There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Idarucizumab for dabigatran reversal

Tumours progress despite being infiltrated by tumour-specific effector T cells. Tumours contain areas of cellular necrosis, which are associated with poor survival in a variety of cancers. Here, we show that necrosis releases intracellular potassium ions into the extracellular fluid of mouse and human tumours, causing profound suppression of T cell effector function. Elevation of the extracellular potassium concentration ([K+]e) impairs T cell receptor (TCR)-driven Akt-mTOR phosphorylation and effector programmes. Potassium-mediated suppression of Akt-mTOR signalling and T cell function is dependent upon the activity of the serine/threonine phosphatase PP2A. Although the suppressive effect mediated by elevated [K+]e is independent of changes in plasma membrane potential (Vm), it requires an increase in intracellular potassium ([K+]i). Accordingly, augmenting potassium efflux in tumour-specific T cells by overexpressing the potassium channel Kv1.3 lowers [K+]i and improves effector functions in vitro and in vivo and enhances tumour clearance and survival in melanoma-bearing mice. These results uncover an ionic checkpoint that blocks T cell function in tumours and identify potential new strategies for cancer immunotherapy.

/pdf/ionic-immune-suppression-within-the-tumour-microenvironment-4x6lhruc94.pdf

Ionic immune suppression within the tumour microenvironment limits T cell effector function

Medically Important Fungi: A Guide to Identification

There are two preferred ways of sharing medical information. One is data centered and for very good reasons has dominated our epistemology for almost a century. The other is empirical, based on a motley collection of hunch and experience. Both ways complement each other, both are important for our growth as physicians and surgeons dedicated to walk with our patients to their recovery.

For some reason that I am not able to explain the wonderful and experienced colleagues from Latin America and Africa are shy about telling their experience and opinion. Perhaps it is because in Latin America academic and professional promotions do not depend on the number of peer reviewed publications. In any case we at Surgical Neurology International feel that those voices need to be heard. Thus, we have launched this series that has been called “How I do it”.

We asked four Pediatric Neurosurgeons from Latin America and asked them to tell us about their approach to a prevalent condition neglected by the designers of public health strategies, neural tube defects.

The original text is in Spanish accompanied by an English translation that while short in nuances manages to be loyal to the intentions of the authors.

The papers are short, it could not be otherwise, and the authors have almost never published before. But the papers are dense in technical insight. In all the papers the reader will hear the undercurrent of devotion to the most forgotten of the patients, the malformed born in a low and middle-income country.

I praise James Ausman, M.D. the editor for accepting, supporting and encouraging this initiative. As I ready the papers for submission I recognize my shortcomings in polishing the message of my colleagues. And while coming contributions on “How I do it” will better the previous, this first series has the charm and innocence of a great dream.

How I Do It

Tumor lysis syndrome (TLS) is a potentially deadly complication of tumors or their treatment. This syndrome consists of a constellation of laboratory findings such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia, known as laboratory TLS. When clinical complications such as seizures, acute renal failure, and cardiac dysrhythmias occur in patients with laboratory TLS, the syndrome is called clinical TLS. TLS is especially common in patients with hematological malignancies with rapid cellular turnover rates such as acute lymphocytic leukemia and Burkitt lymphoma, but is very rare in patients with solid tumors. Nevertheless, there are multiple reports in the literature on the occurrence of TLS in patients with solid tumors. In this review article, we summarize the current data on the occurrence of TLS in patients with solid tumors. We propose an algorithm of risk stratification and prevention of TLS in patients with solid cancers.

https://journals.sagepub.com/doi/pdf/10.4081/rt.2014.5389

Tumor Lysis Syndrome in Solid Tumors: An up to Date Review of the Literature.

Primary malignant melanoma of the anus and rectum is a rare and aggressive neoplasm that tends to invade locally and metastasize early in the course of the disease. It is often misdiagnosed as hemorrhoids or as one of the other benign anorectal conditions and is thus linked to an overall poor prognosis and a 5-year survival rate of less than 20%. Optimal treatment is still controversial, and current evidence does not show any preferential survival benefit from abdominoperineal resection over wide local excision. Chemotherapy or radiotherapy may be used for advanced disease. We report a 71-year-old female presenting with painful bowel movements and blood in stools. She was eventually found to have a mass arising from the anorectal junction with regional lymph node involvement. The patient underwent an abdominoperineal resection and is currently scheduled for chemotherapy.

/pdf/primary-anorectal-melanoma-4i87oo1s0e.pdf

Primary anorectal melanoma.

Pharmacologic toxicities are common and range from mild to life-threatening. The aim of this study is to review and update the data on the role of renal replacement therapy (RRT) in the management of various pharmacologic poisonings. We aim to provide a focused review on the role of RRT in the management of pharmacological toxicities. Relevant publications were searched in MEDLINE with the following search terms alone or in combination: pharmacologic toxicity, hemodialysis, hemofiltration, renal replacement therapy, toxicology, poisonings, critical illness, and intensive care. The studies showed that a pharmacologic substance should meet several prerequisites to be deemed dialyzable. These variables include having a low molecular weight (<500 Da) and low degree of protein binding (<80%), being water-soluble, and having a low volume of distribution (<1 L/kg). RRT should be strongly considered in critically ill patients presenting with toxic alcohol ingestion, salicylate overdose, severe valproic acid toxicity, metformin overdose, and lithium poisoning. The role of RRT in other pharmacologic toxicities is less certain and should be considered on a case-by-case basis.

https://downloads.hindawi.com/journals/ijn/2016/3047329.pdf

The Role of Renal Replacement Therapy in the Management of Pharmacologic Poisonings

Adverse reactions to commonly prescribed medications and to substances of abuse may result in severe toxicity associated with increased morbidity and mortality. According to the Center for Disease Control, in 2013, at least 2113 human fatalities attributed to poisonings occurred in the United States of America. In this article, we review the data regarding the impact of systemic sodium bicarbonate administration in the management of certain poisonings including sodium channel blocker toxicities, salicylate overdose, and ingestion of some toxic alcohols and in various pharmacological toxicities. Based on the available literature and empiric experience, the administration of sodium bicarbonate appears to be beneficial in the management of a patient with the above-mentioned toxidromes. However, most of the available evidence originates from case reports, case series, and expert consensus recommendations. The potential mechanisms of sodium bicarbonate include high sodium load and the development of metabolic alkalosis with resultant decreased tissue penetration of the toxic substance with subsequent increased urinary excretion. While receiving sodium bicarbonate, patients must be monitored for the development of associated side effects including electrolyte abnormalities, the progression of metabolic alkalosis, volume overload, worsening respiratory status, and/or worsening metabolic acidosis. Patients with oliguric/anuric renal failure and advanced decompensated heart failure should not receive sodium bicarbonate.

/pdf/the-role-of-sodium-bicarbonate-in-the-management-of-some-3g0diam230.pdf

The Role of Sodium Bicarbonate in the Management of Some Toxic Ingestions

Patients with nephrotic syndrome are at an increased risk for thrombotic events; deep venous thrombosis, renal vein thrombosis, and pulmonary embolism are quite common in patients with nephrotic syndrome. It is important to note that nephrotic syndrome secondary to membranous nephropathy may impose a greater thrombotic risk for unclear reasons. Increased platelet activation, enhanced red blood cell aggregation, and an imbalance between procoagulant and anticoagulant factors are thought to underlie the excessive thrombotic risk in patients with nephrotic syndrome. The current scientific literature suggests that patients with low serum albumin levels and membranous nephropathy may benefit from primary prophylactic anticoagulation. A thorough approach which includes accounting for all additional thrombotic risk factors is, therefore, essential. Patient counseling regarding the pros and cons of anticoagulation is of paramount importance. Future prospective randomized studies should address the question regarding the utility of primary thromboprophylaxis in patients with nephrotic syndrome.

/pdf/primary-nephrotic-syndrome-in-adults-as-a-risk-factor-for-1czmmrq6po.pdf

Aram Barbaryan

Papers

Tumor Lysis Syndrome in Solid Tumors: An up to Date Review of the Literature.

Primary anorectal melanoma.

The Role of Renal Replacement Therapy in the Management of Pharmacologic Poisonings

The Role of Sodium Bicarbonate in the Management of Some Toxic Ingestions

Primary Nephrotic Syndrome in Adults as a Risk Factor for Pulmonary Embolism: An Up-to-Date Review of the Literature