Does undetectable basal Tg measured with a highly sensitive assay in the absence of antibodies and combined with normal ultrasonography ensure the absence of disease in patients treated for thyroid carcinoma?

It has been proposed that, in patients treated for well-differentiated thyroid carcinoma, undetectable basal thyroglobulin (Tg) levels measured with a highly sensitive assay in the absence of anti-thyroglobulin antibodies (TgAb) and combined with negative neck ultrasonography (US) ensured the absence of disease. We report a series of five patients with well-differentiated (papillary) carcinoma submitted to total thyroidectomy with apparently complete tumor resection, followed by remnant ablation with (131)I (100-150 mCi), who had no distant metastases upon initial post-therapy whole-body scanning. When tumor recurrence or persistence was detected, these patients presented undetectable basal Tg (0.1 ng/mL) in the absence of TgAb, and US showed no anomalies. Two patients had lymph node metastases, one had mediastinal metastases, bone involvement was observed in one patient, and local recurrence in one. We conclude that further studies are needed to define in which patients undetectable basal Tg (negative TgAb) combined with negative US is sufficient, and no additional tests are required.     

Assessment of fracture risk: who should be treated for osteoporosis?

The clinical significance of osteoporosis arises from the fractures that occur. Of these, the hip fracture in particular is associated with high morbidity, mortality and socio-economic costs. The primary goal of osteoporosis treatment is fracture prevention. In this chapter we try to answer the question of how to assess fracture risk and how to identify those above a given risk threshold so that treatment can be given to those in whom fractures can be prevented (cost-) effectively. At first, the two main strategies for fracture prevention--population screening and case finding--are discussed. Then a fracture risk assessment score, based on easily identifiable clinical risk factors, is proposed. This clinical risk factor analysis can guide the decisions whether additional bone assessment is relevant and whether treatment should be started. Finally, we advocate that absolute fracture risk is important for communication with the patient about the decision whether or not to initiate treatment.     

Evolving criteria for post-operative biochemical remission of acromegaly: can we achieve a definitive cure? An audit of surgical results on a large series and a review of the literature

Criteria to define the biochemical remission of acromegaly following surgery have changed over the years, and the current use of stringent criteria needs a critical re-evaluation of the surgical results. On the other hand, few data are currently available concerning the possible impact of pituitary surgery on the quality of life of operated acromegalic patients. In this prospective study, we wished to evaluate the initial outcome and long-term recurrence rate in a large series of acromegalic patients operated on by transsphenoidal surgery (TSS), to carefully analyse predictive factors for surgical outcome and to point out possible additional effects of surgery in these patients. Ninety-two out of 98 operated patients could be considered for follow-up. Biochemical remission was strictly defined as plasma GH levels <1 ng/ml during an oral glucose tolerance test (OGTT) and normalisation of age-related IGF-I levels. Hormonal assessment, including an OGTT, was performed 6 months following surgery and then annually to evaluate pituitary function. Fifty-five per cent of patients achieved a biochemical remission of acromegaly. The remission rate at 6 months was 80% for patients with microadenoma and 50% for macroadenoma. Univariate analysis showed that a large extrasellar extension, preoperative high GH levels and dural invasion were correlated with a poor outcome of surgery while, according to multivariate analysis, only invasion of cavernous sinus and preoperative GH levels > 10 ng/ml were independent negative predictors. Mortality was 0% and the overall complication rate was about 10%. Pituitary function worsened in five patients but improved in 16 out of 30 patients with preoperative pituitary defects. No recurrence was observed during a median follow-up of about 8 years. We conclude that TSS is able to achieve a biochemical remission in more than half of acromegalic patients, and that the current criteria for remission seem to indicate a cure in most cases.     

Cardiovascular disease in lupus patients: should all patients be treated with statins and aspirin?

Premature coronary heart disease (CHD) is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). In certain age groups, the risk can be >50 times that of an age-matched population. This population also has an increased prevalence of several key classic risk factors that contribute to the CHD development. Chronic inflammation, anti-phospholipid antibodies and exposure to steroid therapy are also likely to have an impact. We have adopted a proactive approach to classic risk factor management with 'ideal targets' based on viewing SLE as a CHD equivalent condition. In this context, a significant proportion of SLE patients (approximately 30%) will require statins and the majority would be treated with aspirin prophylaxis. Better control of the underlying inflammatory disease is also likely to play an important role and the relative safety of anti-malarials allows their consideration as an adjunct in a large proportion of patients. Well-conducted clinical trials are now needed to advance beyond these initial recommendations.     

Neutrophil-elastase in chronic inflammatory bowel disease: a marker of disease activity?

BACKGROUND/AIMS: Neutrophil elastase is a proteinase which exists in granulocytes and plays an important role in the pathogenesis of inflammatory disorders. In inflammatory bowel disease there is a leukocyte infiltration of the bowel mucosa. The purpose of this study was to examine whether plasma elastase represents a reliable laboratory marker for establishing the activity of chronic inflammatory bowel disease. METHODOLOGY: We measured plasma elastase concentrations in 61 patients suffering from either Crohn's disease or ulcerative colitis and compared these data with other clinical and laboratory findings and with elastase concentrations in 40 healthy controls. The sensitivity and specificity of the elastase values in chronic IBD were calculated with the use of concomitant measurements of CRP and ESR. RESULTS: Plasma levels were found to be significantly higher in patients (49 micrograms/l) compared with healthy controls (23 micrograms/l). Patients with active disease had higher plasma levels than patients in remission. In general, the sensitivity of elastase to detect active inflammatory bowel disease was about 60%; the specificity was 65%. For patients in remission, the sensitivity was higher than 80%. However, there was a wide range of overlapping values between chronic inactive patients and those with moderately active disease. CONCLUSIONS: We conclude that plasma elastase is a useful independent marker of disease activity in inflammatory bowel disease. Especially for identifying patients in remission, the measurements of elastase seem to be more suitable than other parameters of inflammation, like CRP or ESR.     

What are capillary blood ketone levels in type 1 diabetic patients using CSII in normal conditions of insulin delivery?

OBJECTIVE: The aim of the study was to determine the normal level of capillary ketonemia in type 1 diabetic patients on continuous subcutaneous insulin infusion (CSII). RESEARCH DESIGN AND METHODS: A total of 36 type 1 diabetic patients treated by external pump were studied for 2 to 3 weeks. Patients were instructed to self monitor capillary glucose and capillary ketone bodies at least 4 times per day with a handheld Medisense Optium meter and check for urinary ketone bodies in the morning and when blood glucose exceeded 2.5 g/l with a semiquantitative test. Data were collected and analysed for each period of time defined as the time interval between two changes of the infusion site. A period was considered "normal" when no problem causing any impairment in insulin delivery was detected. RESULTS: 186 periods of 2.1 +/- 0.9 days were recorded; 119 were considered normal. 1281 coupled values of glucose and betahydroxybutyrate were analysed during the so called normal periods. Mean percentage of ketonemia of 0, 0.1, 0.2, > or =0.3 mmole/l were 81.3%, 13%, 3.7% and 2% respectively whereas mean glucose level (g/l) was 1.49 +/- 0.7, 1.48 +/- 0.7, 1.59 +/- 0.8 and 1.89 +/- 0.9 respectively. Only 0.9% of betahydroxybutyrate values were > or =0.3 mmole/l when blood glucose exceeded 2.5 g/l. CONCLUSION: Our study indicates that ketonemia self monitoring can be a valuable tool to screen insulin deficiency in patients on CSII with a low risk of false positive if we consider a threshold of 0.3 mmole/l for ketone bodies.     

Surgery for mitral valvar disease in childhood: should we choose reconstruction or repair?

OBJECTIVE: Modern surgical techniques now offer the potential for reconstructing rather than replacing the mitral valve in those patients who require an operation during childhood. The purpose of this study was to assess the outcome in our centre following mitral valvar surgery in children. METHODS: Between 1992 and 2002, 51 consecutive children, with a mean age of 12.5 +/- 3.5 years, underwent surgical treatment of mitral valvar stenosis and/or insufficiency in the Cardiovascular Surgical Department of Istanbul University. Of the children, 20 underwent repair, whilst we replaced the valve in 31 patients. In one, we inserted a pulmonary valvar autograft in mitral position. RESULTS: There were neither early nor late deaths in those who underwent mitral valvar repair. Similarly, there were no early deaths in those in whom the valve was replaced, but two patients died late, while six outgrew their prosthetic valves and required insertion of a further valve within 10 years of their first operations. CONCLUSION: Our experience shows that procedures designed to repair the mitral valve are effective and reliable when performed in children, with low mortality, and a lower incidence of reoperation when compared with those having replacement of the mitral valve.     

Treatment of acromegaly with SS analogues: should GH and IGF-I target levels be lowered to assert a tight control of the disease?

BACKGROUND: in acromegaly, the criteria for the cure of the disease after neurosurgery have become tighter and tighter. In contrast, the evaluation of control of disease activity during medical treatment is based upon the normalisation of IGF-I levels and epidemiological criteria, i.e. lessening GH (assessed by RIA) to levels reported to normalise increased mortality. The aim of this study was to evaluate GH and IGF-I suppression during prolonged SS analogues (SA) treatment. The concordance between "safe" GH and normalised IGF-I levels during SA was also assessed, according to gender and gonadal status. DESIGN: multicentre, retrospective. Patients. GH/IGF-I levels were evaluated in 207 acromegalic patients (132 females, aged 20-85 yr) during a prolonged treatment (longer than 12 months) with individually tailored doses of depot SA( lanreotide or octreotide-LAR in 97 and 110 patients, respectively). Final IGF-I levels were transformed in z-scores using data collected in a large cohort of normal subjects of 3 different age groups (20-40 yr old, 41-60 yr old, 61-80 yr old, n=160, 148, 115, respectively), that allowed to set up quartiles of normality (I = 3rd-25th percentile, II = 26th-50th, III = 51th-75th, IV = 76th-97th). RESULTS: fifty-nine and 19.3% of patients achieved GH levels <2.5 and <1 microg/l, respectively. IGF-I were normalised (z-score between 2 and -2) in 58.4% of patients. The distribution of normal IGF-I values among quartiles was uneven: 7%, 19%, 25%, and 49% of values were distributed in the I, II, III, and IV quartile, respectively. The concordance between GH and IGF-I values was poor: 28.4% of patients attaining GH values <2.5 microg/l had still pathological IGF-I (even 12.5% of those with GH <1 microg/l), and 39.3% of those with GH levels still above the "safe" limit had "nor IGF-I. Although proportions of IGF-I normalisation were not different between males and females, the regression line obtained between GH and IGF-I z-score showed the same slope but with a significantly lower intercept in regularly cycling women than in males and in postmenopausal females. Thus for any GH value, cycling females had lower IGF-I than menopausal women and males, and their IGF-I normalisation could be achieved by higher GH values. By ROC analysis, the achievement of normal IGF-I was predicted by the GH value of 1.8 microg/l in males and 2.4 microg/l in females. Conclusions: in acromegalic patients on SA treatment, GH and IGF-I levels are often not concordant. In addition to age, sex is to be taken into account in the evaluation of hormonal targets. A better refinement of GH and IGF-I targets to be reached while on treatment with SA is warranted.     

Incident rates of colonic neoplasia in older patients: When should we stop screening?

INTRODUCTION: Current guidelines endorse colon cancer screening every 5-10 years in patients over 50 years of age. However, there is no consensus regarding what age is appropriate to stop screening. The aim of this study was to characterize neoplasia occurrence/recurrence in a large cohort of patients > or =70 years of age undergoing colonoscopy. METHODS: The Mayo Rochester endoscopic database was reviewed to determine the incidence of colonic neoplasia in patients > or =70 years undergoing two colonoscopies at least 12 months apart between January 1996 and December 2000. Patients were classified based on (i) age: 70-74, 75-79, > or =80 years; and (ii) polyp detection on initial examination, that is, subsequent examination for screening or surveillance. RESULTS: Overall, 1353 patients underwent two colonoscopies at least 12 months apart (median interval 140 weeks) with removal of polyp on initial examination in 726 (53.7%) patients (surveillance cohort). On subsequent endoscopy, polyps > or =10 mm were detected in 54 (4.0%) and cancer in 13 (1.0%) patients. All age groups were well matched with respect to detection of neoplasia on index examination (P = 0.9) and polyp size on initial colonoscopy among the surveillance group (P = 0.9). Using a Cox proportional hazards model, adjusted hazard ratios (95% confidence interval [CI]) for neoplasia (polyps > or =10 mm) were: 2.0 (1.50-2.73, P < 0.0001) (surveillance vs screening), 1.33 (0.96-1.79, P = 0.08) (> or =80 vs 70-74), and 1.05 (0.78-1.38, P = 0.75) (75-79 vs 70-74). Adjusted hazard ratios for development of cancer were: 1.87 (1.03-3.97, P = 0.04) (surveillance vs screening), 1.73 (0.84-3.56, P = 0.13) (> or =80 vs 70-74), and 1.38 (0.71-2.77, P = 0.34) (75-79 vs 70-74). CONCLUSIONS: Prior history of neoplasia remains a strong risk factor for colorectal neoplasia development in elderly patients and should be considered when deciding the need for continuing screening/surveillance. Incident neoplasia rates in a previously screened elderly population rise slowly with advancing age although cancer rates rise more sharply. Therefore, screening still retains a role in elderly patients; however, clinical judgment is still required to individualize screening practice. As the risk of competing comorbid illnesses continues to increase over time, the threshold to perform colon screening should increase accordingly.     

Homocysteine as a risk factor for cardiovascular disease: should we (still) worry about?

Cardiovascular disease (CVD) is the leading cause of death worldwide. CVD is causally related to "classical" risk factors such as elevated blood pressure, cholesterol, or glucose level and smoking. A causal role in the development of CVD is also suggested for numerous other factors, including an elevated plasma homocysteine concentration. Variation of homocysteinaemia is mainly due to genetic mutations and/or vitamin deficiency. The homocysteine concentration can be lowered with folate. Vitamin supplementation has thus been proposed in individuals with hyperhomocysteinaemia in order to reduce their CVD risk. On the other hand, population-based studies show little or no association between moderate hyperhomocysteinaemia and CVD risk. Nor has any randomised clinical trial clearly proven the efficacy of lowering the homocysteine concentration as a means of lowering the incidence of CVD. Hence at present it is inappropriate to recommend screening and treatment of hyperhomocysteinaemia in asymptomatic persons with or without other CVD risk. Until new evidence is available, clinicians should focus on better control of the "classical" risk factors for CVD.     

The risk factors for delayed recovery in patients with cardiopulmonary bypass: Why should we care?

Cardiopulmonary bypass (CPB) is very commonly performed among the cardiovascular surgeries, and delayed recovery (DR) is a kind of serious complications in patients with CPB. It is necessary to assess the risk factors for DR in patients with CPB, to provide evidence into the management of CPB patients.Patients undergoing CPB in our hospital from January 2018 to March 2020 were included. Cases that consciousness has not recovered 12 hours after anesthesia were considered as DR. The preoperative and intraoperative variables of CPB patients were collected and analyzed. Logistic regressions were conducted to analyze the potential influencing factor.A total of 756 CPB patients were included, and the incidence of DR was 9.79%. There were significant differences on the age, aspartate aminotransferase (AST), glutamic pvruvic transaminase (ALT), blood urea nitrogen (BUN), and serum creatinine (SCr) between patients with and without DR (all P < .05); there were no significant differences in the types of surgical procedure (all P > .05); there were significant differences on the duration of CPB, duration of aortic cross clamp (ACC), duration of surgery, minimum nasopharyngeal temperature, and transfusion of packed red blood cells between patients with and without DR (all P < .05). Logistic regression analysis indicated that duration of CPB ≥132 minutes (odds ratio [OR] 4.12, 1.02–8.33), BUN ≥9 mmol/L (OR 4.05, 1.37–8.41), infusion of red blood cell suspension (OR 3.93, 1.25–7.63), duration of surgery ≥350 minutes (OR 3.17, 1.24–5.20), age ≥6 (OR 3.01, 1.38–6.84) were the independent risk factors for DR in patients with CPB (all P < .05).Extra attention and care are needed for those CPB patients with duration of CPB ≥132 minutes, BUN ≥9 mmol/L, infusion of red blood cell suspension, duration of surgery ≥350 minutes, and age ≥60.     

Is there a role for minimal residual disease levels in the treatment of ALL patients who receive allogeneic stem cells?

Relapse is the major complication after allogeneic stem cell transplantation (SCT) for acute lymphoblastic leukemia (ALL) in children. Since it has been possible to measure minimal residual disease (MRD) by real-time quantitative polymerase chain reaction, this parameter is used more frequently in the treatment of ALL. In this article, the role of MRD and chimerism in the treatment and monitoring of pediatric transplantation recipients is described. Pre-SCT MRD levels can predict the risk of relapse and can thus be used to adjust treatment. Post-SCT MRD levels and changes in chimerism can predict relapses as well, although not many treatment options are available today, except relying on a graft-versus-leukemia effect mediated by graft-versus-host disease. Finding new treatments will be the challenge for the near future.