Staphylococcus aureus surface adhesins in orthopaedic device infections: are results model-dependent? A collagen receptor on Staphylococcus aureus strains isolated from patients with septic arthritis mediates adhesion to cartilage. Novel animal model for studying the molecular mechanisms of bacterial adhesion to bone-implanted metallic devices: role of fibronectin in Staphylococcus aureus adhesion. Biofilm formation by staphylococci on fresh, fresh-frozen and processed human and bovine bone grafts. Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections. Kalinka J, Hachmeister M, Geraci J, Sordelli D, Hansen U, Niemann S, Oetermann S, Peters G, Loffler B, Tuchscherr L. Staphylococcus aureus isolates from chronic osteomyelitis are characterized by high host cell invasion and intracellular adaptation, but still induce inflammation. Recovery of small colony variants of Staphylococcus aureus following gentamicin bead placement for osteomyelitis. Clinical characteristics and outcomes of prosthetic joint infection caused by small colony variant staphylococci. Persistent wound infection after herniotomy associated with smallcolony variants of Staphylococcus aureus. Small colony variants of Staphylococcus aureus isolated from a patient with infective endocarditis: a case report and review of the literature. Recurrent ventriculoperitoneal shunt infection caused by small-colony variants of Staphylococcus aureus. Initial investigation of small colony variants of Staphylococcus aureus in chronic rhinosinusitis. Tuchscherr L, Heitmann V, Hussain M, Viemann D, Roth J, von Eiff C, Peters G, Becker K, Loffler B. Staphylococcus aureus smallcolony variants are adapted phenotypes for intracellular persistence. Physiology and antibiotic susceptibility of Staphylococcus aureus small colony variants. Antibiotic activity against smallcolony variants of Staphylococcus aureus: review of in vitro, animal and clinical data. Small colony variants in staphylococcal infections: diagnostic and therapeutic implications. Staphylococcus aureus small colony variants: a challenge to microbiologists and clinicians. The role of small-colony variants in failure to diagnose and treat biofilm infections in orthopedics. Microbiological diagnosis of vertebral osteomyelitis: relevance of second percutaneous biopsy following initial negative biopsy and limited yield of post-biopsy blood cultures. Clinical outcomes and costs among patients with Staphylococcus aureus bacteremia and orthopedic device July 2015 Volume 28 Number 3 Clinical Microbiology Reviews cmr. Clinical characteristics and therapeutic outcomes of hematogenous vertebral osteomyelitis caused by methicillinresistant Staphylococcus aureus. Antibiotic treatment for 6 weeks versus 12 weeks in patients with pyogenic vertebral osteomyelitis: an open-label, non-inferiority, randomised, controlled trial. Is switching to an oral antibiotic regimen safe after 2 weeks of intravenous treatment for primary bacterial vertebral osteomyelitis? Incidence and sources of native and prosthetic joint infection: a community based prospective survey. Septic arthritis: an 18 year clinical review of septic arthritis from tropical Australia. No changes in the distribution of organisms responsible for septic arthritis over a 20 year period. Formylated peptides are important virulence factors in Staphylococcus aureus arthritis in mice. Differential arthritogenicity of Staphylococcus aureus strains isolated from biological samples. Role of neutrophils in experimental septicemia and septic arthritis induced by Staphylococcus aureus. Effect of biofilms on recalcitrance of staphylococcal joint infection to antibiotic treatment. Disseminated gonococcal infection: a prospective analysis of 49 patients and a review of pathophysiology and immune mechanisms. Coexistent gout and septic arthritis: a report of two cases and literature review. Native hip joint septic arthritis in 20 adults: delayed presentation beyond three weeks predicts need for excision arthroplasty. Coakley G, Mathews C, Field M, Jones A, Kingsley G, Walker D, Phillips M, Bradish C, McLachlan A, Mohammed R, Weston V, British Society for Rheumatology Standards, Guidelines and Audit Working Group. Uckay I, Tovmirzaeva L, Garbino J, Rohner P, Tahintzi P, Suva D, Assal M, Hoffmeyer P, Bernard L, Lew D. Short parenteral antibiotic treatment for adult septic arthritis after successful drainage. Outcomes with daptomycin versus standard therapy for osteoarticular infections associated with Staphylococcus aureus bacteraemia. Treatment of septic arthritis: comparison of needle aspiration and surgery as initial modes of joint drainage. Addition of corticosteroids to antibiotic treatment ameliorates the course of experimental Staphylococcus aureus arthritis. Dexamethasone therapy for septic arthritis in children: results of a randomized double-blind placebo-controlled study. Mitha A, Boutry N, Nectoux E, Petyt C, Lagree M, Happiette L, Martinot A, Hospital Network for Evaluating the Management of Infectious Diseases in Children, Dubos F. Community-acquired bone and joint infections in children: a 1-year prospective epidemiological study. Grammatico-Guillon L, Maakaroun Vermesse Z, Baron S, Gettner S, Rusch E, Bernard L. Paediatric bone and joint infections are more common in boys and toddlers: a national epidemiology study. Childhood osteomyelitis-incidence and differentiation from other acute onset musculoskeletal features in a population-based study. Changing patterns of acute hematogenous osteomyelitis and septic arthritis: emergence of community-associated methicillin-resistant Staphylococcus aureus. Sensitivity of erythrocyte sedimentation rate and C-reactive protein in childhood bone and joint infections. Differentiating between methicillin-resistant and methicillin-sensitive Staphylococcus aureus osteomyelitis in children: an evidence-based clinical prediction algorithm. Independent analysis of a clinical predictive algorithm to identify methicillin-resistant Staphylococcus aureus osteomyelitis in children. Deep venous thrombosis associated with acute hematogenous osteomyelitis in children. Community-acquired methicillin-resistant Staphylococcus aureus causes severe disseminated infection and deep venous thrombosis in children: literature review and recommendations for management. Deep venous thrombosis in children with musculoskeletal infections: the clinical evidence. Short- versus long-term antimicrobial treatment for acute hematogenous osteomyelitis of childhood: prospective, randomized trial on 131 culture-positive cases. Prospective evaluation of a shortened regimen of treatment for acute osteomyelitis and septic arthritis in children. Complications of central venous catheters used for the treatment of acute hematogenous osteomyelitis. Systematic review of duration and choice of systemic antibiotic therapy for acute haematogenous bacterial osteomyelitis in children. Clinical and laboratory parameters associated with multiple surgeries in children with acute hematogenous osteomyelitis. Prosthetic joint infection risk after total hip arthroplasty in the Medicare population. Risk factors for prosthetic hip and knee infections according to arthroplasty site. The Calgary Biofilm Device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. Pathogenesis of foreign body infection: description and characteristics of an animal model. Prospective evaluation of criteria for microbiologic diagnosis of prosthetic-joint infection at revision arthroplasty. The value of synovial biopsy, joint aspiration and C-reactive protein in the diagnosis of late peri-prosthetic infection of total knee replacements. False-negative rate of gram-stain microscopy for diagnosis of septic arthritis: suggestions for improvement. Sonication technique improves microbiological diagnosis in patients treated with antibiotics before surgery for prosthetic joint infections. Meta-analysis of sonication fluid samples from prosthetic components for diagnosis of infection after total joint arthroplasty. Outcome of debridement and retention in prosthetic joint infections by methicillin-resistant staphylococci, with special reference to rifampin and fusidic acid combination therapy. Outcome and predictors of treatment failure in total hip/knee prosthetic joint infections due to Staphylococcus aureus. Role of rifampin for treatment of orthopedic implant-related staphylococcal infections: a randomized controlled trial. Phenotypic resistance of Staphylococcus aureus, selected Enterobacteriaceae, and Pseudomonas aeruginosa after single and multiple in vitro exposures to ciprofloxacin, levofloxacin, and trovafloxacin. Recommendations for rifampicin therapy of staphylococcal infection in Infectious Diseases Society of America prosthetic joint infection guidelines are not supported by available literature. A large multicenter study of methicillin-susceptible and methicillin-resistant Staphylococcus 652 cmr. Treating foot infections in diabetic patients: a randomized, multicenter, open-label trial of linezolid versus ampicillin-sulbactam/amoxicillin-clavulanate.
Syndromes
Bleeding
Worsening of symptoms after initial improvement
Limited range of motion
Increased pressure inside the skull
Your blood pressure may be normal, high, or low.
Paralysis (paraplegia, quadriplegia)
The lungs inflate and begin working on their own, moving oxygen into the bloodstream and removing carbon dioxide by breathing out (exhalation).
Fainting or feeling light-headed
Arthritis
In lesions involving the airway not responding to more conservative measures cardiovascular disease tests buy procardia 30mg cheap, radiation therapy has been used with success cardiovascular nursing diagnosis procardia 30mg fast delivery. When utilized coronary heart disease icd 10 cheap procardia 30mg with visa, radiation planning using complex or three-dimensional technique and delivered in up to twenty-two sessions is typical cardiovascular system how it works generic 30 mg procardia otc. Policy: cases will require medical review and documentation that non-radiation alternatives have been exhausted arteries restaurant purchase 30mg procardia. Sarcoidosis If primary medical management fails to control those lesions in need of treatment coronary heart disease health promotion order procardia 30mg overnight delivery, the use of radiation therapy is appropriate. Sinusitis Sinusitis caused by infection does not have literature support for treatment by radiation therapy. Splenomegaly Splenomegaly treated by radiation therapy is most commonly caused by leukemic or myeloproliferative diseases, and to a lesser extent by metastases from solid tumors. The policy for the use of radiation therapy in these malignant conditions is not covered in this Guideline for the treatment of non-malignant disorders. Typically radiation is delivered in ten or fewer sessions, planned using complex or three-dimensional technique. While once common, this procedure has been less frequently performed with the availability of drug eluting stents. Support for this has not continued into newer references other than Pigmented Villonodular Synovitis. There is ample world literature that describes the successful use of radiation to treat insertion tendonitis, a practice that is more common in Europe than the Americas. The mainstay of treatment is conservative using a pharmacologic or physical therapy approach. Typical treatment is with photon beam therapy using, at most, complex treatment planning, and delivered in up to five sessions. Policy: Radiation therapy is medically necessary for those cases not responding to conservative measures and case will require medical review. There are several types of thymoma ranging from the benign medullary thymoma to true invasive thymic carcinomas. There is general agreement that thymomas respond to radiation therapy, but controversy exists on the value of using radiation in low and intermediate stages and grades, especially if encapsulated and fully resected. Radiation therapy is appropriate if unresectable or incompletely resected, particularly if causing a paraneoplastic syndrome. Thyroiditis Presently there is no indication for the use of radiation therapy for the treatment of thyroiditis. Tolosa-hunt syndrome (episodic orbital pain) this is caused by nonspecific inflammation of the cavernous sinus or superior orbital fissure. The successful use of low dose radiation has been reported and may be used as a last resort. Policy: Cases will require medical review and documentation that non-radiation alternatives have been exhausted. Tonsillitis In the modern era of antibiotics, the use of radiation to treat inflamed or infected tonsils is obsolete. Total body irradiation For the preparation of patients for bone marrow or stem cell transplant for malignant disorders, see the Guideline for the primary disease. For non-malignant, pre-malignant and quasi-benign marrow disorders such as aplastic anemia or myelodysplastic disorders, total body irradiation prior to transplant may be appropriate if chemotherapeutic preparation is not possible. The use of total body irradiation for immunosuppression as treatment of totally non-malignant disorders, such as auto-immune diseases is not medically appropriate. Total lymphoid irradiation Total lymphoid irradiation has been used for the purpose of immunosuppression in the treatment of immune-mediated disorders. Further research is needed to establish its role, but it remains an option in situations of chronic rejection in which conventional antirejection treatment is no longer viable. Policy: Requests require medical review and confirmation that alternatives have been exhausted. Trigeminal neuralgia (tic douloureux) Radiation therapy is considered appropriate for cases not responding to conservative management if a surgical approach is not possible for technical or medical reasons. Tuberculosis lymphadenitis Prior to the availability of antibiotics for tuberculosis, lymphadenitis caused by this disease responded to therapeutic radiation. Vernal catarrh this disorder is characterized by inflammation of the conjunctiva associated with infiltration by eosinophils, lymphocytes, plasma cells and histiocytes. The resultant hyperplasia of the conjunctival epithelium may respond to ionizing radiation, but alternative therapy is readily available and the use of radiation is no longer supported in any literature. Warts Older literature describes an 80% response rate in treating warts with a relatively low dose of radiation and it is described in at least one modern text (Gunderson). With the availability of alternative therapy, the use of radiation should be reserved for those cases requiring treatment for which alternative, simpler therapy has been unsuccessful. Committee to Review the Use of Ionizing Radiation for the Treatment of Benign Diseases. Preventing Breast Cancer: the Story of a Major, Proven, Preventable Cause of this Disease. Consensus guidelines for radiation therapy of benign diseases: a multicenter approach in Germany. Radiotherapy for non-malignant disorders: state of the art and update of the evidencebased practice guidelines. Has had or who will undergo curative treatment of the primary tumor (based on T and N stage) and 2. Presents with 1 to 3 metastases in the lung or liver in the synchronous setting and 3. A clinical presentation of one 1 to 3 adrenal gland, lung, liver or bone metastases in the metachronous setting when all the following criteria are met: a. Histology is non-small cell lung, colon, breast, sarcoma, renal cell, or melanoma b. Oligometastatic disease found at the time of the diagnosis of the primary tumor C. Progression of a limited number of metastatic sites while other metastatic disease sites remain controlled. Discussion Oligometastases is described as an intermediate state in the spread of cancer between early-stage localized disease and widespread metastases. Specifically, it is a malignancy that has progressed to a limited number of hematogenous metastatic sites, defined in most studies as 1 to 3 sites. Chemotherapy remains the standard of care for patients with metastatic cancer, however this is rarely curative. The concept of oligometastasis has important implications for cancer treatment because it is believed that patients with limited numbers of metastasis previously thought by some clinicians to be incurable may be cured with local treatments such as radiotherapy. The data supporting the treatment of extracranial oligometastases is limited to single institution or registry studies demonstrating improved survival outcomes compared to historical controls. The data with the longest follow-up is the surgical literature examining the resection of non-small cell lung and hepatic metastases. The International Registry of Lung Metastases examined 5,206 patients between 1945 and 1995 at 18 institutions and found 36% survival at 5 years (Pastorino et al. Patients with the best prognosis were those with a single resectable metastasis with a disease free interval > 3 years. In metastatic colorectal cancer to the liver, hepatic resection has resulted in a 5-year survival of 28% in a wellselected population (Nordlinger et al. Similar outcomes have been demonstrated in adrenal metastectomy for non-small cell lung cancer and pulmonary metastatectomy for osteosarcoma in children (Kager et al. These studies have used anywhere from 3 to 10 fractions across a range of total doses. The major limitation of these studies is that they are single arm, non-controlled, with small patient numbers and often limited to single institutions. Furthermore, they are subject to "immortal" time bias that artificially inflates the survival of patients who underwent metastatectomy compared to those who did not. Non-small cell lung There is a population of individuals with non-small cell lung cancer presenting with oligometastatic disease that will benefit from metastases-directed ablative procedures. A recent retrospective analysis of patients with oligometastatic non-small cell lung cancer who underwent metastasis directed treatment (intra and extra cranial) found a 2-year survival of 38% (Griffioen, et al. A recent review of the literature found that while the majority of patients progress within 12 months, there is a subset of long-term survivors (Ashworth et al. Colon Surgical series have shown that selected patients with colorectal cancer undergoing resection of hepatic and/or pulmonary metastases results in a cure for a proportion of patients with a 5-year survival of 38% (Kanas et al. The 30 month survival was 61% in the radiofrequency ablation arm and 56% in the control arm (p = 0. Sarcoma, renal, melanoma A retrospective analysis examining pulmonary metastases from sarcoma found those who received local ablative treatment to have improved median survival of 45 months vs. Previous retrospective literature has demonstrated a survival benefit for patients with metastatic sarcoma who underwent a pulmonary metastasectomy (van Geel, et al. Pulmonary resection for renal cell cancer is associated with a 5-year survival of 20% (Murthy, et al. In the setting of melanoma there have also been retrospective studies demonstrating a benefit to lung resection of metastases. An analysis of melanoma in the international registry of lung metastasis found a 5-year survival of 22% after complete metastasectomy. Combining precision radiotherapy with molecular targeting and immunomodulatory agents: a guideline by the American Society for Radiation Oncology. Extracranial oligometastases: a subset of metastases curable with stereotactic radiotherapy. Effect on survival of local ablative treatment of metastases from sarcomas: a study of the French sarcoma group. Stereotactic radiation therapy can safely and durably control sites of extra-central nervous system oligoprogressive disease in anaplastic lymphoma kinase-positive lung cancer patients receiving crizotinib. Hypofractionated image-guided radiation therapy for patients with limited volume metastatic non-small cell lung cancer. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. Survival after liver resection in metastatic colorectal cancer: review and meta-analysis of prognostic factors. Phase I study of individualized stereotactic body radiotherapy of liver metastases. Oligometastases treated with stereotactic body radiotherapy: long-term follow-up of prospective study. Oligometastatic breast cancer treated with curative-intent stereotactic body radiation therapy. Can we predict long-term survival after pulmonary metastasectomy for renal cell carcinoma? Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. Stereotactic body radiotherapy for the treatment of oligometastatic renal cell carcinoma. Stereotactic body radiotherapy for multisite extracranial oligometastases: final report of a dose escalation trial in patients with 1 to 5 sites of metastatic disease. Outcomes of adrenalectomy for isolated synchronous versus metachronous adrenal metastases in non-small-cell lung cancer: a systematic review and pooled analysis. Surgical treatment of lung metastases: the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group study of 255 patients. Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1-2 trial. Stereotactic body radiation therapy favors long-term overall survival in patients with lung metastases: five-year experience of a single-institution. For such requests, adjudication will be conducted on a case-by-case basis utilizing, as appropriate and applicable: I. Motion management techniques should be employed when respiration significantly impacts on stability of the target volume D. Definitive treatment for medically or surgically inoperable or locally advanced cases following a minimum of 2 cycles of chemotherapy and restaging in which there is no evidence of tumor progression and the disease volume can be entirely encompassed in the radiation treatment volume 2. Postoperative (adjuvant) cases in which there is residual gross disease or positive microscopic margins that can be entirely encompassed in the radiation treatment volume 3. For palliative situations, up to 15 fractions in 1 phase of Complex or 3D external beam photon radiation therapy is considered medically necessary. Resectability is typically defined by a lack of encasement of the superior mesenteric vein and portal veins and clear fat planes around the celiac artery, superior mesenteric artery and hepatic artery. Borderline resectability generally includes involvement of superior mesenteric vein or portal vein, but lack of encasement of the adjacent arteries. In their study, 8 of 17 borderline resectable patients achieved negative margin resection after neoadjuvant therapy. Studies from the Mayo Clinic and Johns Hopkins have supported the use of chemoradiation following resection. Both studies demonstrated improved 5-year overall survivals in the cohorts receiving chemoradiation. A Johns Hopkins-Mayo Clinic Collaborative Study analyzed patients receiving adjuvant chemoradiation compared with surgery alone. In a retrospective review of 1,045 patients with resected pancreatic cancer, 530 patients received chemoradiation. Median and overall survivals were significantly improved in the chemoradiation group. These studies were heavily criticized for trial design, inclusion of more favorable histologies, lack of quality assurance, and use of split course radiation.
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References
Johnson MP, Ramphal R. Beta-lactam-resistant Enterobacter bacteremia in febrile neutropenic patients receiving monotherapy. J Infect Dis. 1990;162(4):981-983.
Tawbi HA, Burgess M, Bolejack V, et al. Pembrolizumab in advanced soft- tissue sarcoma and bone sarcoma (SARC028): a multicentre, two-cohort, single-arm, open-label, phase 2 trial. Lancet Oncol 2017;18(11):1493- 1501.
Orofino L, Marcen R, Gamez C, et al. Visceral leishmaniasis in renal transplant patients. Nephrol Dial Transplant. 1992;7:Kher V, Ghosh AK, Gupta A, et al. Visceral leishmaniasis: an unusual case of fever in a renal transplant recipient. Nephrol Dial Transplant. 1991;6:736-738.
Westendorp WF1, Nederkoorn PJ, Vermeij JD, et al. Post-stroke infection: a systematic review and meta-analysis. BMC Neurol 2011;11:110.
Siedlecki A, Irish W, Brennan DC. Delayed graft function in kidney transplant. AJT. 2011;11(11):2279-2296.
Nolan MA, Sakuta R, Chuang N, et al (2004). Dysembryoplastic neuroepithelial tumors in childhood: long-term outcome and prognostic features. Neurology 62(12):2270-2276.
Bourdillon PDV, Hookman LD, Morris SN, et al. Percutaneous balloon valvuloplasty for tricuspid stenosis: Hemodynamic and pathologic findings. Am Heart J. 1989;117:492.
Sakka SG, Klein M, Reinhart K, et al. Prognostic value of extravascular lung water in critically ill patients. Chest. 2002;122(6):2080-2086.
