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A 10 year follow up study of patients transplanted for autoimmune hepatitis: histological recurrence precedes clinical and biochemical recurrence.

BACKGROUND AND AIM: Autoimmune hepatitis (AIH) has been reported to recur after orthotopic liver transplantation (OLT) in 10-35% of patients in small series with a short follow up. The aim of the present study was to examine the clinical and histological outcome more than 10 years after OLT for AIH. PATIENTS AND METHODS: Seventeen women with a mean age of 30 (12) years at the time of OLT, selected from among 44 patients transplanted for AIH, were followed for more than 10 years. The criteria for definite AIH, as established by the International Autoimmune Hepatitis Group, were met in every case. Liver biopsies were performed 1, 2, 5, and 10 years after OLT, and when indicated by abnormal liver function tests. Specimens were examined for evidence of recurrent AIH, namely interface hepatitis, lobular activity, portal lymphoplasmocytic infiltration, and fibrosis. Other signs of recurrence included hypertransaminasaemia, serum autoantibodies, and the response to steroid reintroduction or significant steroid dose increments. RESULTS: AIH recurred in 7 (41%) of 17 patients. In four patients histological abnormalities were detected by means of protocol biopsies 1-5 years before the onset of biochemical abnormalities. Two patients developed severe recurrences after 10 and 15 years, respectively, and required treatment with steroids and tacrolimus. In the other three patients histological recurrence was detected 0.6-3 years post-OLT, concomitantly with biochemical abnormalities. CONCLUSIONS: AIH recurred in 41% of patients followed for more than 10 years after OLT. As histological signs preceded biochemical abnormalities in four patients (23.5%), regular liver biopsy is warranted after OLT. Detection of isolated histological signs may call for closer follow up and/or a change in immunosuppressive therapy.

Adolescent↗

Recurrent ischemia in the canine heart causes recurrent bursts of free radical production that have a cumulative effect on contractile function. A pathophysiological basis for chronic myocardial "stunning".

Open-chest dogs (total number used, 117) underwent 10 5-min coronary occlusions (O) interspersed with 10 min of reperfusion (R). When systolic thickening fraction was measured 9 min after each R, the first O-R cycle was found to cause the largest decrement, with only a slight additional loss during the next four cycles and no further loss during the last five cycles (group IV), suggesting that the first few episodes of ischemia preconditioned the myocardium against the stunning induced by the last five episodes. However, different results were obtained when the total deficit of wall thickening during the final 4-h R interval was measured. The total deficit was similar after one and three 5-min O (groups V and VI, respectively), indicating that the first ischemic episode did precondition against the next two episodes; however, it was approximately 2.5-fold greater after 10 O (group IV) than after 3, indicating that the first 3 episodes failed to precondition against the next 7. Thus, at some point between the 4th and 10th O, the preconditioning effect was lost and recurrent ischemic episodes started to have a cumulative effect. Measurements of free radicals with alpha-phenyl N-tert-butyl nitrone (PBN) demonstrated a burst of free radical generation immediately after the 1st, 5th, and 10th R (group VIII). The total cumulative release of PBN adducts during the initial 5 min of reflow was 58% less after the 5th R than after the 1st (P < 0.05) but did not differ significantly between the 1st and 10th R. When administered throughout the 10 O-R cycles, the .OH scavenger mercaptopropionyl glycine significantly enhanced the recovery of function (group I) and markedly suppressed the formation of free radicals (group VII). However, the beneficial effects of mercaptopropionyl glycine were completely, or largely, lost if the drug was discontinued after the first five (group II) or eight (group III) O-R cycles, respectively, implying that (a) the oxidative stress associated with the last five, or even two, cycles was sufficient to cause severe postischemic dysfunction, and (b) the cumulative injury caused by repetitive ischemic episodes is mediated by recurrent oxidative stress. This study provides direct in vivo evidence that oxygen radicals play an important role in the pathogenesis of myocardial stunning after repetitive ischemia, and implicates .OH as a primary culprit. Taken together, the data indicate that recurrent brief ischemic episodes result in recurrent bouts of oxyradical-mediated injury that have a cumulative effect on contractility, a situation that could lead to protracted or even chronic myocardial stunning.

Animals↗

Recurrent miscarriage syndrome due to blood coagulation protein/platelet defects: prevalence, treatment and outcome results. DRW Metroplex Recurrent Miscarriage Syndrome Cooperative Group.

Although first-time miscarriages are usually caused by chromosomal defects, about 55% of recurrent miscarriages are caused by procoagulant defects that induce thrombosis and infarction of placental vessels. Of recurrent miscarriages, about 7% are caused by chromosome defects, 15% to hormonal defects, and 10% to 15% to anatomical defects. Recurrent miscarriage involves more than 500,000 women in the United States each year. During the past 4 years, 179 patients, prescreened for chromosomal, hormonal, and anatomical defects, and found to harbor none, underwent hemostasis defect evaluation. A total of 160 of these have been analyzed. A hemostasis defect was found in 150 of 160 women (n = 94% of screened women). The mean age was 33 years; the mean number of miscarriages before referral was three. All women with a procoagulant defect (149) were treated with preconception ASA at 81 mg/d, and unfractionated porcine heparin at 5000 U every 12 hours was added immediately postconception; both agents were used to term delivery. Only two of 149 patients failed therapy. The defects found were as follows: antiphospholipid syndrome, 67%; sticky platelet syndrome, 21%; tissue plasminogen activator (TPA) deficiency, 9%; factor V Leiden, 7%; high PAI-1, 6%; protein S, 5%; high LP(a), 3%; AT, 2%; protein C, 1%. Thirty-eight patients had more than one defect. In the group with antiphospholipid syndrome, 24% only had a subgroup antibody (antiphosphatidyl-serine, -inositol, -ethanolamine, -choline, -glycerol) or antiphosphatidic acid antibody, in the absence of anticardiolipin antibody or lupus anticoagulant. This finding is similar to that recently reported in early age ischemic stroke patients (<50 years old). In summary, about 55% of patients with recurrent miscarriage harbor a procoagulant defect to account for placental vascular occlusion. More than 98% will have a normal term delivery with preconception aspirin (ASA) and addition of postconception heparin to term. Patients should be screened by an obstetrician or by reproductive specialists for hormonal and anatomic defects before initiating a procoagulant evaluation; if such prescreening is done, the yield of a defect is high and appropriate therapy leads to an excellent outcome.

Abortion, Spontaneous↗

Increased fragmentation of von Willebrand factor, due to abnormal cleavage of the subunit, parallels disease activity in recurrent hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and discloses predisposition in families. The Italian Registry of Familial and Recurrent HUS/TTP.

We investigated here the changes in von Willebrand factor (vWF) multimers in recurrent, sporadic and familial forms of hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP) to see whether they are actually proteolyzed in vivo in these patients. Molecular determinants of fragments in vWF were also characterized to identify possible sites of cleavage of the subunit. Unusually large vWF multimers were found in blood of 8 of 10 patients with recurrent HUS/TTP, both in the acute phase and in remission, but never in familial and sporadic cases. Instead, all of the groups showed evidence of enhanced fragmentation of vWF multimers during the acute phase. Increased fragmentation was also shown by decrease in native 225-kD vWF subunit. In recurrent and sporadic HUS/TTP, enhanced fragmentation normalized at remission, but the abnormality persisted in familial HUS/TTP patients. The latter findings suggest that patients with familial HUS/TTP may have a congenital abnormality in vWF processing. Analysis with specific monoclonal antibodies showed the presence of the normal vWF fragments with apparent molecular mass of 189, 176, and 140 kD in all patients; however, in 6 recurrent and in 5 familial cases, novel fragments that differed in size from normal ones were found. The size of these abnormal fragments differed from one patient to another and none of them was ever found in normal plasma. These results documented, for the first time in HUS/TTP, an abnormal cleavage of the vWF subunit that might account for the increased fragmentation observed in these patients.

Acute Disease↗

Association of iron deficiency anaemia in children of 1-2 years of age with low birth weight, recurrent diarrhoea or recurrent respiratory tract infection--a myth or fact?

AIMS AND OBJECTIVE: To investigate for the presence or absence of any association between low birth weight, recurrent diarrhoea or recurrent acute respiratory infections with iron deficiency anaemia in Pakistani children aged 1-2 years. METHODOLOGY: From July 1993 to July 1995 a case control study was conducted at the Community Health Centre (CHC). Fifty cases and 100 controls were included. Informed consent was taken from mothers for the blood tests of their children and a questionnaire was administered to them. Data obtained from the completed questionnaires was analyzed by chi-square and t-tests. RESULTS: There was no statistically significant difference in low birth weight (p = 0.712), recurrent diarrhoea or respiratory infections between anaemic and non-anaemic children at 1-2 years age (OR of 1.71 and 1.48 respectively). CONCLUSION: This study does not uphold the belief that low birth weight, recurrent diarrhoea or respiratory infections have a causal association with iron deficiency anaemia in 1-2 years children.

Anemia, Iron-Deficiency↗

[A case of curative resection of local recurrence after abdominosacral resection of recurrent rectal cancer based on the diagnosis of PET/CT fusion images].

A 76-year-old male with local recurrence after abdominosacral resection of recurrent rectal cancer was admitted to our hospital. Computed tomography (CT) and magnetic resonance imaging (MRI) indicated a recurrent tumor at the back of the prostate and seminal vesicles up to the resected sacral (S3) stump. However, positron emission tomography (PET)/CT fusion images showed no 18F-2-fluoro-2-deoxy-D-glucose (FDG) uptake at the pre-sacral region, which suggested postoperative scarring of the tissue. Based on the PET/CT diagnosis, we performed abdominoperineal en bloc resection of the recurrent tumor with bladder, seminal vesicles, prostate, internal obturator muscle, ischial spine, and gluteal muscle without resection of the sacrum. Specimen revealed no circumferential resection margin involvement by tumor on pathologic examination. The patient was discharged from the hospital on postoperative day 23 without major complications.

Aged↗

[Recurrence patterns and surgical treatment for recurrent colon cancer after radical resection].

OBJECTIVE: To investigate the surgical treatment for recurrent colon cancer after radical resection. METHODS: Clinical data of 87 cases with recurrence colon cancer after radical resection from Jan. 1999 to Dec. 2005 were analyzed retrospectively. RESULTS: The resection rate of recurrent colon cancer was 74.7% . 55.2% (48/87) of the cases received radical resection,and the median survival was 49 months,while 19.5% (17/87) received palliative resection with a median survival of 24 months, 25.3% (22/87) only exploration or by- pass operation with a median survival of 10 months. There were significant differences in survival among the different surgical treatments (P=0.003). CONCLUSION: The resection rate of recurrent colon cancer is high,and reoperation can prolong the survival of such patients.

Adolescent↗

Long-term outcome from a study on the prevention of postoperative recurrence in patients with renal cell carcinoma: could PBL be a predictor of postoperative recurrence in patients postoperatively treated with IFN-gamma?

This study examined the outcome of postoperative recurrence therapy on renal cell carcinoma (RCC) prevention involving treatment with single doses of interferon-gamma (IFN-gamma). From 1990-2000, 37 patients with no distant metastasis at the time they underwent a nephrectomy were enrolled in this investigation. Subcutaneous IFN-gamma was administered once a week. Total and differential white blood cells were counted before the pre-administration of IFN-gamma and then monthly thereafter for all patients. Blood lymphocyte subsets were analyzed phenotypically by direct immunofluorescence. Disease-free survival rates (DFSR) at 5 and 10 years were 81.7% and 75.9%, respectively. To clarify the effects of preoperative peripheral blood lymphocyte (PBL) and NK activity on DFSR, we categorized the patients into two groups according to the median number of PBL before the administration of IFN-gamma. Except for CD11b, PBL level had no effect on DFSR. Multiple logistic regression analysis showed that CD11b levels greater than 16.5% were associated with 25.35 odds ratio increase in the risk of postoperative recurrence. A multivariate analysis found that CD11b may be an independent factor for postoperative recurrence. In terms of preventing postoperative recurrence, our results showed that an elevated CD11b level may indicate patients who can benefit from further combination therapy.

Adult↗

[Effectiveness on the vicryl pad in treatment of primary, recurrent and re-recurrent inguinal hernias--10 years experiences].

After testing the absorbable vicryl pad, which was developed by us in 1985, and having applied the technique as a routine in the surgical therapy of inguinal hernias since 1986, in total 2222 primary inguinal hernias and additional 937 first up to maximum 10th recurrences have been treated at our surgical department by means of the additional vicryl pad implantation. Within 5 to 9 years after surgery, follow-up examinations of the primary inguinal hernias (follow-up rate of 87.8%) showed a recurrence rate of 0.96%; with a follow-up rate of 91% for re- as well as rerecurrent hernias an extremely low re-recurrent rate of only 1.7% was found. By implantation of a vicryl pad the recurrent and rerecurrent rate could therefore be decisively minimized. The vicryl pad is inducing an additional connective tissue growth in the inguinal area of the body resulting in this high success rate.

Antibiotic Prophylaxis↗

Immunotherapy for recurrent miscarriage.

BACKGROUND: Immunologic aberrations might be the cause of recurrent early pregnancy loss in some women. OBJECTIVES: The objective of this review was to assess the effects of leukocyte immunisation or other immunologic treatments such as intravenous immune globulin (IVIG) on the live birth rate in women with previous unexplained recurrent miscarriages. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched. Individual patient data were obtained from the American Society for Reproductive Immunology and by MEDLINE search. Date of last search: December 1999. SELECTION CRITERIA: Randomised trials of immunotherapy in women with three or more prior miscarriages, no more than one live birth, all non-immunologic causes ruled out and no simultaneous treatment intervention. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed by one reviewer. MAIN RESULTS: Eighteen trials of high quality were included. The various forms of immunotherapy did not show significant differences between treatment and control groups. For paternal cell immunisation, the odds ratios was 1.05, 95% confidence interval 0.75 to 1.47. For third party donor cell immunization, the odds ratio was 1.39, 95% confidence interval 0.68 to 2.82. For trophoblast membrane infusion the odds ratio was 0.40, 95% confidence interval 0.11 to 1.45. For intravenous immune globulin (IVIG), the odds ratio was 1.14, 95% confidence interval 0. 66 to 1.95. REVIEWER'S CONCLUSIONS: Paternal cell immunization, third party donor leukocytes, trophoblast membranes, and IVIG provide no significant beneficial effect over placebo in preventing further miscarriages.

Abortion, Habitual↗

[Local recurrence of breast cancer. Isolated local recurrence located at the skin of the latissimus dorsi donor flap after breast reconstruction].

The reasons for local recurrence of breast cancer are currently unknown. Inadequate resection (not RO), undetected multifocal tumors, or absence of postoperative radiation are discussed. Secondary multifocal tumors as well as ipsilateral secondary tumors have been described as potential origins. Partial local recurrences can be considered a sign for general metastasis with an isolated local "reproduction" of the initial tumor. In our patient the observation of isolated local recurrences of the initial breast cancer, located at the skin of the latissimus dorsi donor flap, may be helpful in clarifying the ongoing controversial discussion. Our case study shows that the local recurrence occurred exactly at the initial location of the primary tumor independent of the local epidermal situation. We assume that activated vertical connections exist between the fascial lymphatic system and the dermal lymphatic plexus that "directed" the way to the body wall.

Adenocarcinoma↗

Herpes simplex virus type 2 recurrent meningitis (Mollaret's meningitis): a consideration for the recurrent pathogenesis.

We report a 44-year-old Japanese woman with herpes simplex virus (HSV) type 2 recurrent meningitis (Mollaret's meningitis). The diagnosis was confirmed by nested polymerase chain reaction in her cerebrospinal fluid, but the patient's conventional HSV antibodies by complement fixation, neutralizing test or enzyme immunoassay showed low titres with low lymphoproliferative response. Several similar cases are discussed. Although the reason for the recurrent pathogenesis is uncertain, our report suggests that the low immune response including immune evasion may be involved in the pathogenesis of HSV type 2 recurrent meningitis. For this patient, long-term suppressive and patient-initiated therapies were conducted to prevent the recurrence of meningitis.

Acyclovir↗

Placebo-controlled trial of treatment of unexplained secondary recurrent spontaneous abortions and recurrent late spontaneous abortions with i.v. immunoglobulin.

The aim of this trial was to investigate whether infusions of i.v. immunoglobulins (Ig) to women with secondary recurrent spontaneous abortions and recurrent second trimester spontaneous abortions can increase the rate of successful pregnancy. In a prospective, double-blind, placebo-controlled trial, infusions of i.v. Ig (Nordimmun) or placebo were given during pregnancy to 34 women with a history of either unexplained recurrent spontaneous abortion subsequent to a birth or including at least one second trimester miscarriage. The success rate was 52.9% in the i.v. Ig group compared with 29.4% in the placebo group (not significantly different, therapeutic gain 23.5%, 95% confidence interval -8.6 to 55.7%). No changes in autoantibody concentrations or major lymphocyte subsets were induced by i.v. Ig treatment. In conclusion, an expected 55% therapeutic gain of i.v. Ig in recurrent spontaneous abortion could not be confirmed using the treatment regimen tested. However, to determine whether the trend of therapeutic gain of i.v. Ig in these women may be statistically significant, a larger trial is in progress.

Abortion, Habitual↗

The epidemiology of recurrent miscarriage: a descriptive study of 1214 prepregnant women with recurrent miscarriage.

AIMS: To describe the characteristics of the prepregnant population attending the Recurrent Miscarriage Clinic (RMC) at the National Women's Hospital (NWH), Auckland, between 1986 and 2003, and to compare them with the overall obstetric booking population of the hospital. METHODS: The identifying details of 1214 prepregnant women attending the RMC were obtained. Both hospital and RMC records, which were kept separately, were retrospectively reviewed for demographic information and results of diagnostic investigations. Data from Auckland residents who attended the clinic were compared with data from all Auckland women booking or delivering at NWH. RESULTS: RMC attendees were older than the general NWH population, but had similar parity. Clinic attendees had a higher incidence of personal and family history of antepartum haemorrhage, fetal abnormalities, stillbirths and neonatal deaths than reported rates for the general population. Chromosomal anomalies were detected in 86 women, reproductive tract anomalies were found in 142 women, and polycystic ovarian syndrome was detected in 49 women. The majority (52.7%) of women had no identifiable cause for recurrent miscarriage detected. CONCLUSIONS: These data support the concept of women with recurrent miscarriage being at high risk for adverse obstetric outcomes including fetal abnormalities, stillbirths and neonatal deaths, even when the pregnancies are ongoing. We conclude that recurrent miscarriage is different from subfertility, and provide information of use in planning care for such women.

Abortion, Habitual↗

Aspirin-induced recurrent urticaria and recurrent angioedema in non-atopic children.

Recurrent urticaria and recurrent angioedema are frequent adverse reactions in non-atopic patients who do not tolerate aspirin. Of 1,632 infants and children who visited our allergy department for the first time, nine children (0.55%), five males and four females, presented recurrent urticaria or recurrent angioedema after taking aspirin. No evidence of atopy was disclosed either by clinical history (personal and family), skin testing, eosinophil levels or total IgE. Aspirin intolerance was established by oral challenge. Only three of the nine patients reported aspirin intolerance in their histories.

Angioedema↗

Recurrent laryngeal nerve palsy after thyroidectomy with routine identification of the recurrent laryngeal nerve.

BACKGROUND: The aim of this study was to assess the risk of recurrent laryngeal nerve palsy (RLNP) after thyroidectomy with routine identification of the recurrent laryngeal nerve (RLN) during the operation. METHODS: The present study was confined to 521 patients, 348 total lobectomies and 178 total thyroidectomies, treated by the same surgeon. Temporary and permanent RLNP rates were analyzed for patient groups with stratification of primary operation for benign thyroid disease, thyroid cancer, Graves' disease, and reoperation. Measurement of the RLNP rate was based on the number of nerves at risk. Twenty-six RLNs in 20 thyroid cancer patients with intentional sacrifice were excluded from analysis. RESULTS: Forty RLNs (40 patients) developed postoperative RLNP. Complete recovery of RLN function was documented for 35 of the 37 patients (94.6%) whose RLN integrity had been ensured intraoperatively. Recovery from temporary RLNP ranged from 3 days to 4 months (mean, 30.7 days). Overall incidence of temporary and permanent RLNP was 5.1% and 0.9%, respectively. The rates of temporary/permanent RLNP were 4.0/0.2%, 2.0/0.7%, 12.0/1.1%, and 10.8/8.1% for groups classified according to benign thyroid disease, thyroid cancer, Graves' disease, and reoperation, respectively. CONCLUSIONS: Operations for thyroid cancer, Graves' disease, and recurrent goiter demonstrated significantly higher RLNP rates. Invasion of RLN was identified in 19.4% of patients with thyroid cancer. Postoperatively, the RLN recovered in most of the patients without documented nerve damage during the operation. Total lobectomy with routine RLN identification is recommended as a basic procedure in thyroid operations.

Adolescent↗

The 21-gene recurrence score assay as a tool for predicting recurrence risk and guiding adjuvant treatment selection in early breast cancer.

INTRODUCTION: Estrogen receptor-positive (ER+), HER2-negative breast cancer is the most common breast cancer subtype. While adjuvant endocrine therapy reduces recurrence risk, identifying which patients benefit from the addition of chemotherapy remains a key clinical challenge. The Oncotype DX&#xae; 21-gene Recurrence Score assay (Exact Sciences, via Genomic Health, Inc.) was developed to address this by quantifying distant recurrence risk and informing chemotherapy decisions in early-stage ER+/HER2- disease. AREAS COVERED: This diagnostic profile reviews the development, validation, and clinical evidence for Oncotype DX, including findings from the TAILORx and RxPONDER prospective trials and the subsequent development of hybrid tools integrating genomic and clinicopathological data. Alternative multiparameter molecular tests (MammaPrint, Prosigna, EndoPredict, Breast Cancer Index) are summarized and compared. We review international guideline recommendations, decision impact studies, cost-effectiveness evidence, and ongoing trials. EXPERT OPINION: Oncotype DX has strong prognostic evidence and has meaningfully reduced chemotherapy use, though its case as a biomarker predictive of therapeutic effect from chemotherapy rests on trial designs with important limitations. Its independent prognostic contribution beyond comprehensive clinicopathological assessment requires further clarification, and cost-effectiveness varies substantially by indication and healthcare setting.

Humans↗

[Cytophotometric investigations in recurrent gliomas: correlation of DNA-parameters with WHO-grade, proliferation index and recurrence-free interval].

DNA-cytophotometry is one of the methods that may contribute to a more precise evaluation of the biological behaviour of tumours in addition to the WHO-classification. In this study 121 tumour specimens of 50 patients suffering from gliomas with one or up to three recurrencies were investigated. In all cases the histological type and WHO-grade and the Ki-67/MIB1 labeling index were determined. DNA cytophotometry was performed after single cell preparation on Feulgen-stained preparations, and the following parameters were calculated: stemline ploidy, 5c-exceeding rate, and 2c-deviation index. Statistical evaluation revealed a highly significant correlation between recurrence-free interval and WHO-grade only. The DNA parameters, however, furnished additional information about increasing genetic instability in the majority of the recurrencies independently of changes in the WHO-grade. They thus seem to be useful as additional parameters for the determination of glioma progression.

Adult↗