The HELLP syndrome: Clinical issues and management. A Review

<p>Abstract</p> <p>Background</p> <p>The HELLP syndrome is a serious complication in pregnancy characterized by haemolysis, elevated liver enzymes and low platelet count occurring in 0.5 to 0.9% of all pregnancies and in 10–20% of cases with severe preeclampsia. The present review highlights occurrence, diagnosis, complications, surveillance, corticosteroid treatment, mode of delivery and risk of recurrence.</p> <p>Methods</p> <p>Clinical reports and reviews published between 2000 and 2008 were screened using Pub Med and Cochrane databases.</p> <p>Results and conclusion</p> <p>About 70% of the cases develop before delivery, the majority between the 27th and 37th gestational weeks; the remainder within 48 hours after delivery. The HELLP syndrome may be complete or incomplete. In the Tennessee Classification System diagnostic criteria for HELLP are haemolysis with increased LDH (> 600 U/L), AST (≥ 70 U/L), and platelets < 100·10⁹/L. The Mississippi Triple-class HELLP System further classifies the disorder by the nadir platelet counts. The syndrome is a progressive condition and serious complications are frequent. Conservative treatment (≥ 48 hours) is controversial but may be considered in selected cases < 34 weeks' gestation. Delivery is indicated if the HELLP syndrome occurs after the 34th gestational week or the foetal and/or maternal conditions deteriorate. Vaginal delivery is preferable. If the cervix is unfavourable, it is reasonable to induce cervical ripening and then labour. In gestational ages between 24 and 34 weeks most authors prefer a single course of corticosteroid therapy for foetal lung maturation, either 2 doses of 12 mg betamethasone 24 hours apart or 6 mg or dexamethasone 12 hours apart before delivery. Standard corticosteroid treatment is, however, of uncertain clinical value in the maternal HELLP syndrome. High-dose treatment and repeated doses should be avoided for fear of long-term adverse effects on the foetal brain. Before 34 weeks' gestation, delivery should be performed if the maternal condition worsens or signs of intrauterine foetal distress occur. Blood pressure should be kept below 155/105 mmHg. Close surveillance of the mother should be continued for at least 48 hours after delivery.</p

Assessment of Posttraumatic Stress Disorder and Educational Achievement in Sweden

This population-based cohort study investigates the association between posttraumatic stress disorder and objective indicators of educational attainment across the life span, controlling for familial factors shared by full siblings, psychiatric comorbidity, and general cognitive ability. Question To what extent is posttraumatic stress disorder (PTSD) associated with impaired educational performance over and above familial factors, psychiatric comorbidity, and general cognitive ability? Findings This population-based cohort study of 2 244 193 individuals found that those diagnosed as having PTSD were statistically significantly less likely to achieve all educational milestones, from compulsory education to finishing university, compared with individuals without the disorder independent of familial factors shared between siblings, psychiatric comorbidity, and general cognitive ability. Meaning Findings of this study suggest that posttraumatic stress disorder is associated with lower educational performance across the life span and independent of familial factors, psychiatric comorbidity, and general cognitive ability. Importance Posttraumatic stress disorder (PTSD) has been associated with impaired educational performance. Previous studies on the disorder could not control for important measured and unmeasured confounders. Objective To prospectively investigate the association between PTSD and objective indicators of educational attainment across the life span, controlling for familial factors shared by full siblings, psychiatric comorbidity, and general cognitive ability. Design, Setting, and Participants This population-based cohort study included 2 244 193 individuals born in Sweden between January 1, 1973, and December 31, 1997, who were followed-up until December 31, 2013. Clusters of full siblings were used to account for familial factors. Data analyses were conducted between December 2018 and May 2020. Exposure International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision diagnoses of PTSD in the Swedish National Patient Register. Main Outcomes and Measures Eligibility to access upper secondary education after finishing compulsory education, finishing upper secondary education, starting a university degree, and finishing a university degree. Results Of the final cohort of 2 244 193 individuals (1 151 414 [51.3%] men) included in the analysis, 1 425 326 were assessed for finishing compulsory education (919 with PTSD), 2 001 944 for finishing upper secondary education (2013 with PTSD), and 1 796 407 and 1 356 741 for starting and finishing a university degree (2243 and 2254 with PTSD, respectively). Posttraumatic stress disorder was associated with lower odds of achieving each of the educational milestones during the study period, including 82% lower odds of finishing compulsory education (adjusted odds ratio [aOR], 0.18; 95% CI, 0.15-0.20), 87% lower odds of finishing upper secondary education (aOR, 0.13; 95% CI, 0.12-0.14), 68% lower odds of starting a university degree (aOR, 0.32; 95% CI, 0.28-0.35), and 73% lower odds of finishing a university degree (aOR, 0.27; 95% CI, 0.23-0.31). Estimates in the sibling comparison were attenuated (aOR range, 0.22-0.53) but remained statistically significant. Overall, excluding psychiatric comorbidities and adjusting for the successful completion of the previous milestone and general cognitive ability did not statistically significantly alter the magnitude of the associations. Conclusions and Relevance Posttraumatic stress disorder was associated with educational impairment across the life span, and the associations were not entirely explained by shared familial factors, psychiatric comorbidity, or general cognitive ability. This finding highlights the importance of implementing early trauma-informed interventions in schools and universities to minimize the long-term socioeconomic consequences of academic failure in individuals with PTSD

Pilot clinical trial of type 1 dendritic cells loaded with autologous tumor lysates combined with GM-CSF, pegylated IFN, and cyclophosphamide for metastatic cancer patients

Twenty-four patients with metastatic cancer received two cycles of four daily immunizations with monocyte-derived dendritic cells (DC). DC were incubated with preheated autologous tumor lysate and subsequently with IFN-α, TNF-α, and polyinosinic:polycytidylic acid to attain type 1 maturation. One DC dose was delivered intranodally, under ultrasound control, and the rest intradermally in the opposite thigh. Cyclophosphamide (day -7), GM-CSF (days 1-4), and pegIFN alpha-2a (days 1 and 8) completed each treatment cycle. Pretreatment with cyclophosphamide decreased regulatory T cells to levels observed in healthy subjects both in terms of percentage and in absolute counts in peripheral blood. Treatment induced sustained elevations of IL-12 in serum that correlated with the output of IL-12p70 from cultured DC from each individual. NK activity in peripheral blood was increased and also correlated with the serum concentration of IL-12p70 in each patient. Circulating endothelial cells decreased in 17 of 18 patients, and circulating tumor cells markedly dropped in 6 of 19 cases. IFN-γ-ELISPOT responses to DC plus tumor lysate were observed in 4 of 11 evaluated cases. Tracing DC migration with [(111)In] scintigraphy showed that intranodal injections reached deeper lymphatic chains in 61% of patients, whereas with intradermal injections a small fraction of injected DC was almost constantly shown to reach draining inguinal lymph nodes. Five patients experienced disease stabilization, but no objective responses were documented. This combinatorial immunotherapy strategy is safe and feasible, and its immunobiological effects suggest potential activity in patients with minimal residual disease. A randomized trial exploring this hypothesis is currently ongoing

Risk factors for posttraumatic stress disorder: An umbrella review of systematic reviews and meta-analyses

Approximately one third of individuals who experience a severe traumatic event will develop posttraumatic stress disorder (PTSD). It is crucial to identify what factors may be associated with increased or decreased risk for PTSD. We conducted an umbrella review of systematic reviews and meta-analyses of risk/protective factors for PTSD and assessed and graded the evidence of the association between each factor and PTSD. Thirty-three systematic reviews and meta-analyses were included and 130 potential risk factors were identified. Of those, 57 showed a significant association with PTSD. Being female or being indigenous people of the Americas, among the sociodemographic factors; history of physical disease and family history of psychiatric disorder, among the pretrauma factors; and cumulative exposure to potentially traumatic experiences, trauma severity, and being trapped during an earthquake, among the peritrauma factors, showed convincing or highly suggestive evidence of an association with PTSD. Data from prospective studies were less conclusive. Our results have the potential of helping refine PTSD prediction models and contributing to the design of prevention strategies