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COVID-19 is a syndrome that includes more than just isolated respiratory disease, as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) also interacts with the cardiovascular, nervous, renal, and immune system at multiple levels, increasing morbidity in patients with underlying cardiometabolic conditions and inducing myocardial injury or dysfunction. Emerging evidence suggests that patients with the highest rate of morbidity and mortality following SARS-CoV2 infection have also developed a hyperinflammatory syndrome (also termed cytokine release syndrome). We lay out the potential contribution of a dysfunction in autonomic tone to the cytokine release syndrome and related multiorgan damage in COVID-19. We hypothesize that a cholinergic anti-inflammatory pathway could be targeted as a therapeutic avenue. Graphical Abstract .

Background: Carbamazepine is a first line treatment for focal epilepsy. Tegretol and Tegatard are two trade name of Carbamazepine. Tegretol is produced by Novartis Pharmaceutical Company, Switzerland. Recently, Raha pharmaceutical Company in Iran has produced CBZ which trade named is Tegatard. Extended usage of Tegatard instead of Tegretol has economic benefits for Iranian families. In this clinical trial, we aimed to compare therapeutic efficacy and safety of Tegretol and Tegatard in patients suffering from focal seizures with or without secondary generalization., Methods: 200 patients with provoked or non-provoked focal seizure with or without secondary generalization were screened and 180 patients were fulfilled the criteria to enter this double blinded clinical trial study. Patients were divided into two groups, the first group (A) received Tegretol and the second group (B) Tegatard. Carbamazepine (CBZ) was prescribed with doses 10-20 mg/kg every 12 hours by neurologists. The patients were visited after 1, 3 and 6 months and the side effects and lab data in patients were investigated., Results: Patients were divided into two groups, 88 patients in group A (Tegretol) (50 males and 38 females) and 92 in group B (Tegatard) (51 males and 41 females). Mean age of patients was 35.39±11.17 years. There was no significant difference according to age and gender, Carbamazepine dosage, EEG recording, neuroimaging change and adverse effects of antiepileptic drug between two groups (P>0.05). Regarding the drug efficacy, in group A and B, 60 (68%) and 58 (63%) patients were seizure free after 6 month follow up; respectively. The differences between two groups were not statistically significant ( P value =0.46)., Conclusion: Tegatard is an effective drug with similar efficacy, similar side effects and cost-effectiveness compared with Tegretol and could be used widely when indicated., Competing Interests: None., (AJCEI Copyright © 2020.)

Background: Carpal tunnel syndrome (CTS) is characterized by complications such as pain, paresthesia, and numbness in the fingers. There are some surgical therapies for the management of severe carpal tunnel, but differences exist between the treatments available for creating the opposition. The current study was conducted to compare the effect of modified Camitz and BRAND techniques on thumb opposition in patients with severe CTS., Methods: A total of 40 patients with severe CTS who were candidates for opponensplasty were enrolled in this clinical trial study at Alzahra and Kashani hospitals, Isfahan, Iran, from 2014 to 2018. The patients were divided into two groups of modified Camitz and BRAND. Quick DASH-9 and Kapandji scores as well as pulp and side pinch and pronation angle were assessed before and after the surgeries., Results: Quick DASH-9 score, Kapandji score, pulp and side pinch and pronation angle significantly improved post-operatively ( P=0.0XXX , P=0.0XXX , P=0.0XXX , P=0.0XXX , and P=0.0XXX , respectively). But, no significant differences were seen in the mentioned variables between both groups pre and post-operative ( P>0.05 , for all the studied variables). No postsurgical complications were seen in any of the groups., Conclusion: The findings of the present study demonstrated that, both Modified Camitz and BRAND techniques are effective and safe techniques, yielding high improvements, but no serious complications. Both techniques can be considered for treatment of patients with severe CTS.

Multiple sclerosis is a chronic inflammatory disease of the central nervous system (CNS). Although the exact etiology of multiple sclerosis is unknown, researchers suggest that genetic, environmental, and microbial factors play a central role in causing multiple sclerosis. Pathology of multiple sclerosis is based on inflammation as T cells enter the brain via disruptions in the blood-brain barrier, recognizing myelin as foreign antigen; and as a result, the T cells attack myelin and start the inflammatory processes, enhancing inflammatory cytokines and antibodies. Since previous studies show ethanol can suppress the immune system such as innate, humoral, and cellular immunity and increases the production of anti-inflammatory cytokines, we hypothesized maybe ethanol also have ameliorating effects on multiple sclerosis symptoms. Although alcohol induces apoptosis in oligodendrocytes and neurons, causing demyelination and affects CNS directly, in this study we will investigate ethanol's effects on some aspects of the immune system in multiple sclerosis., Competing Interests: None., (IJPPP Copyright © 2020.)

Left ventricular assist devices (LVADs) are used to support patients with advanced systolic heart failure (HF). These patients might develop LVAD dysfunction and consequent HF symptoms. Occasionally, outflow graft obstruction is responsible for LVAD dysfunction. Here, we describe percutaneous techniques to repair the outflow graft and avoid re-sternotomy., (Copyright © 2019. Published by Elsevier B.V.)

Surgical patients, following procedural interventions or traumatic injury, often bleed due to ongoing blood loss or coagulopathy. Volume resuscitation and transfusion management are critical for the massively bleeding patient. While transfusions may correct coagulopathy, they carry multiple risks including circulatory overload and transfusion-related acute lung injury. Factor concentrates, specifically prothrombin complex concentrates (PCCs), are often used as part of multimodal therapy for bleeding along with laboratory testing to rapidly assess underlying coagulopathy. Although they are commonly used as part of management algorithms, studies evaluating their efficacy against fresh frozen plasma (FFP) or other potential therapies are needed. Further, PCCs are indicated to treat the coagulopathy associated with non-vitamin K oral anticoagulants in the perioperative setting. The focus of this commentary will be the perioperative use of PCCs, plasma, and FFP., Competing Interests: J.H.L. serves on research steering committees or advisory boards for Boehringer-Ingelheim, CSL Behring, Instrumentation Laboratories, Octapharma, and Merck. K.G. receives support from NIGMS T32GM008600 and Duke Health. N.H.W. receives grants for clinical research from Allergan, is supported by AHA Grant 16MCPRP30700010, and the NIGMS T32 postdoctoral training grant T32GM008600, and serves as a consultant to Allergan. J.M.C. reports grants from CSL Behring, personal fees from Portola and Brisol-Meyrs Squibb, outside the submitted work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose of Review: This review will illustrate the importance of heparin-induced thrombocytopenia in the intraoperative and critical care settings., Recent Findings: Heparin-induced thrombocytopenia (HIT) occurs more frequently in surgical patients compared with medical patients due to the inflammatory release of platelet factor 4 and perioperative heparin exposure. Recognition of this disease requires a high index of suspicion. Diagnostic tools and therapeutic strategies have been expanded and refined in recent years., Summary: HIT is a condition where antibodies against the heparin/platelet factor 4 complex interact with platelet receptors to promote platelet activation, aggregation, and thrombus formation. Our review will focus on intraoperative and postoperative considerations related to HIT to help the clinician better manage this rare but often devastating hypercoagulable disease process., Competing Interests: Conflict of InterestIngrid Moreno-Duarte declares that she has no conflict of interest., (© Springer Science+Business Media, LLC, part of Springer Nature 2020.)

Introduction: Current methods for Urethral dilatation include filiforms and followers, metal sounds, balloon dilators, catheters of increasing size, introduction of a Council catheter over a guidewire, and coaxial dilators of increasing size. These methods however are effective but expensive and use of them is limited in many third world countries. In this retrospective study, we report the feasibility, complication and long-term follow-up of the newly Nelaton based urethral dilation method following by self calibration plan as a single referral center experience. Method: We reviewed the records of 333 men with urethral stricture longer than 1 cm over a 16-year period between March 2001 to December 2018. In this method the straight flexi-tip guide-wire is introduced through the urethra and advanced under cystoscopic vision. This wire then was used to guide the dilatation after withdrawal of the cystoscope. The tip of well-lubricated Nelaton urethral catheters incised and then advanced gently over the guide-wire serially from the smallest to the largest appropriate sizes. The patients were followed up regularly after the dilatation 1, 3, 6, 12 months and then annually postoperatively with taking history, PVR and uroflowmetry and all underwent retrograde urethrography at the 6 th and 12 th months of follow-up. Result: The mean age of patients was 39.19±16.9 years old (10 to 86 years). The mean period of the follow-up was 3.6±1.1 years (range, 3 to 4.3 years). Success rate after first attempted was 58.5% and after two attempted was 77.7% in two years follow up. After one year 51 (15.3%), two years 23 (6.9%) and after three years 11 (3.3%) cases required continued self dilatation once a month. Conclusion: Guide wire-assisted urethral dilatation is shown to be acceptable, cost-effective, simple, safe and feasible techniques for urethral dilation. Our technique may be the choice manner in selected patients with short memberanous urethral stricture, because of decrease the risk of incontinency., Competing Interests: None., (AJCEU Copyright © 2019.)

Background: Studies reported that evaluating the interleukin serum level of MS and NMO patients is helpful for differentiating these two diseases from each other. This study aimed to compare the level of IL-6 and IL-17 in MS and NMO patients and healthy subjects., Methods: This study is a case control study that evaluated the serum level of IL-6 and IL-17 in MS and NMO patients in comparison to controls in patients who referred to Kashani hospital clinics. The level of serum IL-6 and IL-17 were measured by ELISA test in all patients. Participants were divided in to three groups include MS patients, NMO patients and controls and the level of IL-6 and IL-17 were compared in this three groups., Results: Mean of serum level of IL-6 in the NMO group was significantly lower than MS and healthy subject (P=0.02 for NMO and MS, P=0.001 for NMO and healthy subjects) but there was no significant difference between MS and healthy subjects (P=0.09). The mean of serum level of IL-17 in the MS and NMO were significantly higher than healthy subjects (P<0.001 for both). Also the mean of serum level of IL-17 in the MS was significantly higher than NMO (P=0.01). A positive significant correlation between age and serum level of IL-6 in all subjects (r=0.23, P=0.01). There was a positive significant correlation between age and serum level of IL-17 in MS and NMO patients (r=0.28, P=0.012)., Conclusion: Using IL-17 and IL-6 were inflammatory markers to diagnosis of NMO, MS and healthy subjects., Competing Interests: None., (IJPPP Copyright © 2019.)

Background: The molecular mechanism of bladder cancer is yet not fully understood. Aim of this study was to compare the levels of BLCA-4 nuclear matrix protein in the urine of patients with bladder cancer and non-affected individuals., Materials and Method: The current cross sectional study was conducted on 45 patients with bladder cancer and 45 patients without bladder cancer who were referred to Alzahra Hospital of Isfahan, Iran in 2017. BCLA-4 Urinary Marker was measured in urine of the patients and individuals. Also correlation between the urine levels of BCLA-4 and other variables were evaluated., Results: The urine levels of BLCA-4 in the patients with bladder cancer was significantly higher than non-bladder cancer group (P<0.001). There was no significant relationship between urine levels of BLCA-4 with tumor stage and size (P>0.05)., Conclusion: The present study indicated that high urine levels of BLCA-4 was presented in patients with bladder cancer and this tumor marker has a high capability for early diagnosis of the disease, which can be used for screening and follow-up of bladder cancer., Competing Interests: None., (IJPPP Copyright © 2019.)

Multiple Sclerosis (MS) is chronic, inflammatory, a neurologic disorder of the central nervous system (CNS). Although the exact mechanisms of MS have not been yet discovered some drugs are found helpful for its treatment. These drugs which are divided into the first line, second line and third-line therapies, have demonstrated to be helpful for MS patients based on immune basic of the disease. Previous studies have been indicated that deterioration of MS condition is associated with a stronger immune system. Most of these therapies impact on the immune system and immune cells including shifting immune cell populations toward a Th2 dominant population or suppression of the immune system so that auto-reactive immune cells cannot attack myelin sheath of neurons. Beside many beneficial effects of these drugs, some adverse effects (AE) have been reported in many experiments and clinical trials among patients suffering from MS. In this review, we conclude some AEs of beta interferon, mitoxantrone, natalizumab and fingolimod, reported in different papers and we continue the rest of the drugs in second part of our review article., Competing Interests: None.

Multiple Sclerosis (MS) is an autoimmune, inflammatory disease of the central nervous system (CNS) mostly affecting young adults. The exact mechanism and pathogenesis of MS remain still undiscovered but there have been useful treatments with different efficacy rates. Most of these therapies are divided into the first line, second line and third line, impact on the immune system and immune cells. These drugs are approved to be useful in MS, but like any other therapies, adverse effects (AE) are associated with these drugs. In this review, we continue the survey over mechanisms of actions and AEs of MS drugs. Physicians must be aware of such AEs and complications to choose the best drug for each patient., Competing Interests: None.

Introduction: Intratympanic therapy, as a widely used treatment for inner ear diseases, is regarded as a therapeutic method in controlling the vertigo of the patients with Meniere's disease. This study was designed to evaluate the effect of the Intratympanic dexamethasone-hyaluronic acid combination on patients suffering from Meniere's disease., Materials and Methods: This study was a clinical trial on patients with Meniere's disease during 2016-2017. Patients received two Intratympanic injections of dexamethasone plus hyaluronic acid as a mixture within a month. Before and 2 weeks after the intervention, pure tone average (PTA) at 0.5, 1, 2, and 4 KHz frequencies, speech discrimination score (SDS), dizziness handicap inventory (DHI), and tinnitus handicap inventory (THI) scores were evaluated for each patient. The obtained scores were statistically analyzed., Results: This study was conducted on a total number of 25 patients with Meniere's disease. The mean age of participants in this study was 44.71±4.92 years. Gender distribution among participants revealed that 36% of patients were male. The mean values of PTA, SDS, and THI were not significantly different before and after the intervention. However, the mean score of DHI decreased significantly after the intervention (P<0.001)., Conclusion: Intratympanic dexamethasone/hyaluronic acid had a positive effect on the vertigo of the investigated patients without any significant improvement in hearing impairment and tinnitus in the short term.

Background/objectives: Prothrombin complex concentrates (PCC) are increasingly administered off-label in the United States to treat bleeding in cardiovascular surgical patients and carry the potential risk for acquired thromboembolic side-effects after surgery. Therefore, we hypothesized that the use of low-dose 3-factor (3F) PCC (20-30 IU/kg), as part of a transfusion algorithm, reduces bleeding without increasing postoperative thrombotic/thromboembolic complications., Materials/methods: After IRB approval, we retrospectively analysed 114 consecutive, complex cardiovascular surgical patients (age > 18 years), between February 2014 and June 2015, that received low-dose 3F-PCC (Profilnine ® ), of which seven patients met established exclusion criteria. PCC was dosed according to an institutional perioperative algorithm. Allogeneic transfusions were recorded before and after PCC administration (n = 107). The incidence of postoperative thromboembolic events was determined within 30 days of surgery, and Factor II levels were measured in a subset of patients (n = 20) as a quality control measure to avoid excessive PCC dosing., Results: Total allogeneic blood product transfusion reached a mean of 12·4 ± 9·9 units before PCC and 5·0 ± 6·3 units after PCC administration (P < 0·001). The mean PCC dose was 15·8 ± 7·1 IU/kg. Four patients (3·8%) each experienced an ischaemic stroke on postoperative day 1, 2, 4 and 27. Seven patients (6·5%) had acquired venous thromboembolic disease within 10 days of surgery. Median factor II level after transfusion algorithm adherence and PCC administration was 87%., Conclusions: 3F-PCC use for refractory bleeding after cardiovascular surgery resulted in reduced transfusion of allogeneic blood and blood products. Adherence to this algorithmic approach was associated with an acceptable incidence of postoperative thrombotic/thromboembolic complications., (© 2019 International Society of Blood Transfusion.)

The syndrome of frailty for patients undergoing heart or lung transplantation has been a recent focus for perioperative clinicians because of its association with postoperative complications and poor outcomes. Patients with end-stage cardiac or pulmonary failure may be under consideration for heart or lung transplantation along with bridging therapies such as ventricular assist device implantation or venovenous extracorporeal membrane oxygenation, respectively. Early identification of frail patients in an attempt to modify the risk of postoperative morbidity and mortality has become an important area of study over the last decade. Many quantification tools and risk prediction models for frailty have been developed but have not been evaluated extensively or standardized in the cardiothoracic transplant candidate population. Heightened awareness of frailty, coupled with a better understanding of distinct cellular mechanisms and biomarkers apart from end-stage organ disease, may play an important role in potentially reversing frailty related to organ failure. Furthermore, the clinical management of these critically ill patients may be enhanced by waitlist and postoperative physical rehabilitation and nutritional optimization., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Recently, to reduce the incidence of oculocardiac reflex (OCR) in strabismus surgery, retrobulbar block and anticholinergic drugs or local anesthesia are also used. The present study evaluated the effects of Tetracaine eye drop as a topical nerve blocker on OCR during strabismus surgery., Methods and Materials: In this randomized trial, 70 strabismus surgery candidates were randomly divided into placebo or synthetic teardrop (E) and Tetracaine eye drop (T) groups, so 3 drops of each solution were dropped in four directions of patients' eye immediately after applying anesthesia and before surgery. The incidence and severity of OCR during the stages of muscle release and incision (cutting), hemodynamic changes, the required time for OCR recovery and atropine dose were assessed., Results: OCR was more seen in release phase compared to cutting phase. There were no significant differences between two group regarding the incidence and severity of OCR in the release phase (p > 0.05), but the incidence and severity of OCR in the cutting phase was more in group E than group T (p = 0.02, for both). The duration of OCR improvement (p-value = 0.74) and Atropine consumption (p-value = 0.92) did not differ between the groups., Conclusion: Tetracaine eye drop only reduces the incidence and severity of OCR during the incision stage of strabismus surgery.

Patients undergoing cardiovascular surgery may be exposed to heparin before surgery, during cardiopulmonary bypass (CPB), or in the immediate postoperative period. For this reason, cardiovascular surgery patients are at increased risk for heparin-induced thrombocytopenia (HIT), occurring in 1 to 3% of patients. The diagnosis of HIT can be difficult, if based solely on the development of thrombocytopenia, because cardiac surgical patients have multiple reasons to be thrombocytopenic. Several clinical scoring systems have been developed to reduce unnecessary testing and better define the pretest probability of HIT, which we will review in detail with a diagnostic algorithm. In addition, we will cover the prevention and treatment HIT., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose of Review: To evaluate the efficacy, dosing, and safety of methylene blue (MTB) in perioperative vasoplegic syndrome (VS)., Recent Findings: Vasoplegic syndrome is a state of persistent hypotension with elevated cardiac output, low filling pressures, and low systemic vascular resistance (SVR). It occurs in up to 25% of patients undergoing cardiac surgery with cardiopulmonary bypass, can last up to 72 h, and is associated with a high mortality rate. MTB has been found to increase SVR and decrease vasopressor requirements in vasoplegic syndrome by inhibiting nitric oxide synthase, thus limiting the generation of nitric oxide, while inhibiting activation of soluble guanylyl cyclase and preventing vasodilation. MTB has been used in postgraft reperfusion during liver transplantation and anaphylaxis in a limited number of cases. Additionally, this medication has been used in septic shock with promising results, but similar to the cardiac surgical population, the effects of MTB administration on clinical outcomes has yet to be elucidated., Summary: MTB should be considered during vasoplegic syndrome in cardiac surgery with cardiopulmonary bypass and usage may be more effective in an early critical window, prior to end-organ hypoperfusion. Other perioperative scenarios of MTB use show promise, but additional studies are required to develop formative conclusions.

The functional aortic annulus offers a clinical approach for the perioperative echocardiographer to classify the mechanisms of aortic regurgitation in acute type-A dissection. Comprehensive examination of the functional aortic annulus in this setting using transesophageal echocardiography can guide surgical therapy for the aortic root by considering the following important aspects: severity and mechanism of aortic regurgitation, extent of root dissection, and the pattern of coronary artery involvement. The final choice of surgical therapy also should take into account factors, such as patient presentation and surgical experience, to limit mortality and morbidity from this challenging acute aortic syndrome. This review explores these concepts in detail within the framework of the functional aortic annulus, detailed anatomic considerations, and the latest literature., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Patients who are critically ill following surgical or traumatic injury often present with coagulopathy as a component of the complex multisystem dysfunction that clinicians must rapidly diagnose and treat in the intensive care environment. Failure to recognize coagulopathy while volume resuscitation with crystalloid or colloid takes place, or an unbalanced transfusion strategy focused on packed red blood cell transfusion can all significantly worsen coagulopathy, leading to increased transfusion requirements and poor outcomes. Even an optimized transfusion strategy directed at correcting coagulopathy and maintaining clotting factor levels carries the risk of a number of transfusion reactions including transfusion-related acute lung injury, transfusion-related circulatory overload, anaphylaxis, and septic shock. A number of adjunctive strategies can be used either to augment a balanced transfusion approach or as alternatives to blood component therapy. Coupled with an appropriate and timely laboratory testing, this approach can quickly diagnose a patient's specific coagulopathy and work to correct it as quickly as possible, minimizing the requirement of blood transfusion and the pathophysiologic effects of excessive bleeding and fibrinolysis. We will review the literature supporting this approach and provide insight into how these approaches can be best used to care for bleeding patients in the intensive care unit. Finally, the increasing use of several novel oral anticoagulants, novel antiplatelet drugs, and low-molecular weight heparin to clinical practice has complicated the care of the coagulopathic patient when these drugs are involved. Many clinicians familiar with heparin and warfarin reversal are not familiar with the optimal way to reverse the action of these new drugs. Patients treated with these drugs for a wide variety of conditions including atrial fibrillation, stroke, coronary artery stent, deep venous thrombosis, and pulmonary embolism will present for emergency surgery and will require management of pharmacologically induced postoperative coagulopathy. We will discuss optimized strategies for reversal of these agents and strategies that are currently under development., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Determine whether moderate or greater paravalvular leak (PVL) after transcatheter aortic valve replacement quantified using intraoperative transesophageal echocardiography (TEE) is associated with mortality and investigate the correlation between PVL grading using intraoperative TEE and postoperative transthoracic echocardiography (TTE)., Design: Retrospective, observational study., Setting: Single academic institution., Participants: The study comprised adult patients undergoing elective transcatheter aortic valve replacement between April 2011 and February 2014., Interventions: Patients were grouped by amount of PVL on intraoperative TEE into "significant" (moderate or greater) and "nonsignificant" (no, trivial, or mild) PVL groups. Demographics and patient characteristics were compared. Continuous variables were assessed with t-tests or Wilcoxon rank sum tests and categorical variables with the chi-square or Fisher exact test. A Cox proportional hazards model adjusted for EuroSCORE was used to test the independent association of PVL with late mortality, and covariate-adjusted survival curves were constructed. A Fleiss-Cohen-weighted kappa value was used to assess agreement between PVL grading using intraoperative TEE and postoperative TTE., Measurements and Main Results: One hundred ninety-six patients were grouped into the "significant" (n = 22) or "nonsignificant" (n = 174) PVL group. Twenty patients (10%) died during the follow-up period. Significant PVL on either TTE (p = 0.62, hazard ratio 1.68, 95% confidence interval [CI] 0.22-12.85) or TEE (p = 0.49, hazard ratio 0.49; 95% CI 0.06-3.68) was not associated with a survival difference. Modest agreement was found between PVL on intraoperative TEE and postoperative TTE (kappa = 0.47, CI 0.37-0.57, p < 0.0001)., Conclusions: Larger studies are needed to evaluate the association of PVL graded on intraoperative TEE with survival. There is modest agreement between the degree of PVL found on TEE and TTE., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Perioperative bleeding remains a major complication during and after surgery, resulting in increased morbidity and mortality. The principal causes of non-vascular sources of haemostatic perioperative bleeding are a preexisting undetected bleeding disorder, the nature of the operation itself, or acquired coagulation abnormalities secondary to haemorrhage, haemodilution, or haemostatic factor consumption. In the bleeding patient, standard therapeutic approaches include allogeneic blood product administration, concomitant pharmacologic agents, and increasing application of purified and recombinant haemostatic factors. Multiple haemostatic changes occur perioperatively after trauma and complex surgical procedures including cardiac surgery and liver transplantation. Novel strategies for both prophylaxis and therapy of perioperative bleeding include tranexamic acid, desmopressin, fibrinogen and prothrombin complex concentrates. Point-of-care patient testing using thromboelastography, rotational thromboelastometry, and platelet function assays has allowed for more detailed assessment of specific targeted therapy for haemostasis. Strategic multimodal management is needed to improve management, reduce allogeneic blood product administration, and minimize associated risks related to transfusion., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objective: Metabolic acidosis after deep hypothermic circulatory arrest (DHCA) for thoracic aortic operations is commonly managed with sodium bicarbonate (NaHCO 3 ). The purpose of this study was to determine the relationships between total NaHCO 3 dose and the severity of metabolic acidosis, duration of mechanical ventilation, duration of vasoactive infusions, and Intensive Care Unit (ICU) or hospital length of stay (LOS)., Methods: In a single center, retrospective study, 87 consecutive elective thoracic aortic operations utilizing DHCA, were studied. Linear regression analysis was used to test for the relationships between the total NaHCO 3 dose administered through postoperative day 2, clinical variables, arterial blood gas values, and short-term clinical outcomes., Results: Seventy-five patients (86%) received NaHCO 3 . Total NaHCO 3 dose averaged 136 ± 112 mEq (range: 0.0-535 mEq) per patient. Total NaHCO 3 dose correlated with minimum pH (r = 0.41, P < 0.0001), minimum serum bicarbonate (r = -0.40, P < 0.001), maximum serum lactate (r = 0.46, P = 0.007), duration of metabolic acidosis (r = 0.33, P = 0.002), and maximum serum sodium concentrations (r = 0.29, P = 0.007). Postoperative hypernatremia was present in 67% of patients and peaked at 12 h following DHCA. Eight percent of patients had a serum sodium ≥ 150 mEq/L. Total NaHCO 3 dose did not correlate with anion gap, serum chloride, not the duration of mechanical ventilator support, vasoactive infusions, ICU or hospital LOS., Conclusion: Routine administration of NaHCO 3 was common for the management of metabolic acidosis after DHCA. Total dose of NaHCO 3 was a function of the severity and duration of metabolic acidosis. NaHCO 3 administration contributed to postoperative hypernatremia that was often severe. The total NaHCO 3 dose administered was unrelated to short-term clinical outcomes.

Multiple sclerosis (MS) is a complex, demyelinating disease of the central nervous system (CNS) with variable phenotypic presentations, while Guillain-Barre Syndrome (GBS) is the prototypic acute inflammatory disorder that affects the peripheral nervous system. Myasthenia gravis (MG) is a T cell dependent and antibody mediated autoimmune disease. Although it has been shown that complement plays a critical role in the pathogenesis of MS, GBS, and MG, the role of mannose-binding lectin (MBL) as a biomarker of immunopathogensis of these diseases and also its association with the severity of them have been poorly investigated. Therefore, in this study we aimed to measure plasma levels of MBL in patients with MS, GBS, and MG. In a case-control study, plasma was obtained from healthy controls (n=100) and also patients with MS (n=120), GBS (n=30), and MG (n=30). Plasma level measurement of MBL was performed using enzyme-linked immunosorbent assay (ELISA). The mean serum level of MBL was significantly different between groups of patients and healthy controls (p<0.001). We also found a positive correlation between plasma levels of MBL and severity scores of MS, MG, and GBS patients including: expanded disability status scale (EDSS) (r=+0.60 and p=<0.001), quantitative myasthenia gravis score (QMGS) (r=+0.56 and p=0.01), and GBS disability scale (GDS) (r=+0.37 and p=0.04). Taken together, our findings suggest that complement activation mediated by MBL contributes to the pathogenesis and also severity of MS, MG, and GBS. However, because the lectin pathway can be involved in several phases of the immune response, further evidence will be required to elucidate the underlying mechanism.

Prothrombin complex concentrates (PCCs) contain vitamin K-dependent clotting factors (II, VII, IX, and X) and are marketed as 3 or 4 factor-PCC formulations depending on the concentrations of factor VII. PCCs rapidly restore deficient coagulation factor concentrations to achieve hemostasis, but like with all procoagulants, the effect is balanced against thromboembolic risk. The latter is dependent on both the dose of PCCs and the individual patient prothrombotic predisposition. PCCs are approved by the US Food and Drug Administration for the reversal of vitamin K antagonists in the setting of coagulopathy or bleeding and, therefore, can be administered when urgent surgery is required in patients taking warfarin. However, there is growing experience with the off-label use of PCCs to treat patients with surgical coagulopathic bleeding. Despite their increasing use, there are limited prospective data related to the safety, efficacy, and dosing of PCCs for this indication. PCC administration in the perioperative setting may be tailored to the individual patient based on the laboratory and clinical variables, including point-of-care coagulation testing, to balance hemostatic benefits while minimizing the prothrombotic risk. Importantly, in patients with perioperative bleeding, other considerations should include treating additional sources of coagulopathy such as hypofibrinogenemia, thrombocytopenia, and platelet disorders or surgical sources of bleeding. Thromboembolic risk from excessive PCC dosing may be present well into the postoperative period after hemostasis is achieved owing to the relatively long half-life of prothrombin (factor II, 60-72 hours). The integration of PCCs into comprehensive perioperative coagulation treatment algorithms for refractory bleeding is increasingly reported, but further studies are needed to better evaluate the safe and effective administration of these factor concentrates.

Andexanet alfa is a specific reversal agent for Factor Xa inhibitors. The molecule is a recombinant protein analog of factor Xa that binds to Factor Xa inhibitors and antithrombin:LMWH complex but does not trigger prothrombotic activity. In ex vivo, animal, and volunteer human studies, andexanet alfa (AnXa) was able to dose-dependently reverse Factor Xa inhibition and restore thrombin generation for the duration of drug administration. Further trials are underway to examine its safety and efficacy in the population of patients experiencing FXa inhibitor-related bleeding.

Objective: To determine the severity, duration, and contributing factors for metabolic acidosis after deep hypothermic circulatory arrest (DHCA)., Design: Retrospective observational study., Setting: University hospital., Patients: Eighty-seven consecutive patients undergoing elective thoracic aortic surgery with DHCA., Interventions: Regression analysis was used to test for relationships between the severity of metabolic acidosis and clinical and laboratory variables., Measurements and Main Results: Minimum pH averaged 7.27±0.06, with 76 (87%) having a pH<7.35; 55 (63%), a pH<7.30; and 7 (8%), a pH<7.20. The mean duration of metabolic acidosis was 7.9±5.0 hours (range: 0.0 - 26.8), and time to minimum pH after DHCA was 4.3±2.0 hours (1.0 - 10.0 hours). Hyperchloremia contributed to metabolic acidosis in 89% of patients. The severity of metabolic acidosis correlated with maximum lactate (p<0.0001) and hospital length of stay (LOS) (r = 0.22, p<0.05), but not with DHCA time, DHCA temperature, duration of vasoactive infusions, or ICU LOS. Patient BMI was the sole preoperative predictor of the severity of postoperative metabolic acidosis., Limitations: This retrospective analysis involved short-term clinical outcomes related to pH severity and duration, which indirectly may have included the impact of sodium bicarbonate administration., Conclusions: Metabolic acidosis was common and severe after DHCA and was attributed to both lactic and hyperchloremic acidosis. DHCA duration and temperature had little impact on the severity of metabolic acidosis. The severity of metabolic acidosis was best predicted by the BMI and had minimal effects on short-term outcomes. Preventing hyperchloremic acidosis has the potential to decrease the severity of metabolic acidosis after DHCA., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose of Review: The current review will address key topics and recommendations of the recent 2014 update of the American College of Cardiology and American Heart Association clinical practice guideline for the perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery., Recent Findings: The completely rewritten guideline provides a stepwise approach for the identification and management of patients at highest risk for major adverse cardiac events and discusses new or updated recommendations. For example, β-blockers should be continued perioperatively but treatment should not be initiated within 24 h of noncardiac surgery. Angiotensin-converting enzyme inhibitors should be continued, but if held, may be restarted as soon as feasible. Routine aspirin therapy is not recommended without previous coronary stent implantation or risk assessment for myocardial ischemia. Elective noncardiac surgery should not be performed within 30 days of bare metal stent or 12 months of drug-eluting stent implantation because of in-stent thrombosis as well as bleeding risk from dual antiplatelet therapy during surgery. Noncardiac surgery may be considered, however, in patients on antiplatelet agents 180 days after drug-eluting stent placement if risk of surgical delay exceeds risk of stent thrombosis from cessation of antiplatelet therapy., Summary: In conclusion, this review will discuss the important topics from the 2014 American College of Cardiology/American Heart Association guideline in order to provide the perioperative physician with the most recent evidence necessary to minimize major adverse cardiac events in patients undergoing noncardiac surgery.

The functional aortic annulus represents a sound clinical framework for understanding the components of the aortic root complex. Recent three-dimensional imaging analysis has demonstrated that the aortic annulus frequently is elliptical rather than circular. Comprehensive three-dimensional quantification of this aortic annular geometry by transesophageal echocardiography and/or multidetector computed tomography is essential to guide precise prosthesis sizing in transcatheter aortic valve replacement to minimize paravalvular leak for optimal clinical outcome. Furthermore, three-dimensional transesophageal echocardiography accurately can quantify additional parameters of the functional aortic annulus such as coronary height for complete sizing profiles for all valve types in transcatheter aortic valve replacement. Although it is maturing rapidly as a clinical imaging modality, its role in transcatheter aortic valve replacement is seen best as complementary to multidetector computed tomography in a multidisciplinary heart team model., (Copyright © 2014. Published by Elsevier Inc.)