Ethyl pyruvate reverses development of Pseudomonas aeruginosa pneumonia during sepsis-induced immunosuppression

Sepsis is characterized by an innate immune response and the following immune dysfunction which can increase the emergence of secondary infections. Ethyl pyruvate (EP) has multiple immunoregulation functions in several serious illnesses, such as burn injury, severe sepsis and acute respiratory syndrome. However, little data was shown the effect of EP administration on immunosuppression post-CLP and the following secondary infection. The cecal ligation and puncture (CLP) followed by the induction of Pseudomonas aeruginosa (PA) was used as a clinically relevant two-hit model of sepsis. We assessed the survival rate, lung damage and lung bacterial clearance in vehicle or EP treatment group to demonstrate the lung response to Pseudomonas aeruginosa of septic mice. Then cytokines including lung IL-6, IL-1β, IL-10 and plasma HMGB1, apoptosis of splenic immune cells and Foxp3 level on regulatory T cells (Tregs) were studied to demonstrate the mechanisms of EP administration on two-hit mice. We found that the susceptibility of septic mice to Secondary Pseudomonas aeruginosa pneumonia could be down-regulated by ethyl pyruvate treatment and the protective effects of EP may via decreasing lung IL-10 and plasma HMGB1 expression, inhibiting the function of Tregs and relieving the apoptosis of splenic immune cells. The “immune paralysis” post-sepsis still remains a rigorous challenge for curing sepsis, our study may aid in the development of new therapeutic strategies to this problem.     

Repeatability and reliability of the diabetic foot self-care questionnaire in Arabic patients: A transcultural adaptation

PurposeThe diabetic foot self-care questionnaire is considered a self-care evaluation tool with 16 questions for assessing diabetic foot health disorders. To date, the DFSQ has been validated in different languages, but an Arabic version was lacking. Consequently, the purpose of this study was to translate and validate the Arabic version of the DFSQ (DFSQ-AR).MethodA suitable method was developed for the translation protocol and cross-cultural validation from Spanish to Arabic. Regarding the total marks from each sub-scale, agreement degrees and confidence were analyzed using Cronbach's α and intraclass correlation coefficient (ICC), respectively. In addition, the mean ± standard deviation differences between pre and post-tests were calculated and completed using Bland-Altman distribution plots.ResultsExcellent agreement between the two versions was demonstrated based on Cronbach's α. Three sub-scales consisting of knowledge of foot hygiene, the appropriate use of footwear and socks, and podiatric self-care were added together to obtain the total score. Excellent retest reliability was shown for the total score. Test/retest reliability was excellent for the self-care and shoe and socks sub-scales. There were no significant differences among any domains (p > 0.05). There were no statistically significant differences (P = 0.000) for the mean ± standard deviations (SD) between pre- and post-tests (98.09 ± 15.42) [93.75–102.43] and 97.96 ± 13.88 [94.5–101.86] points, respectively). Bland-Altman plots or clinically pertinent variations were not statistically significantly different.ConclusionsThe DFSQ-AR is considered a strong and valid questionnaire with adequate repeatability in the Arabic language population.     

Sex difference in the association between surrogate markers of insulin resistance and arterial stiffness

AimsTo investigate the predictive capability of insulin resistance surrogate markers for insulin resistance and arterial stiffness based on sex.MethodsWe assessed the association of triglyceride glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), visceral adiposity index (VAI), and lipid accumulation product (LAP) with homeostasis model assessment-insulin resistance (HOMA-IR) and brachial–ankle pulse wave velocity (baPWV) in both sexes.ResultsA total of 1720 men and 1098 women were evaluated. HOMA-IR showed good correlation with the TyG index (men: r = 0.47, women: r = 0.45), TG/HDL-C (men: r = 0.45, women: r = 0.41), VAI (men: r = 0.51, women: r = 0.48), and LAP (men: r = 0.55, women r = 0.49) (all p-values < 0.001). These markers positively correlated with increased baPWV in both sexes. The standardized partial regression coefficients were 0.11 and 0.14 for the TyG index, 0.13 and 0.16 for TG/HDL-C, 0.14 and 0.19 for VAI, and 0.12 and 0.17 for LAP in men and women, respectively (all p-values < 0.01; all p-values for sex interaction < 0.05).ConclusionsAll insulin surrogate markers showed good correlation with HOMA-IR in both sexes. These indices were also associated with increased baPWV and the associations were stronger in women than in men.     

B cell and B cell-related pathways for novel cancer treatments

B cells are recognized as the main effector cells of humoral immunity which suppress tumor progression by secreting immunoglobulins, promoting T cell response, and killing cancer cells directly. Given these properties, their anti-tumor immune response in the tumor micro-environment (TME) is of great interest. Although T cell-related immune responses have become a therapeutic target with the introduction of immune checkpoint inhibitors, not all patients benefit from these treatments. B cell and B cell-related pathways (CCL19, −21/CCR7 axis and CXCL13/CXCR5 axis) play key roles in activating immune response through humoral immunity and local immune activation via tertiary lymphoid structure (TLS) formation. However they have some protumorigenic works in the TME. Thus, a better understanding of B cell and B cell-related pathways is necessary to develop effective cancer control. In this review, we summarize recent evidences regarding the roles of B cell and B cell-related pathways in the TME and immune response and discuss their potential roles for novel cancer treatment strategies.     

Methods for development of a core outcome set for clinical trials integrating traditional Chinese medicine and Western medicine

Clinical trial outcome reporting differs between studies integrating traditional Chinese medicine (TCM) and Western medicine, so that some clinical trials are not eligible for inclusion in a systematic review. The excluded studies are therefore less widely disseminated, and even valid studies are less likely to yield impact. This problem may be addressed by developing core outcome sets (COSs) for integrative medicine in specific healthcare areas. The first stage of development is to define the scope of the COS for integrative medicine, the second stage is to establish the need for such a COS, and the third stage is to develop a protocol and register the COS. The final stage involves three steps: (i) development of a comprehensive list of outcomes (including efficacy outcomes and safety outcomes and TCM syndromes) using systematic review, qualitative or cross-sectional research, and reviews of package inserts and medical records; (ii) merging and grouping of outcomes within domains; (iii) conducting two rounds of Delphi survey and consensus meetings with a range of stakeholders. The final COS will include a general COS and core TCM syndrome- set. Development of COSs for clinical trials of integrative medicine may help to standardize outcome reporting and reduce publication bias in the future.     

Rathke’s cleft cyst: A case report of recurrence and spontaneous involution

Rathke’s cleft cysts (RCC) are sellar lesions that typically remain asymptomatic throughout life. Symptomatic patients present with headache, visual disturbance and/or pituitary dysfunction and are treated with resection. We present a 61-year-old woman diagnosed with RCC which was resected twice then recurred before undergoing spontaneous resolution. RCC are often managed without surgical intervention. Some of these lesions may spontaneously resolve without surgical intervention while others may become symptomatic. In patients with asymptomatic recurrent RCC conservative management is recommended. Spontaneous involution may occur following initial resection and recurrence of RCC.     

Schizophrenia and neurosurgery: A dark past with hope of a brighter future

Schizophrenia is a chronic and progressive psychiatric disease that remains difficult to manage in the 21st century. Current medical therapies have been able to give reprieve and decrease incidence of psychotic episodes. However, as the disease progresses, patients can become ever more refractory to current pharmaceutical agents and the polypharmacy that is attempted in treatment. Additionally, many of these drugs have significant adverse effects, leaving the practitioner in a difficult predicament for treating these patients. The history of neurosurgery for schizophrenia, among other psychiatric diseases, has a very dark past. Therefore, this review examines peer-reviewed studies on the history of schizophrenia, its medical and surgical therapies, financial costs, and future directions for disease management. We highlight the historically poor relationship between neurosurgery and psychiatric disease and discuss current research in the understandings of schizophrenia. Guided by a strong code of ethics and new technology, including the use of stereotaxis and deep brain stimulation (DBS), the medical communities treating psychiatric disease are beginning to overcome the horrors of the past. DBS is currently being used with moderate success in the treatment of depression, obsessive compulsive disorder, Tourette’s syndrome, and anorexia nervosa. With greater understanding of the neural circuitry of schizophrenia and the evolving role for DBS in psychiatric disease, the authors believe that schizophrenia, like other psychiatric diseases, can be treated with DBS.     

Cerebral vasospasm and delayed ischaemic deficit following elective aneurysm clipping

Although common after subarachnoid haemorrhage, cerebral vasospasm (CVS) and delayed ischaemic neurological deficit (DIND) rarely occur following elective clipping of unruptured aneurysms. The onset of this complication is variable and its pathophysiology is poorly understood. We report two patients with CVS associated with DIND following unruptured aneurysmal clipping. The literature is reviewed and the potential mechanisms in the context of patient presentations are discussed. A woman aged 53 and a man aged 70 were treated with elective clipping of unruptured middle cerebral artery aneurysms, the older patient also having an anterior communicating artery aneurysm clipped. The operations were uncomplicated with no intra-operative bleeding, no retraction, no contusion, no middle cerebral artery (MCA) temporary clipping, and no intra-operative rupture. Routine post-operative CT scan and CT angiogram showed that in both patients the aneurysms were excluded from the circulation and there was no perioperative subarachnoid blood. Both patients had no neurological deficit post-operatively, but on day 2 developed DIND and vasospasm of the MCA. Both patients had angiographic improvement with intra-arterial verapamil treatment. In one patient, this was done promptly and the patient made a complete recovery, but in the other, the diagnosis was delayed for more than 24 hours and the patient had residual hemiparesis and dysphasia due to MCA territory infarction. CVS and DIND following treatment of unruptured aneurysms is a very rare event. However, clinicians should be vigilant as prompt diagnosis and management is required to minimise the risk of cerebral infarction and poor outcome.