Long sleep duration and cardiovascular disease: Associations with arterial stiffness and blood pressure variability

Although short and long sleep duration are both risk factors of cardiovascular disease (CVD), the recent meta‐analyses have been shown that long sleep duration was closely associated with CVD mortality. While the specific mechanism underlying the association between long sleep duration and CVD remains unclear, long sleep duration was shown to be associated with arterial stiffness and blood pressure variability (BPV) in many Asian populations. This review article will focus on the pathophysiology of long sleep duration, arterial stiffness, BPV and their effects on CVD. To set the stage for this review, we first summarize the current insights for the relationship between long sleep duration and CVD in relation to arterial stiffness and BPV.     

Hypertension and erectile dysfunction: The role of endovascular therapy in Asia

The prevalence of erectile dysfunction (ED) is above 40% in both Asian and non‐Asian male populations after the age of 40 years. The prevalence of ED among hypertensive patients is approximately double than that in normotensive population. Pelvic arterial insufficiency is the predominant cause of ED in men aged over 50 years. Stenosis in any segment of the iliac–pudendal–penile arterial system, which is considered an erectile‐related arterial axis, could lead to ED. Pharmacotherapy with lifestyle modification is effective in alleviating sexual dysfunction, yet a substantial number of patients still develop ED. Given the established applicability of angioplasty for the entire iliac–pudendal–penile arterial system, penile duplex ultrasound, and pelvic computed tomography angiography could be considered as the routine screening tools in ED patients with poor response to phosphodiesterase‐5 inhibitors. Endovascular therapy for pelvic arterial insufficiency‐related ED has been shown to be a safe and effective treatment option in patients who have anatomically suitable vessels and functionally significant stenoses. Clinical improvement was achieved in over 60% of patients at one year following pelvic angioplasty in the PERFECT registry from Taiwan. A 30%‐40% restenosis rate in distal internal pudendal and penile arteries remains a hurdle. Angioplasty for pelvic arterial occlusive disease could be considered as a viable approach to arteriogenic ED.     

A randomized controlled pilot study of Pentoxifylline in patients with non-alcoholic steatohepatitis (NASH)

Purpose Tumor necrosis factor-α (TNF-α) is implicated in non-alcoholic steatohepatitis (NASH). Pentoxifylline inhibits TNF-α. We wanted to evaluate the efficacy of Pentoxifylline on NASH patients. Methods Patients with biopsy proven NASH and persistently elevated alanine aminotransferase (ALT) greater than 1.5 times the upper limit of normal were randomized to 3 months of treatment with a step 1 American Heart Association diet and daily exercise with Pentoxifylline or placebo. Liver function tests, serum lipids and TNF-α, Interleukin 6 (IL-6), and plasma hyaluronic acid were measured at baseline, at weeks 6 and 12. Categorical data were analyzed by Fisher’s exact test while independent sample t-test and Mann–Whitney test were used for continuous data. Results Eleven patients were randomized into the Pentoxifylline and nine to the placebo group. After 3 months of treatment body mass index (BMI), ALT and aspartate aminotransferase (AST) decreased significantly in both groups. There was no difference between the two groups in reduction of BMI (P = 0.897). There was significantly greater reduction in AST in the Pentoxifylline group (P = 0.038). There was a trend toward lower ALT level (P = 0.065) in the Pentoxifylline group. TNF-α and IL-6 decreased significantly in both groups after treatment, but there was no significant difference between the two groups. Conclusion Three months of Pentoxifylline treatment in combination with diet and exercise results in significantly greater reduction in AST levels in patients with NASH as compared with controls. This study was funded by the National Healthcare Group Small Innovative Grant NHG-grant number. RPR/04029. It received ethics approval by the National Healthcare Group Domain Specific Research Board D-registration number DSRB-D/04/083.     

Abdominal crisis in a young man with systemic lupus erythematosus

Medium-sized artery aneurysms are rare in patients with systemic lupus erythematosus (SLE). We report on a 21-year-old Chinese man with SLE and secondary antiphospholipid syndrome (APS) who presented with acute abdominal pain due to a ruptured right hepatic artery aneurysm. He was also found to have aneurysms of the left hepatic artery and splenic artery on autopsy. There have been only eight cases of hepatic artery aneurysm and one case of splenic artery aneurysm associated with SLE in the English literature. Abdominal aneurysm must be suspected in SLE patients presenting with acute abdominal pain, haemoperitoneum or occult bleeding.     

Persistence of viral genome into late stages of murine myocarditis detected by polymerase chain reaction.

BACKGROUND. Enteroviruses have been considered as the most common etiologic agents in clinical myocarditis and dilated cardiomyopathy; however, their pathogenetic role remains unknown. Hence, the relation of viral replication and development of cardiomyopathy has been determined in a murine model of myocarditis by evaluating the persistence of viral genome during acute and chronic stages of myocarditis by means of Northern blot hybridization and polymerase chain reaction (PCR). METHODS AND RESULTS. DBA/2 mice (n = 146) were injected peritoneally with 10 plaque-forming units of encephalomyocarditis (EMC) virus, and the control mice (n = 33) were injected with normal saline. Animals were randomly killed at 4, 7, 10, 14, 21, 28, 35, and 42 days after infection. Histology revealed acute myocardial necrosis with massive inflammatory cell infiltrate peaking on day 14 followed by increasing fibrosis and declining chronic inflammation features compatible with dilated cardiomyopathy between days 21 and 42. Northern blot analysis of control and infected hearts showed detectable viral RNA in the infected hearts initially at day 4, peaking by day 7, diminishing between day 7 and day 14, and absent at day 21 and day 28. However, potential viral remnants present in low quantities and undetectable by Northern blot were further detected by PCR followed by confirmation with an internal oligonucleotide probe after day 14 up to day 42. CONCLUSIONS. Viral RNA signals on Northern blot showed a strong correlation with massive myocyte necrosis on day 14, but the viral RNA fragment was consistently detectable into late stages of cardiomyopathy on days 21, 28, 35, and 42 by PCR. This indicated that the mature virions are fully developed early in infection and are capable of persisting in the myocardium after virus-mediated myocytolysis stage. Therefore, PCR is an extremely sensitive method for detecting residual viral genome and viral persistence in the myocardium and may offer insights into the pathogenesis of chronic myocarditis leading to dilated cardiomyopathy.     

Chronic rhinosinusitis and progression of cognitive impairment in dementia

AimThe relationship between chronic inflammatory disease and cognitive decline is still unclear, but there is increasing evidence to support the role of systemic inflammation. The aim of this study was to investigate if chronic rhinosinusitis (CRS) in dementia or mild cognitive impairment (MCI) is associated with the progression of cognitive decline.Material and methodsWe retrospectively reviewed the data of patients who complained of memory impairment, and underwent brain magnetic resonance imaging (MRI) from January 2006 to April 2019. According to the Mini-Mental State Examination (MMSE) score, subjects (n = 661) were divided into three groups: dementia (≤ 17), MCI (18–23), and normal (≥ 24). CRS was defined as a total score of greater than or equal to 4 according to the Lund–Mackay scoring system using brain MRI. Multiple logistic regression analyses estimated adjusted odds ratio (aOR) for the association between CRS and dementia or MCI. Among the subjects with follow-up MMSE (n = 286), a repeated-measures ANOVA was used to assess the difference of changes in MMSE scores between the groups with and without CRS.ResultsAccording to the initial MMSE score, there were 221 subjects with dementia, 195 with MCI, and 245 with normal results. CRS was not significantly associated with dementia (aOR = 1.519, CI = 0.909–2.538, P = 0.111), while being suggestively associated with MCI (aOR = 1.740, CI = 1.041–2.906, P = 0.034). The MMSE scores at follow-up decreased further in subjects with CRS than in those without CRS (P = 0.009). Especially, in the initial dementia group, there was a significant between-group difference in the MMSE score from baseline to follow-up (13.6 ± 4.3 to 11.1 ± 6.3 in CRS group vs. 13.5 ± 3.3 to 14.4 ± 5.4 in no CRS group, P = 0.002).ConclusionThe result of the present study implies a potential association between CRS and progression of cognitive decline. Physicians should be aware of this possibility in patients with clinically diagnosed CRS.     

Interaction of neuropeptide Y genotype and childhood emotional maltreatment on brain activity during emotional processing

Neuropeptide Y (NPY) has been associated with stress reactivity in affective disorders and is most densely expressed in the amygdala. An important stressor associated with affective disorders is the experience of childhood emotional maltreatment (CEM). We investigated whether the interaction of NPY risk genotype and CEM would affect brain activation. From the Netherlands Study of Depression and Anxiety, 33 healthy controls and 85 patients with affective disorders were scanned with functional magnetic resonance imaging while making gender decisions of emotional facial expressions. Results showed interactions between genotype and CEM, within carriers of the risk genotype, CEM was associated with higher amygdala activation, whereas CEM did not influence activation in non-risk carriers. In the posterior cingulate cortex (PCC), less activation was seen in those with CEM and the risk genotype, whereas genotype did not influence PCC activation in those without CEM. In addition, those carrying the risk genotype and with experience of CEM made a faster gender decision than those without CEM. Thus, the combined effect of carrying NPY risk genotype and a history of CEM affected amygdala and PCC reactivity, areas related to emotion, self-relevance processing and autobiographical memory. These results are consistent with the notion that the combination of risk genotype and CEM may cause hypervigilance.     

The attitude toward xenocorneal transplantation in wait‐listed subjects for corneal transplantation in Korea

Shortage of donor cornea is a significant problem in Asia, and xenocorneal transplantation is being actively studied to alleviate this problem. However, the attitudes of subjects who await corneal transplants toward xenocorneal transplantation are not known at all. Thus, this study aimed to investigate the attitudes of subjects on the waiting lists for corneal transplants, toward corneal xenotransplantation. A telephone questionnaire survey comprising six items was conducted in 132 subjects among the wait‐listed individuals (n = 590) who were awaiting corneal transplantation or had undergone corneal transplantation at Seoul National University Hospital from July, 2003 to August, 2012. Among six inquiries, four questions were used to analyze attitudes toward corneal xenotransplantation. Each question pertained to (1) the acceptance of xenocorneal transplantation, (2) willingness to participate in clinical trials, (3) worries in xenocorneal transplantation, and (4) the concern of self‐identity or social life after xenocorneal transplantation. To analyze demographic factors influencing the question, the subjects were arbitrarily divided into two groups: the young (age < 60 yr, n = 58) and the elderly (age ≥ 60 yr, n = 74) or the less‐educated (n = 53) and the well‐educated with high school diploma, college graduation, or higher education (n = 79). Collected demographic data were analyzed as influencing factors on each question using a chi‐square and logistic regression tests. In this study, 42.4% of the subjects (n = 56) expressed favorable views on xenocorneal transplantation using porcine corneas to cure visual loss from corneal blindness. Among those subjects expressing favorable views (n = 56), the willingness to participate in clinical trials, knowing they and their spouses must undergo long‐term surveillance, was 62.5% (n = 35). There were 76.5% of subjects (n = 101) expressing worries regarding xenocorneal transplantation, while 28.8% of subjects (n = 38) expressed their concerns about self‐identity or social life after xenotransplantation. Younger subjects expressed more worry about xenotransplantation than elderly subjects. The well‐educated expressed less concern over self‐identity and social life than the less‐educated. This survey among subjects who are wait‐listed for corneal transplant or who have received a corneal transplant demonstrates that there is an interest in xenocorneal transplantation as an alternate procedure, although there are worries about the procedure that should be further explored in educational campaigns and future studies of the general population.     

Cross‐reactivity between decellularized porcine corneal lamellae for corneal xenobridging and subsequent corneal allotransplants

The purpose of this study is to investigate cross‐reactivity between hypertonic saline‐treated decellularized porcine corneal lamellae for corneal xenobridging and subsequent corneal allotransplants. Five Chinese rhesus macaques, which had undergone anterior partial thickness corneal transplantation using hypertonic saline‐treated decellularized porcine corneal lamellae in preceding experiments, were used as recipients for subsequent full‐thickness corneal allografts. To determine whether sensitization of recipients to xenoantigens leads to cross‐reactivity against alloantigens, we compared; (i) allogeneic one‐way mixed lymphocyte reaction (MLR) of peripheral blood mononuclear cells (PBMCs) from xeno‐sensitized recipients with that of PBMCs from naïve rhesus macaques, and (ii) amounts of IgG antibodies that bound to the PBMCs of a rhesus panel (five monkeys) before and after xeno‐sensitization. Graft survival and immunologic profiles including memory T‐cell subsets and donor rhesus‐specific antibodies were also evaluated. No hyperacute or acute rejection was observed within a month of subsequent allotransplantation in any recipient. Alloreactivity by MLR was not different between xeno‐sensitized rhesus recipients and naïve rhesus monkeys. Panel‐reactive IgG antibodies were unchanged after xeno‐sensitization, and no change in donor rhesus‐specific antibodies was observed in any recipient. No significant changes in memory T‐cell subsets were observed during the early post‐operative period in any recipient. Decellularized porcine corneal lamellae may not increase cross‐reactivity to alloantigens, and thus, porcine corneal lamellae may be used as a bridge to subsequent corneal allografting.