Transorbital endoscopic approaches to the skull base: a systematic literature review and anatomical description

Neurosurgical Review - Transorbital endoscopic approaches are increasing in popularity as they provide corridors to reach various areas of the ventral skull base through the orbit. They can be used...     

Prognostic factors correlated with survival in AIDS patients

The authors present the AIDS cases (CDC '93) observed in Brescia from 1983 to 1994. They observed 1189 subjects (M 84%, F 16%) with a mean age of 32.7 years (intra-venous drug users 75.1%, heterosexuals 14%, homosexuals 9.6%). The mean survival observed was 56.7 weeks from the diagnosis of AIDS (mortality per year 78%). The most frequent AIDS-defining events were Visceral Candidiasis, P.carinii Pneumonia (PCP) and Neurotoxoplasmosis, while the longest and shortest mean survival was for Kaposi's Sarcoma (89 weeks) and Wasting Syndrome (8.4). The mean value of CD4+ lymphocyte counts on AIDS diagnosis was 72.6/l (1166 cases) and the highest and lowest were in non-Hodgkin's Lymphoma (NHL; 147.6/l) and Cryptosporidiosis (18.8/l). Antiretroviral therapy had been given for at least a month in 41.4% subjects (mean treatment duration of 74.8 weeks). The Cox model has demonstrated the favourable effect on survival of high CD4+ lymphocyte counts on diagnosis, antiretroviral therapy, the diagnosis of Tuberculosis (TBC) and PCP as initial markers and the diagnosis of TBC, PCP or Cytomegalovirus infection (CMV) during the entire clinical evolution. Moreover, the unfavourable effect of high age, diagnosis of Progressive Multifocal Leucoencephalopathy (PML), Wasting Syndrome and NHL as initial markers and diagnosis of PML or NHL in any moment of the disease has been demonstrated.     

COVID‐19 and heart failure: from infection to inflammation and angiotensin II stimulation. Searching for evidence from a new disease

Patients with cardiovascular disease and, namely, heart failure are more susceptible to coronavirus disease 2019 (COVID‐19) and have a more severe clinical course once infected. Heart failure and myocardial damage, shown by increased troponin plasma levels, occur in at least 10% of patients hospitalized for COVID‐19 with higher percentages, 25% to 35% or more, when patients critically ill or with concomitant cardiac disease are considered. Myocardial injury may be elicited by multiple mechanisms, including those occurring with all severe infections, such as fever, tachycardia, adrenergic stimulation, as well as those caused by an exaggerated inflammatory response, endotheliitis and, in some cases, myocarditis that have been shown in patients with COVID‐19. A key role may be that of the renin–angiotensin–aldosterone system. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infects human cells binding to angiotensin‐converting enzyme 2 (ACE2), an enzyme responsible for the cleavage of angiotensin II into angiotensin 1–7, which has vasodilating and anti‐inflammatory effects. Virus‐mediated down‐regulation of ACE2 may increase angiotensin II stimulation and contribute to the deleterious hyper‐inflammatory reaction of COVID‐19. On the other hand, ACE2 may be up‐regulated in patients with cardiac disease and treated with ACE inhibitors or angiotensin receptor blockers. ACE2 up‐regulation may increase the susceptibility to COVID‐19 but may be also protective vs. angiotensin II‐mediated vasoconstriction and inflammatory activation. Recent data show the lack of untoward effects of ACE inhibitors or angiotensin receptor blockers for COVID‐19 infection and severity. Prospective trials are needed to ascertain whether these drugs may have protective effects.     

Regression of Renal Disease by Angiotensin II Antagonism Is Caused by Regeneration of Kidney Vasculature

Chronic renal insufficiency inexorably progresses in patients, such as it does after partial renal ablation in rats. However, the progression of renal diseases can be delayed by angiotensin II blockers that stabilize renal function or increase GFR, even in advanced phases of the disease. Regression of glomerulosclerosis can be induced by angiotensin II antagonism, but the effect of these treatments on the entire vascular tree is unclear. Here, using microcomputed tomography and scanning electron microscopy, we compared the size and extension of kidney blood vessels in untreated Wistar rats with those in untreated and angiotensin II antagonist–treated Munich Wistar Frömter (MWF) rats that spontaneously develop kidney disease with age. The kidney vasculature underwent progressive rarefaction in untreated MWF rats, substantially affecting intermediate and small vessels. Microarray analysis showed increased Tgf-β and endothelin-1 gene expression with age. Notably, 10-week inhibition of the renin-angiotensin system regenerated kidney vasculature and normalized Tgf-β and endothelin-1 gene expression in aged MWF rats. These changes were associated with reduced apoptosis, increased endothelial cell proliferation, and restoration of Nrf2 expression, suggesting mechanisms by which angiotensin II antagonism mediates regeneration of capillary segments. These results have important implications in the clinical setting of chronic renal insufficiency.     

Shiga Toxin Promotes Podocyte Injury in Experimental Hemolytic Uremic Syndrome via Activation of the Alternative Pathway of Complement

Shiga toxin (Stx)–producing Escherichia coli is the offending agent of postdiarrhea-associated hemolytic uremic syndrome (HUS), a disorder of glomerular ischemic damage and widespread microvascular thrombosis. We previously documented that Stx induces glomerular complement activation, generating C3a responsible for microvascular thrombosis in experimental HUS. Here, we show that the presence of C3 deposits on podocytes is associated with podocyte damage and loss in HUS mice generated by the coinjection of Stx2 and LPS. Because podocyte adhesion to the glomerular basement membrane is mediated by integrins, the relevance of integrin-linked kinase (ILK) signals in podocyte dysfunction was evaluated. Podocyte expression of ILK increased after the injection of Stx2/LPS and preceded the upregulation of Snail and downregulation of nephrin and α-actinin-4. Factor B deficiency or pretreatment with an inhibitory antibody to factor B protected mice against Stx2/LPS-induced podocyte dysregulation. Similarly, pretreatment with a C3a receptor antagonist limited podocyte loss and changes in ILK, Snail, and α-actinin-4 expression. In cultured podocytes, treatment with C3a reduced α-actinin-4 expression and promoted ILK-dependent nuclear expression of Snail and cell motility. These results suggest that Stx-induced activation of the alternative pathway of complement and generation of C3a promotes ILK signaling, leading to podocyte dysfunction and loss in Stx-HUS.     

Innervation zone locations in 43 superficial muscles: Toward a standardization of electrode positioning

Introduction: We describe the innervation zone (IZ) location in 43 muscles to provide information for appropriate positioning of bipolar electrodes for clinical and research applications. Methods: The IZ was studied in 40 subjects (20 men and 20 women) using multichannel surface electromyography (sEMG). Signal quality was checked visually to identify motor unit action potentials and estimate muscle fiber conduction velocity. Results: Results in 33 muscles were classified as excellent or good, because it was possible to identify an area which is favorable for appropriate positioning of an electrode pair without the need to previously determine the IZ location. Conclusions: Knowledge of IZ location will increase standardization and repeatability of sEMG measures. Muscle Nerve 49 :413–421, 2014     

Evidence-Based Management of Acute Heart Failure

Acute heart failure (AHF) is a complex, heterogeneous, clinical syndrome with high morbidity and mortality, incurring significant health care costs. Patients transition from home to the emergency department, the hospital, and home again and require decisions surrounding diagnosis, treatment, and prognosis at each step of the way. The purpose of this review is to examine the epidemiology, etiology, and classifications of AHF and specifically focus on practical information relevant to the clinician. We examine the mechanisms of decompensation relevant to clinical presentations—including precipitating factors, neuroendocrine interactions, and inflammation—along with how consideration of these factors may help select therapies for an individual patient. The prevalence and significance of end-organ manifestations such as renal, gastrointestinal, respiratory, and neurologic manifestations are discussed. We also highlight how the development of renal dysfunction relates to the choice of a variety of diuretics that may be useful in specific circumstances and review guideline-directed medical therapy. We discuss the practical use (and pitfalls) of a variety of evidence-based clinical scoring criteria available to risk stratify patients with AHF. Finally, evidence-based management of AHF is discussed, including both pharmacologic and nonpharmacologic therapies, including the lack of evidence for using old and new vasodilators and the recent evidence regarding initiation of newer therapies in hospital. Overall, we suggest that clinicians consider implementing the newer data in AHF and subject existing practice patterns and treatments to the same rigour as new therapies.     

Effect of combining ACE inhibitor and statin in severe experimental nephropathy

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor therapy given soon after disease induction uniformly prevents proteinuria in virtually all models of disease progression. This does not necessarily apply to patients with proteinuric nephropathies, who might be referred late in the course of their disease. Here we used a severe rat model of passive Heymann nephritis (PHN), which may mimic advanced phases of human membranous nephropathy, to study the response to ACE inhibitor alone or in combination with a HMG CoA reductase inhibitor (statin) that independently of the cholesterol-lowering effect influences pathways involved in inflammatory and fibrogenic processes. Therapies started when animals had massive proteinuria and renal lesions. METHODS: PHN was accelerated by uninephrectomy seven days after IV injection of rabbit anti-FX1A antibody. Four months later, when massive proteinuria and renal lesions were present, the rats were divided into five groups and daily given orally: vehicle; lisinopril 40 mg/L; lisinopril 400 mg/L; simvastatin 2 mg/kg b.i.d; or lisinopril 40 mg/L plus simvastatin. Six normal rats served as controls. Animals were sacrificed at 10 months. RESULTS: By the end of the study three PHN rats died in the vehicle group, four in the group given lisinopril at 40 mg/L and two in the group at 400 mg/L, whereas all rats on simvastatin or combined therapy were alive. Blood pressure increased during time in PHN and was normalized by treatment with ACE inhibitor and combined therapy. Even at the high dose lisinopril failed to reduce proteinuria. Simvastatin only partially affected proteinuria. However, combining lisinopril with simvastatin had a remarkable antiproteinuric effect, such that at 10 months the urinary proteins were comparable to pre-treatment values and significantly lower than either the vehicle or lisinopril groups. Hypercholesterolemia of PHN rats was limited by combined therapy, and a positive correlation was found between serum cholesterol and proteinuria. Renal function was only partially ameliorated by simvastatin but significantly improved by combined therapy. Drug combination significantly limited glomerulosclerosis, tubular damage and interstitial inflammation, compared to vehicle or drugs alone. Up-regulation of monocyte chemoattractant protein-1 (MCP-1) mRNA in PHN kidneys was not affected by lisinopril, it was inhibited by 30% after simvastatin, and almost completely normalized by lisinopril plus simvastatin. CONCLUSIONS: These data suggest that a combined ACE inhibitor and statin approach could represent a therapeutic option for patients with advanced renal disease in whom ACE inhibitors alone fail to lower proteinuria and injury to any substantial extent.