How robust are recommended waiting times to pacing after cardiac surgery that are derived from observational data?

AIMS: For bradycardic patients after cardiac surgery, it is unknown how long to wait before implanting a permanent pacemaker (PPM). Current recommendations vary and are based on observational studies. This study aims to examine why this variation may exist. METHODS AND RESULTS: We conducted first a study of patients in our institution and second a systematic review of studies examining conduction disturbance and pacing after cardiac surgery. Of 5849 operations over a 6-year period, 103 (1.8%) patients required PPM implantation. Only pacing dependence at implant and time from surgery to implant were associated with 30-day pacing dependence. The only predictor of regression of pacing dependence was time from surgery to implant. We then applied the conventional procedure of receiver operating characteristic (ROC) analysis, seeking an optimal time point for decision-making. This suggested the optimal waiting time was 12.5 days for predicting pacing dependence at 30 days for all patients (area under the ROC curve (AUC) 0.620, P = 0.031) and for predicting regression of pacing dependence in patients who were pacing-dependent at implant (AUC 0.769, P < 0.001). However, our systematic review showed that recommended optimal decision-making time points were strongly correlated with the average implant time point of those individual studies (R = 0.96, P < 0.001). We further conducted modelling which revealed that in any such study, the ROC method is strongly biased to indicate a value near to the median time to implant as optimal. CONCLUSION: When commonly used automated statistical methods are applied to observational data with the aim of defining the optimal time to pacing after cardiac surgery, the suggested answer is likely to be similar to the average time to pacing in that cohort.

Rheumatological Adverse Events Following Immunotherapy for Cancer.

Background and Objectives: The occurrence of rheumatological side effects in a patient after receiving immunotherapy for cancer is becoming increasingly common. Oncologists often fail to diagnose and refer affected patients to rheumatologists. This paper presents the various rheumatological adverse events that occur after immunotherapy in patients as well as their treatment and evolution. Materials and Methods: A total of 36 patients were monitored between November 2018 and March 2020. The oncologist monitoring the immunotherapy-treated patients identified the occurrence of musculoskeletal side effects. The grading of toxicities was performed by both the oncologist and the rheumatologist using common terminology criteria for adverse events (CTCAE). Rheumatological treatment was administered, and for some patients, immunotherapy was discontinued. Results: The clinical presentations of the patients varied. Mild side effects (grade 1-2) were reported in a higher proportion than severe side effects (grade 3-5). Therefore, thirty-one patients had mild-to-moderate side effects, and five patients had severe side effects. Adverse reactions occurred, on average, 10 weeks after the initiation of immunotherapy; this indicated that the severity of the toxicity was dose dependent. Patients were treated with NSAIDs or prednisone, depending on the severity of the side effects, and for patients with severe manifestations, immunotherapy was discontinued. The remission of rheumatic manifestations varied depending on the grade of the manifestations. Conclusions: The clinical, biological, and ultrasound presentations of the patients with adverse events followed by cancer treatments differed from classic rheumatological manifestations. Thorough examinations of these patients by both oncologists and rheumatologists are needed in order to correctly diagnose and treat rheumatological adverse events. Multiple studies that include a larger number of participants are needed in order to better understand the pathogenesis and clinical evolution of these patients under different treatment conditions.

A comparison of different methods to maximise signal extraction when using central venous pressure to optimise atrioventricular delay after cardiac surgery.

Objective: Our group has shown that central venous pressure (CVP) can optimise atrioventricular (AV) delay in temporary pacing (TP) after cardiac surgery. However, the signal-to-noise ratio (SNR) is influenced both by the methods used to mitigate the pressure effects of respiration and the number of heartbeats analysed. This paper systematically studies the effect of different analysis methods on SNR to maximise the accuracy of this technique. Methods: We optimised AV delay in 16 patients with TP after cardiac surgery. Transitioning rapidly and repeatedly from a reference AV delay to different tested AV delays, we measured pressure differences before and after each transition. We analysed the resultant signals in different ways with the aim of maximising the SNR: (1) adjusting averaging window location (around versus after transition), (2) modifying window length (heartbeats analysed), and (3) applying different signal filtering methods to correct respiratory artefact. Results: (1) The SNR was 27 % higher for averaging windows around the transition versus post-transition windows. (2) The optimal window length for CVP analysis was two respiratory cycle lengths versus one respiratory cycle length for optimising SNR for arterial blood pressure (ABP) signals. (3) Filtering with discrete wavelet transform improved SNR by 62 % for CVP measurements. When applying the optimal window length and filtering techniques, the correlation between ABP and CVP peak optima exceeded that of a single cycle length (R = 0.71 vs. R = 0.50, p < 0.001). Conclusion: We demonstrated that utilising a specific set of techniques maximises the signal-to-noise ratio and hence the utility of this technique.

Skin Lesions with Loss of Tissue and Cutaneous-Onset Sepsis: The Skin Infection-Sepsis Relationship.

Infectious and inflammatory dermatoses featuring skin lesions with loss of tissue expose skin layers to microbial invasions, disrupt the normal skin microbiome, and potentially lead to sepsis. However, literature data on the incidence of cutaneous-onset sepsis are scarce. This retrospective observational study assessed hospital admissions for primary skin lesions without bacterial infections and sepsis during 2020-2022 in the largest emergency hospital in NE Romania. Of 509 patients, 441 had infected lesions, 78 had sepsis caused by venous ulcers from microbial eczema cellulitis, superinfected bullous dermatoses, erysipelas, and erythroderma. Cultured samples revealed S. aureus, P. aeruginosa, and E. coli; and K. pneumoniae and S. ß-hemolytic associated with sepsis, even if this was rarer. Clinical manifestations included ulcerations, erosions, fissures, excoriations, bullae, vesicles, pruritus, tumefaction, edema, fever, chills, pain, adenopathy, and mildly altered mental status. Underlying chronic heart failure, atrial fibrillation, anemia, and type-1 diabetes mellitus were comorbidities associated with infection and sepsis. Significant associations and risk factors, including their combined effects, are discussed to draw attention to the need for further research and adequate management to prevent sepsis in adult patients of any age presenting with infected skin lesions (especially cellulitis) and comorbidities (especially type 1 diabetes mellitus and anemia).

Complete revascularization is associated with higher mortality in patients with ST-elevation myocardial infarction, multi-vessel disease and shock defined by hyperlactataemia: results from the Harefield Shock Registry incorporating explainable machine learning.

AIMS: Revascularization strategy for patients with ST-elevation myocardial infarction (STEMI) and multi-vessel disease varies according to the patient's cardiogenic shock status, but assessing shock acutely can be difficult. This article examines the link between cardiogenic shock defined solely by a lactate of ≥2 mmol/L and mortality from complete vs. culprit-only revascularization in this cohort. METHODS AND RESULTS: Patients presenting with STEMI, multi-vessel disease without severe left main stem stenosis and a lactate ≥2 mmol/L between 2011 and 2021 were included. The primary endpoint was mortality at 30 days by revascularization strategy for shocked patients. Secondary endpoints were mortality at 1 year and over a median follow-up of 30 months. Four hundred and eight patients presented in shock. Mortality in the shock cohort was 27.5% at 30 days. Complete revascularization (CR) was associated with higher mortality at 30 days [odds ratio (OR) 2.1 (1.02-4.2), P = 0.043], 1 year [OR 2.4 (1.2-4.9), P = 0.01], and over 30 months follow-up [hazard ratio (HR) 2.2 (1.4-3.4), P < 0.001] compared with culprit lesion-only percutaneous coronary intervention (CLOP). Mortality was again higher in the CR group after propensity matching (P = 0.018) and inverse probability treatment weighting [HR 2.0 (1.3-3.0), P = 0.001]. Furthermore, explainable machine learning demonstrated that CR was behind only blood gas parameters and creatinine levels in importance for predicting 30-day mortality. CONCLUSION: In patients presenting with STEMI and multi-vessel disease in shock defined solely by a lactate of ≥2 mmol/L, CR is associated with higher mortality than CLOP.

Cerebral Tuberculosis in a Patient Following Treatment With Infliximab for Ankylosing Spondylitis: A Case Report.

Ankylosing spondylitis (AS) mainly belongs to the group of axial spondylitis. It is a chronic inflammatory disease that primarily affects the spine, but can also affect peripheral joints. It is characterized by inflammatory lower back pain and morning stiffness. Tuberculosis is still a cause of morbidity and mortality in developing countries. Management of patients with AS consists of patient education, spinal mobility exercises, non-steroidal anti-inflammatory drugs (NSAIDs), corticotherapy, and anti-tumor necrosis factor alpha (TNF-α) biological agents. Anti-TNF-α biological agents have changed the prognosis of patients with AS. They contain anti-TNF-α monoclonal antibodies (golimumab, infliximab, adalimumab, certolizumab) and the soluble TNF-α receptor (etanercept). Hip and knee involvement is common in patients with AS, as evidenced in radiographs as bone erosion and joint space narrowing. The patient may have severe pain, stiffness, and loss of mobility, and the treatment involves surgery for joint arthroplasty. We present the case of a 63-year-old patient with axial spondyloarthritis who was treated with infliximab and developed cerebral tuberculosis after three years of biological therapy. The purpose of the study is to determine the possibility of resuming biological therapy at the time of AS reactivation, given the long-term treatment and adverse reactions of cortisone therapy (aseptic necrosis of the femoral head).

Techniques to aid prediction of pacing dependence at 30 days in patients requiring pacemaker implantation after cardiac surgery.

Permanent pacemaker (PPM) implantation occurs in up to 5 % of patients after cardiac surgery but there is little consensus on how long to wait between surgery and PPM insertion. Predicting the likelihood of a patient being pacing dependent 30 days after implant can aid with this timing decision and avoid unnecessary observation time waiting for intrinsic conduction to recover. In this paper, we introduce a new approach for the prediction of PPM dependency at 30 days after implant in patients who have undergone recent cardiac surgery. The aim is to create an automatic detection model able to support clinicians in the decision-making process. We first applied Synthetic Minority Oversampling Technique (SMOTE) and Bayesian Networks (BN) to the dataset, to balance the inherently imbalanced data and create additional synthetic data respectively. The six resultant datasets were then used to train four different classifiers to predict pacing dependence at 30 days, all using the same testing set. The Bagged Trees classifier achieved the best results, reaching an area under the receiver operating curve (AUC) of 90 % in the train phase, and 83 % in the test phase. The overall classification performance was clearly enhanced when using SMOTE and synthetic data created with BN to create a combined and balanced dataset. This technique could be of great use in answering clinical questions where the original dataset is imbalanced.

Musculoskeletal adverse reactions after immunotherapy for cancer: A case series.

Immunotherapy has revolutionized cancer treatment. Immune checkpoint inhibitors (ICIs) including antibodies targeting cytotoxic T lymphocyte associated antigen-4 and programmed cell death 1 have been shown to be effective in the treatment of certain types of cancer. The benefit of these therapies is to prolong life expectancy in the case of metastatic malignancies. Rheumatic adverse events are not very common. In the present study, 9 patients were monitored between November 2018 and January 2020. The oncologist, who identified the occurrence of rheumatic toxicities after the treatment with ICIs, evaluated the patients. Only oncological patients with rheumatic manifestations after the start of immunotherapy were included. Toxicity grading was performed by both the oncologist and the rheumatologist, on a scale from 1 to 5 (1, mild; 2, moderate; 3, severe; 4, life-threatening; 5, death related to toxicity). The results showed that rheumatoid factor, which was sampled in each patient, was negative in all cases. Patients were treated with nonsteroidal anti-inflammatory drugs or prednisone depending on the severity of the adverse events. The results varied with the severity of the adverse events. In conclusion, as the number of patients treated with ICIs increases, so will the number of patients presenting with immune-related adverse events (irAEs). The collaboration between oncologists and rheumatologists should be intimate to provide optimal treatment to patients. Musculoskeletal manifestations secondary to ICIs are slightly different from other rheumatologically conditions making diagnosis, treatment and monitoring difficult. Thus, irAEs are new and challenging for oncologists, thus understanding of the pathogenesis and clinical characteristics must be improved for better treatment guidelines.

Left Ventricular Diastolic Dysfunction in Type 2 Diabetes-Progress and Perspectives.

In-depth understanding of early cardiovascular manifestations in diabetes is high on international research and prevention agendas given that cardiovascular events are the leading cause of death for diabetic patients. Our aim was to review recent developments in the echocardiographic assessment of left ventricular diastolic dysfunction (LVDD) as a telltale pre-clinical disturbance preceding diabetic cardiomyopathy. We analyzed papers in which patients had been comprehensively assessed echocardiographically according to the latest LVDD guidelines (2016), and those affording comparisons with previous, widely used recommendations (2009). We found that the updated algorithm for LVDD is more effective in predicting adverse cardiovascular events in patients with established LVDD, and less specific in grading other patients (labelled "indeterminate"). This may prove instrumental for recruiting "indeterminate" LVDD cases among patients with type 2 diabetes mellitus (T2DM) in future screening programs. As an interesting consideration, the elevated values of the index E/e' can point to early diastolic impairment, foretelling diabetic cardiomyopathy. Identifying subclinical signs early makes clinical sense, but the complex nature of T2DM calls for further research. Specifically, longitudinal studies on rigorously selected cohorts of diabetic patients are needed to better understand and predict the subtle, slow onset of cardiac manifestations with T2DM as a complicating backdrop.