Acute Episodes Research Articles

Mood disorders and 5-HTR2A genetic variants – the moderator effect of inflammation on expression of affective polarity phenotype

BackgroundAlthough repeatedly confirmed, the molecular nature of gene-environment (GxE) interactions has rarely been investigated in the clinical context of mood disorders. This study assesses the relationship between HTR2A genetic variants and the modulatory effect of inflammation in a collective cohort of patients with major depressive disorder (MDD) and bipolar disorder (BD), as a unified group with two distinct phenotypes.MethodsThe study included 138 patients with acute mood episodes (BD = 83; MDD = 55). HTR2A rs6313 and rs6314 genotyping was performed while measuring platelet-derived indicators of inflammation (platelet count (PLT), mean platelet volume (MPV), plateletcrit, and platelet distribution width) and the MPV/PLT ratio.ResultsThe HTR2A rs6313 variant is a significant predictor of the polarity phenotype in mood disorders, with the MPV/PLT ratio moderating this relationship, but only under low-inflammatory conditions. In more pronounced inflammatory states, genetic influences lose their predictive role.ConclusionsTo our knowledge, this is the first study to investigate the complex interplay between platelet-derived indicators of inflammation and HTR2A variants in the context of mood disorders. Without pro-inflammatory conditions, mood disorders seem to be more genetically determined. Under pro-inflammatory conditions, phenotypic presentation is less dependent on genetic factors. GxE interactions in mood disorders are multifaceted, context-dependent and relevant for assessing their clinical presentation and course.

Hair cortisol concentration, a biomarker of stress, is gradually increased in patients with acute myocardial infarction before the acute episode

Abstract Background/Introduction Chronic stress is considered to be an important element of residual cardiovascular risk and modern guidelines recommend its systematic assessment and treatment. Its pathophysiologic contribution, however, in acute myocardial infarction (AMI) was not, until recently, easy to elucidate. This arises from difficulties in objectively quantifying stress levels using conventional research methods, like questionnaires. Purpose The purpose of our study was to measure stress levels at the days preceding an acute myocardial infarction using a solid biomarker, Hair Cortisol Concentration (HCC). Methods 102 consecutive patients with AMI (71 patients with ST-elevation Myocardial Infarction [STEMI] and 31 with Non ST-elevation Myocardial Infarction) from our institution were recruited for this study. We took hair samples from them to precisely measure HCC, which reflects cumulative cortisol levels for the time period preceding the acute event. We also did full clinical, biochemical and psychological evaluation. HCC levels were then compared with 50 age-matched healthy controls. Results To assess the temporal trend of HCC in hair segments, corresponding to specific time periods, we fitted linear mixed models. The mixed effects linear model including the main effects of time and group (AMI versus controls) and their interaction showed that cortisol concentration in hair increased over time with higher rate of increase in AMI patients versus controls (beta of interaction = 3.57; 95%CI: 1.74, 5.40; p < 0.001) The model explained a high percentage of the variance (conditional R2=0.940). No other baseline variable had a significant effect when added to the basic model. There was no significant difference between STEMI and NSTEMI (beta of interaction = 1.15; 95%CI: -1.330, 3.59; p = 0.358) Conclusions Hair cortisol levels, presumably reflecting stress levels, were gradually increasing before an acute myocardial infarction with higher rate of increase in patients compared to healthy controls. There was no significant difference between STEMI and NSTEMI patients. Picture 1. Predicted hair concentrations of cortisol over time prior to the event, based on linear mixed models.

Kidney status and events preceding death in heart failure: A real world data study on 18,456 patients with heart failure

Abstract Background Despite advancements in heart failure (HF) management, kidney dysfunction remains a significant clinical challenge, and is associated with higher mortality rates and other adverse outcomes. However, there are few studies of kidney events preceding death in patients with HF in the real world. Methods Using registry-based data, the prevalence of kidney events preceding death in patients with HF over the period 2014-2018 in Denmark. All deaths in patients with a diagnosis of HF within the previous 10 years were included. Kidney events occurring during within 1 year of death compromised of: acute kidney injury, chronic renal replacement therapy, sustained eGFR<15 mL/min/1.73 m2, or renal transplantation. The prevalence of kidney events preceding death was calculated and different subgroups were compared. Results Among the 18,586 HF patients who died, a total of 3107 (16.7%) experienced kidney events during within 1 year of death. The prevalence of HF patients with kidney events before death was 15.5% for acute kidney injury, 5.8% for chronic renal replacement therapy, 7.4% for an eGFR<15 mL/min/1.73 m2, and 0.18% for renal transplantation (see Figure 1). Acute kidney injury episodes were frequently observed in the last month before death (7.5%) (Figure 2). Age-specific analysis revealed a higher proportion of deaths associated with kidney dysfunction in patients under the age of 65 years compared to those aged 80 years and above (24.3% vs 13.4%). Furthermore, male sex, death in-hospital, reduced pre-existing kidney function, a higher degree of frailty, and lower educational status were associated with higher frequency of death associated with kidney dysfunction. Conclusion In this real-world study, a significant proportion of deaths among HF patients were associated with kidney dysfunction, particularly with acute kidney injury. Further research and awareness of renal complications are necessary to improve outcomes in this population.

Quality of life measures with etripamil self-administration for acute episodes of paroxysmal supraventricular tachycardia in a medically unsupervised setting: patient-reported outcomes from NODE-303

Abstract Background Etripamil nasal spray (NS) is a fast-acting, self-administered calcium-channel blocker in development for the conversion of AV-nodal dependent paroxysmal supraventricular tachycardia (PSVT) in a medically unsupervised setting. Prior studies show favorable safety and efficacy in converting single episodes of PSVT to sinus rhythm (SR). Purpose In NODE-303, patient-reported outcome (PRO) instruments assessed quality of life (QoL) over multiple etripamil-treated episodes of PSVT. Methods NODE-303 was an event-driven, multi-center, open-label Phase 3 study in North and South American patients with documented PSVT that evaluated the safety and efficacy of etripamil in PSVT termination, over multiple episodes and without the need for prior test dosing. Enrolled patients who perceived PSVT symptoms applied an ambulatory ECG cardiac monitoring system (CMS), performed a pre-trained vagal maneuver and, if symptoms persisted, self-administered etripamil NS 70 mg. A study amendment allowed a repeat dose (etripamil NS, 70 mg) if symptoms persisted 10 min after the first dose. Each patient could self-treat up to 4 episodes. Safety was assessed through adverse events, clinical data, and ECG CMS recordings. The Treatment Satisfaction Questionnaire for Medication (TSQM; validated for acute episodic assessments) and other PROs were administered, and healthcare utilization data were acquired. Patients completed PROs at baseline (BL), monthly, and per PSVT episode, which collected information on symptoms, episode characteristics, rescue medications, and emergency room visits. Additional PROs were the Brief Illness Perception Questionnaire (BIPQ), Cardiac Anxiety Questionnaire (CAQ), and 36-Item Short Form Health Survey (SF-36). Results There were higher proportions of patients reporting mild, minimal or no disease severity, every 6 months, than at BL; extremely severe, severe, and moderate disease severity was reported by smaller proportions of patients than at BL, though incomplete surveys at later visits may limit this analysis. Anxiety and stress about future PSVT episodes were consistently reduced from BL. Measures of treatment satisfaction, effectiveness, and convenience were consistent across multiple episodes, and were at levels considered favorable for the TSQM instrument (Table 1). Rates of emergency-room visits and hospital admissions across multiple, treated PSVT episodes were similar to those observed in trials assessing single episodes (Table 2). The BIPQ, CAQ or SF-36 had no notable changes from BL. Conclusions Etripamil self-administration was associated with patient-reported improvements in degree of disease severity, decreased anxiety and stress over future PSVT episodes, and levels of treatment satisfaction, effectiveness, and convenience considered favorable for respective PRO instrument. Using a symptom-prompted, self-administered treatment for PSVT could potentially improve QoL measures and reduce healthcare resource utilization.

Cardio Policy Optimiser: an integrated public health approach to enhancing cardiovascular health

Abstract Background Cardiovascular diseases (CVDs) remain a leading cause of mortality in Europe, with atherosclerotic-related conditions accounting for 80% of CVD deaths - a third of them premature. Despite extensive efforts over the past five decades, the decline in these deaths over the last 20-25 years has plateaued, highlighting the need for innovative approaches. Additionally, the co-occurrence of CVDs with other chronic conditions such as diabetes, hypertension, and renal and hepatic diseases, adds complexity to their management and prevention. Methods In Portugal, the pilot phase implemented a novel integrated approach combining a Bayesian epidemiological model - which incorporates genetic, sociodemographic, comorbidity, and lifestyle data - with an adaptive conjoint analysis model focusing on atherosclerosis policy intervention. These models are part of a comprehensive response framework that incorporates health outcomes and associated costs resulting from better prevention and diagnosis. Results Currently in the development and calibration stage, the model is expected to yield initial results by early September. Conclusions This modeling approach offers new opportunities for public health to intervene at early stages in the natural history of CVDs. It emphasizes enhancing prevention and early diagnosis to potentially reduce the incidence of acute episodes and associated mortalities. Moreover, the model facilitates rapid evaluation of the economic benefits derived from preventive policies, thereby supporting more informed public health decision-making. Key messages • The CPO model combines epidemiological and policy models to address cardiovascular morbidity and mortality. • It boosts early diagnosis and prevention, and assesses economic benefits from policies.

Memory impairment after one year of the acute episode of Covid-19 infection

Abstract Introduction Memory impairment is one of the most frequently reported sequelae of COVID-19 infection. The aim of our study was to estimate the risk of memory disorders one year after the acute episode of COVID-19 infection in the Tunisian population of Monastir. Methods This is a cohort study conducted in Monastir University Hospital. The study included two groups: Exposed subjects were randomly selected among those with a positive diagnosis of COVID-19 between September 2021 and January 2022. The non exposed group was selectd among subjects with a negative COVID-19 diagnosis during the same period and who had no COVID infection during the following year. The Mac Nair scale was used to assess memory impairment after one year of follow up. Results Our study included 140 subjects diagnosed with Covid-19 and 139 subjects who had never been in contact with this virus. The incidence rate of memory impairment at one year post-Covid-19 infection was 17.9% (IC95% [11.5 - 24.2%]), whereas in the non exposed group it was 9.4% (IC95% [4.45% -14.5%]). Multivariate analysis revealed that the group exposed to Covid-19 had a significantly higher Mac-Nair Total score after one year of the acute episode of infection compared with the non exposed group (exp β = 1.25, IC95% [1.10; 1.42]). The other main predictors of memory impairment in the study population were age (exp β = 1.006, IC95% [1.001; 1.01]), diabetes (exp β = 1.67, IC95% [1.44; 1.95]), history of anxiety and depression ((exp β = 1.71, IC95% [1.35; 2.17]) and obesity (exp β = 1.25, IC95% [1.10; 1.42]), whereas vaccination with two or more doses prior to COVID-19 infection (exp β = 0.84, IC95% [0.74; 0.96]) and male gender (exp β = 0.65, IC95% [ 0.57; 0.73]) were found to be protective against these disorders. Conclusions Our study allowed us to estimate the risk of long-term memory disorders following Covid-19 infection. This could help better guide preventive measures to reduce the incidence of these disorders. Key messages • The incidence rate of memory impairment at one year post-Covid-19 infection was 17.9%. • The main other predictors of memory impairment were age, female gender, diabetes, history of anxiety and depression and obesity whereas vaccination prior to COVID-19 infection was a protective factor.

Echocardiography in acute pulmonary embolism for the prediction of subsequent CTEPH

Abstract Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a long term complication of acute pulmonary embolism (APE) with poor outcomes if untreated. Identifying already at APE diagnosis patients at risk of subsequent CTEPH can lead to earlier goal-directed management. Since standard echocardiography (TTE) is frequently performed during APE episode for short term risk stratification we aimed to asses prediction vale of echocardiography for subsequent CTEPH. Methods We analyzed retrospectively TTE performed at admission due to APE in consecutive patients, without known CTEPH who were anticoagulated for at least 3 months and were followed up for at least 24 months. After follow-up all patients underwent diagnostic workup for CTEPH according to ESC recommendations. We tried to define a set of echocardiographic parameters recorded during the acute episode predictive for CTEPH. Results The study included consecutive 625 patients with APE diagnosed at computed tomography pulmonary angiogram and managed according to ESC recommendations. During follow up 25 (4%) pts were diagnosed with CTEPH. At APE diagnosis CTEPH(+) group presented more prominent echocardiographic signs of right ventricular (RV) overload than pts without CTEPH (CTEPH(-))(table 1). However, multivariate analysis revealed that only increased TRPG and RV/LV ratio were significant CTEPH predictors with AUC 0.792 (95% CI: 0.683-0.900), p<0.001 and 0.777 (95% CI: 0.675-0.878), p<0.001 respectively (fig 1). Using Youden index in ROC analysis we defined following cut off values useful to identify patients at CTEPH risk and subjects with low probability of CTEPH development. TRPG >44mmHg and RV/LV>1.15 showed PPV for CTPEH 12.9 (95% CI: 9.8-16.7) and 13.8 (95% CI: 10.4-18.1), with high NPV of 98.4 (95% CI: 97.1-99.2) and 98.2 (95% CI: 96.8-99.0) respectively. Importantly, in the group of 61 (9.7%) patients with both signs of RV overload present in the acute phase CTEPH during follow-up was diagnosed in 14 patients (23.0%). Conclusion TRPG above 44 mmHg recorded at APE diagnosis identifies patients at risk of subsequent CTEPH especially in patients with increased RV/LV ratio.

Acute Manic Episode and Psychosis as Early Manifestations of Systemic Lupus Erythematosus with Lupus Nephritis: A Case Report

Background: Neurological and psychiatric conditions seen in SLE in the absence of other causes are broadly termed Neuropsychiatric SLE (NPSLE). Case Presentation: This case report was of a 37-year-old, separated female Banker who presented initially with symptoms of mania with psychosis at the Psychiatry Department. She was initially managed as such but represented again with similar symptoms in addition to fluffy brownish hair with hair loss, and hyper-pigmented patches along the bridge of her nose, glabella, and zygomatic regions, extending to the ears and retro auricular region. Annular hypo-pigmentation, atrophic patches were also observed on the extensor surface of both forearms. She developed fever, and epigastric tenderness with several episodes of vomiting and diarrhea which were initially non-bloody at 48hrs into admission on account of which she was placed on antibiotics. The patient improved significantly after which she discharged herself against medical advice however represented 2 days after with a worsened condition. Proactive management was ensured with some sessions of hemodialysis. An assessment of acute flare of systemic lupus erythematosus SLE, precipitated by sepsis was made and was managed as such. The patient recovered tremendously and was discharged to the clinic. Conclusion: The need for comprehensive examinations and investigations in this regard to exclude other differentials cannot be jettisoned. In this case, it could be said that the psychiatric symptoms came before the obvious signs of SLE, however, it is still possible to think of these symptoms as early signs of SLE or SLE aggravating an underlying mental disorder.

A Case Report of Isovaleric Acidemia without Acidosis

The deficiency of isovaleryl-CoA dehydrogenase leads to an inborn recessive error of leucine metabolism named isovaleric acidemia (IVA). Its presentation may be either in the neonatal period as an acute episode of metabolic acidosis or later as a “chronic intermittent form.” Normal development is promoted by early diagnosis and treatment with a protein-restricted diet and supplementation with carnitine and glycine. The present case was a 35-day-old boy admitted with seizures, whose initial screening test was in favor of organic acidemia of the isovaleric acidemia type (Ammonia: 200 μmol/L). As the venous blood gas (VBG) analysis revealed no acidosis, newborn metabolic screening was repeated. Typical laboratory findings and elevated levels of C5 and C5/C2 confirmed isovaleric acidemia again. As the above patient had no acidosis while the other tests, including laboratory and genetic analysis, were in favor of IVA, he was considered to be a rare case.

Endothelial Biomarkers Are Superior to Classic Inflammatory Biomarkers in Community-Acquired Pneumonia.

Background: Complications in community-acquired pneumonia (CAP), including cardiovascular events (CVE), can occur during an acute episode and in the long term. We aimed to analyse the role of endothelial damage biomarkers (C-terminal endothelin-1 precursor fragment [CT-proET-1] and mid-regional pro-adrenomedullin [MR-proADM]), in contrast to classic inflammation markers (C Reactive Protein [CRP] and procalcitonin [PCT]) in patients admitted for CAP and their relationship with ICU admission, CVE and mortality in the short and long term; Methods: Biomarkers were analysed in 515 patients with CAP at day 1, 285 at day 5 and 280 at day 30. Traditional inflammatory biomarkers and endothelial damage biomarkers were measured. ICU admission, CVE and mortality (in-hospital and 1-year follow-up) were assessed using receiver operating characteristic (ROC) curve analysis and univariate logistic regression. Results: A statistically significant association was observed between initial, raised CT-proET-1 and MR-proADM levels, the need for ICU admission and the development of in-hospital CVE or in-hospital mortality. Both endothelial markers maintained a strong association at day 30 with 1-year follow-up CVE. At day 1, CRP and PCT were only associated with ICU admission. On day 30, there was no association between inflammatory markers and long-term CVE or death. The odds ratio (OR) and area under the curve (AUC) of endothelial biomarkers were superior to those of classic biomarkers for all outcomes considered. Conclusions: Endothelial biomarkers are better indicators than classic ones in predicting worse outcomes in both the short and long term, especially CVE. MR-proADM is the best biomarker for predicting complications in CAP.

Conservative Management of Necrotizing Enterocolitis in Newborns: Incidence and Management of Intestinal Strictures.

Necrotizing enterocolitis (NEC) is one of the main causes of acute abdomen in neonates. Surgical treatment entails important morbidity and mortality and conservative management, when possible, offers better outcomes. Post-NEC intestinal strictures are one of the main complications. Retrospective analysis from June 2011 to November 2022 of post-NEC strictures (PNS) after conservative management of neonates diagnosed with NEC (modified Bell stage IIA or higher) at a tertiary neonatal surgery center. Out of 219 NEC, 126 received initial conservative management (57.5%), 24 (19%) of which eventually underwent surgery for PNS. Average gestational age and weight at birth of our cohort were 31.3 ± 4.9 weeks and 1,694 ± 1,009 g.PNS diagnosis was made 38.4 ± 16.5 days after the NEC episode. 6/24 (25%) were asymptomatic and diagnosed by screening enema, 11 (46%) presented signs of intestinal obstruction before the enema could be performed and 7 (29%) after a normal previous protocol study.Median age at PNS surgery was 56 ± 17.9 days. A total of 2/3 strictures were found in cecum, ascendent, and transverse colon. Primary resection and anastomosis were performed in all cases. Feeds were restarted on postoperative day 4.3 ± 2.9. Two cases presented anastomotic complications (1 dehiscence and 1 stenosis), and no deaths were recorded. PNS is a frequent complication after conservative management. Deffered surgical treatment after the acute NEC episode is resolved allows for safer surgeries (since patients have reached hemodynamical stability and overcome septic shock), shorter resections, and favorable postoperative outcomes.

Low availability of haematin (hemin) in Pakistan.

Madam, Acute Intermittent Porphyria (AIP) is an autosomal dominant disorder that results from a defect in the enzyme named porphobilinogen deaminase.1 It is symptomatic porphyria, involving the accumulation of porphyrins and porphyrin precursors due to impaired conversion in haeme synthesis. Acute Intermittent Porphyria is clinically characterized by acute episodes of multiple gastrointestinal and neurologic symptoms; during which the patient remains healthy between episodes.2 Acute Intermittent Porphyria episodes are commonly observed in post pubertal females. The most common symptoms include periodic abdominal pain, vomiting and hypertension followed by neurologic damage that leads to peripheral and autonomic neuropathies (mostly motor) and psychiatric manifestations.2 Hormonal cycle regulation may worsen porphyria, since its symptoms coincide with the menstrual cycle. Although positive response has been noted in hormonal suppression by gonadotropin releasing hormone agonists.3 Currently, the most widely used treatment is hemin, a form of haeme that can be given intravenously. Its administration reduces the haeme deficit, hence limits the production of porphyrins precursors by the body. Availability of hemin in Pakistan is not promising while alternatives such as intravenous infusion of glucose, and pain relievers like Nalbuphine, a man-made opioid analgesic, and Morphine are short-term treatments. Haeme Arginate (HA), a compound of haeme and arginine, is equivalent to hematin in the treatment of AIP. Long-term weekly intravenous infusions of prophylactic HA prevent severity and frequency of porphyric attacks in patients with AIP.4 While haeme therapy is recommended if a patient exhibits neurological impairment, liver transplant appears to be the last resort in patients with recurrent clinical manifestations. To effectively mediate the growing need of Hemin in Pakistan, a systematic plan with effective and immediate steps must be introduced. The regulatory authorities must expedite the approval and licensing process of appropriate medication that would meet the growing need of the country, while not compromising on its quality. The possibility of local production should be explored, while strengthening international ties aimed at importing affordable medication. The government should focus on initiating partnerships with international organizations, non-governmental organizations (NGOs) and global health initiatives. Nationwide workshops and informative campaigns towards healthcare work should be a priority, to raise awareness of the situation and the proper steps that should be taken to minimize its adverse effects. Empowering patient advocacy groups would be beneficial in recognizing any shortcomings of the plan and to divert resources accordingly.

An evaluation of the efficacy and side effects of a single dose of ketamine in major depressive disorder.

This study aims to provide a comprehensive overview of the antidepressant and antisuicidal efficacy of ketamine in patients with unipolar depression, with a focus on the clinical evidence and safety profile. In our study, the data of 120 major depressive disorder patients who received single-dose ketamine infusion therapy were evaluated retrospectively, with Montgomery-Asberg Depression Rating Scale (MADRS) applied by the clinician before treatment and at the 4th and 24th hours after treatment and side effects at 4 and 24hours after treatment. There was a statistically significant difference between MADRS and MADRS-Suicide scores of all participants before the ketamine infusion (0th hour) and at the 4th and 24th hours after the ketamine infusion. Also, male and female, RAT(+) and RAT(-), and SA(+) and SA(-) participants have statistically significant differences on all three times for both MADRS and MADRS-S scores. The findings of this study are in line with those from previous research that demonstrated the rapid and robust antidepressant effects of ketamine, even in individuals with severe, treatment-resistant depression. Moreover, the observed reduction in suicidal ideation is particularly noteworthy, given the critical need for interventions that can provide rapid relief in acute suicidal crises. Key message What is already known on this topic - Ketamine is known for its rapid antidepressant and antisuicidal effects in treatment-resistant major depressive disorder, demonstrating significant symptom relief within hours of administration. What this study adds - This study provides additional evidence supporting ketamine's rapid efficacy in reducing depressive symptoms and suicidal ideation, highlighting statistically significant improvements observed at 4 and 24hours post-treatment. How this study might affect research, practice, or policy - The findings may encourage broader clinical adoption of ketamine for acute depressive episodes and suicidality, emphasizing the need for controlled medical settings to manage potential side effects, and could influence future research on optimizing dosing protocols and long-term safety.

Development, implementation, and acceptability of a bedside mindfulness intervention for adults with sickle cell disease

ABSTRACT Acute and chronic pain are the most frequent complications of sickle cell disease (SCD), often severely reducing quality of life and requiring management with long-term pharmacological interventions. A biopsychosocial approach conceptualizing pain in SCD as the result of complex biological, psychological, and social factors could facilitate targeted behavioral interventions. Mindfulness is one procedure for management of pain in individuals with chronic pain/illness. The goal of the current project was to design and implement a bedside mindfulness intervention to help patients with SCD enhance self-efficacy of pain management and reduce distress. As part of a quality improvement project in SCD clinics in a large health system, we developed a bedside mindfulness intervention to be provided during infusion sessions for patients presenting for acute vaso-occlusive episodes (VOE). The approach to development and implementation involved engagement of professionals working directly with patients. Concept planning meetings with these professionals along with qualitative patient and provider feedback informed feasibility, design, and intervention application. During a quantitative phase, patients completed validated surveys items on acceptability. Interview data (N = 11) supported patient interest in mindfulness skills and highlighted a need for tailored, person-centered interventions and non-pharmacological treatment strategies. On quantitative items, participants (N = 14) liked the intervention and agreed mindfulness skills would help manage disease-related distress. Following the interventions, participants reported increased mindfulness (p = .005). While preliminary, these results provide support for the continued development of evidence-based, mindfulness-oriented services to help individuals with SCD manage pain and other psychological difficulties.

Association of circulating monocyte number and monocyte–lymphocyte ratio with cardiovascular disease in patients with bipolar disorder

BackgroundCardiovascular disease (CVD) is the leading cause of excessive and premature mortality in patients with bipolar disorder (BD). Despite immune cells participating considerably in the pathogenesis of CVD, limited data are available regarding leukocyte phenotypes in patients with BD and CVD. This study aimed to evaluate associations between circulating leukocyte subset and CVD among patients with BD.MethodsA total of 109 patients with BD-I and cardiologist-confirmed CVD diagnosis (i.e., case) were matched with 109 BD-I patients without CVD (i.e., control) according to the age (± 2 years), sex, and date of most recent psychiatric admission because of acute mood episode (± 2 years). Leukocyte subset data were retrieved from complete blood count tests performed on the next morning after the most recent acute psychiatric admission.ResultsDuring the most recent acute psychiatric hospitalization, circulating monocyte counts in the case group were significantly higher than those in the age- and sex-matched controls (p = 0.020). In addition, monocyte–lymphocyte ratios (MLRs) in the case group were significantly higher than those in the control group (p = 0.032). Multiple logistic regression showed that together with serum levels of uric acid and manic symptoms, circulating monocyte counts (95% CI, OR: 1.01–1.05) and MLRs (95% CI, OR: 1.01–1.09) were significantly associated with CVD in patients with BD, respectively.ConclusionsMonocyte activation in an acute manic episode may play a critical role in the pathogenesis of CVD among patients with BD. Future research is required to investigate markers of monocyte activation and indices of cardiovascular structure and function across the different mood states of BD.

Bipolar disorder and early childhood trauma

Case Background There is a reported 48.8 million case of bipolar disorder (BD) world- wide. It can also be one of the most challenging disorders to manage clinically as patients often have poor medical compliance and numerous relapses throughout their lifetime. The etiology of this illness is still poorly understood, but it is recognized to compromise both genetic and environmental factors. Regarding the latter, abuse and instability in childhood and adolescence was reported as an important area of consideration in regard to the development and prognosis of bipolar disorder. We report here the case of a female who exemplifies the significance of early childhood experience in this disorder. Case Presentation Isabelle is a 21 year old, female, with a background history of bipolar disorder. She presented to the Cork University Hospital accident and emergency 2 weeks after discharge after a 4 week admission for a depressive episode. Isabelle was referred from the home-based team with an acute episode of mania and was detained involuntarily under the Mental Health Act. Her history is significant for childhood neglect, physical, emotional and sexual abuse, along with multiple foster care placements. She was managed as an inpatient with antipsychotics and a mood stabilizer before being discharged after a lengthy, arduous, admission. Conclusion Childhood trauma is an important consideration in BD. Therefore, practitioner awareness of the role of such trauma with regard to its etiology and prognosis is of great importance. It is also essential to the practice of preventive medicine. Patient Consent Obtained: Yes

Analysis of the outcomes of postdiverticulitis investigations: a multicentre cohort study including 1,120 patients.

The aim of this study was to assess the yield of the endoscopic investigations performed following the resolution of acute diverticulitis. A retrospective multicentre study included patients with multislice computed tomography (MSCT)-proven diverticulitis, in four NHS hospitals, between January 2016 and April 2023. The primary outcome was the rate of colonic cancer in the diseased segment. Secondary outcomes included the rate of malignancy in the nondiseased colonic segments, the benign colonic polyp detection rate, the rate of malignancy in the resected surgical specimens in patients who underwent an emergency surgery on the index admission and the rate of complications in the investigated group. A total of 1,120 patients were included in the study, out of which 604 were females, with a median age of 61 years; 731 patients (65%) had uncomplicated diverticulitis (Hinchey 1A) while 389 (35%) had complicated diverticulitis (Hinchey 1B-4). Following the acute episode, 757 (74%) patients had subsequent endoscopic evaluation. The incidence of colorectal cancer (CRC) or advanced adenomas (AA) in patients with uncomplicated diverticulitis was 0.14%. In the complicated diverticulitis group, the incidence of CRC/AA in patients with Hinchey 1b and Hinchey 2 was 1.4% and 5.4%, respectively. Out of the 102 patients who underwent emergency colonic resection for suspected perforated diverticulitis, 18 (17.6%) had histological evidence of colonic malignancy. Endoscopic investigations following uncomplicated diverticulitis have a low yield for sinister colonic pathology. Colonoscopy should be planned following complicated diverticulitis and in patients with uncomplicated diverticulitis with suspicious radiological finding on index imaging or in patients with ongoing clinical manifestations. In patients who undergo emergency surgery, oncological principles should be applied whenever possible.

Within-episode relations among simultaneous alcohol and cannabis use and continued drinking: The role of momentary subjective responses, craving, and drinking context.

Simultaneous alcohol and cannabis use is associated with riskier daily drinking. However, little research has tested momentary mechanisms through which simultaneous use predicts continued drinking during acute drinking episodes. The current study tested whether simultaneous use moments predicted within-episode increases in subjective responses, craving, and continued drinking, and whether these relations were potentiated in social versus solitary settings. Emerging adults who co-use alcohol and cannabis (N = 85) completed 21 days of ecological momentary assessment with event-contingent reports during drinking episodes. Three-level multilevel models tested whether simultaneous (vs. alcohol-only) use moments indirectly predicted subsequent, continued drinking through subjective responses (i.e., high-arousal positive/stimulant, high-arousal negative/aggression, low-arousal positive/relaxation, low-arousal negative/impairment) and alcohol craving, and whether relations differed by social versus solitary contexts. Within drinking episodes, simultaneous (vs. alcohol-only) use moments were associated with increased stimulation, which was indirectly associated with continued drinking through increased alcohol craving. Additionally, the relation between simultaneous (vs. alcohol-only) use and stimulating effects was potentiated during solitary drinking moments, whereas the relation between stimulating effects and craving was potentiated during social drinking moments. However, stimulating effects were higher in social contexts across all moments. Finally, simultaneous (vs. alcohol-only) use moments were associated with increased relaxation, which was indirectly associated with a lower likelihood of continued drinking through lesser craving. Simultaneous use predicted both continued within-episode drinking and cessation of drinking, with acute subjective effects and craving as mechanisms, dependent upon context. Just-in-time interventions should consider targeting affect, craving, and context in event-specific interventions.

A Bayesian analysis of heart rate variability changes over acute episodes of bipolar disorder

Bipolar disorder (BD) involves autonomic nervous system dysfunction, detectable through heart rate variability (HRV). HRV is a promising biomarker, but its dynamics during acute mania or depression episodes are poorly understood. Using a Bayesian approach, we developed a probabilistic model of HRV changes in BD, measured by the natural logarithm of the Root Mean Square of Successive RR interval Differences (lnRMSSD). Patients were assessed three to four times from episode onset to euthymia. Unlike previous studies, which used only two assessments, our model allowed for more accurate tracking of changes. Results showed strong evidence for a positive lnRMSSD change during symptom resolution (95.175% probability of positive direction), though the sample size limited the precision of this effect (95% Highest Density Interval [−0.0366, 0.4706], with a Region of Practical Equivalence: [-0.05; 0.05]). Episode polarity did not significantly influence lnRMSSD changes.

Historical perspectives of heat-related illness part 2: the present and future

Part one of this series on heat-related illness described how the disease has been known and written about for thousands of years. Since then, there have been some improvements in our understanding of its risks, mechanisms and treatments. However, heat-related illness remains a significant problem, and can be fatal or cause ongoing disability even after the acute episode has passed. This narrative review, the second article in a two-part series describes current understanding of heat-related illness and offers an insight into what we may learn in the future about its cause and potential new treatments and strategies.