Mineralocorticoid receptor antagonists and atrial fibrillation: a meta-analysis of clinical trials.

BACKGROUND AND AIMS: Mineralocorticoid receptor antagonists (MRAs) improve cardiovascular outcomes in a variety of settings. This study aimed to assess whether cardioprotective effects of MRAs are modified by heart failure (HF) and atrial fibrillation (AF) status and to study their impact on AF events. METHODS: MEDLINE, Embase, and Cochrane Central databases were searched to 24 March 2023 for randomized controlled trials evaluating the efficacy of MRAs as compared with placebo or usual care in reducing cardiovascular outcomes and AF events in patients with or at risk for cardiovascular diseases. Random-effects models and interaction analyses were used to test for effect modification. RESULTS: Meta-analysis of seven trials (20 741 participants, mean age: 65.6 years, 32% women) showed that the efficacy of MRAs, as compared with placebo, in reducing a composite of cardiovascular death or HF hospitalization remains consistent across patients with HF [risk ratio = 0.81; 95% confidence interval (CI): 0.67-0.98] and without HF (risk ratio = 0.84; 95% CI: 0.75-0.93; interaction P = .77). Among patients with HF, MRAs reduced cardiovascular death or HF hospitalization in patients with AF (hazard ratio = 0.95; 95% CI: 0.54-1.66) to a similar extent as in those without AF (hazard ratio = 0.82; 95% CI: 0.63-1.07; interaction P = .65). Pooled data from 20 trials (21 791 participants, mean age: 65.2 years, 31.3% women) showed that MRAs reduce AF events (risk ratio = 0.76; 95% CI: 0.67-0.87) in both patients with and without prior AF. CONCLUSIONS: Mineralocorticoid receptor antagonists are similarly effective in preventing cardiovascular events in patients with and without HF and most likely retain their efficacy regardless of AF status. Mineralocorticoid receptor antagonists may also be moderately effective in preventing incident or recurrent AF events.

Surgical items retained in the abdominal cavity in diagnostic imaging tests: a series of 10 cases and literature review.

Despite improvements in the safety of surgical procedures, leaving a foreign object in a patient's body is still one of the complications of surgical procedures. The literature lacks an analysis of the effectiveness of specific diagnostic tests in detecting foreign objects. The authors present a discussion of the effectiveness of selected techniques and examples of the appearance of foreign bodies in radiological images based on the description of 10 cases. Leaving surgical haemostatic material in the abdominal or pelvic cavity is an underestimated phenomenon that poses a serious diagnostic problem. Computed tomography is the most sensitive method for detecting a foreign body, while a chest or abdominal X-ray is the simplest and most effective way to identify the surgical material. Ultrasound, although widely available, has not shown utility in diagnosing foreign bodies in our cases. Awareness of this problem is necessary to avoid unnecessary mortality in surgical patients.

Lung clearance index predicts persistence of preschool wheeze.

BACKGROUND: The lung clearance index (LCI) is a measure of pulmonary function. Variable feasibility (50->80%) in preschool children has been reported. There are limited studies exploring its relationship to respiratory symptoms and how it predicts persistent wheeze. We aimed to assess the association with respiratory symptoms in preschool-aged children with LCI and determine its utility in predicting persistent wheeze. METHODS: LCI was measured in a subcohort of the CHILD Cohort Study at age 3 years using SF6  multiple breath washout test mass spectrometry. Respiratory symptom phenotypes at age 3 were derived from children's respiratory symptoms reported by their parents. Responses were used to categorize children into 4 symptom groups: recurrent wheeze (3RW), recurrent cough (3RC), infrequent symptoms (IS), and no current symptoms (NCS). At age 5 years, these children were seen by a specialist clinician and assessed for persistent wheeze (PW). RESULTS: At age 3 years, 69% (234/340) had feasible LCI. Excluding two children with missing data, 232 participants were categorized as follows: 33 (14%) 3RW; 28 (12%) 3RC; 17 (7%) IS; and 154 (66%) NCS. LCI z-score at age 3 years was highest in children with 3RW compared to 3RC (mean (SD): 1.14 (1.56) vs. 0.09 (0.95), p < .01), IS (mean (SD): -0.14 (0.59), p < .01), and NCS (mean (SD): -0.08 (1.06), p < .01). LCI z-score at age 3 was predictive of persistent wheeze at age 5 (PW) (AUROC: 0.87). CONCLUSIONS: LCI at age 3 was strongly associated with recurrent wheeze at age 3, and predictive of its persistence to age 5.

Assessing the feasibility of hyperpolarized 129 Xe multiple-breath washout MRI in pediatric cystic fibrosis.

PURPOSE: To assess the feasibility of hyperpolarized 129 Xe multiple-breath washout MRI in pediatric cystic fibrosis (CF) participants with preserved lung function. Fractional ventilation (r), defined as the fractional gas replacement per breath, was mapped using 2 signal models: (1) constant T1 and (2) variable T1 as a function of the hyperpolarized gas washout. METHODS: A total of 17 pediatric participants were recruited (mean age 11.7 ± 2.8 years), including 7 children with clinically stable CF and 10 aged-matched healthy controls. Pulmonary function tests were performed, including spirometry, to measure the forced expiratory volume in 1 second and nitrogen multiple-breath washout to measure the lung clearance index. Hyperpolarized 129 Xe MRI was performed during consecutive breaths of air following a single 129 Xe inhalation, and fractional ventilation maps were calculated. RESULTS: The forced expiratory volume in 1 second was similar in both groups (P = .32), but there was a statistically significant difference in lung clearance index between healthy and CF participants (P = .001). With variable T1 modeling, CF participants had a mean r of 0.44 ± 0.08 and healthy participants had a mean r of 0.37 ± 0.12 (P = .20). With constant T1 modeling, CF participants had a mean r' of 0.48 ± 0.08, and healthy participants had a mean r' of 0.43 ± 0.12 (P = .32). Therefore, assuming a constant T1 leads to a relative bias in r of 15.1% ± 6.4% and 20.8% ± 7.4% for CF and healthy participants, respectively (P = .12). CONCLUSION: This study demonstrates that hyperpolarized 129 Xe multiple-breath washout imaging is feasible in pediatric participants with CF, and inclusion of variable T1 modeling reduces bias in the fractional ventilation measurements.

Persistent ventilation inhomogeneity after an acute exacerbation in preschool children with recurrent wheezing.

BACKGROUND: Preschool children with recurrent wheezing suffer high morbidity. It is unclear whether objective measures of asthma control, such as pulmonary function tests (PFTs), provide additional information to the clinical assessment. METHODS: We recruited children between 3 and 6 years old, with a history of recurrent wheezing in the preceding year and treated for acute wheezing exacerbation in the emergency department (ED) into an observational cohort study. Children attended two outpatient visits: the first study visit within five days of discharge from the ED and the second study visit 12 weeks after the ED visit. We performed standardized symptom score (test for respiratory and asthma control in kids (TRACK)), multiple breath washout (MBW), spirometry, and clinical assessment at both visits. RESULTS: Seventy-four children, mean (standard deviation (SD)) age of 4.32 years (0.84), attended both visits. Paired FEV0.75 and lung clearance index (LCI) measurements at both time points were obtained in 37 and 34 subjects, respectively. Feasibility for all tests improved at visit 2 and was not age-dependent. At the second study visit, a third had controlled asthma based on the TRACK score, and the mean lung clearance index (LCI) improved from 9.86 to 8.31 (P = .003); however, 46% had an LCI in the abnormal range. FEV0.75 z-score improved from -1.66 to -1.17 (P = .05) but remained in the abnormal range in 24%. LCI was abnormal in more than half of the children with "well-controlled" asthma based on the TRACK score. There was no correlation between PFT measures and TRACK scores at either visit. CONCLUSIONS: Lung clearance index demonstrates a persistent deficit post-exacerbation in a large proportion of preschoolers with recurrent wheezing, highlighting that symptom scores alone may not suffice for monitoring these children.

Ventilation inhomogeneity in infants with recurrent wheezing.

BACKGROUND: The care of infants with recurrent wheezing relies largely on clinical assessment. The lung clearance index (LCI), a measure of ventilation inhomogeneity, is a sensitive marker of early airway disease in children with cystic fibrosis, but its utility has not been explored in infants with recurrent wheezing. OBJECTIVE: To assess ventilation inhomogeneity using LCI among infants with a history of recurrent wheezing compared with healthy controls. METHODS: This is a case-control study, including 37 infants with recurrent wheezing recruited from outpatient clinics, and 113 healthy infants from a longitudinal birth cohort, the Canadian Healthy Infant Longitudinal Development study. All infants, at a time of clinical stability, underwent functional assessment including multiple breath washout, forced expiratory flows and body plethysmography. RESULTS: LCI z-score values among infants with recurrent wheeze were 0.84 units (95% CI 0.41 to 1.26) higher than healthy infants (mean (95% CI): 0.26 (-0.11 to 0.63) vs -0.58 (-0.79 to 0.36), p<0.001)). Nineteen percent of recurrently wheezing infants had LCI values that were above the upper limit of normal (>1.64 z-scores). Elevated exhaled nitric oxide, but not symptoms, was associated with abnormal LCI values in infants with recurrent wheeze (p=0.05). CONCLUSIONS: Ventilation inhomogeneity is present in clinically stable infants with recurrent wheezing.

Pharmacoeconomic evaluation of treatment effectiveness with selected biologic treatment in rheumatoid arthritis therapy.

OBJECTIVES: Modern treatment of autoimmune diseases is becoming increasingly widely used. We owe it to the continuous and rapid development of biotechnology, molecular biology, immunology, and biochemistry. The proven effectiveness of biological therapy in rheumatoid arthritis (RA) should result in its widespread use. At present, only about 1% of patients with RA have access to biological therapy in Poland. MATERIAL AND METHODS: The study material was retrospectively collected in the Rheumatology and Systemic Tissue Diseases Clinic and Rheumatology Outpatient Clinic in dr Jan Biziel University Hospital No. 2 in Bydgoszcz 2009-2014. Patients were divided into 3 groups: patient receiving infliximab, etanercept and adalimumab. RESULTS: The study involved analyses of cost effectiveness. The time horizon of patient documentation analysis ranged from the time a patient was enrolled to infliximab, etanercept or adalimumab therapy until remission of the disease. The majority of patients achieved remission in the case of adalimumab treatment (85.29%), followed by etanercept (74.07%), then infliximab (37.21%). Taking into account the DAS28 parameter, analysis was performed using medical costs of the analyzed treatment regimens. For this purpose, the incremental cost-effectiveness ratio (ICER) was calculated. According to the analysis, obtaining one DAS28 unit, replacing infliximab with etanercept, would cost PLN 40 964 67. Higher costs would be required in the case of replacement of infliximab with adalimumab - PLN 43 076 08. Obtaining one additional DAS28 unit (in this case, a decrease in DAS28 by one unit) by introducing adalimumab instead of etanercept would amount to PLN 45 409 74. CONCLUSIONS: Undoubtedly, the pharmacoeconomic analysis makes it easier to decide on the appropriate treatment. Therefore, its implementation should be a widely used solution not only for RA, but also for other diseases. Health care and other entities' systems should also be improved in such a way that the data needed for pharmacoeconomic analysis are fully available.

Pharmacoeconomic evaluation of costs of rheumatoid arthritis therapy with selected biological treatment.

OBJECTIVES: Among autoimmune diseases, rheumatoid arthritis (RA) is the most common chronic inflammatory disease of the joints. Its pathogenesis is still not fully understood, but the gained knowledge has contributed to the development of modern treatment. The introduction of biological therapy for RA has been a breakthrough in the standard approach to the treatment of this disease. MATERIAL AND METHODS: The study material was retrospectively collected in the Rheumatology and Systemic Tissue Diseases Clinic and Rheumatology Outpatient Clinic in dr. Jan Biziel University Hospital No. 2 in Bydgoszcz. Patients were divided into 3 groups: patients receiving infliximab - 43 patients, etanercept - 27 patients and adalimumab - 34 patients. In the study, the pharmacoeconomic analysis included direct and indirect medical costs. Direct medical costs analyzed in the study included costs for the purchase of medications, diagnostic and imaging costs, and medical consultations and hospitalization costs. The analysis included all direct medical costs incurred by the hospital and the patient, as well as indirect costs outside the healthcare sector - that is, the Polish Social Insurance Institution benefits (disability benefits, rehabilitation benefits, sickness absences). Direct medical costs are also presented from the perspective of the payer - The Polish National Health Fund - taking into account the cost and percentage share of medical expenses. RESULTS: The analysis concerned resources used since the beginning of treatment with a given biological medication for 24 months or earlier if disease remission occurred.A cost-benefit analysis was carried out in the study using biosimilar medications present on the market in relation to the treatment regimens. Considering the total cost, if only Inflectra were used in therapy, PLN 18 151.98 per patient could be saved, and in the case of Remsima, PLN 16 385.14. In less than 19 months, to use infliximab for 43 patients, PLN 780 475.80 more would have to be spent than in the case of the biosimilar medication Inflectra, and PLN 704 561 in the case of Remsima.The highest total cost is generated by treatment with adalimumab, followed by etanercept, and infliximab. Of the costs analyzed, a significant majority was for biological treatment. CONCLUSIONS: Given the Polish financial conditions, the best solution now is to reduce the prices of biological medications. This is possible through the introduction of biosimilar medications that, when placed on the market, reduce the price of the original medication, as is currently the case with Remicade and Enbrel. The introduction of Inflectra and Remsima, as well as Benepali and Erelzi, has reduced the price base of original medications to similar levels of treatment with biosimilar medications. The wider use of biological treatment would also reduce indirect costs.

Atrial Fibrillation Ablation in Heart Failure With Reduced vs Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

Importance: Catheter ablation is associated with reduced heart failure (HF) hospitalization and death in select patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). However, the benefit in patients with HF with preserved ejection fraction (HFpEF) is uncertain. Objective: To investigate whether catheter ablation for AF is associated with reduced HF-related outcomes according to HF phenotype. Data Source: A systematic search of MEDLINE, Embase, and Cochrane Central was conducted among studies published from inception to September 2023. Study Selection: Parallel-group randomized clinical trials (RCTs) comparing catheter ablation with conventional rate or rhythm control therapies in patients with HF, New York Heart Association functional class II or greater, and a history of paroxysmal or persistent AF were included. Pairs of independent reviewers screened 7531 titles and abstracts, of which 12 RCTs and 4 substudies met selection criteria. Data Extraction and Synthesis: Data were abstracted in duplicate according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Pooled effect estimates were calculated using random-effects Mantel-Haenszel models. Interaction P values were used to test for subgroup differences. Main Outcomes and Measures: The primary outcome was HF events, defined as HF hospitalization, clinically significant worsening of HF, or unscheduled visits to a clinician for treatment intensification. Secondary outcomes included cardiovascular and all-cause mortality. Results: A total of 12 RCTs with 2465 participants (mean [SD] age, 65.3 [9.7] years; 658 females [26.7%]) were included; there were 1552 participants with HFrEF and 913 participants with HFpEF. Compared with conventional rate or rhythm control, catheter ablation was associated with reduced risk of HF events in HFrEF (risk ratio [RR], 0.59; 95% CI, 0.48-0.72), while there was no benefit in patients with HFpEF (RR, 0.93; 95% CI, 0.65-1.32) (P for interaction = .03). Catheter ablation was associated with reduced risk of cardiovascular death compared with conventional therapies in HFrEF (RR, 0.49; 95% CI, 0.34-0.70) but a differential association was not detected in HFpEF (RR, 0.91; 95% CI, 0.46-1.79) (P for interaction = .12). Similarly, no difference in the association of catheter ablation with all-cause mortality was found between HFrEF (RR vs conventional therapies, 0.63; 95% CI, 0.47-0.86) and HFpEF (RR vs conventional therapies, 0.95; 95% CI, 0.39-2.30) groups (P for interaction = .39). Conclusions and Relevance: This study found that catheter ablation for AF was associated with reduced risk of HF events in patients with HFrEF but had limited or no benefit in HFpEF. Results from ongoing trials may further elucidate the role of catheter ablation for AF in HFpEF.

Spermatic vein thrombosis as a rare cause of testicular pain - review of the literature.

Introduction: The authors in this paper discuss a rare disease entity that can cause testicular pain and mimic varicocele. Material and methods: Citing data from a review of the world literature, spermatic cord thrombosis is most often misdiagnosed as an incarcerated inguinal hernia. Patients usually complain of pain and swelling of the testicle, pain in the inguinal region, and sometimes a palpable mass in the inguinal region. Results: Ultrasonography with colour Doppler usually establishes the correct diagnosis. Currently, there are no official recommendations for the treatment of this disease.There are reports of conservative treatment of spermatic cord thrombosis in the world literature. However, it seems that the gold standard of management remains surgical exploration, which allows us to unequivocally establish the correct diagnosis. In cases of co-morbid thrombosis with spermatic cord varicocelectomy is recommended. Conclusions: Due to the rarity of this disease, the topic of this article was undertaken. The paper reviews the world literature relating to the diagnosis and treatment of this disease entity. Our own algorithm for the management of spermatic cord thrombosis is proposed.

Operative material left in the abdominal cavity during surgical procedures.

The authors present seven cases of surgical drape left in body cavities during surgical operations. The most common symptoms reported by these patients are analysed and the consequences of leaving a foreign body in the abdominal cavity are summarised. In the majority of cases, the time elapsed from the operation to the detection of the foreign body was an average of 17 months. In one case, the foreign body remained in the abdomen for 7 years. The most common symptom reported by patients was abdominal pain. Some patients also developed wound healing disorders with leakage of pus from the wound, fever, nausea and vomiting, weight loss or intermittent tarry stools. In most cases, the foreign body required reoperation to remove it. Major surgery with stoma creation or bowel resection was required. In one case described, the consequence of leaving a surgical drape was the death of the patient. In three cases, there was spontaneous expulsion of the surgical sling by the patient by natural means.

Newly developed multiple-breath washout reference equations from the CHILD Cohort Study: implications of poorly fitting equations.

Using inappropriate reference equations would provide incorrect estimate of z-scores, which would cause misdiagnosis. Appropriate representative normative reference data must be available to correctly interpret individual lung function results. https://bit.ly/3dcNZ5p.

Lung clearance index is elevated in young children with symptom-controlled asthma.

BACKGROUND: Pulmonary function testing has been recommended as an adjunct to symptom monitoring for assessment of asthma control. Lung clearance index (LCI) measures ventilation inhomogeneity and is thought to represent changes in the small airways. It has been proposed as a useful early marker of airway disease in asthmatic subjects, and determining it is feasible in preschool children. This study aims to assess whether LCI remains elevated in symptomatically controlled asthmatic children with a history of severe asthma, compared with healthy controls. A secondary aim was to determine whether the results were consistent across the preschool and school-aged populations. METHODS: Using a case-control design, we compared 33 children with currently well-controlled symptoms who had a history of severe asthma, to 45 healthy controls (age 3-15 years) matched by age, height, and sex. We performed multiple breath washout tests using sulfur hexafluoride as a tracer gas, to determine their LCI and Scond values. RESULTS: In the overall study, LCI z-score values were on average 0.86 units (95% confidence interval: 0.24-1.47, P = 0.01, t-test) higher in children with a history of severe asthma with current well-controlled symptoms compared with healthy controls. In addition, within the subgroup of preschool children (age ≤ 6), the asthmatic had significantly higher LCI z-score values than their healthy controls peers (mean (SD), 0.57 (2.18) vs -1.10 (1.00), P = 0.03, t-test). Twenty-seven percent (27%; 9/33) of subjects had an LCI value greater than the upper limit of our healthy controls despite being symptom controlled. Amongst preschool children, 5 (42%; 5/12) of the asthmatic children had abnormal LCI at the individual level. CONCLUSIONS: LCI is elevated in children with asthma, which may be driven by differences in the preschool population. LCI may be useful in defining preschool asthma endotypes with persistent ventilation inhomogeneity despite symptomatic control.

Reference equations for the interpretation of forced expiratory and plethysmographic measurements in infants.

BACKGROUND: Pulmonary function testing is commonly performed for diagnosis and clinical management of respiratory diseases. It is important to use appropriate reference equations from healthy subjects for interpretation of data from infants with lung disease. This study aimed to determine if published reference equations were similar to forced flow measures and plethysmographic infant pulmonary function testing data collected in the Canadian Healthy Infant Longitudinal Development (CHILD) Study. METHODS: Reference equations for five pulmonary function variables (FEV0.5 , FVC, FEF25-75 , FEV0.5 /FVC ratio and plethysmography (FRCpleth )) were developed using data from the nSpire system. New reference equations developed using healthy data from the CHILD Study were compared to previously published reference equations for forced flow and plethysmographic measures. RESULTS: The current analysis included 131 infants (on 181 test occasions) with forced flow measures and 161 infants (on 246 test occasions) with plethysmography measures, aged 3-24 months. Age and length were major determinants of both forced flow and plethysmography measures. In addition, ethnicity (Caucasian vs non-Caucasian) was significantly associated with FEV0.5 /FVC and FEF25-75 measures. We found that the published reference equations based on custom-built equipment or commercially available systems provided poor fit to our current pulmonary function testing data, resulting in placing a large proportion of our healthy population outside the normal ranges. CONCLUSIONS: Our current data support the need for population and device specific reference data for infant pulmonary function studies. By deriving new equipment-specific reference equations for our healthy population, we provide normative data to other centers utilizing this equipment.

Changes in multiple breath washout measures after raised volume rapid thoracoabdominal compression maneuvers in infants.

Multiple breath inert gas washout (MBW) measurements in infants are performed supine and often obtained under sedation and thus are combined with other lung function tests such as raised volume rapid thoracoabdominal compression (RVRTC). In this study, we sought to determine the effects of RVRTC maneuvers on MBW measures. Compared with tests performed prior to RVRTC, MBW measured after RVRTC was associated with a small reduction in functional residual capacity and a more pronounced decrease in cumulative expired volume in both healthy children and children with obstructive lung disease (cystic fibrosis or recurrent wheeze) indicating a more efficient washout after the raised volume maneuvers. Lung Clearance Index (LCI) decreased significantly in infants with respiratory disease (change in LCI of -0.24 units post RVRTC; standard error (SE) ± 0.07 units; P = 0.0004), but not in healthy infants (change in LCI of -0.08 units; SE ± 0.11 units; P = 0.44). As the RVRTC maneuver affects MBW measurements in infants, the timing of testing procedures needs to be standardized in longitudinal studies.