Background: The long‐term association between the status of the false lumen and poor patient outcomes in acute aortic dissection ( AAD ) remains unclear. This systematic review and meta‐analysis investigated whether the status of the false lumen was a predictor of poor long‐term survival in AAD . Methods and Results: Eleven cohort studies (2924 participants) exploring the association between the false lumen status and long‐term outcomes (>1 year) in AAD were included. All studies reported multivariate‐adjusted hazard ratios ( HR s) with 95% CI s for long‐term outcomes, according to false lumen status. Pooled HR s for mortality and aortic events were computed and weighted using generic inverse‐variance and random‐effect modeling. Residual patent false lumen was an independent predictor of long‐term mortality in AAD type A ( HR , 1.71; 95% CI , 1.16–2.52; P =0.007) and type B ( HR , 2.79; 95% CI , 1.80–4.32; P <0.001). AAD patients with residual patent false lumen exhibited an increased risk of aortic events ( HR , 5.43; 95% CI , 2.95–9.99; P <0.001). Partial false lumen thrombosis was independently associated with long‐term mortality in type B AAD ( HR , 2.24; 95% CI , 1.37–3.65; P =0.001). This association was not observed in AAD type A patients ( HR , 1.75; 95% CI , 0.88–3.45; P =0.211). Conclusions: The false lumen status influences late outcomes in AAD . Residual patent false lumen is independently associated with poor long‐term survival in AAD . However, only type B AAD patients with partial false lumen thrombosis had an increased late mortality risk.

Sphingosine kinase 1 (SK1) is a key regulator of the dynamic ceramide/sphingosine 1-phosphate rheostat balance and important in the pathological cancer genesis, progression, and metastasis processes. Many studies have demonstrated SK1 overexpressed in various cancers, but no meta-analysis has evaluated the relationship between SK1 and various cancers. We retrieved relevant articles from the PubMed, EBSCO, ISI, and OVID databases. A pooled odds ratio (OR) was used to assess the associations between SK1 expression and cancer; hazard ratios (HR) were used for 5-year and overall survival. Review Manager 5.0 was used for the meta-analysis, and publication bias was evaluated with STATA 12.0 (Egger’s test). Thirty-four eligible studies (n = 4,673 patients) were identified. SK1 positivity and high expression were significantly different between cancer, non-cancer, and benign tissues. SK1 mRNA and protein expression levels were elevated in the cancer tissues, compared with the normal tissues. SK1 positivity rates differed between various cancer types (lowest [27.3%] in estrogen receptor-positive breast cancer and highest [82.2%] in tongue squamous cell carcinoma). SK1 positivity and high expression were associated with 5-year survival; the HR was 1.86 (95% confidence interval [CI], 1.18–2.94) for breast cancer, 1.58 (1.08–2.31) for gastric cancer, and 2.68 (2.10–3.44) for other cancers; the total cancer HR was 2.21 (95% CI, 1.83–2.67; P < 0.00001). The overall survival HRs were 2.09 (95% CI, 1.35–3.22), 1.56 (1.08–2.25), and 2.62 (2.05–3.35) in breast, gastric, and other cancers, respectively. The total effect HR was 2.21 (95% CI, 1.83–2.66; P < 0.00001). SK1 positivity and high expression were significantly associated with cancer and a shorter 5-year and overall survival. SK1 positivity rates vary tremendously among the cancer types. It is necessary to further explore whether SK1 might be a predictive biomarker of outcomes in cancer patients.

To hypothesize that in severe states of cardiogenic shock with profound decreases in buccal microcirculation, the cerebral microcirculation may be selectively protected. Decreases in buccal microcirculatory flow are closely associated with the severity and outcomes of circulatory shock. We investigated the concurrent changes in cerebral and buccal microcirculation, in a rat model of cardiogenic shock caused by left ventricular failure. Randomized prospective animal study. University-affiliated animal research laboratory. Sprague-Dawley rats. Studies were performed in ten male Sprague-Dawley rats, weighing between 450 and 550 g. After intraperitonial pentobarbital anesthesia and tracheostomy, a craniotomy exposed the parietal cortex for visualization of microcirculation. Animals then underwent thoracotomy and banding of ascending aorta producing left ventricular failure and cardiogenic shock. Over a 4-hr interval, effects on arterial pressure, cardiac output, left ventricular end-diastolic volume, and ejection fractions were measured. The cerebral and buccal microcirculations were visualized concurrently with the aid of orthogonal polarization spectral imaging. Animals were randomized to identically treated controls in which the aorta was not ligated. Mean arterial pressure, cardiac output, and ejection fraction decreased strikingly and end-diastolic left ventricular volume more than doubled within 30 mins after aortic banding. The buccal microcirculation was concurrently reduced. However, cerebral microcirculatory flow was fully preserved. In contrast to striking reduction in cardiac output and arterial pressures together with buccal microcirculatory flow, cerebral cortical microcirculatory flow was fully preserved during cardiogenic shock. These findings further document a dissociation between the systemic and cerebral circulations and potentially explain earlier clinical and experimental observations that the brain is selectively protected during severe states of cardiogenic shock in the absence of cardiac arrest.

Decreases in buccal microcirculation are indicative of the severity of hemorrhage, but incidental observations suggest that this may not apply to the cerebral microcirculation. We therefore hypothesized that the cerebral microcirculation may be preserved in hemorrhagic shock in which systemic and buccal microcirculatory flow are reduced. We propose to relate changes in the macrocirculation to the buccal and cerebral microcirculations during hemorrhage and after fluid resuscitation. Prospective, randomized, controlled animal study. University-affiliated research laboratory. Sprague-Dawley rats. Fifteen male Sprague-Dawley rats were anesthetized and endotracheally intubated. Craniotomy exposed the parietal cortex for orthogonal polarization spectral imaging. Mean arterial pressure, cardiac output, arterial blood gases, and lactate were measured concurrently with determination of microcirculatory indices in buccal and cerebral areas. Animals were randomly assigned to bleeding either 35% or 25% of estimated total blood volume and compared with sham bled animals. Hypovolemia was maintained for 60 mins in test animals, after which saline in amounts to 2 times the blood loss, was administered over 30 mins. Cerebral and buccal microvascular indices were measured in vessels smaller than 20 mum, representing capillaries. Mean arterial pressure and cardiac output were reduced and arterial blood lactate was increased in relationship to the magnitude of blood loss. Saline infusion increased mean arterial pressure and cardiac output. Buccal microcirculation decreased after bleeding but was restored after saline infusion. However, the cerebral microcirculation was essentially unaffected by hemorrhage and saline infusion. In contrast to the systemic decreases in pressure and flow characteristics of hemorrhagic shock, including decreases in microcirculations of buccal mucosa, cerebral microvascular flow was preserved during moderate and severe blood losses.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly defined condition encompassing hepatic steatosis and metabolic dysfunction. However, the relationship between MAFLD and multi-system diseases remains unclear, and the time-dependent sequence of these diseases requires further clarification. Methods: After propensity score matching, 163,303 MAFLD subjects and 163,303 matched subjects were included in the community-based UK Biobank study. The International Classification of Diseases, Tenth Revision (ICD-10), was used to reclassify medical conditions into 490 and 16 specific causes of death. We conducted a disease trajectory analysis to map the key pathways linking MAFLD to various health conditions, providing an overview of their interconnections. Results: Participants aged 59 (51–64) years, predominantly males (62.5%), were included in the study. During the 12.9-year follow-up period, MAFLD participants were found to have a higher risk of 113 medical conditions and eight causes of death, determined through phenome-wide association analysis using Cox regression models. Temporal disease trajectories of MAFLD were established using disease pairing, revealing intermediary diseases such as asthma, diabetes, hypertension, hypothyroid conditions, tobacco abuse, diverticulosis, chronic ischemic heart disease, obesity, benign tumors, and inflammatory arthritis. These trajectories primarily resulted in acute myocardial infarction, disorders of fluid, electrolyte, and acid–base balance, infectious gastroenteritis and colitis, and functional intestinal disorders. Regarding death trajectories of MAFLD, malignant neoplasms, cardiovascular diseases, and respiratory system deaths were the main causes, and organ failure, infective disease, and internal environment disorder were the primary end-stage conditions. Disease trajectory analysis based on the level of genetic susceptibility to MAFLD yielded consistent results. Conclusions: Individuals with MAFLD have a risk of a number of different medical conditions and causes of death. Notably, these diseases and potential causes of death constitute many pathways that may be promising targets for preventing general health decline in patients with MAFLD.