Relationship between ω3 and ω6 polyunsaturated fatty acids and atrial fibrillation in acute ischemic stroke.

BACKGROUND & AIMS: Some ω3 polyunsaturated fatty acids (PUFAs) are said to demonstrate a dose-related risk of atrial fibrillation (AF), conversely, some ω6 PUFAs might have AF protective potential. However, few investigated the relation among ischemic strokes. Primarily, we aimed to examine a relation between ω3 and ω6 PUFAs and the presence of AF in ischemic strokes. Further, since, some PUFAs are said to affect the cardiac load, we secondarily aimed to investigate the association between ω3 and ω6 PUFAs and brain natriuretic peptide (BNP) and the occurrence of cerebral large vessel occlusion (LVO) in ischemic strokes with AF. METHODS: Consecutive patients with ischemic stroke admitted between 2012 and 2022 were retrospectively screened. Plasma levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid, dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), were assayed. Data were analyzed using a Poisson regression analysis with a robust variance estimator and a multiple linear regression analysis. RESULTS: We screened 2112 consecutive ischemic strokes, including 1574 (1119 [71%] males, median age 69 years). Lower DGLA (prevalence ratio (PR) 0.885, 95% CI 0.811-0.966, p = 0.006), lower AA (PR 0.797, 95% CI 0.649-0.978, p = 0.030), and higher EPA/AA ratio (PR 1.353, 95% CI 1.036-1.767, p = 0.026) were associated with AF. Checking the linearity between AF and PUFAs, negative linear trends were observed between DGLA quartiles (Q1: PR 1.901, Q2: PR 1.550, Q3: PR 1.423, Q4: 1.000, p < 0.001 for trend) and AA quartiles (Q1: PR 1.499, Q2: PR 1.204, Q3: PR 1.125, Q4: 1.000, p = 0.004 for trend), with positive linear trends between EPA/AA ratio quartiles (Q1: 1.000, Q2: PR 1.555, Q3: PR 1.612, Q4: PR 1.797, p = 0.001 for trend). Among patients with AF, a negative association between AA and BNP (unstandardized coefficient -1.316, 95% CI -2.290∼-0.342, p = 0.008) was observed, and lower AA was associated with LVO (PR 0.707, 95% CI 0.527-0.950, p = 0.021). CONCLUSION: Lower DGLA and AA and a higher EPA/AA ratio might be related to the development of AF in ischemic strokes. Further, AA might have a cardio-cerebrovascular protective role in ischemic strokes with AF.

Small ischemic lesions accompanying intracerebral hemorrhage: The underlying influence of old lacunes and polyunsaturated fatty acids.

BACKGROUND AND AIMS: Small ischemic lesions (SILs) accompanying intracerebral hemorrhage (ICH) might be induced by small-vessel vulnerability and hypercoagulation. Some polyunsaturated fatty acids (PUFAs) have been associated with hypercoagulation in cardiovascular diseases. Our aim here is to determine how pre-existing small-vessel disease (SVD) and PUFAs may affect SILs. METHODS AND RESULTS: We screened consecutive ICH patients (October 2012-December 2021) meeting two inclusion criteria: (1) the patients were hospitalized for acute ICH and were undergoing magnetic resonance imaging and (2) the patients' PUFA measurements were available. After excluding patients with isolated intraventricular hemorrhage, we evaluated whether three SVD markers (white matter hyperintensities, old lacunes, cerebral microbleeds) and PUFAs might be associated with the development of SILs. We selected 319 participants from 377 screened consecutive ICH patients (median age = 64, males = 207 [65 %]). Of the 319 patients, 45 patients (14 %) developed SILs. In a multivariable logistic regression analysis, the factors associated with SILs were old lacunes (OR 3.255, 95 % CI 1.101-9.622, p = 0.033) and DHA/AA ratio (OR 0.180, 95 % CI 0.046-0.704, p = 0.013). Furthermore, in our multivariable analysis using DHA/AA ratio tertiles with and without SILs, we observed a linear trend between SILs and the Higher Tertile of the DHA/AA ratio (DHA/AA ratio Mid-Tertile: OR 1.330, 95%CI 0.557-3.177, p = 0.521, and DHA/AA ratio Lower Tertile: OR 2.632, 95%CI 1.124-6.162, p = 0.026). CONCLUSION: The presence of old lacunes and lower DHA/AA ratios might be associated with SILs accompanying ICH.

Arachidonic acid level is related to early motor recovery following intracerebral hemorrhage with severe motor paralysis.

BACKGROUND: Low arachidonic acid (AA) levels are reportedly associated with unfavorable outcomes in intracerebral hemorrhage (ICH). OBJECTIVE: We aimed to clarify whether serum AA levels might be associated with a good recovery from severe motor paralysis in the early stage of hospitalization. METHODS: From among consecutive ICH patients between October 2012 and December 2021, patients with a sum of upper and lower extremity National Institutes of Health stroke scale (NIHSS) scores of 4-8 at admission (severe motor paralysis) were included. We defined good early recovery from severe motor paralysis as a sum of upper and lower extremity NIHSS scores of 0-3 on day 7 after admission, and that of individual upper and lower extremities as NIHSS scores of 0-1 on day 7 after admission. We aimed to assess whether serum AA levels might be associated with good early recovery from severe motor paralysis. RESULTS: We screened 377 consecutive ICH patients, including 140 with severe motor paralysis (88 (63%) males, median age 64 years). Recovery from severe motor paralysis was seen in 48 (34%). Higher AA levels (PR 1.243, 95% CI 1.042 to 1.483, p = 0.016) were independently associated with good overall recovery, and good recovery of upper and lower extremities separately (upper extremity: PR 1.319, 95% CI 1.101 to 1.580, p = 0.003; lower extremity: PR 1.293, 95% CI 1.115 to 1.499, p = 0.001). CONCLUSIONS: Higher AA levels may contribute to a good early motor recovery in patients with severe motor paralysis due to ICH.

Intestinal evisceration and Staphylococcus aureus bacteremia due to ruptured umbilical hernia in a patient with liver cirrhosis: a case report and literature review.

Rupture of umbilical hernias is a potentially life-threatening condition that can occur in cirrhotic patients due to ascites. To the best of our knowledge, there are no previous reports on bacteremia following intestinal evisceration due to a ruptured umbilical hernia. Herein, we report a case of a 42-year-old female with a history of complicated alcoholic liver cirrhosis and schizophrenia who presented with intestinal evisceration and Staphylococcus aureus bacteremia secondary to a ruptured umbilical hernia. Due to a 2-day delay from presentation to hospitalization, the patient had a high risk for infection with skin flora. Initiation of appropriate antibiotic therapy, prompt surgical repair and adequate postoperative control of ascites markedly improved the patient's condition. In cases of prolonged intestinal evisceration in adults with a ruptured umbilical hernia, bacteremia treatment with antibiotics coverage for skin flora should be considered.

Systemic capillary leak syndrome requiring fasciotomy for limb compartment syndrome: A case report and literature review.

Background: Limb compartment syndrome (LCS), a rare but serious complication of systemic capillary leak syndrome (SCLS)-related systemic edema, warrants prompt decompressive fasciotomy. We report a case of SCLS complicated by LCS of four extremities requiring emergent fasciotomies; furthermore, we reviewed existing published reports on SCLS with LCS. Case Presentation: A 36-year-old man was diagnosed with SCLS based on profound vascular permeability with no other underlying conditions. Within a few hours of admission, LCS was noted in the patient's lower legs and thighs and he was treated using decompressive fasciotomy. Additional forearm fasciotomy was subsequently carried out. After fluid management, vasopressor support, mechanical ventilation, and renal replacement therapy, the patient was discharged without any neuromuscular deficits caused by LCS. Literature review suggested that lower legs are prone to LCS in patients with SCLS. Conclusion: Limb compartment syndrome is a serious complication that clinicians must be aware of and requires prompt decompressive fasciotomy.

Low dihomo-γ-linolenic acid is associated with susceptibility vessel sign in cardioembolism.

BACKGROUND AND AIMS: The susceptibility vessel sign (SVS) on susceptibility-weighted image, a magnetic resonance imaging technique, reveals thrombi as hypointense signals. We aimed to examine the association between polyunsaturated fatty acid (PUFA) levels and the presence of the SVS and its length in cardioembolism due to atrial fibrillation (AF). METHODS: Consecutive ischemic stroke patients who met the following inclusion criteria were screened: 1) patients with cardioembolism, defined by Trial of ORG 10172 in Acute Stroke Treatment, secondary to AF; 2) onset to door time within 24 h; 3) availability of magnetic resonance images, including susceptibility-weighted images, obtained at our hospital before performing recanalizing therapy; and 4) availability of PUFA measurements on the day of or the day after the hospital visit. We evaluated whether PUFA levels might be associated with the presence of the SVS and its length. RESULTS: We retrospectively screened 1720 consecutive ischemic stroke patients, and included 137 patients (95 (69%) male, median age 73 years) who met the inclusion criteria in the analyses. In binomial logistic regression analysis, lower dihomo-γ-linolenic acid (DGLA) level was associated with the presence of SVS (odds ratio 0.545, 95% confidence interval 0.374 to 0.794, p = 0.002). Multiple linear regression analysis revealed a significant negative association between DGLA levels and SVS length (unstandardized coefficient -7.430, 95% confidence interval -13.256 to -1.603, p = 0.013). CONCLUSION: Low DGLA level is associated with the presence of SVS and its length in patients with cardioembolism secondary to AF.

Middle Cerebral Artery Pulsatility Index Correlates with Prognosis and Diastolic Dysfunctions in Acute Ischemic Stroke.

OBJECTIVE: To determine transcranial Doppler ultrasonography (TCD) parameters related to unfavorable outcomes, and to clarify the correlations between those parameters and heart functions in acute ischemic stroke without major vessel stenoses and occlusions. MATERIALS AND METHODS: Patients were selected from a comprehensive stroke center between October 2012 and June 2019. Inclusion criteria were: 1) acute ischemic stroke without major vessel stenoses and occlusions; and 2) ability to measure blood flow in the middle cerebral artery by TCD. Unfavorable outcomes were defined as a modified Rankin Scale score of 2-6 at 3 months after onset. First, we investigated TCD parameters related to unfavorable outcomes. Second, correlations between those parameters and heart functions as assessed by transthoracic echocardiography were evaluated. RESULTS: We screened 1,527 consecutive ischemic stroke patients, including 130 patients (109 [83%] male; median age, 60 years). Middle cerebral artery pulsatility index (M1 PI) (Odds ratio (OR) 0.057, 95%confidence interval (CI) 0.007-0.494, p = 0.009) was independently associated with unfavorable outcomes. Concerning the relation between M1 PI and heart functions, peak early filling velocity/velocity of mitral annulus early diastolic motion (E/e') (OR 1.195, 95%CI 1.011-1.413, p = 0.037) was a factor independently associated with high M1 PI. CONCLUSIONS: High M1 PI predicts unfavorable outcome regardless of ischemic stroke subtype without major vessel stenoses and occlusions. High M1 PI correlates with high E/e', suggesting diastolic dysfunction.

Employment Status Prior to Ischemic Stroke and Weekly Variation of Stroke Onset.

OBJECTIVES: To investigate the differences in clinical backgrounds, especially weekly variations of stroke occurrence, between hyper-acute ischemic stroke patients with and without regular employment (RE), as well as the impact of RE on outcome. MATERIALS AND METHODS: Symptomatic ischemic stroke patients with ≤4.5 h from onset to door were enrolled. First, we divided patients into the RE and non-RE group to analyze differences in clinical characteristics, especially relation between weekly variations of stroke occurrence and RE. Second, we divided the same patients into those with and without favorable outcomes (modified Rankin Scale score of 0 to 2 at 3 months from stroke onset) to analyze the impact of RE on outcomes. RESULTS: We screened 1,249 consecutive symptomatic ischemic stroke patients and included 377 patients (284 [75%] males; median age, 67 years). Of these patients, 248 (66%) were included in RE group. First, RE was independently associated with occurrence of stroke on Monday in reference to Sunday or a public holiday (OR 2.562, 95% CI 1.004-6.535, p = 0.049). Second, RE (OR 2.888 95% CI 1.378-6.050, p = 0.005) was a factor independently associated with a favorable outcome. CONCLUSIONS: Patients with RE were more likely to have a hyper-acute ischemic stroke on Monday in reference to Sunday or a public holiday. However, RE before stroke onset appears to have a positive impact on outcome.

Out-of-hospital cardiac arrest patients with an initial non-shockable rhythm could be candidates for extracorporeal cardiopulmonary resuscitation: a retrospective study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is a promising treatment for refractory out-of-hospital cardiac arrest (OHCA). Most studies evaluating the effectiveness of ECPR include patients with an initial shockable rhythm. However, the effectiveness of ECPR for patients with an initial non-shockable rhythm remains unknown. This retrospective single-center study aimed to evaluate the effectiveness of ECPR for patients with an initial non-shockable rhythm, with reference to the outcomes of OHCA patients with an initial shockable rhythm. METHODS: Adult OHCA patients treated with ECPR at our center during 2011-2018 were included in the study. Patients were classified into the initial shockable rhythm group and the non-shockable rhythm group. The primary outcome was the cerebral performance category (CPC) scale score at hospital discharge. A CPC score of 1 or 2 was defined as a good outcome. RESULTS: In total, 186 patients were eligible. Among them, 124 had an initial shockable rhythm and 62 had an initial non-shockable rhythm. Among all patients, 158 (85%) were male, with a median age of 59 (interquartile range [IQR], 48-65) years, and the median low flow time was 41 (IQR, 33-48) min. Collapse was witnessed in 169 (91%) patients, and 36 (19%) achieved return of spontaneous circulation (ROSC) transiently. Proportion of female patients, presence of bystander cardiopulmonary resuscitation, and collapse after the arrival of emergency medical service personnel were significantly higher in the non-shockable rhythm group. The rate of good outcomes at hospital discharge was not significantly different between the shockable and non-shockable groups (19% vs. 16%, p = 0.69). Initial shockable rhythm was not significantly associated with good outcome after controlling for potential confounders (adjusted odds ratio 1.58, 95% confidence interval: 0.66-3.81, p = 0.31). In the non-shockable group, patients with good outcomes had a higher rate of transient ROSC, and pulmonary embolism was the leading etiology. CONCLUSIONS: The outcomes of patients with an initial non-shockable rhythm are comparable with those having an initial shockable rhythm. OHCA patients with an initial non-shockable rhythm could be candidates for ECPR, if they are presumed to have reversible etiology and potential for good neurological recovery.

A sporadic COVID-19 pneumonia treated with extracorporeal membrane oxygenation in Tokyo, Japan: A case report.

INTRODUCTION: An ongoing outbreak of a novel coronavirus disease (coronavirus disease 2019, COVID-19) has become a global threat. While clinical reports from China to date demonstrate that the majority of cases remain relatively mild and recover with supportive care, it is also crucial to be well prepared for severe cases warranting intensive care. Initiating appropriate infection control measures may not always be achievable in primary care or in acute-care settings. CASE: A 45-year-old man was admitted to the intensive care unit due to severe pneumonia, later confirmed as COVID-19. His initial evaluation in the resuscitation room and treatments in the intensive care unit was performed under droplet and contact precaution with additional airborne protection using the N95 respirator mask. He was successfully treated in the intensive care unit with mechanical ventilation and extracorporeal membrane oxygenation for respiratory support; and antiretroviral treatment with lopinavir/ritonavir. His total intensive care unit stay was 15 days and was discharged on hospital day 24. CONCLUSIONS: Strict infection control precautions are not always an easy task, especially under urgent care in an intensive care unit. However, severe cases of COVID-19 pneumonia, or another novel infectious disease, could present at any moment and would be a continuing challenge to pursue appropriate measures. We need to be well prepared to secure healthcare workers from exposure to infectious diseases and nosocomial spread, as well as to provide necessary intensive care.

Development of lymphatic vasculature and morphological characterization in rat kidney.

BACKGROUND: The mechanisms and morphological characteristics of lymphatic vascular development in embryonic kidneys remain uncertain. METHODS: We examined the distribution and characteristics of lymphatic vessels in developing rat kidneys using immunostaining for podoplanin, prox-1, Ki-67, type IV collagen (basement membrane: BM), and α-smooth muscle actin (αSMA: pericytes or mural cells). We also examined the expression of VEGF-C. RESULTS: At embryonic day 17 (E17), podoplanin-positive lymphatic vessels were observed mainly in the kidney hilus. At E20, lymphatic vessels extended further into the developing kidneys along the interlobar vasculature. In 1-day-old pups (P1) to P20, lymphatic vessels appeared around the arcuate arteries and veins of the kidneys, with some reaching the developing cortex via interlobular vessels. In 8-week-old adult rats, lymphatic vessels were extensively distributed around the blood vasculature from the renal hilus to cortex. Only lymphatic capillaries lacking continuous BM and αSMA-positive cells were present within adult kidneys, with none observed in renal medulla. VEGF-C was upregulated in the developing kidneys and expressed mainly in tubules. Importantly, the developing lymphatic vessels were characterized by endothelial cells immunopositive for podoplanin, prox-1, and Ki-67, with no surrounding BM or αSMA-positive cells. CONCLUSION: During nephrogenesis, lymphatic vessels extend from the renal hilus into the renal cortex along the renal blood vasculature. Podoplanin, prox-1, Ki-67, type IV collagen, and αSMA immunostaining can detect lymphatic vessels during lymphangiogenesis.

Analysis of the mechanism of antibody-dependent enhancement of feline infectious peritonitis virus infection: aminopeptidase N is not important and a process of acidification of the endosome is necessary.

Infection of the monocyte/macrophage lineage with feline infectious peritonitis virus (FIPV) is enhanced in the presence of anti-FIPV antibodies (antibody-dependent enhancement or ADE). We investigated the following unclear points concerning ADE of FIPV infection: (i) involvement of the virus receptor, feline aminopeptidase N (fAPN), in ADE activity in FIPV infection; (ii) necessity of acidification of the endosome in cellular invasion of FIPV. Virus receptor-blocking experiments using anti-fAPN antibodies at 4 or 37 degrees C and experiments using fAPN-negative U937 cells revealed that fAPN is not involved in ADE of FIPV infection. Experiments using lysosomotropic agents clarified that acidification of the endosome is necessary for cellular invasion by FIPV, regardless of the presence or absence of antibodies. These findings may be very important for understanding the mechanism of ADE of FIPV infection.

The infectivity and pathogenicity of a group 2 bovine coronavirus in pups.

Canine respiratory coronavirus (CRCoV), which is more closely related to the bovine coronavirus (BCoV), has recently been detected in dogs. In this study, we examined whether BCoV was capable of infecting and exhibiting pathogenicity in dogs. Three 1-month-old pups were oronasally given field isolates of BCoV, and were kept together with 2 control animals. As a result, increases in BCoV-neutralizing antibody titers were confirmed in all pups in the challenged and control groups. Moreover, the virus gene was also detected in oral and rectal swabs by RT-PCR. These results indicate that BCoV infects dogs, and easily infects other dogs that are kept together. However, no clinical symptoms such as respiratory symptoms and diarrhea were observed.

TNF-alpha, produced by feline infectious peritonitis virus (FIPV)-infected macrophages, upregulates expression of type II FIPV receptor feline aminopeptidase N in feline macrophages.

The pathogenicity of feline infectious peritonitis virus (FIPV) is known to depend on macrophage tropism, and this macrophage infection is enhanced by mediation via anti-S antibody (antibody-dependent enhancement, ADE). In this study, we found that TNF-alpha production was increased with viral replication in macrophages inoculated with a mixture of FIPV and anti-S antibody, and demonstrated that this culture supernatant had feline PBMC apoptosis-inducing activity. We also demonstrated that the expression level of the FIPV virus receptor, feline aminopeptidase N (fAPN), was increased in macrophages of FIP cats. For upregulation of TNF-alpha and fAPN in macrophages, viral replication in macrophages is necessary, and their expressions were increased by ADE of FIPV infection. It was demonstrated that a heat-resistant fAPN-inducing factor was present in the culture supernatant of FIPV-infected macrophages, and this factor was TNF-alpha: fAPN expression was upregulated in recombinant feline TNF-alpha-treated macrophages, and FIPV infectivity was increased in these macrophages. These findings suggested that FIPV replication in macrophages increases TNF-alpha production in macrophages, and the produced TNF-alpha acts and upregulates fAPN expression, increasing FIPV sensitivity.

A "possible" involvement of TNF-alpha in apoptosis induction in peripheral blood lymphocytes of cats with feline infectious peritonitis.

Feline infectious peritonitis (FIP) cats show a decrease in peripheral blood lymphocyte counts, and a particularly marked decrease in T cells including CD4+ and CD8+ cells. In this study, we showed that lymphopenia observed in FIP cats was due to apoptosis, and that the ascitic fluid, plasma, and culture supernatant of peritoneal exudate cells (adherent cells with macrophage morphology, or PEC) from FIP cats readily induced apoptosis in specific pathogen-free cat peripheral blood mononuclear cells, particularly CD8+ cells. In addition, TNF-alpha released from macrophages and TNF-receptor (TNFR) 1 and TNFR2 mRNA expression in lymphocytes were closely involved in this apoptosis induction. In particular, in CD8+ cells cultured in the presence of the PEC culture supernatant, the expression levels of TNFR1 and TNFR2 mRNA were increased, indicating that CD8+ cells are more susceptible to apoptosis induction by TNF-alpha than other lymphocyte subsets, particularly B cells (CD21+ cells). The results of this study suggest that TNF-alpha, produced by virus-infected macrophages, is responsible for induction of apoptosis in uninfected T cells, primarily CD8+ T cells.