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Bioengineering (Basel, Switzerland) May 2024This work introduces Spiromni, a single device incorporating three different pressurised metered-dose inhaler (pMDI) accessories: a pMDI spacer, an electronic monitoring...
This work introduces Spiromni, a single device incorporating three different pressurised metered-dose inhaler (pMDI) accessories: a pMDI spacer, an electronic monitoring device (EMD), and a spirometer. While there are devices made to individually address the issues of technique, adherence and monitoring, respectively, for asthma patients as laid out in the Global Initiative for Asthma's (GINA) global strategy for asthma management and prevention, Spiromni was designed to address all three issues using a single, combination device. Spiromni addresses the key challenge of measuring both inhalation and exhalation profiles, which are different by an order of magnitude. Moreover, the innovative design prevents exhalation from entering the spacer chamber and prevents medication loss during inhalation using umbrella valves without a loss in flow velocity. Apart from recording the peak exhalation flow rate, data from the sensors allow us to extract other key lung volume and capacities measures similar to a medical pulmonary function test. We believe this low-cost portable multi-functional device will benefit both asthma patients and clinicians in the management of the disease.
PubMed: 38927788
DOI: 10.3390/bioengineering11060552 -
Biomedicines Jun 2024The immune system's amplified response to SARS-CoV-2 may lead to the production of autoantibodies, but their specific impact on disease severity and outcome remains...
The immune system's amplified response to SARS-CoV-2 may lead to the production of autoantibodies, but their specific impact on disease severity and outcome remains unclear. This study aims to assess if hospitalized COVID-19 patients face a worse prognosis based on ANA presence, even without autoimmune diseases. We performed a retrospective, single-center, observational cohort study, enrolling 638 COVID-19 patients hospitalized from April 2020 to March 2021 at Hospital "Policlinico Riuniti" of Foggia (Italy). COVID-19 patients with a positive ANA test exhibited a significantly lower 30-day survival rate (64.4% vs. 83.0%) and a higher likelihood of severe respiratory complications during hospitalization than those with negative ANA screening (35.4% vs. 17.0%) ( < 0.001). The association between poor prognosis and ANA status was identified by calculating the HALP score (Hemoglobin-Albumin-Lymphocyte-Platelet), which was lower in COVID-19 patients with a positive ANA test compared to ANA-negative patients (108.1 ± 7.4 vs. 218.6 ± 11.2 AU; < 0.011). In detail, COVID-19 patients with a low HALP showed a lower 30-day survival rate (99.1% vs. 83.6% vs. 55.2% for high, medium, and low HALP, respectively; < 0.001) and a higher incidence of adverse respiratory events compared to those with high and medium HALP (13.1% vs. 35.2% vs. 64.6% for high, medium, and low HALP, respectively; < 0.001). In summary, ANA positivity in COVID-19 patients appears to be linked to a more aggressive disease phenotype with a reduced survival rate. Furthermore, we propose that the HALP score could serve as a valuable parameter to assess prognosis for COVID-19 patients.
PubMed: 38927513
DOI: 10.3390/biomedicines12061306 -
Biomedicines Jun 2024DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people...
BACKGROUND
DNA methylation may be a link between HIV, aging, and the increased risk of lung comorbidities. We investigated whether bronchoalveolar lavage (BAL) cells of people living with HIV (PLWH) demonstrate epigenetic disruptions and advanced epigenetic aging.
METHODS
BAL cell DNA methylation from 25 PLWH and 16 HIV-uninfected individuals were tested for differential methylation of Alu and LINE-1 sites, markers of aging. We used a weighted gene correlation network analysis to identify HIV- and age-associated co-methylation networks. We tested the effect of HIV on DNA methylation using a robust linear model (false discovery rate < 0.10).
RESULTS
The BAL cells of PLWH were marked by global hypomethylation in both Alu and LINE-1 elements. Six co-methylated CpG networks were identified that were significantly associated with age; of these, the red module was significantly differentially methylated in PLWH and enriched pathways (e.g., Ras signaling and T-cell receptors). We identified 6428 CpG sites associated with HIV.
CONCLUSIONS
We have shown here for the first time that alterations in the DNA methylation of BAL cells in the lung with HIV show a pattern of advanced aging. This study strongly supports that HIV may contribute to an increased the risk of lung comorbidities through the epigenetics of aging.
PubMed: 38927468
DOI: 10.3390/biomedicines12061261 -
Antibiotics (Basel, Switzerland) May 2024This paper aimed to evaluate the effects of the COVID-19 pandemic on prescription rates and antibiotic resistance in a university hospital. A retrospective study was...
This paper aimed to evaluate the effects of the COVID-19 pandemic on prescription rates and antibiotic resistance in a university hospital. A retrospective study was conducted on the medical records of patients admitted to the Bihor Emergency Clinical County Hospital in Romania in 2019 (pre-pandemic) and 2021 (during the pandemic period). We evaluated the antibiotic consumption index (ACI) and susceptibility rates. The overall percentage of antibiotic prescribing increased in 2021, while the total number of patients decreased. Genito-urinary, digestive, respiratory infections, heart diseases and wounds were the most common conditions for antibiotic prescriptions, but the number of them decreased in 2021. There was a decrease in the proportion of antibiotics from the Watch and Reserve class and an increase in the proportion of antibiotics from the Access class. Antibiotic use has been reduced despite an increase in the number of patients, with a high consumption in the Watch group in the ICU wards. By contrast, surgical wards had the highest rate of antibiotic prescriptions, but a decrease in the number of patients. The patients who were administered antibiotics were hospitalized for diagnoses other than COVID-19. Almost all prescribed antibiotics displayed decreasing sensitivity rates. The number of isolated ESKAPE pathogens, except for methicillin-resistant strains, were increased. Strategies to control antibiotic prescriptions and the spread of resistant pathogens should be improved.
PubMed: 38927144
DOI: 10.3390/antibiotics13060477 -
BMC Pulmonary Medicine Jun 2024Sedation during flexible bronchoscopy (FB) should maintain an adequate respiratory drive, ensure maximum comfort for the patient, and warrant that the objectives of the... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
Dexmedetomidine-ketamine combination versus fentanyl-midazolam for patient sedation during flexible bronchoscopy: a prospective, single-blind, randomized controlled trial.
BACKGROUND
Sedation during flexible bronchoscopy (FB) should maintain an adequate respiratory drive, ensure maximum comfort for the patient, and warrant that the objectives of the procedure are achieved. Nevertheless, the optimal sedation method for FB has yet to be established. This study aimed to compare the standard recommended combination of midazolam-fentanyl (MF) with that of dexmedetomidine-ketamine (DK) for patient sedation during FB.
METHODS
Patients subjected to FB were randomly assigned to a DK (n = 25) and an MF group (n = 25). The primary outcome was the rate of critical desaturation events (arterial oxygen saturation < 80% with nasal oxygen supply 2 L/min). Secondary outcomes included sedation depth, hemodynamic complications, adverse events, and patient and bronchoscopist satisfaction.
RESULTS
The incidence rates of critical desaturation events were similar between the two groups (DK: 12% vs. MF: 28%, p = 0.289). DK achieved deeper maximum sedation levels (higher Ramsay - lower Riker scale; p < 0.001) and was associated with longer recovery times (p < 0.001). Both groups had comparable rates of hemodynamic and other complications. Patient satisfaction was similar between the two groups, but bronchoscopist satisfaction was higher with the DK combination (p = 0.033).
CONCLUSION
DK demonstrated a good safety profile in patients subjected to FB and achieved more profound sedation and better bronchoscopist satisfaction than the standard MF combination without increasing the rate of adverse events.
Topics: Humans; Dexmedetomidine; Bronchoscopy; Fentanyl; Male; Midazolam; Ketamine; Female; Middle Aged; Prospective Studies; Hypnotics and Sedatives; Single-Blind Method; Aged; Patient Satisfaction; Adult; Conscious Sedation
PubMed: 38926768
DOI: 10.1186/s12890-024-02988-w -
BMC Pulmonary Medicine Jun 2024This study aims to construct a model predicting the probability of RF in AECOPD patients upon hospital admission.
BACKGROUND
This study aims to construct a model predicting the probability of RF in AECOPD patients upon hospital admission.
METHODS
This study retrospectively extracted data from MIMIC-IV database, ultimately including 3776 AECOPD patients. The patients were randomly divided into a training set (n = 2643) and a validation set (n = 1133) in a 7:3 ratio. First, LASSO regression analysis was used to optimize variable selection by running a tenfold k-cyclic coordinate descent. Subsequently, a multifactorial Cox regression analysis was employed to establish a predictive model. Thirdly, the model was validated using ROC curves, Harrell's C-index, calibration plots, DCA, and K-M curve.
RESULT
Eight predictive indicators were selected, including blood urea nitrogen, prothrombin time, white blood cell count, heart rate, the presence of comorbid interstitial lung disease, heart failure, and the use of antibiotics and bronchodilators. The model constructed with these 8 predictors demonstrated good predictive capabilities, with ROC curve areas under the curve (AUC) of 0.858 (0.836-0.881), 0.773 (0.746-0.799), 0.736 (0.701-0.771) within 3, 7, and 14 days in the training set, respectively and the C-index was 0.743 (0.723-0.763). Additionally, calibration plots indicated strong consistency between predicted and observed values. DCA analysis demonstrated favorable clinical utility. The K-M curve indicated the model's good reliability, revealed a significantly higher RF occurrence probability in the high-risk group than that in the low-risk group (P < 0.0001).
CONCLUSION
The nomogram can provide valuable guidance for clinical practitioners to early predict the probability of RF occurrence in AECOPD patients, take relevant measures, prevent RF, and improve patient outcomes.
Topics: Humans; Male; Female; Retrospective Studies; Aged; Intensive Care Units; Middle Aged; Databases, Factual; ROC Curve; Risk Assessment; Aged, 80 and over; Nomograms; Risk Factors; Pulmonary Disease, Chronic Obstructive
PubMed: 38926685
DOI: 10.1186/s12890-024-03099-2 -
Epilepsy & Behavior : E&B Jun 2024Seizures are characterized by periictal autonomic changes. Wearable devices could help improve our understanding of these phenomena through long-term monitoring. In this...
PURPOSE
Seizures are characterized by periictal autonomic changes. Wearable devices could help improve our understanding of these phenomena through long-term monitoring. In this study, we used wearable electrocardiogram (ECG) data to evaluate differences between temporal and extratemporal focal impaired awareness (FIA) seizures monitored in the hospital and at home. We assessed periictal heart rate, respiratory rate, heart rate variability (HRV), and respiratory sinus arrhythmia (RSA).
METHODS
We extracted ECG signals across three time points - five minutes baseline and preictal, ten minutes postictal - and the seizure duration. After automatic Rpeak selection, we calculated the heart rate and estimated the respiratory rate using the ECG-derived respiration methodology. HRV was calculated in both time and frequency domains. To evaluate the influence of other modulators on the HRV after removing the respiratory influences, we recalculated the residual power in the high-frequency (HF) and low-frequency (LF) bands using orthogonal subspace projections. Finally, 5-minute and 30-second (ultra-short) ECG segments were used to calculate RSA using three different methods. Seizures from temporal and extratemporal origins were compared using mixed-effects models and estimated marginal means.
RESULTS
The mean preictal heart rate was 69.95 bpm (95 % CI 65.6 - 74.3), and it increased to 82 bpm, 95 % CI (77.51 - 86.47) and 84.11 bpm, 95 % CI (76.9 - 89.5) during the ictal and postictal periods. Preictal, ictal and postictal respiratory rates were 16.1 (95 % CI 15.2 - 17.1), 14.8 (95 % CI 13.4 - 16.2) and 15.1 (95 % CI 14 - 16.2), showing not statistically significant bradypnea. HRV analysis found a higher baseline power in the LF band, which was still significantly higher after removing the respiratory influences. Postictally, we found decreased power in the HF band and the respiratory influences in both frequency bands. The RSA analysis with the new methods confirmed the lower cardiorespiratory interaction during the postictal period. Additionally, using ultra-short ECG segments, we found that RSA decreases before the electroclinical seizure onset. No differences were observed in the studied parameters between temporal and extratemporal seizures.
CONCLUSIONS
We found significant increases in the ictal and postictal heart rates and lower respiratory rates. Isolating the respiratory influences on the HRV showed a postictal reduction of respiratory modulations on both LF and HF bands, suggesting a central role of respiratory influences in the periictal HRV, unlike the baseline measurements. We found a reduced cardiorespiratory interaction during the periictal period using other RSA methods, suggesting a blockade in vagal efferences before the electroclinical onset. These findings highlight the importance of respiratory influences in cardiac dynamics during seizures and emphasize the need to longitudinally assess HRV and RSA to gain insights into long-term autonomic dysregulation.
PubMed: 38924968
DOI: 10.1016/j.yebeh.2024.109917 -
Thoracic Cancer Jun 2024We present the case of a 34-year-old Japanese man with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer and brain metastases. After central nervous...
Successful intracranial response of lorlatinib after resistance with alectinib and brigatinib in patients with ALK-positive lung adenocarcinoma: Implications of CNS penetration rate of brigatinib.
We present the case of a 34-year-old Japanese man with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer and brain metastases. After central nervous system (CNS) disease progression with alecintib and brigatinib, treatment with lorlatinib resulted in a good intracranial response. In this case, we investigated brain penetration ratio of brigatinib using cerebrospinal fluid and paired serum samples, and the ratio was 0.012. Further, we investigated resistance mechanisms via next-generation sequencing (NGS) using lung biopsy at lung cancer diagnosis and brain biopsy sample at progressive disease of brigatinib. No apparent resistance mechanism of known ALK resistance, such as ALK mutations, amplifications, epithelial-mesenchymal transition (EMT) and bypass pathway activation were detected. Taken together, we speculate that the low CNS penetration rate of brigatinib confers CNS progression. Further studies are warranted to reveal the resistance mechanism and propose a treatment strategy for CNS progression in ALK-positive patients.
PubMed: 38924375
DOI: 10.1111/1759-7714.15395 -
Immunity, Inflammation and Disease Jun 2024The ongoing outbreak of the respiratory disease coronavirus disease 2019 (COVID-19) is currently presenting a major global health threat. This pandemic is unprecedented...
OBJECTIVE
The ongoing outbreak of the respiratory disease coronavirus disease 2019 (COVID-19) is currently presenting a major global health threat. This pandemic is unprecedented in recent human history. The objective of this study was to examine the relationship between cycle quantitation (Cq) and laboratory parameters in COVID-19 patients, aiming to determine if Cq levels can provide valuable insights into the COVID-19 disease.
METHODS
This study involved 234 participants who were divided into case and control groups. Real-time PCR tests were used to diagnose COVID-19 cases in the study participants. Blood tests, including complete blood count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), D-dimer, IgG, and IgM, were also conducted. Statistical analysis was performed using SPSS 22 software.
RESULTS
The findings showed that COVID-19-positive cases had significantly higher levels of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), D-dimer, ESR, CRP, and LDH compared to normal cases. Additionally, the case group had significantly lower lymphocyte and platelet counts. There was a statistically significant positive correlation between Cq levels and lymphocyte count (r = .124, p = .014). Conversely, there was a statistically significant inverse correlation between Cq levels and NLR (r = -.208, p = .017). Furthermore, the evaluation of hematological, inflammatory, and biochemical indexes in COVID-19 patients using the receiver-operating characteristics curve demonstrated statistically appropriate sensitivity and specificity.
CONCLUSION
Our outcomes indicated a significant association between Cq levels and PLR, NLR, D-dimer, CRP, and ESR in COVID-19 patients. Consequently, including the report of laboratory parameters alongside Cq values offers a promising prognosis.
Topics: Humans; COVID-19; Male; Female; Middle Aged; SARS-CoV-2; Adult; C-Reactive Protein; Fibrin Fibrinogen Degradation Products; Blood Sedimentation; Aged; Neutrophils; Platelet Count; L-Lactate Dehydrogenase; Case-Control Studies; Lymphocytes
PubMed: 38923849
DOI: 10.1002/iid3.1326 -
ESC Heart Failure Jun 2024Diagnosing acute heart failure (AHF) remains particularly challenging in older patients. Natriuretic peptides are recommended as valuable diagnostic tools in this...
AIMS
Diagnosing acute heart failure (AHF) remains particularly challenging in older patients. Natriuretic peptides are recommended as valuable diagnostic tools in this context. This study aims to establish the diagnostic thresholds of B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for AHF in patients aged over 75 years, both with and without co-morbidities.
METHODS AND RESULTS
In this retrospective longitudinal multicentre cohort study, data were gathered from 12 071 hospitalized patients aged 75 years or older, presenting with acute dyspnoea and undergoing BNP or NT-proBNP measurement within 48 h of admission across 10 Assistance Publique-Hôpitaux de Paris facilities between 2011 and 2022, encompassing geriatrics, cardiology, and pulmonology departments. Final diagnoses were categorized using ICD-10 criteria as either AHF or other acute respiratory conditions such as COPD exacerbation, pulmonary embolism, and pneumonia. The mean (SD) age of the population was 84.0 (80.0, 89.0) years, with 52.7% being female. Out of these, 7946 (65.8%) were diagnosed with AHF upon discharge. For NT-proBNP, the identified 'optimal' threshold for diagnosing AHF was 1748 ng/L, with a positive predictive value (PPV) of 84%. Among patients aged over 85 years, a threshold of 2235 pg/mL for NT-proBNP was associated with an 84% PPV. In patients with atrial fibrillation (AF), a threshold of 2332 pg/mL for NT-proBNP demonstrated a PPV of 90% for AHF diagnosis. Additionally, in patients with an estimated glomerular filtration rate (eGFR) < 30 mL/min, a threshold of 3474 pg/mL for NT-proBNP yielded a 90% PPV for AHF diagnosis. In male patients, a threshold of 1800 pg/mL showed an 85% PPV for AHF diagnosis, while in patients with obesity, a threshold of 1375 pg/mL demonstrated an 85% PPV for AHF diagnosis.
CONCLUSIONS
In older patients, we found significant effects of co-morbidities on natriuretic peptides results, particularly in patients over 85 years old, older patients with abnormal renal function, obesity, and atrial fibrillation. Despite the consideration of those co-morbid conditions, NT-proBNP and BNP level continue to demonstrate utility in the diagnosis of AHF in older patients.
PubMed: 38923835
DOI: 10.1002/ehf2.14894