Next Generation of Cancer Treatments: Chimeric Antigen Receptor T-Cell Therapy and Its Related Toxicities: A Review for Perioperative Physicians.

Cancer immunotherapy has entered a new era with the recent introduction of genetically engineered T-cells that express chimeric antigen receptors (CARs) capable of recognizing and destroying tumor cells. Several clinical trials in patients with relapsed or refractory B-cell malignancies have demonstrated complete remission rates ranging from 50% to 90%, with long-term data suggestive of a possible curative response. CAR T-cell therapy is currently under investigation for earlier use in these disease processes and in various other solid and liquid tumors. CAR T-cell therapy is associated with a unique postinfusion toxicity profile including cytokine-release syndrome and neurotoxicity. These toxicities are usually reversible but can be fatal, requiring close vigilance and prompt treatment often in an intensive care unit (ICU) setting. CAR T-cell therapy is currently restricted to designated centers possessing expertise in acute toxicity management, but wider use is likely if early therapeutic successes are replicated. As perioperative and critical care physicians, anesthesiologists may encounter such patients in the perioperative or ICU setting and should become familiar with this unique and novel therapeutic modality capable of causing extreme cardiovascular and respiratory compromise. This review will describe the immunobiology of CAR T-cells, their relevance to cancer treatment, clinical aspects of their therapeutic use in cancer chemotherapy, toxicities related to CAR T-cell use, and their therapeutic management.

ROUTINE USE OF SUGAMMADEX DOES NOT SHORTEN PACU LENGTH OF STAY: A PROSPECTIVE DOUBLE-BLINDED RANDOMIZED CONTROLLED TRIAL.

BACKGROUND: The reversal agent sugammadex has been shown to be more efficacious at reversal from neuromuscular blockade (NMB) induced by the aminosteroid class of non-depolarizing muscle relaxants than the traditionally used medication neostigmine. However, whether these differences lead to significantly faster PACU discharge readiness remains unknown. Given the increased acquisition cost of sugammadex as compared to neostigmine we compared these two reversal agents in our surgical population to determine if its pharmacokinetic superiority warranted a change in current practice. METHODS: We conducted a single-center randomized patient and assessor blinded clinical trial. A total of 201 patients presenting for surgery requiring NMB with an estimated duration of ≤ 6 hours were included in the intention-to-treat (ITT) analysis. The primary outcome was time from reversal agent administration to PACU discharge readiness, measured by either the institutional discharge scoring tool or bedside clinical assessment by a PACU physician or advanced practice provider. Secondary outcomes included subjective assessment of recovery by the patient (pain, visual changes, speaking difficulty, swallowing difficulty, PONV, anxiety) and a simple strength assessment. RESULTS: Median time from reversal administration to PACU discharge readiness was 3.59 hours (IQR 2.49-5.09) in the neostigmine group and 3.62 hours (IQR 2.70-5.87) in the sugammadex group. Patients who received sugammadex had 8% longer reversal to PACU discharge times (exp(estimate) 1.08, 95% CI [0.87-1.34], p=0.499). Patients age 70 or older had 28% longer reversal to PACU discharge times (exp(estimate) of 1.28, 95% CI [0.91-1.80], P=0.158). In the a modified ITT analysis, sugammadex patients were estimated to be in PACU 13% longer than neostigmine arm patients (exp(estimate) 1.13, 95% CI [0.91-1.40], p=0.265) and patients older than or equal to 70 years 31% longer than patients less than 70 years old (exp(estimate) 1.31, 95% CI [0.93-1.84], p=0.121). Treatment arm was not associated with any of the secondary outcomes. CONCLUSION: There was no significant difference in time to readiness to discharge from PACU, and there were no subjective or objective clinically relevant differences in recovery from neuromuscular blockade between the groups. Findings of this study support continued use of either agent at the anesthesiologist's discretion.

The relationship between oxygen and adenosine in astrocytic cultures.

Brain tissue oxygenation affects cerebral function and blood flow (CBF). Adenosine (Ado), a purine nucleoside, moderates neuronal activity, and arterial diameter. The cellular source of Ado in brain remains elusive; however, astrocytes are a logical site of production. Using astrocytic cultures, we tested the hypothesis that astrocytic derived Ado reflects cerebral oxygenation. We found that during alterations in pO(2), extracellular levels of Ado [Ado](e) changed rapidly. Graded reductions of oxygen tension revealed that[Ado](e) reached 10(-7) M to 10(-6) M with a pO(2) of 30-10mmHg, comparable with [Ado](e) and oxygen levels found in brain tissue during normoxemia. Higher O(2) levels were associated with a depression of [Ado](e). Under conditions of low pO(2) (pO(2)

Hematologic Disorders.

The hematologic system is responsible for several of the body's most critical functions, including delivery of oxygen and nutrients to tissues, clearance of toxic metabolic byproducts, defense against offending pathogens, and maintenance of hemostasis in the setting of trauma. Its exquisite complexity is difficult to overstate and poses a great challenge to review in short form. This article provides highlights and clinical pearls in managing patients suffering from some of the most common hematologic afflictions encountered in the perioperative setting.

Introduction to urinalysis: historical perspectives and clinical application.

Urinalysis was the first laboratory test performed in medicine and has been used for several thousand years. Today urinalysis continues to be a powerful tool in obtaining crucial information for diagnostic purposes in medicine. Urine is an unstable fluid, and changes to its composition begin to take place as soon as it is voided. As such, collection, storage, and handling are important issues in maintaining the integrity of this specimen. In the laboratory, urine can be characterized by physical appearance, chemical composition, and microscopically. Physical examination of urine includes description of color, odor, clarity, volume, and specific gravity. Chemical examination of urine includes the identification of protein, blood cells, glucose, pH, bilirubin, urobilinogen, ketone bodies, nitrites, and leukocyte esterase. Finally, microscopic examination entails the detection of crystals, cells, casts, and microorganisms.

Role of adenosine A2 receptors in regulation of cerebral blood flow during induced hypotension.

The mechanisms responsible for vascular autoregulation in the brain during changes in mean arterial blood pressure are ambiguous. Potentially, adenosine, a purine nucleoside and potent vasodilator, may be involved as earlier studies have documented an increase in brain adenosine concentrations with cerebral ischemia and hypotension. Consequently, we tested the hypothesis that adenosine is involved in vasodilatation during hypotension within the autoregulatory range (>50 mm Hg) by exposing adenosine 2a receptor (A2aR) knockout and wild type (WT) mice to short (2 to 5 mins) periods of hypotension. We found that autoregulation was significantly (P<0.05) impaired by 29% in A2a knockout mice as compared with WT animals. Furthermore, the A2R antagonist (A2a>A2b:10-85>1), ZM-241385, in a dose (1, 5, 10 mg/kg, intraperitoneally)-related manner, attenuated autoregulation in WT mice. In knockout mice treated with ZM-2413585 (5 and 10 mg/kg), autoregulation was further impaired indicating that A2b receptors also participated in cerebral vasodilatation. Treatment with dipyridamole (1.0 mg/kg) that increases extracellular concentrations of adenosine improved autoregulation in the A2aR knockout mice. We would conclude that adenosine through both A2a and A2b receptors is involved in physiologic vascular regulation during hypotension even within the autoregulatory range.

Aspectos sociales en el control del cáncer uterino en el departamento de Caldas / Social aspects in the control of the uterine Cancer in the department of Caldas

Este trabajo y su impacto es el resultado dela unión del sector político administrativo, académicoy comunitario; está dentro de las propuestasde la atención primaria elaboradas enla conferencia internacional en 1.978 enKazacstan (Unión de Republicas SocialistaSovieticas) con el eslogan ®Salud para todosen el año 2000¼ que planteó: La Atención Primariarefleja las condiciones económicas, políticasy socioculturales de las comunidades yse basa fundamentalmente en la aplicación delos resultados obtenidos en las investigacionessociales y biomédicas y está orientada hacialos principales problemas de salud de la comunidad,utilizando los servicios de promoción,prevención, tratamiento y rehabilitación, necesariospara enfrentarlos...

Paracoccidioidomicosis genital femenina: informe de un caso / Female genital paracoccidioidomycosis: report of a case

Se presenta el caso de una mujer de 47 anos de edad quien fue remitida a la Unidad de Ginecologia del Hospital General Universitario Santa Sofia para estudio colposcopico por citologia anormal. Imagen fue sugestiva de Neoplasia Intraepitelial Cervical pero en estudio histologico de biopsias tomadas de zonas acetoblancas, con mosaico y punteado revelaron la presencia de reaccion granulomatosa con estructuras de hongos de doble pared y morfologia del Paracoccidioides Braziliensis. Estudio sistemico de la paciente habia revelado compromiso pulmonar con cambios de laboratorio de infeccion paracoccidioidal que fue tratado un ano antes en forma inconstante con sulfas. Este informe presenta un caso observado recientemente, con compromiso sistemico y presentacion clinica prominente en genitales femeninos (cervis-uretra-vagina) siendo su manifestacion clinica y colposcopicocitologica, sugestiva de Neoplasia