Severe Life-threatening Events Research Articles

Insights from assessment for arrhythmia after CoViD-19 vaccination among Indians.

Post-vaccination myocarditis is usually moderate and transient, recovering quickly with conservative treatment. Therefore, it is of interest to assess for arrhythmia after CoViD-19 vaccination among Indians. We looked for ECG abnormalities in a small cohort of 50 participants after 52 weeks after receiving the Oxford/AstraZeneca CoViD-19 vaccination. Data shows that post-vaccination myocarditis is typically mild and transient, with most cases resolving swiftly through conservative management. Thus, it is unlikely that this vaccine will induce severe arrhythmias or life-threatening cardiac events in the general population.

A real-world pharmacovigilance study of FDA adverse event reporting system events for sildenafil.

Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is widely used for the treatment of erectile dysfunction (ED). However, the safety profile of sildenafil, including adverse event (AEs), requires comprehensive evaluation. This retrospective pharmacovigilance study aimed to evaluate AEs linked to sildenafil by analyzing data sourced from the FDA Adverse Event Reporting System (FAERS) database. A case/non-case design was utilized, and various algorithms including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) were employed to measure the signals indicating the presence of sildenafil-related AEs. Among 339,230 reports, 33,692 specifically mentioned sildenafil use. Most of AEs occurred in males over 60 years old. The United States accounted for the highest proportion of reported AEs. Severe outcomes, including death, disability, and life-threatening events, were reported. Significant system organ class (SOC) included "Reproductive system and breast disorders" (SOC: 10038604), "Neoplasms benign, malignant and unspecified" (SOC: 10038738), "Vascular disorders" (SOC: 10047065), and "Blood and lymphatic system disorders" (SOC: 10005329). Noteworthy preferred terms (PTs) associated with sildenafil included "Vision blurred," "Flushing," "sudden hearing loss," "Painful erection," and "Priapism." Unexpected AEs, such as "Malignant melanoma," "Pulmonary hypertension," "Malignant melanoma in situ," "Pulmonary arterial hypertension," "Metastatic malignant melanoma," "Malignant melanoma stage III," "Malignant melanoma stage II," "Acquired hemophilia," "Aortic dissection rupture," and "Intracranial artery dissection" were also identified. These findings emphasize the importance of monitoring and understanding the potential risks associated with sildenafil. Further investigation is warranted to validate these associations and address previously unrecognized safety concerns.

Surgical management of acute life-threatening events affecting esophageal atresia and/or tracheoesophageal fistula patients

BackgroundFollowing surgical correction, many patients with esophageal atresia with or without tracheoesophageal fistula (EA/TEF) present to the emergency department (ED) with acute airway complications. We sought to determine the incidence and risk factors for severe acute life-threatening events (ALTEs) in pediatric patients with repaired congenital EA/TEF and the outcomes of operative interventions. MethodsA retrospective cohort chart review was performed on patients with EA/TEF with surgical repair and follow-up at a single centre from 2000 to 2018. Primary outcomes included 5-year ED visits and/or hospitalizations for ALTEs. Demographic, operative, and outcome data were collected. Chi-square tests and univariate analyses were performed. ResultsIn total, 266 EA/TEF patients met inclusion criteria. Of these, 59 (22.2%) had experienced ALTEs. Patients with low birth weight, low gestational age, documented tracheomalacia, and clinically significant esophageal strictures were more likely to experience ALTEs (p < 0.05). ALTEs occurred prior to 1 year of age in 76.3% (45/59) of patients with a median age at presentation of 8 months (range 0–51 months). Recurrence of ALTEs after esophageal dilatation was 45.5% (10/22), mostly due to stricture recurrence. Patients experiencing ALTEs received anti-reflux procedures (8/59, 13.6%), airway pexy procedures (7/59, 11.9%), or both (5/59, 8.5%) within a median age of 6 months of life. The resolution and recurrence of ALTEs after operative interventions are described. ConclusionSignificant respiratory morbidity is common among patients with EA/TEF. Understanding the multifactorial etiology and operative management of ALTEs have an important role in their resolution. Type of StudyOriginal Research, Clinical Research. Level of EvidenceLevel III Retrospective Comparative Study.

White scorpion (&lt;em&gt;Hottentotta tamulus&lt;/em&gt;) sting induced autonomic hyperactivity and myocardial ischemia in a child

Scorpion bite is one of the common emerging toxicological problems in Jaffna peninsula of Northern Sri Lanka. Majority of the patients have an uncomplicated course, but some people may have severe systemic envenomation and life-threatening cardiovascular events. This case report is of a child admitted to Paediatric professorial unit, Teaching Hospital Jaffna following white scorpion (Hottentotta tamulus) bite. Subsequently he developed myocardial ischemia. There was no literature available in paediatric population with myocardial ischemia following sting of Hottentotta tamulus.

Determination of starting dose of the T cell-redirecting bispecific antibody ERY974 targeting glypican-3 in first-in-human clinical trial

Currently, ERY974, a humanized IgG4 bispecific T cell-redirecting antibody recognizing glypican-3 and CD3, is in phase I clinical trials. After a first-in-human clinical trial of an anti-CD28 agonist monoclonal antibody resulting in severe life-threatening adverse events, the minimal anticipated biological effect level approach has been considered for determining the first-in-human dose of high-risk drugs. Accordingly, we aimed to determine the first-in-human dose of ERY974 using both the minimal anticipated biological effect level and no observed adverse effect level approaches. In the former, we used the 10% effective concentration value from a cytotoxicity assay using the huH-1 cell line with the highest sensitivity to ERY974 to calculate the first-in-human dose of 4.9 ng/kg, at which maximum drug concentration after 4 h of intravenous ERY974 infusion was equal to the 10% effective concentration value. To determine the no observed adverse effect level, we conducted a single-dose study in cynomolgus monkeys that were intravenously infused with ERY974 (0.1, 1, and 10 μg/kg). The lowest dose of 0.1 μg/kg was determined as the no observed adverse effect level, and the first-in-human dose of 3.2 ng/kg was calculated, considering body surface area and species difference. For the phase I clinical trial, we selected 3.0 ng/kg as a starting dose, which was lower than the first-in-human dose calculated from both the no observed adverse effect level and minimal anticipated biological effect level. Combining these two methods to determine the first-in-human dose of strong immune modulators such as T cell-redirecting antibodies would be a suitable approach from safety and efficacy perspectives.Clinical trial registration: JapicCTI-194805/NCT05022927.

Safety and Adverse Events Related to Inactivated COVID-19 Vaccines and Novavax;a Systematic Review.

Introduction:Knowledge of the safety of vaccines is crucial, both to prevent and cure them and to decrease the public hesitation in receiving vaccines. Therefore, this study aimed to systematically review the adverse events reported for inactivated vaccines and Novavax.Methods:In this systematic review, the databases of PubMed, Scopus, Cochrane, and Web of Science were searched on September 15, 2021. Then we identified the eligible studies using a two-step title/abstract and full-text screening process. Data on the subjects, studies, and types of adverse events were extracted and entered in a word table, including serious, mild, local, and systemic adverse events as well as the timing of side effects’ appearance.Results:Adverse effects of inactivated coronavirus vaccines side effects were reported from phases 1, 2, and 3 of the vaccine trials. The most common local side effects included injection site pain and swelling, redness, and pruritus. Meanwhile, fatigue, headache, muscle pain, fever, and gastrointestinal symptoms including abdominal pain and diarrhea were among the most common systemic adverse effects. Conclusion:This systematic review indicates that inactivated COVID-19 vaccines, including Sinovac, Sinopharm, and Bharat Biotech, as well as the protein subunit vaccines (Novavax) can be considered as safe choices due to having milder side effects and fewer severe life-threatening adverse events.

Critical care management of chimeric antigen receptor T-cell therapy recipients.

Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapeutic treatment concept that is changing the treatment approach to hematologic malignancies. The development of CAR T-cell therapy represents a prime example for the successful bench-to-bedside translation of advances in immunology and cellular therapy into clinical practice. The currently available CAR T-cell products have shown high response rates and long-term remissions in patients with relapsed/refractory acute lymphoblastic leukemia and relapsed/refractory lymphoma. However, CAR T-cell therapy can induce severe life-threatening toxicities such as cytokine release syndrome, neurotoxicity, or infection, which require rapid and aggressive medical treatment in the intensive care unit setting. In this review, the authors provide an overview of the state-of-the-art in the clinical management of severe life-threatening events in CAR T-cell recipients. Furthermore, key challenges that have to be overcome to maximize the safety of CAR T cells are discussed.

Limited Utility of Routine Tests Prior to Ophthalmologic Surgery: An Observational Study in a Japanese Hospital.

Introduction: Routine preoperative testing for low-risk surgeries without a clinical indication should be avoided; however, such tests are still frequently performed in Japan. This study was performed to assess the impact of routine preoperative tests in low-risk surgery in a Japanese medical setting. Methods: We performed a retrospective chart review to examine the utility of routine tests with respect to anesthetic management and postoperative complications in all patients aged ≥ 18 years whom ophthalmologists consulted with anesthesiologists before ophthalmologic surgery under general anesthesia. Results: During the 10-year study period, 1,234 anesthetic consultations and 1,211 routine preoperative tests (laboratory tests, chest X-rays, and electrocardiograms) were performed in Toyama University Hospital. In total, 59 patients (4.8% of the study population) canceled surgery after a battery of preoperative evaluation. Among them, 10 patients had incidental abnormalities that necessitated additional tests, and only three patients (0.2%) canceled surgery. In-hospital postoperative complications developed in nine patients (0.7%) whose routine test results made it difficult to predict development of these adverse events. No severe life-threatening events were noted in this survey. Conclusions: Routine tests prior to eye surgery for adults were of low value for perioperative management and prediction of development of in-hospital complications in this Japanese medical setting. Anesthesiologists and ophthalmologists should selectively order preoperative tests based on the medical interview and physical examination.

Enhanced Contextual Fear Memory and Elevated Astroglial Glutamate Synthase Activity in Hippocampal CA1 BChE shRNA Knockdown Mice.

Butyrylcholinesterase (BChE) efficiently hydrolyzes acetylcholine (ACh) at high concentrations when acetylcholinesterase (AChE) is substrate-inhibited. Recent studies have shown that BChE also has a function that is independent of ACh, but it has not been fully explored. Low BChE expression is accompanied with higher stress-induced aggression and ghrelin levels in stress models, and BChE knockout mice exhibit cognitive and memory impairments. However, the role of BChE in posttraumatic stress disorder (PTSD) remains unclear. In the present study, we investigated the role of BChE in contextual fear memory and its regulatory effect on the expression of factors related to the glutamate (Glu)-glutamine (Gln) cycle via knockdown studies. We used AAVs and lentiviruses to knockdown BChE expression in the mouse hippocampal CA1 region and C8D1A astrocytes. Our behavioral data from those mice injected with AAV-shBChE in the hippocampal CA1 region showed strengthened fear memory and increased dendritic spine density. Elevated Glu levels and glutamine synthetase (GS) enzyme activity were detected in contextual fear conditioned-BChE knockdown animals and astrocytes. We observed that an AAV-shBChE induced lowering of BChE expression in the hippocampus CA1 region enhanced contextual fear memory expression and promoted the astrocytic Glu-Gln cycle but did not elevate ACh-hydrolyzing activity. This study provides new insight into the regulatory role of BChE in cognition and suggests potential target for stress-related psychiatric disorder such as PTSD where patients experience fear after exposure to severe life-threatening traumatic events.

Attack, flare-up, or exacerbation? The terminology preferences of patients with severe asthma

Background: People with severe asthma experience frequent life-threatening acute asthma events. A Lancet commission recently highlighted that terms “exacerbations” and “flare-ups” are seen to trivialize these episodes and recommended use of the term “attacks.” Clinicians however, preferentially use the term “exacerbation” and some guidelines recommend the use of “exacerbation” with patients.Objective: This descriptive qualitative study aimed to understand the patient’s experience and perspectives of these events and language used to describe them.Methods: Semi-structured one-on-one interviews were conducted in Australia and the UK in 18 people with severe asthma and 10 with mild-moderate asthma regarding their usage and preferences for such terminologies. Additionally, nine people with severe asthma participated in two focus groups in which use of preferred terminology was explored.Results: Mean age of participants was 57 ± 14.03 yr and 65% were female. A total 67 quotes were recorded in which 16 participants with severe asthma spontaneously used either the term “attack,” “flare-up” and/or “exacerbation.” Of these quotes, all 16 participants used “attack,” one used all three terms and two used both “exacerbation” and “attack.” The term “attack” was used to describe frightening events having major impacts on participant’s lives, whereas “exacerbation” and “flare-up” were used to refer to both severe and mild, transient asthma-related events.Conclusion: Usage of the term “attack” was preferred by patients with severe asthma. Adoption of this language may assist in patient-clinician communication and disease management and outcomes. Wider stakeholder engagement is needed to confirm this suggestion.AbbreviationsFEV1forced expiratory volume in 1 secondATSAmerican Thoracic SocietyERSEuropean Respiratory SocietyACQAsthma Control QuestionnaireICSinhaled corticosteroidsOCSoral corticosteroidsBTSBritish Thoracic SocietySIGNScottish Intercollegiate Guidelines NetworkWAPwritten action plan.

Etiology and Outcome of Severe Apparent Life-Threatening Events in Infants.

An apparent life-threatening event (ALTE) is defined as "an episode that is frightening to the observer and is characterized by some combination of apnea, color change, marked change of muscle tone, choking, or gagging." The aims of this study were to determine etiology and outcome of severe ALTE (requiring resuscitation measures) and to review diagnostic approaches in infants hospitalized after such an episode of ALTE. Retrospective analysis included patients hospitalized at the Intensive Care Unit, Institute of Child and Youth Healthcare of Vojvodina, after an episode of severe ALTE over a 4-year period. The study included 23 infants, 18 male (78.3%), and 5 female (21.7%). The average age at presentation was 78 days (1 day to 11 months). In 8 infants (34.7%), ALTE resulted in death. The most frequent conditions after diagnostic evaluation were lower respiratory tract infections (39.1%), intracranial and extracranial hemorrhages (13.0%), and central nervous system infections (8.6%). The cause remained unknown in 8.7% of cases. Initial investigations included complete blood cell count, C-reactive protein or procalcitonin, blood gasses, lactate, electrolytes, glucose, blood culture, urinalysis, and chest x-ray. Apparent life-threatening event represents a diverse disorder. Lower respiratory tract infections and neurological disorders were the most common established etiology. Prematurity and congenital heart diseases stood out as important risk factors. Diagnostic evaluation varied according to suspected cause and trigger factors.

Management of Acute Contrast Reactions—Understanding Radiologists' Preparedness and the Efficacy of Simulation-Based Training in Canada

PurposeAcute radiologic emergencies, primarily severe contrast reactions, are rare but life-threatening events. Given a generalized paucity of formalized or mandated training, studies have shown that radiologists and trainees perform poorly when acutely managing such events. Moreover, skill base, knowledge, and comfort levels precipitously decline over time given the infrequent occurrence of these events during one's daily practice.The primary aim of this study was to assess radiologists' preparedness for managing acute radiologic emergencies and to determine the efficacy of a high-fidelity simulation based training model in an effort to provide a rationale for similar programs to be implemented on a provincial or national level. MethodsThis was a prospective, observational study of radiology residents and attending radiologists throughout the province who were recruited to attend a full-day simulation-based course presenting various cases of acute radiologic emergencies. Participant demographics were collected at the time of commencement of the workshop. Course materials were disseminated 4 weeks prior to the workshop, and a 17-question knowledge quiz was administered before and after the workshop. Likert-type questionnaires were also distributed to survey comfort levels and equipment familiarity. The knowledge quiz and questionnaire were redistributed at 3- and 6-month intervals for acquisition of follow-up data. ResultsA total of 14 attending radiologists and 7 residents attended the workshop, with all participants completing the preworkshop questionnaire and 90.5% (19 of 21) completing the post-workshop questionnaire. Participants' principle locations of practice were as follows: academic institutions (50%), community hospitals (36.9%), and private clinics (13.1%). A significant increase in knowledge was demonstrated, with average scores of 10 out of 17 (59%) and 14.5 out of 17 (85%) (P < .001) before and after the workshop, respectively. A significant increase in participants' comfort levels in recognizing acute anaphylactic reactions (3.5; 4.7, P < .001), commencing initial management for acute radiologic emergencies (3.3; 5.0, P < .001), and administering the correct dose for anaphylactic reactions (2.5; 4.8, P < .001) was also demonstrated. Moreover, participants became increasingly familiar with the contents and equipment found within contrast reaction kits (2.8; 3.8, P < .01). Repeat evaluations at 3 and 6 months found an average knowledge test score of 13.8 out of 17 (81%) and 10.8 out of 17 (64%), respectively. Comfort levels were also reassessed in recognizing acute anaphylactic reactions (4.5; 4.1), commencing initial management (4.0; 3.9) and administering the correct dose of medication (4.0; 3.7) at 3- and 6-month intervals. ConclusionsAcute radiologic emergencies are rare but life-threatening events that require rapid diagnosis and treatment to mitigate associated morbidity and mortality. Simulation-based workshops are a highly efficacious training model to increase knowledge, comfort levels, and equipment familiarity for radiologists and trainees alike; however, retraining at regular intervals is required.

Chapter 5 - Concussive and subconcussive brain trauma: the complexity of impact biomechanics and injury risk in contact sport

Head impacts that transfer mechanical energy to the skull and create brain injuries have unique dynamic responses and brain tissue trauma characteristics. The magnitude of the impact energy and how it is transmitted creates three-dimensional linear and rotational accelerations of the head, resulting in unique strains on brain tissue. Biomechanical investigations of head injuries in contact sports have historically focused on attenuating energy transfer to the skull and brain. Typically, severe life-threatening events are caused by high-energy impact events that result in anatomic damage. Protective equipment attenuates energy transmission to neural tissues to decrease the risk of structural damage. In addition to reducing risk of skull fracture, helmets work by increasing impact compliance, to decrease the magnitude of the head's dynamic response and increase the duration of the event. This strategy helps prevent severe traumatic brain injuries and shifts the risk to concussion and repetitive head impact exposure. Metabolic, cellular, and physiologic responses characterize cumulative brain trauma that may manifest years later. Relying on the presence of symptoms to establish injury is subjective and limited in capturing the risks associated with neural tissue trauma. To more effectively capture brain injury risks in contact sports, we present the concept of brain trauma profiling, involving impact magnitude, frequency, interval, and duration of exposure. Brain trauma profiling captures and describes the cumulative and acute trauma-associated injury risks unique to each sport, level of play, and player position.

中枢性急性眩晕综合征是否会威胁病人的生命?单个ICU连续3年的调查报告

目的：研究中枢性急性眩晕综合症(acute vertigo syndrome, AVS)是否存在威胁生命的事件。方法：自2014年1月至2016年12月期间，所有中枢性AVS连续在一个ICU逗留的临床资料被纳入研究。入选标准为最初均以AVS为首发症状起病，并且后来都伴有危及生命事件的患者。结果：总共2466例成人危重症住入我院ICU，其中有25例以中枢性AVS为首发症状并后来伴威胁生命事件的患者，其患病率大约占ICU危重症患者的1.0%。这些患者的中位数年龄为60岁(23, 81)男：女之比为1.8:1。引起中枢性AVS的原因包括局灶性脑出血15例(60%)，脓毒性休克7例(28%)，脑梗塞2例(12%)。最频繁的威胁生命的事件是急性脑衰竭(24/25)。最常见的导致威胁生命的原因是病灶扩大(52.0%，包括早起血肿扩大8例，大面积梗塞2例，脑室出血进展2例，新缺血灶1例)，其次为脓毒性休克和继发性脓毒症事件(44.0%, 11/25)。所有威胁生命事件的病死率为64%。与生存组比较，非生存组的病灶扩大(68.8% vs. 22.2%, p < 0.05)、呼吸衰竭(93.8% vs. 55.6%, p < 0.05)、乳酸水平(5.3 vs. 1.3, p < 0.05)和序贯器官功能评分(6.9 vs. 3.4, p < 0.0001)明显高于生存组，而后续平均动脉血压(84.6 vs. 124, p < 0.0001)、GCS分(5.0 vs. 15.0, p < 0.0001)明显低于生存组的患者。多因素Cox回归分析证实，只有低GCS分与死亡的风险密切相关(RR = 0.784, 95%CI, 0.670~0.918; p < 0.005)。结论：中枢性急性AVS伴有威胁生命事件的患病率大约占成人ICU危重症的1.0%。而且发现只有低GCS分(<6分)是独立预报威胁中枢性AVS患者生命的事件，并伴有高死亡的风险。 Objective: To investigate whether the central acute vestibular syndrome (AVS) would be present a severe life-threatening events. Methods: Between Jan. 2014, and Dec. 2016, the clinical data of cases with central AVS from an ICU were conducted. Inclusion criteria for all cases were the onset of AVS, and then the patients with a severe life-threatening event were diagnosed. Results: A total of 2466 adult critically ill patients were admitted to our hospital, including 25 patients with central AVS as the first symptom and later with life-threatening events. The prevalence rate of them was about 1.0% of the ICU critical patients. The median age of these patients was 60 years (range 23 to 81 years), male: female ratio was 1.8:1. The causes of central AVS included focal cerebral hemorrhage in 15 cases (60%), shock in 7 cases (28%), and cerebral infarction in 3 cases (12%). The most frequent life-threatening event was acute brain failure (24/25), and the most common cause leading to brain failure was the lesion enlarged (54.2%, including hematoma enlargement in 8 cases, large area infarction or new infarction in 3 cases, and intraventricular hemorrhage in 2 cases). The next life-threatening event was septic shock/secondary sepsis (44.0%, 11/25). The fatality rate for all life-threatenheing events was 64%. Compared with the survival group, the patients with lesion enlarged (68.8% vs. 22.2%, p < 0.05), respiratory failure (93.8% vs. 55.6% p < 0.05), lactate level (5.3 mmol/l vs. 1.3 mmol/l, p < 0.05) and sequential organ failure assessment (SOFA) score (6.9 vs. 3.4, p < 0.0001) in the non-survival group were significantly higher, while late mean arterial blood pressure (84.6 mmHg vs. 124 mmHg, p < 0.0001), GCS score (5.0 score vs. 15 score, p < 0.0001) in the non-survival group were significantly lower. Conclusion: The prevalence of central AVS associated with life-threatening events accounts for about 1% of adult ICU critical illness. These central AVS may be a potential life-threatening event and with a high risk of death.

Expression of Circulating Muscarinic Receptors in Infants With Severe Idiopathic Life-Threatening Events.

Expression of Circulating Muscarinic Receptors in Infants With Severe Idiopathic Life-Threatening Events.

Therapy of ANCA-associated vasculitis with severe renal manifestation under routine conditions

In the MEPEX trial the poor prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with severe renal manifestation (AAVr) could be significantly improved in the first year by plasmapheresis. How and to what extent is this knowledge of AAVr therapy implemented into routine practice and what effectiveness and adverse events resulted? This was a retrospective cohort study in which all patients who received remission induction therapy for AAVr under routine clinical conditions (RCC) in this hospital from 2009 to 2014 after publication of the MEPEX trial (n= 22) were compared with those in the plasmapheresis arm of the MEPEX trial (n= 70). Endpoints were dialysis-dependent chronic kidney disease and mortality after 3 and 12 months and severe life-threatening adverse events during the first 12 months. All patients with AAVr were treated by plasmapheresis under RCC. The two groups showed no differences with respect to the rate of dialysis dependency (after 3 months RCC 14 % versus MEPEX 16 %, P= 1.00 and after 12 months RCC 23 % versus MEPEX 14 %, P= 0.55) or mortality (after 3 months RCC 18 % versus MEPEX 16 %, P= 0.75 and after 12 months RCC 18 % versus MEPEX 27 %, P= 0.57). The rate of severe life-threatening adverse events was similar under RCC and under controlled study conditions (64 % versus 69 %, P= 0.87). Under RCC there is a high quality of medical treatment for AAVr. All patients received plasmapheresis for remission induction with comparable effectiveness and safety compared to controlled study conditions.

How does multilevel upper airway surgery influence the lives of dogs with severe brachycephaly? Results of a structured pre- and postoperative owner questionnaire

Brachycephalic airway syndrome in dogs is typified by a variety of anatomical abnormalities causing a diverse spectrum of clinical signs of varying intensity. This variability makes the assessment of the surgical outcome after upper airway surgery difficult. Using a structured questionnaire, the present study investigated the dog owner-perceived severity and frequency of a broad spectrum of welfare-relevant impairments 2 weeks before and 6 months after brachycephalic dogs underwent a recently developed multi-level upper airway surgery. All dogs underwent surgical treatment of stenotic nares (ala-vestibuloplasty), the nasal cavity (laser-assisted turbinectomy, LATE), the pharynx (palatoplasty and tonsillotomy), and if indicated, laryngeal surgery (laser-assisted ablation of everted ventricles and partial cuneiformectomy). Owners of brachycephalic dogs (n = 102) referred for upper airway surgery were eligible to participate.Questionnaire data from owners of 37 Pugs and 25 French bulldogs were evaluated. In all dogs, the clinical signs associated with brachycephaly improved markedly after surgery. Most encouraging was the striking reduction in life-threatening events by 90% (choking fits decreased from 60% to 5% and collapse from 27% to 3%). The incidence of sleeping problems decreased from 55% to 3%, and the occurrence of breathing sounds declined by approximately 50%. There was a marked improvement in exercise tolerance and a modest improvement in heat tolerance. Dogs with severe brachycephaly benefitted substantially from multi-level surgery, and there were particular improvements in the incidences of severe impairment and life-threatening events. However, despite the marked improvement perceived by dog owners, these dogs remained clinically affected and continued to show welfare-relevant impairments caused by these hereditary disorders.

Drug-Induced Hyperglycaemia and Diabetes.

Drug-induced hyperglycaemia and diabetes is a global issue. It may be a serious problem, as it increases the risk of microvascular and macrovascular complications, infections, metabolic coma and even death. Drugs may induce hyperglycaemia through a variety of mechanisms, including alterations in insulin secretion and sensitivity, direct cytotoxic effects on pancreatic cells and increases in glucose production. Antihypertensive drugs are not equally implicated in increasing serum glucose levels. Glycaemic adverse events occur more frequently with thiazide diuretics and with certain beta-blocking agents than with calcium-channel blockers and inhibitors of the renin-angiotensin system. Lipid-modifying agents may also induce hyperglycaemia, and the diabetogenic effect seems to differ between the different types and daily doses of statins. Nicotinic acid may also alter glycaemic control. Among the anti-infectives, severe life-threatening events have been reported with fluoroquinolones, especially when high doses are used. Protease inhibitors and, to a lesser extent, nucleoside reverse transcriptase inhibitors have been reported to induce alterations in glucose metabolism. Pentamidine-induced hyperglycaemia seems to be related to direct dysfunction in pancreatic cells. Phenytoin and valproic acid may also induce hyperglycaemia. The mechanisms of second-generation antipsychotic-associated hyperglycaemia, diabetes mellitus and ketoacidosis are complex and are mainly due to insulin resistance. Antidepressant agents with high daily doses seem to be more frequently associated with an increased risk of diabetes. Ketoacidosis may occur in patients receiving beta-adrenergic stimulants, and theophylline may also induce hyperglycaemia. Steroid diabetes is more frequently associated with high doses of glucocorticoids. Some chemotherapeutic agents carry a higher risk of hyperglycaemia, and calcineurin inhibitor-induced hyperglycaemia is mainly due to a decrease in insulin secretion. Hyperglycaemia has been associated with oral contraceptives containing high doses of oestrogen. Growth hormone therapy and somatostatin analogues may also induce hyperglycaemia. Clinicians should be aware of medications that may alter glycaemia. Efforts should be made to identify and closely monitor patients receiving drugs that are known to induce hyperglycaemia.

Recommendations for the use of long-term central venous catheter (CVC) in children with hemato-oncological disorders: management of CVC-related occlusion and CVC-related thrombosis. On behalf of the coagulation defects working group and the supportive therapy working group of the Italian Association of Pediatric Hematology and Oncology (AIEOP).

Central venous catheters (CVC), used for the management of children with hemato-oncological disorders, are burdened by a significant incidence of mechanical, infective, or thrombotic complications. These complications favor an increasing risk in prolongation of hospitalization, extra costs of care, and sometimes severe life-threatening events. No guidelines for the management of CVC-related occlusion and CVC-related thrombosis are available for children. To this aim, members of the coagulation defects working group and the supportive therapy working group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) reviewed the pediatric and adult literature to propose the first recommendations for the management of CVC-related occlusion and CVC-related thrombosis in children with hemato-oncological disorders.

Successful Percutaneous Coronary Intervention of a Stenotic Aberrant Circumflex Artery: A Rare Cause of Acute Coronary Syndrome

Successful Percutaneous Coronary Intervention of a Stenotic Aberrant Circumflex Artery: A Rare Cause of Acute Coronary Syndrome Most coronary artery origin abnormalities are incidentally determined during coronary angiography. However, some cases of coronary artery abnormalities are related to severe life-threatening events such as myocardial ischemia, arrhythmia and acute myocardial infarction. A 55-years-old male was hospitalized due to acute coronary syndrome. Coronary angiography reveal that aberrant circumflex coronary artery (Cx) originated from right aortic sinus and with proximal and distal Cx severe stenosis. Coronary intervention was successfully carried out on a severe stenosis at the proximal and distal Cx artery. Determination of the anomalous origin of the coronary artery and the cardiovascular system is of great clinical importance due to its severe life-threatening complications. Cardiologists should be aware of the possibility aberrant coronaries may be cause of acute coronary syndrome.