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Recent years have seen a paradigm shift in the management of patients with diabetes mellitus. Rather than good glycaemic control being the sole primary aim, the therapeutic focus has broadened to consider potential additional cardiovascular and renal benefits. Sodium-glucose co-transporter 2 inhibitors, such as empagliflozin, canagliflozin and dapagliflozin, have gained increasing prominence, with evidence suggesting significant improvement in outcomes in patients with established cardiovascular and renal disease. Here, we discuss the benefits and relative risks of these novel agents and highlight important clinical issues of relevance to general physicians.

Transient loss of consciousness (TLOC) is a frequent cause of referral to an emergency room. In view of the impact on treatment and the patients’ daily life activities (e. g. profession, driving license), an accurate and timely diagnosis is of uttermost importance. This article provides key features and suggests a practical step-by-step approach of how to differentiate syncope, epileptic and psychogenic non-epileptic seizures as the commonest causes of nontraumatic TLOC.

Current research aims at improving early detection and treatment of cognitive impairment (CI), particularly in patients at high risk for progression to dementia. It is important to treat signs and symptoms as early as possible to normalize quality of life. In older cognitively impaired patients, dentists and physicians should consider polypharmacy, uncontrolled cardiovascular risk factors, depression, metabolic or endocrine derangements, delirium due to intercurrent illness, and dementia, all of which may increase risk for CI and other negative outcomes. An interdisciplinary team approach is a necessity for a responsible and safe treatment sequence.

Despite numerous measures, bacterial sepsis associated with the transfusion remains a major threat. The incidence of septic events induced by platelets transfusion is approximately 10 times higher than with transfused red blood cells due to their storage temperature. This caused new Standard that implements the methods for the detection and reduction of bacteria in the platelet concentrates (PC). The aim is to consider the possibility of wider application of this tests in order to extend the shelf-life of PC. Sterility testing of PC is done once or twice per month using BacT/Alert BPA and BacT/Alert BPN bottles. If positive, all products from the initial unit were tested to confirm or deny the status. During six years period, 67236 PC units were made and 872 of them were tested. Only two were found initially positive. After testing the other products from the same initial unit, results were negative so, final results proclaimed false positive. Pretransfusion bacterial detection is an important potential method for reducing the risk of bacteriemia and transfusion-associated septic reactions. In addition to routine measures, Mirasol PRT pathogen inactivation system, could be included. This allows certain amount of PC to be inactivated during the first 32 hours. Untreated PC units would be stored in standard conditions and for given time (three days) potentially present bacteria would reach a detectable level. This way the quantity of samples for sterility testing could be reduced, taking only 2 ml of each of four units of PC. Samples would be planted at the same vial-aerobic bottle, which would also, double the capacity in BacT/Alert 3D automated system.

Background and Objectives The literature supporting Mohs micrographic surgery and staged excision in treating primary cutaneous melanoma is growing but has not been critically reviewed for bias. Methods Articles concerning Mohs micrographic surgery and staged excision for melanoma were assessed using modified “Risk of Bias in Non-randomized Studies of Interventions” (ROBINS-I) criteria, which measures bias in 7 categories. Results Forty-seven of 48 (97.9%) studies reviewed had serious or critical bias. None were randomized controlled trials. The most frequent cause of critical bias was poorly defined outcomes. The least frequent form of bias observed was change in intervention. Limitations The modified ROBINS-I criteria cannot account for all study limitations. Modification of the criteria leads to some degree of subjectivity. Conclusion The current body of literature suffers from limitations due to serious or critical bias in 1 or more ROBINS-I criteria. Local recurrence rate definitions are often poorly defined or not defined at all. Longer follow-up times, clear tumor classifications, and prospective, randomized study designs are necessary to improve the quality of future research.

The recognition of cardiogenic shock in the setting of myocardial ischaemia has important prognostic and therapeutic implications. Resuscitative efforts should focus on stabilizing circulatory and respiratory function, with early restoration of coronary blood flow to avoid multi-organ dysfunction and death. However, despite recent progress, the mortality rate remains high, in the order of 40–50%. This article highlights several key recent advances in the management of ischaemic cardiogenic shock, including the use of early bedside echocardiography to confirm the diagnosis, and culprit only lesion strategies of early revascularization. Furthermore, we appraise the variety of mechanical cardiac supports that are increasingly being used to assist the management of ischaemic cardiogenic shock in those cases refractory to pharmacological intervention.

Background Despite high utilization of complementary and alternative medicine (CAM) for alopecia areata (AA), efficacy and safety remain unclear. Objective To identify all CAM therapies studied for treatment of AA. Outcomes of interest included disease course and psychological well-being. Methods PubMed and Embase were searched to identify English articles containing original data investigating CAM in human subjects with AA from 1950-2018. Quality was assessed with Oxford Centre for Evidence Based Medicine criteria. Results Of 1,015 initial citations, 16 articles met inclusion criteria: 5 randomized controlled trials, 5 prospective controlled cohorts, 4 prospective non-controlled cohorts, 1 retrospective cohort, and 1 case series. CAM therapies with best evidence and efficacy for hair growth in AA include essential oil aromatherapy, topical garlic, and oral glucosides of peony with compound glycyrrhizin. Hypnosis and mindfulness psychotherapy represent low quality evidence for improvement of psychological and quality of life outcomes. Adverse events were rare and mild for all therapies evaluated. Limitations Inconsistent or poorly reported study methodology and non-standardized outcomes limit the conclusions that can be made from these studies. Conclusions This work serves to inform physician management of patients with AA seeking CAM, while encouraging further investigation into these therapies to address some of the therapeutic challenges of AA.

Cardiorespiratory complications are among the most common causes of postoperative morbidity and mortality and impose a significant financial burden on the NHS. Patients with premorbid cardiorespiratory diseases can be identified preoperatively with a thorough history taking along with targeted investigations. Preoperative evaluation, risk assessment and stratification allows for clear identification of higher risk patients who would benefit from preoperative medical optimization, appropriate planning of perioperative care including anaesthetic management, modification of surgical procedure and the level of postoperative care required as a part of risk reduction strategies.

Background: The Rhode Island State Legislature passed the Uniform Controlled Substances Act in 2016 to limit opioid prescriptions. We aimed to objectively evaluate its effect on opioid prescribing for hand surgery patients and also identify risk factors for prolonged opioid use. Methods: A 6-month period (January-June 2016) prior to passage of the law was compared with a period following its implementation (July-December 2017). Thumb carpometacarpal arthroplasty and distal radius fracture fixation were classified as “major surgery” and carpal tunnel and trigger finger release as “minor surgery.” Prescription Drug Monitoring Database was used to review controlled substances filled during the study periods. Results: A total of 1380 patients met our inclusion criteria, with 644 prelaw and 736 postlaw patients. Patients undergoing “major surgery” saw a significant decrease in the number of pills issued in the first postoperative prescription (41.1 vs 21.0) and a corresponding decrease in morphine milligram equivalents (MMEs) (318.6 vs 159.2 MMEs) after implementation. A 30% decrease in MMEs was also seen in those undergoing “major surgery” in the first 30 days postoperatively (544.7 vs 381.7 MMEs). Risk factors for prolonged opioid use included male sex and preoperative opioid use. Conclusions: In Rhode Island, opioid-limiting legislation resulted in a significant decrease in the number of pills and MMEs of the initial prescription and a 30% decrease in total MMEs in the 30-day postoperative period after “major hand surgery.” Additional research is needed to explore the association between legislation and clinical outcomes.

Background Allergic bronchopulmonary aspergillosis (ABPA) is an allergic reaction to colonisation of the lungs with the fungus Aspergillus fumigatus and affects around 10% of people with cystic fibrosis. ABPA is associated with an accelerated decline in lung function. High doses of corticosteroids are the main treatment for ABPA; although the long-term benefits are not clear, their many side effects are well-documented. A group of compounds, the azoles, have activity against Aspergillus fumigatus and have been proposed as an alternative treatment for ABPA. Of this group, itraconazole is the most active. A separate antifungal compound, amphotericin B, has been employed in aerosolised form to treat invasive infection with Aspergillus fumigatus, and may have potential for the treatment of ABPA. Antifungal therapy for ABPA in cystic fibrosis needs to be evaluated. This is an update of a previously published review. Objectives The review aimed to test the hypotheses that antifungal interventions for the treatment of ABPA in cystic fibrosis: 1. improve clinical status compared to placebo or standard therapy (no placebo); 2. do not have unacceptable adverse effects. If benefit was demonstrated, we aimed to assess the optimal type, duration and dose of antifungal therapy. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. In addition, pharmaceutical companies were approached. Date of the most recent search of the Group's Trials Register: 29 September 2016. Selection criteria Published or unpublished randomised controlled trials, where antifungal treatments have been compared to either placebo or no treatment, or where different doses of the same treatment have been used in the treatment of ABPA in people with cystic fibrosis. Data collection and analysis Four trials were identified by the searches; none of which was judged eligible for inclusion in the review. Main results No completed randomised controlled trials were included. Authors' conclusions At present, there are no randomised controlled trials to evaluate the use of antifungal therapies for the treatment of ABPA in people with cystic fibrosis, although trials in people who do not have cystic fibrosis have shown clinical and serological evidence of improvement and a reduction in the use of corticosteroids with no increase in adverse effects. Trials with clear outcome measures are needed to properly evaluate this potentially useful treatment for cystic fibrosis.

Sarcopenia is the loss of muscle mass and function related to aging, undereating, disease conditions, or inactivity. Pre-existing sarcopenia diminishes the functional reserve of patients with cancer which increases their risk for frailty, cancer cachexia, and worse outcomes from treatments. The pathogenesis of sarcopenia is multi-factorial: opening opportunities for clinicians to work across disciplines to improve patient outcomes and quality of life. The purpose of this essay is to describe sarcopenia, discuss clinical screening and assessment for sarcopenia, and highlight potential interventions to manage sarcopenia in the urologic oncology population.

Narcolepsy and idiopathic hypersomnia cannot be cured; all available treatments are symptomatic. It is of paramount importance for patients, and their relatives, to be informed about the consequences of these chronic diseases and to become ready to accept the consequences of the diagnosis before starting any treatment. This facilitates the implementation of behavioral modifications and the proper use of medication to decrease the disease burden. A supportive social environment (eg, family members, friends, employer, colleagues, and patient support groups) is instrumental. Current treatment options are discussed with a focus on pharmacologic treatment, including future directions.

Hemolytic-Uremic Syndrome (HUS) is a clinical syndrome with a triad of non-immune Microangiopathic Hemolytic Anemia (MAHA), thrombocytopenia and renal failure. Together with the Thrombotic Thrombocytopenic Purpura (TTP), it belongs to a group of diseases characterized as the Thrombotic Microangiopathy (TMA), which represents a microvascular occlusive disorder with the formation of a predominantly thrombocytic thrombus in the renal and/or systemic circulation. In the period starting from 2001 to 2017, 14 patients with a HUS were diagnosed at the Clinic for Nephrology (unfortunately ADAMTS 13 could not have been done due to technical reasons). In a retrospective clinical laboratory analysis and monitoring, we obtained the following results. Out of 14 patients, 10 were female (or 71.43%) and 4 were male (28.57%), the youngest patient was aged 17 and the oldest one 78, the average age of our patients was 55.33 years, the annual number of patients with the diagnosis of HUS was 0.93 patients per year, or 0.00116 in relation to the total number of patients treated. After monitoring the patients individually for the period ranging from 1 to 14 years, a stable remission was achieved in 5 patients, while a chronic renal insufficiency occurred in 3 patients. In two of our patients, a percutaneous kidney biopsy was performed with pathohistological findings described in references. Having done this retrospective analysis, we can conclude that the survival and complications of this rare, but serious disease correspond to the available world data.

The study was conducted at the Clinical Centre Kragujevac, during the period March-May 2016. The study population consisted of patients older than 65 that were treated at different departments of the Clinic for Internal Medicine. Data were collected from hospital medical records of patients and anonymous semi-structured questionnaires. STOPP (screening tool of older people's prescriptions)/ START (screening tool to alert to right treatment) criteria from 2014 were used to monitor the outcome of interest. Based on the outcome PIM (potentially inappropriate drugs)/PPO (potential prescribing omissions), respondents were divided into groups of cases - patients to whom at least one potentially inappropriate drug determined by STOPP criteria was prescribed and those with at least one potential prescribing omission determined by START criteria. Control groups were patients without these outcomes. Most commonly, PIM was detected in the treatment of cardiovascular system diseases (27.12%), followed by the use of drugs that predispose falls in elderly (20.34%). The most important risk factors for the occurrence of PIM were female gender (OR=3.27; 95% CI 1.01-10.64), polypharmacy (5-8 drugs used simultaneously) (OR=3.10; 95% CI 1.11-12.04) and with whom the patient lives (OR=11.26; 95% CI 1.46-86.68). The use of STOPP/START criteria is proved to be efficient in the detection of PIM/PPO at the secondary level of health care. Full attention should always be paid to patients who are at the highest risk for inappropriate drug prescription. Doctors should make their decisions conscientiously and in line with clinical evidence, not blindly believing the pharmaceutical representatives.

The incidence of atherosclerotic cardiovascular disease has increased in the developed countries. Dyslipidemia is a primary major risk factor for atherosclerotic cardiovascular disease and LDL lowering is one of the main objectives. Although treatment goals for dyslipidemias should be personalized in every patient, statins are cost-effective in primary and secondary prevention of atherosclerotic cardiovascular disease. New treatments with higher power and greater decreases in LDL, PSCK9 inhibitors, have made a new breakthrough in atherosclerotic cardiovascular disease treatment. The 2019 guidelines for de management of dyslipidemias: lipid modification to reduce cardiovascular risk (European Society of Cardiology/European Atherosclerosis Society) with the level of evidence and the strength of the recommendations can facilitate the best decisions and benefits to our patients in clinical practice.

The bleeding from the upper gastrointestinal tract represent a significant medical but also socio-economic problem.A special group of patients et increased risk consists of critically ill patients in intensive care units. Particularly significant cause of bleeding in intensive care unit patients is bleeding resulting from the stress ulcers caused by damage of themucosa of the stomach and duodenum. The purpose of this review is to present current experience in prevention of upper gastrointestinal tract bleeding using proton pump inhibitors in intensive care units. Combination of endoscopic hemostatic methods and proton pump inhibitors represents golden standard in most cases. Despite some adverse effects treatment with proton pump blockers is essential when upper gastrointestinal tract bleeding appears in critically ill patients in intensive care units. Proton pump inhibitors are more effective in acid suppression, as well as in the prevention of recurrent bleeding after endoscopic hemostasis than histamine 2 receptor blockers. The efficacy of proton pump blockers is higher in the case of a continuous intravenous infusion than in the intermittent mode of administration of the drug. The need for highly elaborate strategy for the prophylaxis of bleeding from the upper parts of gastrointestinal tract in intensive care units is essential, because when it occurs in intensive care units, mortality is high, and therapeutic options become narrow.

Cardiovascular complications from drugs of abuse are becoming more apparent because of increased usage worldwide. Substance abuse can cause acute and chronic cardiovascular complications and is increasing in prevalence especially in young adults. These substances contribute to the development of acute coronary syndrome, type 2 myocardial injury, arrhythmias, and cardiomyopathies, and have numerous other cardiovascular complications. Although no screening guidelines exist, clinical awareness of these potential complications and their prevention, clinical presentation, diagnosis, and treatment are critically important. Management of cardiovascular disease should be coupled with appropriate social and mental health interventions to provide sustained clinical benefit. The higher the number of substances used recreationally, the greater the risk of premature heart disease. Epidemiological studies showed that 1 in 5 young adults misuse several substances and often start using at younger ages with a greater risk for adverse health outcomes over the long term. The aim of this review is to highlight the basic epidemiology, cardiac complications, and disease-specific treatment options of commonly abused substances including methamphetamine, cocaine, alcohol, anabolic-androgenic steroids, cannabis, and tobacco.

Despite huge advances in the diagnosis and treatment of pediatric cancers over the past several decades, it remains one of the leading causes of death during childhood in developed countries. The development of new targeted treatments for these diseases has been hampered by two major factors. First, the extremely heterogeneous nature of the types of tumors encountered in this age group, and their fundamental differences from common adult carcinomas, has made it hard to truly get a handle on the complexities of the underlying biology driving tumor growth. Second, a reluctance of the pharmaceutical industry to develop products or trials for this population due to the relatively small size of the 'market', and a too-easy mechanism of obtaining waivers for pediatric development of adult oncology drugs based on disease type rather than mechanism of action, led to significant difficulties in getting access to new drugs. Thankfully, the field has now started to change, both scientifically and from a regulatory perspective, in order to address some of these challenges. In this review, we will examine some of the recent insights into molecular features which make pediatric tumors so unique and how these might represent therapeutic targets; highlight ongoing international initiatives for providing comprehensive, personalized genomic profiling of childhood tumors in a clinically-relevant timeframe, and look briefly at where the field of pediatric precision oncology may be heading in future.

Acquired haemophilia A (AHA) is an uncommon but severe acquired bleeding disorder caused by the development of antibodies against clotting factor VIII, impairing secondary haemostasis. It is more common in older individuals and characteristically presents with spontaneous soft tissue bleeding that can rapidly become life-threatening. Definitive treatment requires immunosuppression to eradicate anti-FVIII antibodies, while providing haemostatic support to manage bleeding. Transfusions of fresh frozen plasma or cryoprecipitate, typically used to treat severe bleeding, are ineffective in patients with AHA. Instead, highly specialised clotting factor concentrates are required. While the appearance and extent of the soft tissue bleeding and the markedly prolonged activated partial thromboplastin time are characteristic, lack of familiarity with this disease process can lead to significant treatment delays. We report the clinical course and management of a 65-year-old woman who presented with severe anaemia of unclear aetiology with unrecognised soft tissue bleeding who was subsequently diagnosed with AHA.

Background: Critically ill patients are at increased risk for fluid overload, but objective prediction tools to guide clinical decision-making are lacking. The MRC-ICU scoring tool is an objective tool for measuring medication regimen complexity. Objective: To evaluate the relationship between MRC-ICU score and fluid overload in critically ill patients. Methods: In this multi-center, retrospective, observational study, the relationship between MRC-ICU and the risk of fluid overload was examined. Patient demographics, fluid balance at day 3 of ICU admission, MRC-ICU score at 24 hours, and clinical outcomes were collected from the medical record. The primary outcome was relationship between MRC-ICU and fluid overload. To analyze this, MRC-ICU scores were divided into tertiles (low, moderate, high), and binary logistic regression was performed. Linear regression was performed to determine variables associated with positive fluid balance. Results: A total of 125 patients were included. The median MRC-ICU score at 24 hours of ICU admission for low, moderate, and high tertiles were 9, 15, and 21, respectively. For each point increase in MRC-ICU, a 13% increase in the likelihood of fluid overload was observed (OR 1.128, 95% CI 1.028-1.238, p = 0.011). The MRC-ICU score was positively associated with fluid balance at day 3 (β-coefficient 218.455, 95% CI 94.693-342.217, p = 0.001) when controlling for age, gender, and SOFA score. Conclusions: Medication regimen complexity demonstrated a weakly positive correlation with fluid overload in critically ill patients. Future studies are necessary to establish the MRC-ICU as a predictor to identify patients at risk of fluid overload.

Introduction: As the therapeutic options in the management of type 2 diabetes increase, there is an increase confusion among health care professionals, thus leading to the phenomenon of therapeutic inertia. This is the failure to escalate or de-escalate treatment when the clinical need for this is required. It has been studied extensively in various settings, however, it has never been reported in any studies focusing solely on primary care physicians with an interest in diabetes. This group is increasingly becoming the focus of managing complex diabetes care in the community, albeit with the support from specialists. Methods: In this retrospective audit, we assessed the prevalence of the phenomenon of therapeutic inertia amongst primary care physicians with an interest in diabetes in UK. We also assessed the predictive abilities of various patient level characteristics on therapeutic inertia amongst this group of clinicians. Results: Out of the 240 patients reported on, therapeutic inertia was judged to have occurred in 53 (22.1%) of patients. The full model containing all the selected variables was not statistically significant, p = 0.59. So the model was not able to distinguish between situations in which therapeutic inertia occurred and when it did not occur. None of the patient level characteristics on its own was predictive of therapeutic inertia. Conclusion: Therapeutic inertia was present only in about a fifth of patient patients with diabetes being managed by primary care physicians with an interest in diabetes.

Subcapsular haematoma of the liver in pregnancy is a rare complication, however life-threatening for both mother and fetus. Although it is usually associated with pre-eclampsia, a wide range of presentations can occur. Given its consequences, early diagnosis and management are essential for a successful outcome. Due to paucity of evidence, there is no current guidelines on this topic. Our aim is to add a new insight into diagnosis and management of subcapsular hepatic haematoma in pregnancy, for which new technologies in the fields of image, and minimal invasive surgery are playing an important role.

As a greater number of households have pets, the likelihood of zoonotic infections can rise too. Although in most healthy individuals these infections are self-limiting, they are more serious and can lead to adverse outcomes in the immunocompromised. There is minimal information available for the immunocompromised patient who are pet owners or on pet handling. We report a case of cat scratch disease-related sepsis in an immunocompromised patient. This case illustrates the need for a detailed history, including a pet history, in immunocompromised patients presenting with fever of unknown origin and the need for UK-based information for the immunocompromised on pet care and risks associated with having a pet.

Pleuroparenchymal fibroelastosis (PPFE) is an uncommon disease of which diagnosis should be established multidisciplinary fashion and has no effective medical therapy. Pulmonary rehabilitation (PR) can be applied, but lung transplantation is the only therapeutic option. There have been few reported cases or studies showing the efficacy of PR in patients with PPFE in the literature. We present our multidisciplinary PR programme including confirmation of the diagnosis and a structured follow-up programme in two PPFE patients. In both cases, after multidisciplinary PR the diagnoses were confirmed and body composition, quality of life, exercise capacity and psychological status improved and some improvements preserved for 6–12 months. They underwent lung transplantation about 2 years after PR. Patients with PPFE should be directed and encouraged to participate in comprehensive multidisciplinary PR programmes. Long-term structured follow-up programmes could preserve the improvements, increase adherence and save time while waiting on the transplant list.

Atopic dermatitis (AD) is a common presenting complaint by children and their caretakers to their primary care providers. On testing, children with AD frequently exhibit positive food-specific IgE levels in the absence of immediate allergic reactions. Misinterpretation of these false positive tests can lead to unnecessary food avoidance, which can have tremendous psychosocial, economic and nutritional consequences and, in some cases, facilitate the development of an immediate hypersensitivity to the food. We present a child with persistent AD who underwent broad testing that led to unnecessary food avoidance resulting in Vitamin D deficiency, growth failure and the development of an IgE-mediated food allergy. This case underscores the need for caution by primary care clinicians in using food avoidance diets as a treatment for AD and the importance of limiting allergy testing to foods only when the clinical history indicates an immediate hypersensitivity reaction.

Pulmonary rehabilitation of asthma and COPD patients can improve their physical performance and quality of life, maintain participation in social and professional life and actively promote self-help. In addition, the resources for acute medical treatment can be spared. In case of COPD, rehabilitation directly after exacerbation can also improve the poor survival prognosis and reduce the risk of emergency hospital readmission. Therefore, pulmonary rehabilitation is an essential component of evidence-based long-term management of both bronchial asthma and, in particular, COPD. In the German healthcare system, however, pneumological rehabilitation is offered only for a small fraction of patients. Despite a very good evidence of pulmonary rehabilitation, especially in COPD patients, their share in all rehabilitation services is remarkably low. It does not even amount to 3 % of all medical rehabilitation measures approved by the German Pension Insurance.

Liver transplantation is associated with significant blood loss, often requiring massive blood product transfusion. Transfusion-related acute lung injury (TRALI) is a devastating cause of transfusion-related deaths. While reports have investigated the general incidence of TRALI, the incidence of TRALI specifically following transfusion during liver transplant remains unclear. This scoping review summarizes existing literature regarding TRALI during the liver transplantation perioperative period. Databases were searched for all articles and abstracts reporting on TRALI after liver transplantation. Data collected included number of patients studied, patient characteristics, incidences of TRALI, TRALI characteristics, and patient outcomes. The primary outcome investigated was the incidence of TRALI in the setting of liver transplantation. Thirteen full-text citations were included in this review. The incidence of TRALI post-liver transplant was 0.68% (65 of 9,554). Based on reported transfusion data, patients diagnosed with TRALI received an average of 10.92 ± 10.81 units of packed red blood cells (pRBC), 20.05 ± 15.72 units of fresh frozen plasma, and 5.75 ± 10.00 units of platelets. Common interventions following TRALI diagnosis included mechanical ventilation with positive end-expiratory pressure, inhaled high-flow oxygen, inhaled pulmonary vasodilator, and pharmacologic treatment using pressors or inotropes, corticosteroids, or diuretics. Based on reported mortality data, 26.67% of patients (12 of 45) diagnosed with TRALI died during the postoperative period. This scoping review underscores the importance of better understanding the incidence and presentation of TRALI after liver transplant surgery. The clinical implications of these results warrant the development of identification and management strategies for liver transplant patients at increased risk for developing TRALI.

Intravenous lipid emulsions (ILEs) have been used widely for the treatment of local anesthetic (LA) poisoning and have been proposed as a treatment for intoxication by other drugs. However, the degree of evidence for this kind of therapy is not strong, as it comes mostly from clinical cases. The aim of this narrative review is to describe the proposed mechanisms of action for ILEs in poisoning by LA and other drugs and to evaluate recent studies in animals that support the recommendations for their use and the experience in humans that support the use of ILESs in both LA and other drug poisoning. For this purpose, a search was performed in the Embase, Medline and Google Scholar databases covering relevant articles over the last 10 years. In the case of AL poisoning, we recommend applying the protocols dictated by international guidelines, knowing that the degree of evidence is not very high. In poisoning by other drugs, ILEs are recommended in serious situations induced by liposoluble xenobiotics that do not respond to standard treatment.

Physical activity (PA) has been demonstrated to have a powerful role in reducing cardiovascular risk and is therefore universally recommended by international guidelines. Although there is a dose-dependent risk reduction with increasing levels of PA, there is some concern that extreme levels of PA can result in adverse cardiovascular outcomes. It is important to adapt PA advice to each individual, and in particular to note that there are conditions that are not compatible with competitive sport because of increased cardiovascular risk. Exercise also has an key role in the assessment of patients presenting with symptoms that could potentially result from cardiovascular disease, both as a measure of the impact of the disease and as a diagnostic tool.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide, with an individual lifetime risk of approximately 37% in the United States. Broadly defined as a supraventricular tachyarrhythmia with disorganized atrial activation, AF results in an increased risk of stroke, heart failure, valvular heart disease, and impaired quality of life, and confers a significant burden on the health of individuals and society. AF in the perioperative setting is common and a significant source of perioperative morbidity and mortality worldwide. The latest iteration of the European Society of Cardiology AF guidelines published in 2020 provide the clinician a valuable road map for the management of this arrythmia. This expert review will comprehensively analyze the 2020 European Society of Cardiology guidelines and provide perioperative management tools for the clinician.

Intraoperative hypotension (IOH) is a major concern to the anesthesiologist. Its appropriate identification and management require an understanding of the physiology of blood pressure regulation, prudent blood pressure monitoring, and treatment. Even short durations of low mean arterial pressure have been associated with adverse postoperative clinical outcomes. The challenge is for the clinician to respond proactively, address the specific etiology of IOH, and keep in mind any changes to the patient's physiology. Predictive technology, such as the Hypotension Prediction Index, offers the clinician new insight into IOH. It has been shown to predict hypotension up to 15 minutes before occurrence. It also calculates stroke volume variation, dynamic arterial elastance, and left ventricular contractility, which can inform the anesthesiologist of the etiology of IOH to direct management. This new technology has the potential to reduce duration or even prevent IOH. In the authors' opinion, it is an example of how human-machine interaction will contribute to future advances in medicine. Additional studies should evaluate the effects of its use on postoperative outcomes.

Genetic and genomic testing in pediatric CHD is becoming increasingly routine, and can have important psychosocial, clinical and reproductive implications. In this paper we highlight important challenges and considerations when providing genetics consults and testing in pediatric CHD and illustrate the role of a dedicated CHD genetics clinic. Key lessons include that a) a genetic diagnosis can have clinical utility that justifies testing early in life, b) adequate genetic counselling is crucial to ensure families are supported, understand the range of possible results, and are prepared for new or unexpected health information, and c) further integration of the clinical genetics and cardiology workflows will be required to effectively manage the burgeoning information arising from genetic testing. Our experience demonstrates that a dedicated CHD genetics clinic is a valuable addition to a multidisciplinary team providing care to children with CHD.

Advances in surgical techniques and outpatient cardiac care have led to a growing population of pediatric patients surviving well into adulthood with previous single-ventricle palliation. Continued improvement in survival has resulted in subsequent increases in the number of patients with single-ventricle physiology listed for heart transplantations. Some of these patients require mechanical circulatory support as a bridge to transplantation, although establishing successful mechanical circulatory support in these complex patients remains challenging. Only limited published data exist describing the perioperative anesthetic management and key considerations dedicated to patients with failing single-ventricle physiology presenting for ventricular assist devices. This clinical review aims to provide a focused evaluation of the vital perioperative considerations encountered in this novel population.

Introduction The efficacy and safety of the rapid intravenous rehydration (RIR) guidelines in children affected by dehydration secondary to acute gastroenteritis is supported by current scientific evidence, but there is also great variability in its use in clinical practice. Objective To prepare a document with evidence-based recommendations about RIR in paediatric population. Methods The project was developed based on GRADE methodology, according to the following work schedule: Working Group training; creation of a catalogue of questions about research and definition of «relevant outcomes»; score and selection criteria for each item; bibliographic review; scientific evidence evaluation and synthesis (GRADE); review, discussion and creation of recommendations. 10 clinical questions and 15 relevant outcomes were created (7 about efficacy and 8 about security). Results Sixteen recommendations were set up, from which we can highlight as the main ones: (1) RIR is safe for children affected by mild-moderate dehydration secondary to acute gastroenteritis, unless expressly contraindicated or acute severe comorbidity (strong recommendation and moderate evidence). (2) Its use is recommended in this situation when oral rehydration has failed or due to contraindication (strong and high). (3) Isotonic fluids are recommended (strong and high), suggesting saline fluid as the first option (light and low), supplemented by glucose (2.5%) in those patients showing normoglycemia and ketosis (strong and moderate). (4) A rhythm of 20 cc/kg/h is recommended (strong and high) during 1-4 h (strong and moderate). Conclusions This document establishes consensus recommendations, based on the available scientific evidence, which could contribute to the standardisation of the use of RIR in our setting.

ZusammenfassungAtypische Infektionen an der Hand treten selten auf und werden deshalb häufig fehlinterpretiert. Erfolgt die korrekte Therapie erst verspätet, können irreversible Schäden entstehen, schlimmstenfalls kann es zu lebensgefährlichen septischen Verläufen kommen. Der Artikel soll eine Übersicht über einige der häufigsten atypischen Infektionen und deren Erscheinungsbild an der Hand (Mykobakterien, Vibrionen, Francisella, Aktinomyceten) geben und diese mit 2 Fallberichten illustrieren. Das Wissen um die Pathogenese der häufigsten atypischen Infektionen erleichtert es, diese differenzialdiagnostisch im Alltag zu berücksichtigen, spezielle diagnostische Schritte einzuleiten und eine adäquate Therapie frühzeitig durchzuführen.

CFTR modulators have dramatically changed the clinical course of CF in those fortunate enough to receive them. Inevitably, randomised controlled trials during the development of these drugs are too short to use mortality as an outcome. Evidence for their effect on life expectancy are best gained from real world registry studies specifically looking at mortality, but these are only available for ivacaftor to date. Therefore, indirect evidence must be obtained by looking at outcomes known to affect mortality and seeing the effect of these drugs on those outcomes.

The primary aim of this retrospective study was to estimate significance of determining C-reactive protein and procalcitonine for a diagnosis of sepsis in adult patients in early triage. Also, the aim of this study was to measure the sensitivity of the SIRS criteria, PCT and CRP levels and sepsis definitions to identify the most serious sepsis cases in the prehospital setting and at the Emergency Department (ED) triage. All patients were divided into two groups according to specific criteria for defining sepsis. First group (SIRS+ group) of patients were patients with clinically and/or laboratory confirmed sepsis (or systemic inflammatory response syndrome (SIRS) to bacterial infection with different localization). For confirmation of the SIRS we consider positive two or more clinical criteria (≥2 clinical criteria). The SIRS criteria use the clinical criteria of the Surviving Sepsis Campaign (SSC) for the SIRS, comprising at least two of the following criteria: HR > 90/min, RR > 20/min and temperature < 36° or ≥ 38.3°C and the next laboratory parameters such as leucocytosis > 15x109/L, leucopenia < 4x109/L, > 10% immature leucocytes. Second group of patients were patients with the SIRS negative criteria as a diagnostic tool (SIRS- group). We have founded that the CRP showed high sensitivity but no specificity in patients with sepsis, but on the other side, the PCT as a diagnostic marker showed a high sensitivity and high specificity in these patients. Also, the PCT is in positive correlation with the SIRS criteria, which could be of a clinical significance in early diagnosis of septic infections.

Degenerative valve disease (DVD) is the leading cause of heart disease and congestive heart failure (CHF) in the dog. The first published consensus statement provided guidelines for the diagnosis and treatment of DVD. Although treatment was not recommended in stage B1 DVD, consensus was not reached regarding evidence-based recommendations for treatment of stage B2 DVD. This article addresses the impact of new evidence on historical recommendations for stage B DVD and gives the reader a glimpse into possible future therapies. Management of common sequelae of DVD that can result in clinical signs that are not attributable to CHF is also discussed.

Valvular heart disease contributes to a large burden of morbidity and mortality in the United States. During the last decade there has been a paradigm shift in the management of valve disease, primarily driven by the emergence of novel transcatheter technologies. In this article, the latest update of the American College of Cardiology/American Heart Association valve heart disease guidelines is reviewed.

Drug deposition into the intrapericardial space is favourable for achieving localised effects and targeted cardiac delivery owing to its proximity to the myocardium as well as facilitating optimised pharmacokinetic profiles and a reduction in systemic side effects. Access to the pericardium requires invasive procedures but the risks associated with this have been reduced with technological advances, such as combining transatrial and subxiphoid access with different guidance methods. A variety of introducer devices, ranging from needles to loop-catheters, have also been developed and validated in pre-clinical studies investigating intrapericardial delivery of therapeutic agents. Access techniques are generally well-tolerated, self-limiting and safe, although some rare complications associated with certain approaches have been reported. This review covers these access techniques and how they have been applied to the delivery of drugs, cells, and biologicals, demonstrating the potential of intrapericardial delivery for treatments in cardiac arrhythmia, vascular damage, and myocardial infarction.

Knee osteoarthritis (OA) is a common and morbid condition. No disease-modifying therapies exist; hence the goals of current treatment are to palliate pain and to retain function. OA is significantly influenced by the placebo effect. Nonpharmacologic interventions are essential and have been shown to improve outcomes. Canes, unloading braces, and therapeutic heating/cooling may be valuable. Pharmacotherapy options include topical and oral nonsteroidal anti-inflammatory drugs, duloxetine, and periodic intra-articular glucocorticoids and hyaluronans. Opioids, intra-articular stem cells, and platelet-rich plasma are not recommended. Novel targets such as nerve growth factor are under investigation and may be approved soon for OA pain.

The gold standard treatment of end-stage liver disease continues to be liver transplantation (LT). The challenges of LT require skilled anesthesiologists to anticipate physiologic changes associated with end-stage liver disease and surgical considerations that affect multiple organ systems. While on the waiting list, patients may be placed on new anticoagulation medications that can confound already complex coagulopathy in LT patients. Pain management often is an afterthought for such a complex procedure, but appropriate medications can help control pain while limiting opioid medications. Surgical stress and medications for immunosuppression can affect perioperative glucose management in ways that have implications for patient and graft survival. The coronavirus disease 2019 pandemic in 2020 provided a new challenge for anesthesiologists. The uncertainty of the novel respiratory virus challenged providers beyond just LT patients.

BACKGROUND: CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal/spinal) syndrome is a rare and progressive genetic disorder resulting from somatic mosaicism in activating mutations in the phosphatidylinositol-4,5- bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. PIK3CA is a cell growth master regulator where gain of function mutations give rise to abnormal activation of the PI3K-AKT- mammalian target of rapamycin (mTOR) pathway. Treatment with sirolimus, an mTOR inhibitor, may therefore be of benefit in patients with CLOVES syndrome. OBJECTIVE: Here we describe the efficacy and toxicity of sirolimus in a pediatric patient with progressive CLOVES syndrome. RESULTS: The child presented with a large and painful abdominal malformation, massive overgrowth of his feet, limb length discrepancy and genu valgum. There was dramatic clinical and radiographic improvement in the size and comfort of his abdominal mass within several months of initiating medical therapy. This, combined with orthopaedic care of his genu valgum, leg length discrepancy, and overgrowth of his feet, has allowed for significant functional gains. CONCLUSIONS: Multidisciplinary care is essential for comfort and functional gains in patients with CLOVES syndrome, particularly those with severe symptoms. Close monitoring while on sirolimus medical therapy combined with frequent reassessment of orthopedic needs can dramatically improve patient quality of life and outcomes.

Cardiac surgery is associated with significant mortality rates. Careful selection of surgical candidates is, therefore, vital to optimize morbidity and mortality outcomes. Risk scores can be used to inform this decision-making process. The European System for Cardiac Operative Risk Evaluation Score and the Society of Thoracic Surgeons score are among the most commonly used risk scores. There are many other scoring systems in existence; however, no perfect scoring system exists, therefore, additional research is needed as clinicians strive toward a more idealized risk stratification model. The purpose of this review is to discuss the advantages and limitations of some of the most commonly used risk stratification systems and use this to determine what an ideal scoring system might look like. This includes not only the generalizability of available scores but also their ease of use and predictive power.

Congenital heart disease can lead to notable lymphatic complications such as chylothorax, plastic bronchitis, protein-losing enteropathy, and ascites. Recent improvements in lymphatic imaging and the development of new lymphatic procedures can help alleviate symptoms and improve outcomes.

Pertussis is a highly contagious, vaccine-preventable respiratory tract infection, with high morbidity and mortality and a particularly severe effect on newborns and infants under 2 months. The first pertussis vaccines were introduced in the 1940s. Since 1980, however, the incidence of cases has risen despite the extensive vaccination programmes and antibiotic adjuvant treatments available. Transition from the use of whole-cell vaccines to acellular vaccines and the antigenic modifications of Bordetella pertussis have contributed, among other factors, to a reduction in vaccine-acquired immunity and reemergence of the disease. Today, there are still unmet needs not covered by conventional prevention measures and existing antibiotic treatments. This review aims to update the available data, and to discuss which vaccine strategies might contribute to better disease control and prevention.

Chronic kidney disease is one of the major worldwide public health problems. Traditional Chinese medications have been widely used for chronic kidney disease treatment. As the development of modern phytochemistry technology, natural products have been isolated from traditional Chinese medications, which provide a more precise method for the investigation of traditional Chinese medications. In this article, we selected eight natural products from traditional Chinese medications for chronic kidney disease therapy to summarize the recent advances for the development of new medications.

The laboratory plays an essential role in the diagnosis of sexually transmitted infections (STIs). The ability to make an accurate diagnosis is essential because of the individual and public health implications associated with an STI diagnosis. This is achieved through a combination of direct microscopy, bacterial culture, molecular detection and serological testing. The choice of test is guided by the method with the highest sensitivity and specificity; in most cases, this is nucleic acid amplification testing. With antimicrobial resistance a significant global concern, monitoring resistance trends is crucial in guiding antimicrobial prescribing. STI testing must be both accessible and acceptable to patients, with testing now available in a variety of community and healthcare settings. Self-sampling for STIs offers a suitable alternative to clinician-taken swabs for those who do not want or need an examination. This paper summarizes the current methods available in the diagnosis of STIs and genital infections.

Tay-Sachs disease, or GM2 gangliosidosis, is a congenital and neurodegenerative disease caused by the absence or deficiency of the essential enzyme B-hexosaminidase. The timing of the development of neurological manifestations and their severity depend on the mutation, time since disease onset and the patient's characteristics. The disease impairs quality of life and increases mortality. In the most aggressive forms, life expectancy is 3 years. Despite various clinical trials and ongoing research, there is currently no cure for Tay-Sachs disease. Treatment focuses on symptom control and ensuring greater patient wellbeing. Consequently, rehabilitation plays a fundamental role in the management of these patients and in enhancing their quality of life.