Low‐molecular‐weight heparin added to aspirin in the prevention of recurrent early‐onset pre‐eclampsia in women with inheritable thrombophilia: the FRUIT‐RCT

Summary. Background: Early‐onset hypertensive disorders (HD) of pregnancy and small‐for‐gestational age infants (SGA) are associated with placental vascular thrombosis, these often recur and are also associated with inheritable thrombophilia. Aspirin reduces the recurrence risk. Objectives: Adding low‐molecular‐weight heparin (LMWH) to aspirin at < 12 weeks gestation reduces the recurrence of HD in women with previous early‐onset HD (pre‐eclampsia, hemolysis, elevated liver enzymes and low platelets [HELLP] syndrome and eclampsia) and/or SGA, in the context of inheritable thrombophilia without antiphospholipid antibodies. Patients/methods: In a multicenter randomized control trial (RCT), 139 women included were < 12 weeks gestation. Inclusion criteria: previous delivery < 34 weeks gestation with HD and/or SGA; inheritable thrombophilia (protein C deficiency, protein S deficiency, activated protein C resistance, factor V Leiden heterozygosity and prothrombin gene G20210A mutation heterozygosity); and no antiphospholipid antibodies detected. Intervention: either daily LMWH (dalteparin, 5000 IU weight‐adjusted dosage) with aspirin 80 mg or aspirin 80 mg alone. Main outcome measures: Primary outcomes: recurrent HD onset (i) < 34 weeks gestation and (ii) irrespective of gestational age. Secondary outcomes: recurrent SGA, preterm birth, maternal/neonatal hospitalization, spontaneous abortion and individual HD. Analysis by intention‐to‐treat. Results: Low‐molecular‐weight heparin with aspirin reduced recurrent HD onset < 34 weeks gestation (risk difference [RD] 8.7%: confidence interval [CI] of RD 1.9–15.5%; P = 0.012; number needed to treat [NNT] 12). Recurrent HD irrespective of gestational age was not different between the arms. No women withdrew as a result of adverse effects. Trial Registration: http://www.isrctn.org ) (isrctn87325378). Conclusions: Adding LMWH to aspirin at < 12 weeks gestation reduces recurrent HD onset < 34 weeks gestation in women with inheritable thrombophilia and prior delivery for HD/SGA <34 weeks. However, close monitoring of the mother and fetus remains important throughout pregnancy.     

Mortality and cancer incidence in persons with Down's syndrome, their parents and siblings

A cohort study of 1425 persons with Down's syndrome (DS), and of their parents (447 mothers, 435 fathers) and siblings (1176), was set up to investigate death rates from various causes and cancer incidence patterns. In individuals with DS the all-cause death rate was six times that of the national population (SMR = 622: 95% CI 559–693), the excess being attributable to many different causes. These included: leukaemia (SMR = 1304: 95% CI 651–2334); diabetes mellitus (SMR = 982: 95% CI 267–2515); Alzheimer's disease (SMR = 22028: 95% CI 7137–51326); epilepsy (SMR = 1727: 95% CI 744–3403); and congenital anomalies (SMR = 4987: 95% CI 4175–5955). The overall survival showed marked improvements for successive birth cohorts, particularly at young ages. For mothers and fathers of persons with DS, all-cause death rates were 20% lower than national rates and there were no significant excesses from any specific cause. For siblings, all-cause death rates were similar to national rates; the only condition with a significantly raised mortality ratio was colo-rectal cancer (SMR = 793: 95% CI 216–2031), but this may well be a chance finding.     

CHRONIC SACRAL NEUROMODULATION IN PATIENTS WITH LOWER URINARY TRACT SYMPTOMS: RESULTS FROM A NATIONAL REGISTER

PURPOSE: The Italian Register was created in February 1997 to collect the national results of sacral neuromodulation. All Italian centers at which sacral neuromodulation is performed were invited to participate in our study. We present the results from retrospective and prospective registers. MATERIALS AND METHODS: A total of 196 patients underwent permanent implantation of sacral neuromodulation and were enrolled in the Italian register. There were 18 males and 75 females in the retrospective, and 28 males and 75 females in the prospective studies. Student's t test was used to compare paired values, and the Wilcoxon rank sum and nonparametric tests were used when necessary. RESULTS: Mean incontinent episodes daily plus or minus standard deviation for patients with detrusor instability went from 5.4 +/- 3.9 to 1.1 +/- 1.6 (median 5 and 0, respectively) at 12-month followup (p <0.001). For idiopathic retention average residual volume decreased from 277 to 108 cc (median 287 and 80, respectively), and 50% of patients stopped catheterization and another 13% catheterized once daily at 1-year after implantation. With neurogenic voiding disturbances, the results fluctuated with time from a minimum of 33% to a maximum 66% of patients who did not catheterize at 6-month followup and 12 months after implantation, respectively. At 12-month followup, 50% of patients with hyperreflexia had less than 1 incontinent episode daily. The problem was completely solved in 66% of patients in the retention group. Of patients in the urge incontinent population 39% were completely dry and 23% had less than 1 incontinent episode daily. CONCLUSIONS: Sacral neuromodulation is effective therapy for treating lower urinary tract symptoms resistant to less invasive therapy.     

Reduction of immunosuppression for transplant-associated skin cancer: expert consensus survey

BACKGROUND: Reduction of immunosuppression is considered a reasonable adjuvant therapeutic strategy in solid-organ transplant recipients experiencing multiple or high-risk skin cancers. However, the literature provides no guidance about what threshold of cancer development would warrant initiation of reduction of immunosuppression. OBJECTIVES: To develop expert consensus guidelines for initiation of reduction of transplant-associated immunosuppression for solid-organ transplant recipients with severe skin cancer. METHODS: An expert consensus panel was convened by the International Transplant Skin Cancer Collaborative and Skin Care for Organ Transplant Patients Europe Reduction of Immunosuppression Task Force. Thirteen hypothetical patient scenarios with graduated morbidity and mortality risks were presented and mean and mode expert opinions about appropriate level of reduction of systemic immunosuppression (mild, moderate, severe) were generated. RESULTS: Mild reduction of transplant-associated immunosuppression was considered warranted once multiple skin cancers per year developed or with individual high-risk skin cancers. Moderate reduction was considered appropriate when patients experienced > 25 skin cancers per year or for skin cancers with a 10% 3-year risk of mortality. Severe reduction was considered warranted only for life-threatening skin cancers. CONCLUSIONS: Reduction of immunosuppression is considered a reasonable adjuvant management strategy for transplant recipients with numerous or life-threatening skin cancers. Proposed guidelines are presented for the graduated reduction of immunosuppression coincident with the increasing skin cancer risks.     

Rituximab and immune tolerance in severe hemophilia A: a consecutive national cohort

Summary.  Background and objectives:  he management of patients with severe hemophilia A and inhibitors to factor VIII (FVIII) resistant to standard immune tolerance is challenging. There have been recent case reports of the successful use of rituximab in up to 57% of patients as part of rescue immune tolerance regimens. Because case reports and small series are prone to the potential bias of reporting good outcomes and relatively short follow up, a consecutive cohort of all patients treated in the UK with prolonged follow up was analyzed. Methods:  A national survey of all Comprehensive Care Haemophilia Cente in the UK. Results:  A total of 15 patients were reported of whom six (40%) achieved a negative inhibitor titer by Bethedsa assay. Durable responses were unusual, observed in only 14% of cases. Clinically significant responses with either a negative inhibitor or an inhibitor titer < 5 BU mL⁻¹ and no spontaneous bleeding with FVIII replacement were observed in seven (47%) cases. Concomitant use of FVIII appeared to be important. Of the 12 patients treated with rituximab and FVIII, six (50%) achieved a negative inhibitor titer and seven (58%) had a clinically beneficial response. None of the three patients treated without FVIII responded. Conclusions:  hese data suggest that the use of rituximab combined with FVIII is a potentially useful treatment for patients with inhibitors resistant to standard immune tolerance, although sustained inhibitor eradication is uncommon.     

经阴道、会阴超声诊断直肠肿瘤的临床价值

目的探讨经阴道、会阴超声诊断直肠肿瘤的临床价值。方法直肠灌水后经阴道、会阴超声检查直肠肿瘤病人28例,并与正常人20例,直肠腔内超声16例对照,同时5例肿瘤作了标本超声检查。结果 28例患者中,26例检出直肠肿瘤28个,其部位在距肛门口2.5～15cm范围内,2例经阴道、会阴超声未发现肿瘤。直肠灌水后经阴道会阴超声检查可直观显示肿瘤的形态,与标本超声显示一致;其病理分期的符合率分别为80.8％。发现淋巴结肿大5例。尤其对高位直肠肿瘤或肿瘤致直肠严重狭窄的病例或Miles手术后,更具有价值。结论经阴道、会阴超声可作为直肠肿瘤检查的补充方法。     

Medical Illustration of Today

The spectrum for the differential diagnosis of jaundice is more limited in the aged than in younger patients. Obstruction is the usual cause. The history is as helpful as biochemical and other investigations in excluding the causes of nonobstructive jaundice.

The first principle in management is to bring the patient to an optimal state for operation by a planned program. Other principles are to define the obstruction at operation, to employ simple measures to overcome it, and to insure a postoperative course free of complication.