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Recurrence of conduction following radiofrequency catheter ablation procedures: relationship to ablation target and electrode temperature. The Atakr Multicenter Investigators Group.

INTRODUCTION: More than 1 in 10 patients may develop recurrence of conduction after undergoing a successful radiofrequency catheter ablation procedure. The physiologic basis for recurrence following successful ablation procedures remains uncertain. The purpose of this study was to evaluate the role of electrode temperature as a predictor of recurrence following radiofrequency catheter ablation procedures. METHODS AND RESULTS: The subjects of this study were 538 patients who underwent a successful attempt at radiofrequency catheter ablation of AV nodal reentrant tachycardia, an accessory pathway, and/or the AV junction. Patients were followed for a mean of 215 +/- 138 days. Conduction recurred in 35 (6.5%) of the 538 patients. Recurrence of conduction occurred in 25 (9.3%) of 270 patients undergoing ablation of an accessory pathway, 7 (3.5%) of 201 patients undergoing ablation of AV nodal reentrant tachycardia, and in 3 (4.5%) of 67 patients undergoing ablation of the AV junction. The electrode temperature achieved at successful sites associated with recurrence was not different from the temperature achieved at successful sites without recurrence (61.1 +/- 8.9 vs 61.6 +/- 9.1; P = 0.8). The likelihood of developing a recurrence was higher following ablation of accessory pathways than following ablation of AV nodal reentrant tachycardia or the AV junction (P = 0.03). Patients experiencing a recurrence following ablation of an accessory pathway had longer procedure durations (P = 0.0001). Ablation of left free-wall pathways was associated with a lower incidence of recurrence as compared with all other locations (P = 0.008). CONCLUSION: The results of this study suggest that electrode temperature at the successful ablation site cannot be used to identify patients at highest risk of recurrence.

Adolescent↗

Recurrence of acute gallstone pancreatitis and relationship with cholecystectomy or endoscopic sphincterotomy.

OBJECTIVES: To determine the prevalence of recurrence of gallstone pancreatitis, its clinical features, and the presence of prognostic factors of recurrence. METHODS: From January 1, 2000 to August 31, 2003, 233 patients admitted with acute gallstone pancreatitis (AGP) were prospectively studied. Patients were divided into two groups: recurrent and nonrecurrent group. Clinical, analytical, radiological, prognostic parameters, and severity (Atlanta criteria) were assessed, along with the performance of cholecystectomy or endoscopic sphincterotomy (ES). Clinical features of recurrence were analyzed. Univariate (chi(2), Student's t-test) and multivariate tests were performed. Statistical significance was assumed if p < 0.05. RESULTS: Two hundred and eighty-six attacks were identified. Forty-two patients (18.2%) recurred, suffering 53 recurrent attacks, which took place within 30 days in 23.3%. Patients who did not undergo surgery after the first attack had 31-fold risk of recurrence (OR = 31.5%, CI = 95%[7.22-137.84], p < 0.001). In patients not operated, recurrence was more frequent if ES was not performed (37.04%vs 0%, p= 0.019). Among patients with surgical risk, none who recurred underwent ES, compared with 27.9% of those who did not recur. Patients in the nonrecurrent group underwent cholecystectomy within the first 30 days or ES more frequently (31.2%vs 7.3%, p= 0.001). CONCLUSIONS: Recurrence of gallstone pancreatitis is a frequent event. Delay of cholecystectomy implies an increased risk of recurrence. ES could be an acceptable option to prevent recurrence in patients who are not candidates for surgery or who do not desire to undergo cholecystectomy.

Acute Disease↗

Imiquimod 5-percent cream does not alter the natural history of recurrent herpes genitalis: a phase II, randomized, double-blind, placebo-controlled study.

Present strategies for control of herpes genitalis recurrences require multiple daily doses of antiviral medication. Imiquimod, an immune response modifier, induces alpha interferon and interleukin-12; application in the presence of local herpes antigens during a recurrence may augment herpes simplex virus (HSV)-specific cell-mediated immunity. To test this theory, we performed a randomized, double-blind, placebo-controlled study of imiquimod 5% cream to assess safety and efficacy for decreasing recurrences. Patients with six or more recurrences of herpes genitalis per year applied study cream (imiquimod or placebo) to lesions one, two, or three times per week for 3 weeks for each recurrence during a 16-week treatment period. This was followed by a 16-week observation period. Of 124 patients randomized to the study, 103 completed the treatment period and 93 completed the observation period. The median times to first genital herpes recurrence were 53 days for those receiving placebo (n = 30) and 54, 60, and 64 days for those receiving imiquimod one time per week (n = 34), two times per week (n = 32), and three times per week (n = 28), respectively. The median annualized recurrence rates during the treatment period were 3.8, 4.9, 3.2, and 3.1, respectively. There were no statistically significant differences in the time to first recurrence or in the annualized recurrence rate between the imiquimod and placebo groups in either the treatment or the observation period. A trend in increased rates of local adverse events at the application site and a delay in lesion healing with more frequent dosing suggested a pharmacologic effect. Although clinical efficacy has been observed for imiquimod in other conditions in which a TH1-type immune response may be beneficial, including other viral infections such as those caused by human papillomavirus, no apparent effect on the short-term natural history of herpes genitalis recurrences was observed.

Adjuvants, Immunologic↗

Recurrent bleb infections.

AIM: To report the patient characteristics, causative organisms, and clinical outcomes in patients with recurrent bleb related ocular infections. METHODS: The medical records of all patients diagnosed with bleb related ocular infection at the New York Eye and Ear Infirmary over a 10 year period were reviewed. Recurrent bleb infection was defined as at least two episodes of bleb purulence with or without associated intraocular inflammation separated by a quiescent period of at least 3 months. RESULTS: Recurrent bleb infections developed in 12 eyes of 12 patients (10 men, two women) a mean of 16.3 (SD 17.9) months (range 3-51 months) after the initial infection. Two patients developed a third episode 3 and 20 months, respectively, after the second infection, yielding a total of 14 recurrent infection episodes. Recurrent infection developed after trabeculectomy in 11 eyes (adjunctive 5-fluorouracil, nine eyes; mitomycin C, one eye; no antifibrosis agent, one eye) and following cataract extraction with inadvertent bleb formation in one eye. Four (36.4%) of the filtered eyes had undergone trabeculectomy at the inferior limbus. The mean follow up time from filtering surgery to the first bleb related infection was 28 months for the nine patients treated with 5-fluorouracil and 14 months for the single patient treated with mitomycin C. 11 (78.6%) cases had a documented bleb leak in the 4 week period before or at the time of recurrent infection. Topical, prophylactic antibiotics had been used in 7/14 (50%) cases. The same organism was cultured from the initial and recurrent infections in 2/14 (14.3%) cases. CONCLUSION: Eyes that have been successfully treated for bleb related infection remain at risk for recurrent infection. No apparent correlation exists between organisms responsible for the initial and recurrent infections. The increased rate of recurrent bleb related infection in patients receiving adjunctive 5-fluorouracil compared to mitomycin C may have been related to the longer follow up of the 5-fluorouracil eyes.

Adult↗

Association between transfusion of whole blood and recurrence of cancer.

Transfusion affects the immune response to renal transplantation and may be associated with recurrence of various human neoplasms. Data from patients with colonic, rectal, cervical, and prostate tumours showed an association between transfusion of any amount of whole blood or larger amounts of red blood cells at the time of surgery and later recurrence of cancer. Recipients of one unit of whole blood had a significantly higher incidence of recurrence (45%) than recipients of a single unit of red cells (12%) (p = 0.03). Recipients of two units of whole blood also had a higher rate of recurrence (52%) than those receiving two units of red cells (23%) (p = 0.03). Recipients of any amount of whole blood had similar recurrence rates (38-52%). Recipients of four or more units of red blood cells had a higher rate of recurrence (55%) than those receiving three or fewer units of red blood cells (20%) (p = 0.005). Mortality due to cancer in patients receiving three or fewer units of red blood cells (2%) was similar to that in patients who did not have transfusions (7%) and significantly lower than that observed in patients receiving three or fewer units of whole blood (20%) (p = 0.003). A proportional hazards risk analysis showed that transfusion of any whole blood or more than three units of red blood cells was significantly associated with earlier recurrence and death due to cancer. These data support an association between transfusion and recurrence of cancer. They also suggest that some factor present in greater amounts in whole blood, such as plasma, may contribute to the increased risk of recurrence in patients who have undergone transfusion. Until the questions raised by retrospective studies of cancer recurrence and transfusion can be answered by prospective interventional trials with washed red blood cells, red blood cells should be transfused to patients with cancer in preference to whole blood when clinically feasible.

Blood Transfusion↗

Mucin expression in pleomorphic adenoma of salivary gland: a potential role for MUC1 as a marker to predict recurrence.

BACKGROUND: Pleomorphic adenoma of the salivary gland (PA) is essentially a benign neoplasm. However, patients with recurrent PA are difficult to manage. There are rare reports on useful immunohistochemical markers to detect a high risk of recurrence when the primary lesions are resected. AIMS: To find a new marker to predict the recurrence of PA. METHODS: Primary lesions of PA were collected from nine patients showing subsequent recurrence and from 40 patients without recurrence during at least 10 years of follow up of the disease. Paraffin wax embedded tumour samples of the two groups were examined for the expression profiles of MUC1 (differentially glycosylated forms), MUC2, MUC4, MUC5AC, and MUC6 using immunohistochemistry. Several clinicopathological factors were also examined. RESULTS: In univariate analysis of the factors examined, MUC1/DF3 high expression (more than 30% of the neoplastic cells stained) in the primary lesions was seen more frequently in patients with recurrence (four of nine) than in those without recurrence (three of 40; p = 0.011). Larger tumour size (more than 3.0 cm) of the primary PA was also a significant (p = 0.035) risk factor for the recurrence of PA. In multivariate analysis, only high expression of MUC1/DF3 was found to be a significant independent risk factor for the recurrence of PA (p = 0.021). CONCLUSIONS: Expression of MUC1/DF3 in PA is a useful marker to predict its recurrence. Those patients with PA showing positive MUC1/DF3 expression should be followed up carefully.

Adenoma, Pleomorphic↗

Twenty four hour pulse pressure predicts long term recurrence in acute stroke patients.

OBJECTIVES: The impact of different blood pressure (BP) components during the acute stage of stroke on the risk of recurrent stroke is controversial. The present study aimed to investigate by 24 hour BP monitoring a possible association between acute BP values and long term recurrence. METHODS: A total of 339 consecutive patients with first ever acute stroke underwent 24 hour BP monitoring within 24 hours of ictus. Known stroke risk factors and clinical findings on admission were documented. Patients given antihypertensive medication during BP monitoring were excluded. The outcome of interest during the one year follow up was recurrent stroke. The Cox proportional hazard model was used to analyse association of casual and 24 hour BP recordings with one year recurrence after adjusting for stroke risk factors, baseline clinical characteristics, and secondary prevention therapies. RESULTS: The cumulative one year recurrence rate was 9.2% (95% CI 5.9% to 12.3%). Multivariate Cox regression analyses revealed age, diabetes mellitus, and 24 hour pulse pressure (PP) as the only significant predictors for stroke recurrence. The relative risk for one year recurrence associated with every 10 mm Hg increase in 24 hour PP was 1.323 (95% CI 1.019 to 1.718, p = 0.036). Higher casual PP levels were significantly related to an increased risk of one year recurrence on univariate analysis, but not in the multivariate Cox regression model. CONCLUSIONS: Elevated 24 hour PP levels in patients with acute stroke are independently associated with higher risk of long term recurrence. Further research is required to investigate whether the risk of recurrent stroke can be reduced to a greater extent by decreasing the pulsatile component of BP in patients with acute stroke.

Acute Disease↗

Recurrence of primary spontaneous pneumothorax.

BACKGROUND: Primary spontaneous pneumothorax (PSP) is a common clinical problem and its incidence is thought to be increasing. The risk of recurrence is high and various studies quote rates of 20-60%. Factors which may or may not predispose to recurrence have not yet been established. METHODS: In a study period of four years 291 cases with a diagnosis of pneumothorax were reviewed; 153 patients with PSP were included in the study. Their risk of recurrence was analysed with particular reference to the following variables: age, sex, height and body mass index (BMI) of the patient, the initial size of pneumothorax, the smoking status of the patient, and the primary form of treatment employed. Univariate analysis was carried out by chi 2 testing and multivariate analysis was calculated by a logistic regression model. RESULTS: A retrospective study of 275 episodes of PSP in 153 patients over a four year period confirmed a high incidence of recurrence (54.2%). PSP was twice as common in men as in women, though women were significantly more likely to develop a recurrence (chi 2 = 7.58, df = 1, p < 0.01). Male height was the second most important factor, and smoking cessation the only other variable which significantly influenced the risk of recurrence. CONCLUSIONS: Analysis of several potential risk factors revealed that recurrence was not related to the BMI of the patient, the initial treatment of the pneumothorax, nor to its size. Recurrence was more common in taller men and in women. Smoking cessation appeared to reduce the risk of recurrence. These findings are discussed in the context of the possible aetiology of spontaneous pneumothorax, recurrences, and the management thereof.

Adolescent↗

Cohypermethylation of p16 and FHIT promoters as a prognostic factor of recurrence in surgically resected stage I non-small cell lung cancer.

Despite advances in the detection and treatment of lung cancer, the prognosis for patients with lung cancer is poor, partly as a result of recurrences. We retrospectively analyzed the relationship between recurrence and survival in patients with non-small cell lung cancers (NSCLC), and the promoter methylation of p16, GSTP1, FHIT, H-cadherin, and RARbeta2 genes to identify a prognostic molecular marker associated with the recurrence of NSCLC. Methylation status from 335 paraffin blocks was determined by methylation-specific PCR. Of the 335 NSCLC samples, promoter methylation was detected in 35% for p16, 39% for RARbeta2, 42% for H-cadherin, 7% for GSTP1, and 21% for FHIT. Recurrence was observed in 39% (132 of 335) of the patients. Recurrence was significantly associated with histology (P = 0.001) and pathologic stage (P = 0.009). Hypermethylation of any single gene was not associated with recurrence in patients. However, cohypermethylation of p16 and FHIT genes in stage I NSCLCs was associated with an increased risk of recurrence [odds ratio, 6.43; 95% confidence interval (CI), 1.04-20.19; P = 0.02] and poor recurrence-free survival after surgery (hazard ratio, 2.03; 95% CI, 1.09-6.23; P = 0.02). In addition, their survival after recurrence was also 4.62 times poorer (95% CI, 1.27-16.48; P = 0.005) than for those without cohypermethylation of both genes. In conclusion, the present study suggests that cohypermethylation of p16 and FHIT genes in patients with stage I NSCLC may be a valuable biomarker for predicting the recurrence-associated prognosis of the disease.

Acid Anhydride Hydrolases↗

Steroid 5alpha-reductase isozymes I and II in recurrent prostate cancer.

PURPOSE: Prostate cancer recurs during androgen deprivation therapy despite reduced circulating androgens. We showed that recurrent prostate cancer tissue has testosterone levels similar to androgen-stimulated benign prostate, whereas dihydrotestosterone levels were reduced 82% to 1.45 nmol/L, sufficient for androgen receptor activation. The altered testosterone/dihydrotestosterone ratio in recurrent prostate cancer suggests loss of 5alpha-reducing capability. The aim of this study was to characterize steroid 5alpha-reductase isozymes I (S5alphaRI) and II (S5alphaRII) in prostate tissues. EXPERIMENTAL DESIGN: A tissue microarray was constructed from 22 recurrent prostate cancer specimens and matched pairs of androgen-stimulated benign prostate and androgen-stimulated prostate cancer from 23 radical prostatectomy specimens. Immunoblots were constructed from eight recurrent prostate cancers, eight androgen-stimulated benign prostate, and eight androgen-stimulated prostate cancer specimens. Isozyme expression was examined in microarray sections and immunoblots using S5alphaRI and S5alphaRII polyclonal antibodies. Isozyme activities were measured in 12 recurrent prostate cancer, 12 androgen-stimulated benign prostate, and 12 androgen-stimulated prostate cancer specimens. RESULTS: Nuclear immunostaining exhibited higher S5alphaRI expression than S5alphaRII in recurrent prostate cancer, androgen-stimulated benign prostate, and androgen-stimulated prostate cancers (P < 0.0001); mean expression was 125, 150, and 115 for S5alphaRI versus 10, 29, and 37 for S5alphaRII, respectively. Cytoplasmic immunostaining was moderate and similar for both isozymes in the three tissue types (P > 0.05). Immunoblots confirmed immunohistochemistry; S5alphaRI was expressed in recurrent prostate cancer specimens and S5alphaRII was not detected. The activity of S5alphaRI (114.4 pmol/mg epithelial protein/minute) was 3.7-fold higher than S5alphaRII (30.7 pmol/mg epithelial protein/minute) in recurrent prostate cancer specimens. CONCLUSIONS: Expression levels and isozyme activity shifts from S5alphaRII toward S5alphaRI in recurrent prostate cancer. Dual inhibition of S5alphaRI and S5alphaRII should reduce dihydrotestosterone biosynthesis and may prevent or delay growth of recurrent prostate cancer.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Nucleotide excision repair gene polymorphisms and recurrence after treatment for superficial bladder cancer.

PURPOSE: Interindividual differences in DNA repair capacity not only modify individual susceptibility to carcinogenesis, but also affect individual response to cancer treatment. Nucleotide excision repair (NER) is one of the major DNA repair pathways in mammalian cells involved in the removal of a wide variety of DNA lesions. Polymorphisms in NER genes may influence DNA repair capacity and affect clinical outcome of bladder cancer treatment. EXPERIMENTAL DESIGN: To test the influence of NER gene polymorphisms on superficial bladder cancer outcome (recurrence and progression), we conducted a follow-up study of 288 patients with superficial bladder cancer. Median follow-up among patients who were recurrence-free at the end of observation was 21.7 months from diagnosis. The specific polymorphic loci examined include XPA [A/G at 5' untranslated region (UTR)], XPC (poly AT, Ala(499)Val, Lys(939)Gln), XPD (Asp(312)Asn, Lys(751)Gln), XPG (His(1104)Asp), ERCC 1 (G/T at 3' UTR), and ERCC6 (Met(1097)Val, Arg(1230)Pro). RESULTS: The ERCC6 (Met(1097)Val) polymorphism had a significant impact on recurrence: carriers of at least one variant allele (Val) had a significantly higher recurrence risk than carriers of the wild-type allele (Met/Met; hazard ratio, 1.54; 95% confidence interval, 1.02-2.33). There were no overall statistically significant differences in the distributions of the other polymorphisms between patients with and without recurrence. However, when we combined these variant genotypes, there was a significant trend for an increased recurrence risk with an increasing number of putative high-risk alleles. Using individuals with five or fewer putative high-risk alleles as the reference group, individuals with six to seven risk alleles and individuals with eight or more risk alleles had higher recurrence risks, with hazard ratios of 0.92 (0.54-1.57) and 2.53 (1.48-4.30), respectively (P for trend < 0.001). There was also a significant trend for shorter recurrence-free survival time with increasing number of variant alleles (log rank test, P = 0.0007). When we stratified the patients according to intravesical Bacillus Calmette-Guerin treatment, we found a significant trend for shorter recurrence-free survival time in patients with variant alleles of XPA or ERCC6 polymorphisms who received Bacillus Calmette-Guerin treatment (log rank test, P = 0.078 and 0.022, respectively). There were no significant individual or joint associations between these polymorphisms and progression. CONCLUSIONS: These data suggest that interindividual differences in DNA repair capacity may have an important impact on superficial bladder cancer recurrence. A pathway-based approach is preferred to study the effects of individual polymorphism on clinical outcomes.

Aged↗

Comparison of fibronectin content in urinary macromolecules between normal subjects and recurrent stone formers.

OBJECTIVES: Fibronectin (FN: 230 kD) is a multifunctional alpha(2)-glycoprotein distributed throughout the extracellular matrix and body fluids. Recent studies have shown that a variety of molecules, including FN, inhibit the endocytosis of calcium oxalate (CaOx) crystals in vitro. We recently reported that FN was oversecreted from the renal tubular cells as a result of the stimulation of CaOx crystals, and inhibited the aggregation of CaOx crystals and the adhesion of CaOx crystals to the renal tubular cells. In the present study, we investigated the difference of FN content in urinary macromolecules (UMMs) between normal subjects and recurrent stone formers. MATERIALS AND METHODS: Urinary parameters in relation to urolithiasis of normal subjects and recurrent stone formers were measured. Proteins in extracted UMMs from urine of normal subjects and recurrent stone formers were measured with a BioRad protein assay, GAGs in each UMMs with a modified DMB assay and the FN content with the ELISA method. RESULTS: In urinary parameters, citrate was significantly higher in urine from normal subjects (female) than normal subjects (male) or recurrent stone formers, and the other parameters showed no differences between each group. The protein concentrations in UMMs showed no differences between each group. Normal subjects (male and female) showed a significantly higher concentration of GAGs than recurrent stone formers (with and without silent stone). Compared with normal subjects and recurrent stone formers without silent stones, higher FN levels were found in recurrent stone formers with silent stones. Normal subjects showed a significantly higher concentration of FN than recurrent stone formers without silent stones. No difference in FN level was shown between normal subjects (male) and normal subjects (female). CONCLUSION: Recurrent stone formers with silent stones showed a significantly higher concentration of FN in UMMs than normal subjects. This finding suggests that FN might be oversecreted from the renal tubular cells as a result of the stimulation of CaOx stones in vivo. Recurrent stone formers without silent stones showed a significantly lower concentration of FN in UMMs than normal subjects. From this finding it is suggested that FN might play a role as a potent inhibitor of CaOx urolithiasis in a clinical setting.

Adult↗

Factor V Leiden and risks of recurrent idiopathic venous thromboembolism.

BACKGROUND: Whether Leiden mutation in the gene coding for coagulation factor V is associated with recurrent idiopathic venous thromboembolism (VTE) is unknown, but such data are necessary to evaluate the merits of genetic screening in secondary prevention of thromboembolic disease. METHODS AND RESULTS: Among 14,916 apparently healthy men who provided DNA samples and were followed in the Physicians' Health Study through August 1994, 77 suffered an idiopathic VTE. These 77 men were followed for an additional average period of 68.3 months, during which time 11 (14.3%) suffered a recurrent idiopathic VTE. Factor V Leiden status was assessed in these men, and incidence rates of recurrence were calculated by genotype. All recurrent events occurred after cessation of anticoagulation. Seven recurrences occurred among 63 genetically unaffected subjects (11.1%; incidence rate, 1.82 per 100 person-years), while four occurred among those 14 heterozygous for factor V Leiden (28.6%; incidence rate, 7.46 per 100 person-years). Thus, factor V Leiden was associated with a fourfold to fivefold increase in risk of recurrent VTE (crude relative risk, 4.1; P = .04; age- and smoking-adjusted relative risk, 4.7; P = .047). There was no difference in mean time between index and recurrent events by genotype. Among heterozygous men, 76% of recurrent events were attributable to mutation. CONCLUSIONS: In prospective evaluation of 77 men with a history of idiopathic VTE, factor V Leiden was associated with a fourfold to fivefold increased risk of recurrent thrombosis. These data raise the possibility that patients with VTE affected by factor V Leiden may require more prolonged anticoagulation to prevent recurrent disease compared with those without mutation.

Adult↗

Risk of recurrence of bipolar disorder in pregnant and nonpregnant women after discontinuing lithium maintenance.

OBJECTIVE: Pregnancy poses major challenges for the treatment of bipolar disorder, and information to guide clinical care remains very sparse. The authors sought to determine the illness recurrence risk for women with bipolar disorder who discontinue lithium maintenance during pregnancy. METHOD: The authors retrospectively compared recurrence rates and survival functions for 101 women with DSM-IV bipolar disorder (68 type I, 33 type II) during pregnancy and postpartum (N=42) or during equivalent periods (weeks 1-40 and 41-64) for age-matched nonpregnant subjects (N=59) after either rapid (1-14 days) or gradual (15-30 days) discontinuation of lithium. Recurrence rates also were obtained for the year before discontinuing lithium. RESULTS: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant (52%) and nonpregnant women (58%) but had been much lower for both in the year before treatment was discontinued (21%). Among subjects who remained stable over the first 40 weeks after lithium discontinuation, postpartum recurrences were 2.9 times more frequent than recurrences in nonpregnant women during weeks 41-64 (70% versus 24%). Depressive or dysphoric-mixed episodes were more prevalent in pregnant than nonpregnant women (63% versus 38% of recurrences). Recurrence risk was greater after rapid than after gradual discontinuation, and for patients with more prior affective episodes, but was similar for diagnostic types I and II. CONCLUSIONS: Rates of recurrence during the first 40 weeks after lithium discontinuation were similar for pregnant and nonpregnant women but then sharply increased postpartum. Risk was much lower during preceding treatment and less with gradual discontinuation. Treatment planning for potentially pregnant women with bipolar disorder should consider the relative risks of fetal exposure to mood stabilizers versus the high recurrence risks after discontinuing lithium.

Age of Onset↗

Multiple recurrences of major depressive disorder.

OBJECTIVE: The authors of this study examined multiple recurrences of unipolar major depressive disorder. METHOD: A total of 318 subjects with unipolar major depressive disorder were prospectively followed for 10 years within a multicenter naturalistic study. Survival analytic techniques were used to examine the probability of recurrence after recovery from the index episode. RESULTS: The mean number of episodes of major depression per year of follow-up was 0. 21, and nearly two-thirds of the subjects suffered at least one recurrence. The number of lifetime episodes of major depression was significantly associated with the probability of recurrence, such that the risk of recurrence increased by 16% with each successive recurrence. The risk of recurrence progressively decreased as the duration of recovery increased. Within subjects, there was very little consistency in the time to recurrence. CONCLUSIONS: Major depressive disorder is a highly recurrent illness. The risk of the recurrence of major depressive disorder progressively increases with each successive episode and decreases as the duration of recovery increases.

Adolescent↗

A simple computer program for calculating PSA recurrence in prostate cancer patients.

BACKGROUND: Prostate cancer is the most common tumor in men. The most commonly used diagnostic and tumor recurrence marker is Prostate Specific Antigen (PSA). After surgical removal or radiation treatment, PSA levels drop (PSA nadir) and subsequent elevated or increased PSA levels are indicative of recurrent disease (PSA recurrence). For clinical follow-up and local care PSA nadir and recurrence is often hand calculated for patients, which can result in the application of heterogeneous criteria. For large datasets of prostate cancer patients used in clinical studies PSA measurements are used as surrogate measures of disease progression. In these datasets a method to measure PSA recurrence is needed for the subsequent analysis of outcomes data and as such need to be applied in a uniform and reproducible manner. This method needs to be simple and reproducible, and based on known aspects of PSA biology. METHODS: We have created a simple Perl-based algorithm for the calculation of post-treatment PSA outcomes results based on the initial PSA and multiple PSA values obtained after treatment. The algorithm tracks the post-surgical PSA nadir and if present, subsequent PSA recurrence. Times to PSA recurrence or recurrence free intervals are supplied in months. RESULTS: Use of the algorithm is demonstrated with a sample dataset from prostate cancer patients. The results are compared with hand-annotated PSA recurrence analysis. The strengths and limitations are discussed. CONCLUSIONS: The use of this simple PSA algorithm allows for the standardized analysis of PSA recurrence in large datasets of patients who have undergone treatment for prostate cancer. The script is freely available, and easily modifiable for desired user parameters and improvements.

Algorithms↗

Osteosarcoma recurrences in pediatric patients previously treated with intensive chemotherapy.

PURPOSE AND METHODS: Between January 1981 and June 1993, 137 children and adolescents were each treated at the Institut Gustave Roussy for an initially nonmetastatic osteosarcoma of the extremities. We report the retrospective analysis of 42 cases of recurrence that occurred in this population. RESULTS: The median interval between the diagnosis of the primary osteosarcoma and the first recurrence was 21 months (range, 5 to 60). The site of the first recurrence was limited to the lung in 20 patients, the bone in seven patients, was local in six patients, and was confined to soft tissue in one patient. In eight patients, the first recurrence affected multiple sites. Subsequent recurrences often involved unusual or multiple sites. Management of recurrences included surgery and/or various regimens of second-line chemotherapy, and in one case involved high-dose chemotherapy followed by autologous bone marrow transplantation. Overall survival and event-free survival were, respectively, 36% and 27% at 36 months. At present, 13 patients are alive without evidence of disease. Response of the primary tumor to preoperative chemotherapy, the time between the diagnosis and the first recurrence, and the number of metastatic lesions did not correlate with survival. The survival rate is better in patients with a local or a pulmonary first recurrence. CONCLUSION: The most important prognostic indicator at first recurrence seems to be the possible complete resection of disease. Patients not amenable to surgery and patients with a second or a third recurrence have a poor prognosis. The potential benefit of more aggressive treatments such as high-dose chemotherapy and autologous bone marrow transplantation should be investigated for these patients.

Adolescent↗

Sleep state and the risk of seizure recurrence following a first unprovoked seizure in childhood.

In a prospective study, we have followed 347 children identified at the time of a first unprovoked seizure for a mean of 46 months. To date, 135 (39%) have experienced a seizure recurrence. In this study, we analyzed recurrence risk as a function of whether the child was asleep or awake at the time of the first seizure. The cumulative recurrence risks for children whose first seizure occurred in sleep was 28% at 0.5 years, 39% at 1 year, 53% at 2 years, and 55% at 4 years, compared with recurrence risks of 18%, 23%, 30%, and 35% at the same intervals in children whose first seizure occurred while awake (p < 0.001). The association of a first seizure during sleep with an increased recurrence risk was present primarily in children with idiopathic seizures. It occurred in both those with a normal and an abnormal EEG. On multivariable analysis, sleep state, etiology, and the EEG were statistically significant predictors of recurrence risk. In children who experienced a seizure recurrence, the recurrences occurred in the same sleep state in 73% of the cases (p < 0.0001). This was also true of subsequent recurrences. We conclude that the occurrence of a first seizure in sleep is associated with an increased risk of recurrence. Subsequent seizures, if they do occur, usually occur in the same sleep state as the initial seizure.

Adolescent↗