A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

Spinal cord injury(SCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after SCI,explaining the progression and detrimental consequences related to this condition.Psychoneuroimmunoendocrinology(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a whole.The initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and well-being.In the present review,we will explore the most important local and systemic consequences of SCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are interconnected.Finally,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

Update on the treatment of type 2 diabetes mellitus

To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus(T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2 DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2 DM, with an emphasis on agents introduced within the last decade.

WJD 5^(th) Anniversary Special Issues(2): Type 2 diabetes Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?

Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality,and are disproportionately affected by cardiovascular disease.Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension,dyslipidaemia and obesity in these patients.However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors.Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus.Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events.Many of these risk factors could be common history for both di-abetes mellitus and cardiovascular disease,reinforcing the postulate that both disorders come independently from"common soil".The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.

Mechanisms of hypoglycemia unawareness and implications in diabetic patients

Hypoglycemia unawareness(HU) is defined at the onset of neuroglycopenia before the appearance of autonomic warning symptoms.It is a major limitation to achieving tight diabetes and reduced quality of life.HU occurs in approximately 40% of people with type 1 diabetesmellitus(T1DM) and with less frequency in T2 DM.Though the aetiology of HU is multifactorial,possible mechanisms include chronic exposure to low blood glucose,antecedent hypoglycaemia,recurrent severe hypoglycaemia and the failure of counter-regulatory hormones.Clinically it manifests as the inability to recognise impeding hypoglycaemia by symptoms,but the mechanisms and mediators remain largely unknown.Prevention and management of HU is complex,and can only be achieved by a multifactorial intervention of clinical care and structured patient education by the diabetes team.Less know regarding the impact of medications on the development or recognition of this condition in patients with diabetes.Several medications are thought to worsen or promote HU,whereas others may have an attenuating effect on the problem.This article reviews recent advances in how the brain senses and responds to hypoglycaemia,novel mechanisms by which people with insulin-treated diabetes develop HU and impaired counter-regulatory responses.The consequences that HU has on the person with diabetes and their family are also described.Finally,it examines the evidence for prevention and treatment of HU,and summarizes the effects of medications that may influence it.

Beta-blocker therapy in elderly patients with renal dysfunction and heart failure

OBJECTIVE To assess the role of beta-blockers(BB)in patients with chronic kidney disease(CKD)aged≥75 years.METHODS AND RESULTS From January 2008 to July 2014,we included 390 consecutive patients≥75 years of age with ejection fraction≤35%and glomerular filtration rate(GFR)≤60 m L/min per 1.73 m^2.We analyzed the relationship between treatment with BB and mortality or cardiovascular events.The mean age of our population was 82.6±4.1 years.Mean ejection fraction was 27.9%±6.5%.GFR was 60-45 m L/min per 1.73 m^2 in 50.3%of patients,45-30 m L/min per 1.73 m^2 in 37.4%,and<30 m L/min per 1.73 m^2 in 12.3%.At the conclusion of follow-up,67.4%of patients were receiving BB.The median follow-up was28.04(IR:19.41-36.67)months.During the study period,211 patients(54.1%)died and 257(65.9%)had a major cardiovascular event(death or hospitalization for heart failure).BB use was significantly associated with a reduced risk of death(HR=0.51,95%CI:0.35-0.74;P<0.001).Patients receiving BB consistently showed a reduced risk of death across the different stages of CKD:stage IIIa(GFR=30-45 m L/min per 1.73 m^2;HR=0.47,95%CI:0.26-0.86,P<0.0001),stage IIIb(GFR 30-45 m L/min per 1.73 m^2;HR=0.55,95%CI:0.26-1.06,P=0.007),and stages IV and V(GFR<30 m L/min per 1.73 m~2;HR=0.29,95%CI:0.11-0.76;P=0.047).CONCLUSIONS The use of BB in elderly patients with HFr EF and renal impairment was associated with a better prognosis.Use of BB should be encouraged when possible.

Role of sex on psychological distress,quality of life,and coping of patients with advanced colorectal and non-colorectal cancer

BACKGROUNDPatients with advanced gastrointestinal cancer must cope with the negative effects of cancer and complications.AIM To evaluate psychological distress,quality of life,and coping strategies in patients with advanced colorectal cancer compared to non-colorectal cancer based on sex.METHODS A prospective,transversal,multicenter study was conducted in 203 patients;101(50%)had a colorectal and 102(50%)had digestive,non-colorectal advanced cancer.Participants completed questionnaires evaluating psychological distress(Brief Symptom Inventory-18),quality of life(EORTC QLQ-C30),and coping strategies(Mini-Mental Adjustment to Cancer)before starting systemic cancer treatment.RESULTS The study included 42.4%women.Women exhibited more depressive symptoms,anxiety,functional limitations,and anxious preoccupation than men.Patients with non-colorectal digestive cancer and women showed more somatization and physical symptoms than subjects with colorectal cancer and men.Men with colorectal cancer reported the best health status.CONCLUSION The degree of disease acceptance in gastrointestinal malignancies may depend on sex and location of the primary digestive neoplasm.Future interventions should specifically address sex and tumor site differences in individuals with advanced digestive cancer.

New perspectives in the management of small cell lung cancer

The treatment of small cell lung cancer(SCLC)is a challenge for all specialists involved.New treatments have been added to the therapeutic armamentarium in recent months,but efforts must continue to improve both survival and quality of life.Advances in surgery and radiotherapy have resulted in prolonged survival times and fewer complications,while more careful patient selection has led to increased staging accuracy.Developments in the field of systemic therapy have resulted in changes to clinical guidelines and the management of patients with advanced disease,mainly with the introduction of immunotherapy.In this article,we describe recent improvements in the management of patients with SCLC,review current treatments,and discuss future lines of research.

HIV screening and retention in care in people who use drugs in Madrid, Spain: a prospective study

Background::The burden of human immunodeficiency virus(HIV)infection in people who use drugs(PWUD)is significant.We aimed to screen HIV infection among PWUD and describe their retention in HIV care.Besides,we also screen for hepatitis C virus(HCV)infection among HIV-seropositive PWUD and describe their linkage to care.Methods::We conducted a prospective study in 529 PWUD who visited the"Ca?ada Real Galiana"(Madrid,Spain).The study period was from June 1,2017,to May 31,2018.HIV diagnosis was performed with a rapid antibody screening test at the point-of-care(POC)and HCV diagnosis with immunoassay and PCR tests on dried blood spot(DBS)in a central laboratory.Positive PWUD were referred to the hospital.We used the Chi-square or Fisher’s exact tests,as appropriate,to compare rates between groups.Results::Thirty-five(6.6%)participants were positive HIV antibodies,but 34 reported previous HIV diagnoses,and 27(76%)had prior antiretroviral therapy.Among patients with a positive HIV antibody test,we also found a higher prevalence of homeless(P<0.001)and injection drug use(PWID)(P<0.001),and more decades of drug use(P=0.002).All participants received HIV test results at the POC.Of the 35 HIV positives,28(80%)were retained in HIV medical care at the end of the HIV screening study(2018),and only 22(62.9%)at the end of 2020.Moreover,12/35(34.3%)were positive for the HCV RNA test.Of the latter,10/12(83.3%)were contacted to deliver the HCV results test(delivery time of 19 days),5/12(41.7%)had an appointment and were attended at the hospital and started HCV therapy,and only 4/12(33.3%)cleared HCV.Conclusions::We found almost no new HIV-infected PWUD,but their cascade of HIV care was low and remains a challenge in this population at risk.The high frequency of active hepatitis C in HIV-infected PWUD reflects the need for HCV screening and reinforcing the link to care.