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Mechanical circulatory support (MCS) devices, such as left ventricular assist devices (LVADs) are very useful in improving outcomes in patients with advanced-stage heart failure. Despite recent advances in LVAD development, pump thrombosis is one of the most severe adverse events caused by LVADs. The contact of blood with artificial materials of LVAD pumps and cannulas triggers the coagulation cascade. Heat spots, for example, produced by mechanical bearings are often subjected to thrombus build-up when low-flow situations impair washout and thus the necessary cooling does not happen. The formation of thrombus in an LVAD may compromise its function, causing a drop in flow and pumping power leading to failure of the LVAD, if left unattended. If a clot becomes dislodged and circulates in the bloodstream, it may disturb the flow or occlude the blood vessels in vital organs and cause internal damage that could be fatal, for example, ischemic stroke. That is why patients with LVADs are on anti-coagulant medication. However, the anti-coagulants can cause a set of issues for the patient-an example of gastrointestinal (GI) bleeding is given in illustration. On account of this, these devices are only used as a last resort in clinical practice. It is, therefore, necessary to develop devices with better mechanics of blood flow, performance and hemocompatibility. This paper discusses the development of LVADs through landmark clinical trials in detail and describes the evolution of device design to reduce the risk of pump thrombosis and achieve better hemocompatibility. Whilst driveline infection, right heart failure and arrhythmias have been recognised as LVAD-related complications, this paper focuses on complications related to pump thrombosis, especially blood coagulopathy in detail and potential strategies to mitigate this complication. Furthermore, it also discusses the LVAD implantation techniques and their anatomical challenges., (© 2022 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Introduction: The determination of age of majority (the 18-year-old threshold) using the popular Demirjian tooth staging method is unreliable, so other maturity markers are required. This study examines whether the Root Pulp Visibility (RPV) of the mandibular third molar is a useful indicator of age., Methods: One thousand six dental panoramic radiographs (DPTs) were examined and the left mandibular third molar assessed according to the RPV stages using the method of Olze et al. (Int J Legal Med 124:183-186, 2010) as modified by Lucas et al. (Forensic Sci Int 270:98-102, 2017). Six hundred sixty-two DPTs, 288 males and 374 females, satisfied the inclusion criteria., Results: Individuals who had reached stages RPV-A and RPV-B were represented in a wide range of ages spanning the 18-year-old threshold. Individuals who had reached stages RPV-C and RPV-D were all above the 18-year-old threshold. It was not possible to analyse a large number of DPTs for various reasons., Discussion: Individuals whose mandibular third molar exhibited stages RPV-C and RPV-D may be deemed to have reached the age of majority. These results are consistent with other published studies. Variation in the rate of development of the third molar limits the applicability of this method., Conclusions: RPV staging is an accurate method of determining the 18-year-old threshold. Substitute methods are required in a large number of cases.

Preeclampsia is a common and major cause of maternal and perinatal morbidity and mortality. Human leucocyte antigen (HLA) susceptibility and impaired adaptation of the T lymphocyte sub-population and a bi-directional effect of T helper cytokines on the outcome of pregnancy have been reported in patients with preeclampsia. The association between maternal HLA class II and T helper cytokines in women with preeclampsia was investigated in seventy-six preeclamptic women and normotensive controls using Terasaki microlymphocytotoxicity test. T helper cytokines interleukin (IL)-8, IL-6, IL-4, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma were estimated in the maternal blood and placenta by enzyme-linked immunosorbent assay (ELISA). Histopathological evaluation of the placenta was also carried out. HLA class II DR2, DR4, DR5, DRw8, DRw10, DRw11, DRw18, and DQw2 had significant relative risk ratios for preeclampsia, while DQw3 was more common in the controls. DR4-DRw11-DQw2 haplotype was more common in preeclamptic women with intrauterine growth restriction, low birth weight and placental weight, increased expression of T helper cytokines IL-8, TNF-alpha and IFN-gamma and abnormal uteroplacental vasculature. These findings suggest that HLA class II DR4-DRw11 -DQw2 haplotypes may be associated with preeclampsia with intrauterine growth restriction through low placental weight from impaired placental development, as a result of increased expression of T helper 1 cytokines IL-8, TNF-alpha and IFN-gamma.

Objective: To investigate the incidence of leukocytospermia and relation to T helper cytokines, tumor necrosis factor alpha (TNFalpha) and interleukin-4 (IL-4), antisperm antibodies and antioxidant activity., Design: Semen samples from 176 infertile men and 24 fertile controls were investigated., Methodology: The protocol included tubal patency test, hysterosalpingography and laparoscopy and dye test and ovulation through mid-luteal phase progesterone for the wives. The husbands had semen analysis, cytomorphology evaluation and semen culture. Seminal TNFalpha and IL-4, antisperm antibodies, total antioxidant activity, superoxide dismutase and zinc were determined., Results: Leukocytospermia occurred in 44.3% of the infertile men compared to 12.5% of the fertile men (P<0.01). Thirty-six (20.5%) men had pathogenic bacterial organisms which constituted 46.2% of those with leukocytospermia. Sperm parameters were worse with leukocytospermia in terms of sperm count (P<0.01), total motility progressive motility (P<0.01), morphology, asthenozoospermia, sperm membrane integrity and antisperm antibodies. TNFalpha and IL-4 had an inverse relationship; the expression of TNFalpha was higher with leukocytospermia and bacteriospermia (P<0.001), while IL-4 was higher in fertile controls (P<0.005). Incidence of antisperm antibodies was higher with leukocytospermia. Total antioxidant activity, superoxide dismutase and zinc were lower with leukocytospermia., Conclusion: Leukocytospermia impairs sperm function through reduced antioxidant activity and enhanced T helper 1 modulation.

Background: There are suggestions that T helper 1 cytokines may be detrimental to early pregnancy and T helper 2 cytokines protective of the pregnancy. Their role in preeclamptic pregnancy, labor and puerperium, is not clear., Materials and Methods: Twenty-eight preeclamptic women and their matched controls were evaluated, at the Departments of Obstetrics and Gynecology, Faculty of Medicine, Kuwait University and Maternity Hospital, Kuwait. Outcome measures evaluated were serum levels of TNF alpha and interleukin-4 at 12, 24, 36 weeks of gestation, advanced labor and at 1 hour and daily postpartum until they were undetectable, using ELISA technique., Results: T helper cytokines showed higher serum levels in preeclampsia than normotensive pregnancy (p < 0.01, 0.01), in established labor (p < 0.05) and at 1 hour postpartum (p < 0.01 for IL-4) and p < 0.02 for TNF alpha. There was significant increase of IL-4 between 12 to 24 weeks in normal pregnancy compared to preeclampsia (p < 0.001) but not for TNF alpha. By 24 hours postpartum, IL-4 was still detectable in eight parturients compared to one patient with detectable TNF alpha (p < 0.04). Detectable IL-4 levels after 24 hours postpartum were associated with intrauterine growth retardation (p < 0.03)., Conclusion: IL-4 has a dichotomous role in pregnancy. Normotensive pregnancy is associated with high increase in IL-4 in the first half of the pregnancy, but in the second half of pregnancy and puerperium, high levels of IL-4 are associated with preeclampsia.

Purpose: The association between unexplained infertility, human leukocyte antigens (HLA) and expression of circulating antisperm antibodies was studied in 52 couples with unexplained infertility and 15 infertile and 9 fertile couples., Methodology: Evaluation parameters included Terasaki's HLA microlymphocytotoxicity test, circulating antisperm antibodies using immunofluorescence technique., Results: Fifty-two couples (8.7%) out of 600 consecutive clinic attendants had unexplained infertility. Unexplained infertility was associated with circulating antisperm antibodies (22 versus 13 and 0% for men and 18.5 versus 13 and 0% for women). HLA class 1 B6 and B52 and Cw7 and HLA class 2 DR4 and DR6 and sharing of HLA B6, DR4 and DR6 were found more in couples with unexplained infertility. Combined expression of antisperm antibodies by couples, demonstrated more homozygosity for HLA B6 and DR4., Conclusion: Homozygosity for these antigens, B6, DR4 and DR6, may enhance the expression of antisperm antibodies, and cause infertility.

The use of steroids for treating male immunological infertility is controversial. The effect of low dose prednisolone on sperm quality in men with antisperm antibodies and the conception rate, was evaluated in 40 men and their wives. Significant circulating antisperm antibodies were detected by immunofluorescence technique. Prednisolone (5 mg) was administered orally, daily for 3-6 months in men with significant antisperm antibodies. Another group of 37 men with significant antisperm antibodies, formed the control group. Both groups had initial pre- and post therapy semen analysis and hypoosmotic swelling (HOS) test. They were followed up for 12-18 months and the pregnancy outcome documented. There were significant improvement in sperm motility and hypoosmatic swelling test with therapy (P < 0.01, P > 0.05) of 13 and 15%, respectively. The pregnancy rate of 20% was much greater than 5% in the control group (P < 0.01). There were no side effects of prednisolone. Low dose prednisolone is useful in Antisperm antibody associated infertility, by improving the sperm quality and giving rise to pregnancies.

Background: Hypertension in pregnancy is associated with increased maternal and fetal morbidity and mortality. The aim of this prospective study was to evaluate the obstetric outcome of patients with pregnancy induced hypertension (PIH) that delivered at the Maternity Hospital Kuwait within a period of six months and evaluate the economic implications of present management strategies., Methods: This was a comparative study with age and parity, as matching variables, in 224 pregnant hypertensive women and 224 normotensive controls., Results: During the study period, the incidence of PIH was 4.9 percent. They were more associated with diabetes mellitus and multiple pregnancy than controls (p < 0.02). About 43 percent of the hypertensive parturients used antihypertensive therapy. More of them had induction of labor (p < 0.001), preterm delivery (p < 0.0002) and cesarean section (p < 0.001), and babies with low birthweight (p < 0.01). In the linear regression analysis, hypertension in pregnancy gave rise to more hospitalisation, intrauterine growth retardation and operative deliveries than the normotensive controls. The perinatal mortality was higher (p < 0.001)., Conclusion: Despite the economic expenditure of about five times more for hypertensive women in pregnancy than in controls, both obstetric and neonatal outcome, are still significantly worse in the former. This study therefore advocates more research into the prevention, prediction and management, including neonatal care, of hypertensive disorders of pregnancy.

Cytokines are of central importance in the regulation of immunity, inflammation, tissue remodeling, and embryonic development. Uncontrolled or excessive cytokine production may contribute to the pathophysiology of acute and constant infections, autoimmune disease, and neoplasia. Interleukin-4 was first observed as a costimulator of B-cell DNA synthesis in response to antiimmunoglobulin M antibodies. Within hours of contact with interleukin-4, resting B cells and macrophages increase their expression of the class II histocompatibility antigen needed for immune cell interaction. The aim of this study was to evaluate the levels of interleukin-4 in the sera of preeclamptic women and the cord blood of their newborn infants. Five milliliters of blood were withdrawn from the cubital vein of 25 women with preeclampsia at 24 and 36 wk gestation, at term, and just before onset of labor or in early labor. At delivery, cord blood was withdrawn from each woman's corresponding newborn. The control group was 25 women without any obstetric complication. Interleukin-4 levels were significantly higher in the preeclamptic women than the control women (p < 0.05). Similarly, the interleukin-4 level was significantly higher in the maternal blood of the preeclamptic women than in the cord blood of their newborns (p < 0.01). Because interleukin-4 increases the expression of class II histocompatibility, it may be important in immunorecognition and immunosuppression. However, excessive interleukin-4 production may contribute to the pathophysiology of preeclampsia.