Single-center Prospective Observational Study Research Articles

Predictors of quality of life, economic impact, and loss to follow-up after open tibial shaft fractures in Ghana.

Open tibia fractures are associated with substantial morbidity and impact on quality of life. Despite increasing incidence in low-resource settings, most open tibia fracture research comes from high-resource settings. This study aimed to assess the impact of socioeconomic status on treatment modality and evaluate predictors of health-related quality of life following open tibia fractures in Ghana. A single-center prospective observational study was conducted in Kumasi, Ghana, from May 2020 to April 2022. Adults with open tibial shaft fractures presenting within 2 weeks of injury were eligible. Demographics, comorbidities, socioeconomic factors, and hospital course were collected at enrollment. Follow-up was scheduled at 8, 12, 26, and 52 weeks. A telephone survey assessing reasons for loss to follow-up was initiated on enrollment completion. A total of 180 patients were enrolled. Most patients were employed before injury (79.9%), had government insurance (67.2%), and were from rural areas (59.4%). Fracture classification was primarily Gustilo-Anderson type 3A (49.1%). No relationship between socioeconomic predictors and treatment modality was identified. The largest barriers to follow-up were preference for bonesetter treatment (63.1%), treatment cost (48.8%), and travel cost (29.8%). Of the lost to follow-up patients contacted, 67 (79.8%) reported receiving traditional bonesetter care. Reasons for seeking traditional bonesetter care included ease of access (83.6%), lower cost (77.6%), and familial influence (50.7%). No association was identified between socioeconomic predictors and choice of treatment. Bonesetter treatment plays a substantial role in the care of open tibia fractures in Ghana, largely because of ease of access and lower cost.

Acute toxicity of hypofractionated radiotherapy for Japanese breast cancer patients after surgery: a single center prospective observational study (HyPORT-BC).

This single center prospective observational study was conducted to evaluate the acute toxicity of hypo-fractionated radiotherapy for Japanese breast cancer patients after surgery. This study recruited patients who were scheduled for moderately hypo-fractionated radiotherapy including supraclavicular lymph node area (Cohort M) or ultra-hypo-fractionated radiotherapy for the conserved breast (Cohort U) as postoperative treatment for breast cancer. Radiotherapy plans were generated using automated planning system. Irradiation of 42.5Gy/16 fractions (Cohort M) or 26Gy/5 fractions (Cohort U) was delivered, and boost irradiation of 10Gy/5 fractions was added as needed. The primary endpoint was the proportion of grade ≥ 2 acute adverse events within 90days. The toxicities were evaluated using CTCAE ver 5.0. Between January 2023 and December 2023, 123 patients (81 in Cohort M and 42 in Cohort U) were enrolled. All the included patients were Japanese and completed their planned radiotherapy and were also able to be evaluated for acute adverse events. Grade 1/2/3-5 acute adverse events were observed in 67/12/0 for Cohort M and 31/4/0 for Cohort U. The proportion of grade ≥ 2 acute adverse events within 90days was 15% (95% confidence interval 8-24%) for Cohort M and 10% (95% confidence interval 3-23%) for Cohort U. The proportion of acute toxicity of hypo-fractionated radiotherapy for Japanese breast cancer patients after surgery was shown to be acceptable in this study.

Factors associated with difficult intravenous access in the paediatric emergency department: A prospective cohort study.

Although it is the most performed invasive procedure, peripheral intravenous catheter (PIVC) insertion in children can be difficult. The primary objective of the study was to identify the factors associated with difficult intravenous access (DIVA) in the paediatric ED, including patient, proceduralist and situational factors. This was a single-centre prospective observational cohort study conducted over 28 consecutive days. Research assistants observed PIVC insertion attempts for children under 16 years of age and recorded data for variables relating to the patient, proceduralist and event. Univariate logistic regression modelling was performed to identify factors associated with DIVA, defined as unsuccessful PIVC insertion on the first attempt. A total of 134 participants were recruited; 66 were male (49%) with a median age of 5.7 years. Fifty-two (39%) were classified as having DIVA. There was a total of 207 PIVC insertion attempts with two or more attempts needed for 48 children (36%). Patient factors associated with DIVA included age of 3 years or less and limited vein options. Proceduralist factors included gestalt of 50% or less chance of success, use of a larger gauge (smaller bore) PIVC and less PIVC insertion experience. Situational factors included a combative child, higher pain score and loud ambient noise. The present study identified multiple patient, proceduralist and situational factors that were associated with DIVA in the paediatric ED. Future studies should explore the development and implementation of a package to address DIVA in children, with the patient-centred goals of reducing pain and improving success.

Clinical Profile of Febrile Neutropenia in Children with Malignancies in a Tertiary Care Hospital: A Prospective Observational Study

Abstract Introduction: Febrile neutropenia is a dreadful complication associated with malignancies. Knowledge of locally prevalent pathogens and their resistance pattern is of paramount importance in guiding antimicrobial therapy. Aims/Objectives: The aim of the study was to identify the common infectious agent, antibiotic susceptibility of culture positive patients, and outcome Methods: We conducted a single-center prospective observational study. Forty-three children with febrile neutropenia episodes admitted in KKCTH, Chennai, were included in the study. The duration of the study was 1 year. Relevant patient and disease specific details were obtained, results were analyzed, and conclusions were drawn. Results: There were 90 episodes of febrile neutropenia. Overall culture positivity was identified in 37 cases (41.11%). Bacteremia (23.3%) was the most common cause of microbiologically documented infection. Gram-positive organisms (60%) were more commonly documented. Among the gram-positive organisms, coagulase-negative Staphylococcus aureus was the predominant isolate followed by Streptococcus. Central line–associated bloodstream infections were documented in 13.33%. Chemo-port removal was done in four children. Three had invasive fungal disease. The majority of the gram-negative isolates were resistant strains. Morbidity was significantly more in gram-negative infections. Overall outcome was good though three children succumbed to sepsis. Conclusion: A vigilant management of illness is essential. Chemo-port carries risk of severe infection. Protocol-based management of catheter-related bloodstream infection (CRBSI) can limit the number of chemo-port removal. Though gram-positive organisms are in the rise, gram-negative organisms are still responsible for significant morbidity. Early initiation of broad-spectrum empirical antibiotics with optimal gram-positive coverage is crucial. Children with suspected fungal infections should be aggressively evaluated and treated. An organized approach is the key in successful management.

Cardiac biomarkers for screening and prognostication of cardiac dysfunction in critically ill patients.

This study aimed to assess the use of high-sensitivity troponin T (hsTNT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in screening for cardiac dysfunction [left ventricular (LV) systolic or diastolic dysfunction or right ventricular (RV) dysfunction] in mixed intensive care unit (ICU) patients and establish whether these biomarkers are independently associated with an increased risk of death. We performed a secondary analysis of a single-centre prospective observational study in which consecutive ICU patients were examined with transthoracic echocardiography (TTE) and cardiac biomarkers. Patients with systolic or diastolic LV dysfunction, RV dysfunction or a combination of these were compared with patients with normal cardiac function. Sensitivity and specificity for different cut-off levels were calculated using receiver operating characteristic curves. Regression models were used to evaluate the associations between cardiac biomarkers, sepsis, renal failure and mortality. A total of 276 patients were included. Most of the patients had cardiac dysfunction on TTE (64%). Combined cardiac dysfunction was most prevalent (71 patients, 26%), followed by isolated diastolic LV dysfunction (40 patients, 15%). Levels of hsTNT and NT-proBNP were higher in all types of cardiac dysfunction versus patients with normal cardiac function. The area under the curve (AUC) for hsTNT to detect any cardiac dysfunction was 0.75. An optimal cut-off at 30.5ng/L rendered a positive predictive value (PPV) of 80% and a negative predictive value (NPV) of 58%. The AUC for NT-proBNP to detect any cardiac dysfunction was 0.788. Using an optimal cut-off at 1145ng/L rendered a PPV of 86% and an NPV of 58%. Using a clinically relevant 90% sensitivity for detecting cardiac dysfunction put the cut-offs at 14.1ng/L for hsTNT and 247ng/L for NT-proBNP, resulting in a specificity of 48% and 46%, respectively. Levels of NT-proBNP were associated with sepsis and renal failure (P<0.001), while levels of hsTNT were associated with renal failure only (P<0.001) after adjustment for cardiac dysfunction. Levels of biomarkers were associated with an increased risk of 90day mortality after adjustments for age, Simplified Acute Physiology Score 3, cardiac dysfunction and factors independently associated with biomarker increase (sepsis and renal failure) (P=0.048 for hsTNT and P<0.006 for NT-proBNP). Cardiac biomarkers, hsTNT and NT-proBNP, are strongly correlated to cardiac dysfunction in ICU patients and have a robust association with increased mortality. However, the relatively low NPV and the low specificity at relevant sensitivity levels of the biomarkers make them unsuitable for use in screening for cardiac dysfunction.

Prevalence, Clinical Features, Treatment, and Outcomes in Patients With Myocardial Infarction With Non-Obstructive Coronary Arteries.

To study clinical and demographic characteristics, treatment options, and clinical outcomes in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) compared with patients with myocardial infarction with obstructive coronary arteries (MIOCA). This single-center prospective observational study included 712 successive patients diagnosed with acute myocardial infarction (MI), who routinely underwent direct coronary angiography. Based on the presence of stenosing coronary atherosclerosis, the patients were divided into two groups: MIOCA (coronary stenosis ≥50%) and MINOCA (coronary stenosis &lt;50% without other, alternative causes). Clinical outcomes included in-hospital and long-term overall mortality, and cardiovascular rehospitalization. The median follow-up was 1.5 years. MINOCA was diagnosed in 73 (10.3%) patients, 37 (50%) of whom were women. The median age of patients with MINOCA was 61 years and in the MIOCA group 65 years. No significant differences in cardiovascular risk factors were found between patients with MINOCA and MIOCA. In 53.4% of cases, the cause of MINOCA was a discrepancy between the myocardial oxygen demand and supply, and in 35.6% of cases, the cause was hypertensive crisis and pulmonary edema. The factors associated with MINOCA included an age ≤58 years, female gender, absence of the ST-segment elevation, absence of areas of impaired local contractility, and presence of aortic stenosis and bronchopulmonary infection. Patients with MINOCA were less likely to be prescribed acetylsalicylic acid, P2Y12 inhibitors, dual antiplatelet therapy, beta-blockers, and statins (p&lt;0.05). Data on long-term outcomes were available for 87.5% of patients (n=623). The prognosis of patients with MIOCA was comparable for in-hospital mortality (1.5% vs. 6.2%; p=0.161) and long-term overall mortality (6.1% vs. 14.7%; p=0.059). Cardiovascular rehospitalizations were more frequent in the MINOCA group (33.3% vs. 21.5%; p=0.042). The prevalence of MINOCA in our study was 10.3% among all patients with acute MI. MINOCA patients had comparable generally recognized cardiovascular risk factors with MIOCA patients. MINOCA patients had a comparable prognosis for in-hospital and long-term mortality and more often required cardiovascular rehospitalization.

Evaluation of nontarget lesions in femoropopliteal disease using near-infrared spectroscopy intravascular ultrasound imaging.

In coronary artery disease (CAD), lipid-core-containing plaque (LCP) in nontarget lesions detected using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) was related to increased major adverse cardiovascular events in patients with CAD. In the endovascular therapy field, few previous studies using NIRS-IVUS revealed the presence of LCPs in severe stenotic lesions of femoropopliteal disease. This study aimed to assess the plaque morphology of nontarget lesions, especially LCPs, and compare it with that of target lesions using NIRS-IVUS in patients with femoropopliteal disease. This single-center prospective observational study included 14 patients who underwent endovascular therapy for FP disease. NIRS-IVUS assessment was performed on the entire FP arterial segment. Forty-one LCP lesions with a maximum lipid-core burden index in any 4-mm region (max LCBI4mm) > 100 were detected using NIRS-IVUS. We evaluated the patient and lesion characteristics. LCP lesions were divided into the target (n = 18) and nontarget (n = 23) lesion groups for comparison. Patient characteristics were notable for advanced age (76.8 ± 6.6 years); high proportion of males (78.7%); and high incidence of hypertension (100%), dyslipidemia (78.6%), diabetes (64.3%). Regarding NIRS findings, the target lesion group exhibited a significantly smaller proportion of LCPs concerning the lesion length (25.9 ± 15.7% vs. 50.6 ± 29.2%, p = 0.002) than the nontarget lesion group. Conversely, there were no significant differences in the value of max LCBI4mm (284.4 ± 153.4 vs. 289.5 ± 113.1, p = 0.90), length of LCP lesion (9.8 ± 9.7 mm vs. 10.7 ± 6.9 mm, p = 0.74), and distribution of LCPs (p = 0.08) between the groups. In addition, the number of LCPs in the target FP artery positively correlated with max LCBI4mm in the target FP artery (r = 0.671, p = 0.008). NIRS-IVUS findings demonstrated the presence of LCPs in nontarget lesions in patients with FP disease. Moreover, the abundance of LCPs in nontarget lesions was similar to that in target lesions in FP disease.

Bioimpedance analysis predicts worsening events in outpatients with heart failure and reduced ejection fraction.

Heart failure (HF) with reduced left ventricle ejection fraction (LVEF) is an entity with poor prognosis characterized by decompensations. Bioelectrical impedance analysis (BIA) is used to assess volume overload (VO) and may be useful to identify apparently stable HF outpatients at risk of decompensation. The aim of this study is to analyse whether VO assessed by BIA is associated with worsening heart failure (WHF) in stable outpatients with HF and reduced LVEF (HFrEF). This is a prospective single-centre observational study. Consecutive stable HF outpatients with LVEF below 40% underwent BIA, transthoracic echocardiography, blood sampling, and physical examination and were followed up for 3months. VO was defined as the difference between the measured weight and the dry weight assessed by BIA. Demographic, clinical, anthropometric, echocardiographic, and analytical parameters were recorded. The primary endpoint was WHF, defined by visits to the emergency department for HF or hospitalization for HF. A total of 100 patients were included. The median VO was 0.5L (interquartile range 0-1.6L). Eleven patients met the primary endpoint. Univariate binary logistic regression analysis showed that left ventricle filling pressures assessed by E/e', N-terminal pro B-type natriuretic peptide, inferior vena cava dilatation (≥21mm), signs of congestion, and VO were associated with the primary endpoint. Binary logistic regression multivariate analysis showed that VO was the only independent predictor for the primary endpoint (adjusted OR 2.7; 95% CI 1.30-5.63, P=0.008). Multivariate Cox regression analysis also showed an adjusted hazard ratio (HR) for VO of 2.03; 95% CI 1.37-3.02, P<0.001. Receiver-operating characteristic curve analysis showed an area under the curve for VO of 0.88 (95% CI 0.79-0.97, P<0.001) with an optimal cut-off of 1.2L. VO assessed by BIA is independently associated with WHF in stable outpatients with HFrEF at 3months.

A smart device application for acute pain service in surgical patients at a tertiary hospital in South Korea: a prospective observational feasibility study.

Pain assessment and patient education are essential for successful postoperative pain management. However, the provision of personnel for performing these tasks is often insufficient. Recently, attempts have been made to implement smartphone applications for educating and monitoring surgical patients. We developed a smartphone application (app) for postoperative pain management, and conducted a feasibility study. This single-center prospective observational study included 60 patients aged < 70 years who underwent elective surgery. This study evaluated the SmartAPS application, which offers tools for postoperative pain assessment and educational materials for pain management. The primary outcome was the active usage rate, defined as responding at least twice daily on postoperative days (PODs) 1 and 2. Additionally, we investigated patient satisfaction with the app and educational videos as well as any challenges encountered during use. Sixty patients were enrolled in the study and active app use was achieved in 56.7% of them. Response rates peaked at 85.0% for pain intensity and 83.3% for opioid-related side effects at 14:00 on POD 1 but dropped to 56.7% and 58.3%, respectively, at 18:00 on POD 2. Among the patients who responded to the survey regarding the app usage, 84.0% reported satisfaction with the app and 80% found it beneficial for managing postoperative pain. Furthermore, 92.0% did not encounter difficulties using the app, indicating a generally positive user experience. Our findings support the utility of the SmartAPS application in acute pain services, highlighting its potential for improving postoperative pain management.

The effect of protein administration during critical illness depends on body composition: A secondary analysis of a prospective, observational study

Background & AimsThe most adequate amount of protein that should be administered to critically ill patients is still debated and diverging findings are recently accumulating. We hypothesized that the effect of protein administration might depend on the amount of muscle mass. MethodsA secondary analysis of a single-centre prospective observational study of body composition in critically ill patients. Mechanically-ventilated subjects with an expected intensive care unit (ICU) stay >72h were enrolled. Within 24h from ICU admission, bioimpedance-derived muscle mass (BIA MM) and rectus femoris cross-sectional area (RF CSA) were measured. The amount of proteins and calories administered on the 7th ICU day was recorded. ResultsWe enrolled 94 subjects (65 males, actual body weight 72.9±14.4 Kg, BMI 26.0±4.8 kg/m2). Actual body weight was only weakly related to BIA MM (R=0.478, p<0.001) and not related to RF CSA (R=0.114, p=0.276). A higher protein intake was associated with a reduced mortality in the highest quartile of BIA MM (OR 0.68 [0.46; 0.99] per each 10g of proteins administered) and in the third (OR 0.74 [0.57; 0.98]) and highest quartile of RF CSA (OR 0.68 [0.48; 0.96]). ConclusionA higher protein intake was associated with lower ICU mortality only in patients admitted with a higher muscle mass, as either assessed by BIA or muscle ultrasound.

Impact of Protein Intake after Intensive Care Unit on Discharge Destination for Critically Ill Patients: A Single-Center Prospective Observational Study.

Although nutritional therapy may be able to enable intensive care unit (ICU) survivors to return home instead of being discharged to a rehabilitation facility, post-ICU discharge nutritional therapy lacks investigation. This study evaluated the impact of nutritional therapy after ICU on discharge destination in critically ill patients. We enrolled consecutive adult patients who spent &gt;72 h in the ICU from December 2020 to March 2023. The primary outcome was discharge destination. Energy and protein intake during the ICU stay and on days 7 and 14 after ICU discharge were evaluated. The target protein intake during the intensive treatment and general ward phases were 0.8 and 1.0 g/kg/day, respectively. Patients were categorized into home discharge (group A) and rehabilitation transfer (group B) groups. Factors affecting the discharge destination were evaluated using logistic regression analysis. Of the 183 patients included, 134 belonged to group A and 49 to group B. In group A, more patients reached the protein intake target than in group B. Logistic regression analysis identified achieving the protein intake target as an independent predictor of home discharge. Further studies are required to confirm the relationship between nutritional therapy during general ward and patient outcomes.

Study of pediatric appendicitis scores and management strategies: A prospective observational feasibility study.

The objective was to investigate the feasibility of prospectively validating multiple clinical prediction scores (CPSs) for pediatric appendicitis in an Australian pediatric emergency department (ED). A literature search was conducted to identify potential CPSs and a single-center prospective observational feasibility study was performed between November 2022 and May 2023 to evaluate the performance of identified CPSs. Children 5-15 years presenting with acute right-sided or generalized abdominal pain and clinician suspicion of appendicitis were included. CPSs were calculated by the study team from prospectively clinician-collected data and/or review of medical records. Accuracy of CPSs were assessed by area under the receiver operating characteristic curve (AUC) and proportions correctly identifiable as either low-risk or high-risk with the best performing CPS compared to clinician gestalt. Final diagnosis of appendicitis was confirmed on histopathology or by telephone/email follow-up for those discharged directly from ED. Thirty CPSs were identified in the literature search and 481 patients were enrolled in the study. A total of 150 (31.2%) patients underwent appendectomy with three (2.0%) having a normal appendix on histopathology. All identified CPSs were calculable for at least 50% of the patient cohort. The pediatric Appendicitis Risk Calculator for pediatric EDs (pARC-ED; n = 317) was the best performing CPS with AUC 0.90 (95% confidence interval [CI] 0.86-0.94) and specificity 99.0% (95% CI 96.4%-99.7%) in diagnosing high-risk cases and a misclassification rate of 4.5% for low-risk cases. The study identified 30 CPSs that could be validated in a majority of patients to compare their ability to assess risk of pediatric appendicitis. The pARC-ED had the highest predictive accuracy and can potentially assist in risk stratification of children with suspected appendicitis in pediatric EDs. A multicenter study is now under way to evaluate the potential of these CPSs in a broader range of EDs to aid clinical decision making in more varied settings.

Cefepime trough levels and clinical outcomes in patients undergoing universal therapeutic drug monitoring: A prospective cohort study

BackgroundCefepime is an essential beta-lactam antibiotic for which therapeutic drug monitoring (TDM) is not performed routinely in many centers. Current literature on cefepime levels consists of retrospective reports of TDM applied selectively by clinicians, i.e., in the setting of suspected toxicity. In an effort to capture and define therapeutic plasma concentration thresholds, this prospective study applied TDM uniformly to consecutive inpatients with suspected or confirmed bacterial infections and observed their ensuing 30-day clinical course. MethodsThis single-center prospective observational study included adult patients hospitalized in the hematology, intermediate- or intensive-care units of Geneva University Hospitals between January 2019 and December 2021. Participants in steady state (receiving cefepime for ≥24 hours) uniformly underwent TDM at least once and thereafter were assessed for the primary and secondary outcomes of occurrence of adverse events and clinical response, respectively, through 30 days. ResultsAmong 151 included patients, 104 had at least one trough level. Most (95/104, 91%) experienced clinical success. Six (6%) experienced an adverse event possibly related to cefepime; no neurotoxicity was observed. Median trough level was 8.5 mg/L (IQR 5.8-13.3); trough levels of those with or without adverse events and those with or without clinical success did not differ significantly. Trough levels increased significantly with renal insufficiency and age. ConclusionCefepime TDM conducted uniformly in hospitalized patients with severe infections reveals lower trough levels than previously reported. Toxicity is rare and clinical effectiveness is high, such that the determination of a strict therapeutic range remains elusive.

Diagnostic accuracy of point-of-care cardiac ultrasound for acute coronary syndromes in patients presenting with chest pain to the emergency department: a single-center prospective study.

The diagnostic accuracy of focused cardiac ultrasound (FoCUS) performed in patients presenting to the emergency department (ED) with chest pain is currently unknown. The objective of this study was to assess the diagnostic accuracy of regional wall motion abnormalities detected with FoCUS for non-ST-elevation acute coronary syndrome (NSTE-ACS) diagnosis. A Single-center prospective observational study conducted in 2022 in the ED of the University Hospital Careggi, Italy. Adult patients presenting to the ED with acute nontraumatic chest pain were enrolled, irrespective of the presence of previous regional wall motion abnormalities. Patients with ST-segment elevation myocardial infarctions and patients with hemodynamic instability were excluded. FoCUS was performed at presentation by a trained ED physician. The final diagnosis of NSTE-ACS vs. alternative diagnosis was adjudicated by an ED physician blinded to FoCUS results after a 30-day follow-up. To assess if regional wall motion abnormalities were an independent predictor of NSTE-ACS, a multivariable logistic regression model was built. Diagnostic performance measures were calculated. A sensitivity analysis considering only type-1 NSTEMIs (i.e. plaque rupture/thrombosis) was conducted. Among 686 patients, NSTE-ACS was adjudicated in 106 (15.5%) patients, 67 of which were NSTEMIs. A total of 87 (12.7%) patients had regional wall motion abnormalities detected by FoCUS, which were an independent predictor of NSTE-ACS in the multivariable logistic regression analysis. Regional wall motion abnormalities had a sensitivity of 42.5% (33.0-51.9), a specificity of 92.8% (90.6-94.9), a negative predictive value of 89.8% (87.4-92.2), and a positive predictive value of 51.7% (41.2-62.2), for NSTE-ACS. Results were consistent in the sensitivity analysis. In ED patients with chest pain and no ST elevation, the detection of regional wall motion abnormalities was a predictor of NSTE-ACS. Despite a high specificity, which indicated a possible role of FoCUS in the rule-in of NSTE-ACS, sensitivity was too low to allow a safe rule-out using FoCUS results alone.

Body mass index is associated with pulmonary gas and blood distribution mismatch in COVID-19 acute respiratory failure. A physiological study.

The effects of obesity on pulmonary gas and blood distribution in patients with acute respiratory failure remain unknown. Dual-energy computed tomography (DECT) is a X-ray-based method used to study regional distribution of gas and blood within the lung. We hypothesized that 1) regional gas/blood mismatch can be quantified by DECT; 2) obesity influences the global and regional distribution of pulmonary gas and blood; 3) regardless of ventilation modality (invasive vs. non-invasive ventilation), patients' body mass index (BMI) has an impact on pulmonary gas/blood mismatch. This single-centre prospective observational study enrolled 118 hypoxic COVID-19 patients (92 male) in need of respiratory support and intensive care who underwent DECT. The cohort was divided into three groups according to BMI: 1. BMI<25kg/m2 (non-obese), 2. BMI = 25-40kg/m2 (overweight to obese), and 3. BMI>40kg/m2 (morbidly obese). Gravitational analysis of Hounsfield unit distribution of gas and blood was derived from DECT and used to calculate regional gas/blood mismatch. A sensitivity analysis was performed to investigate the influence of the chosen ventilatory modality and BMI on gas/blood mismatch and adjust for other possible confounders (i.e., age and sex). 1) Regional pulmonary distribution of gas and blood and their mismatch were quantified using DECT imaging. 2) The BMI>40kg/m2 group had less hyperinflation in the non-dependent regions and more lung collapse in the dependent regions compared to the other BMI groups. In morbidly obese patients, gas and blood were more evenly distributed; therefore, the mismatch was lower than in other patients (30% vs. 36%, p < 0.05). 3) An increase in BMI of 5kg/m2 was associated with a decrease in mismatch of 3.3% (CI: 3.67% to -2.93%, p < 0.05). Neither the ventilatory modality nor age and sex affected the gas/blood mismatch (p > 0.05). 1) In a hypoxic COVID-19 population needing intensive care, pulmonary gas/blood mismatch can be quantified at a global and regional level using DECT. 2) Obesity influences the global and regional distribution of gas and blood within the lung, and BMI>40kg/m2 improves pulmonary gas/blood mismatch. 3) This is true regardless of the ventilatory mode and other possible confounders, i.e., age and sex. Clinicaltrials.gov, identifier NCT04316884, NCT04474249.

Initiation of vedolizumab did not provoke new-onset spondylarthritis in patients with inflammatory bowel disease: A prospective 24-week study with imaging assessments.

A temporal relationship between vedolizumab and new-onset spondyloarthritis (SpA) has been suggested. We evaluated the relationship between vedolizumab initiation and development of new-onset SpA in patients with inflammatory bowel disease (IBD) through serial clinical evaluation and magnetic resonance imaging (MRI). A single-centre prospective observational study of 24 patients with IBD. Patients were eligible if they had active ulcerative colitis or Crohn's disease (CD), were initiating vedolizumab, had no prior history of arthritis or SpA and were suitable for serial MRI. A rheumatologist performed clinical evaluation prior to the first dose and 8 and 24weeks. Axial MRI was evaluated by a blinded central reader and performed at baseline 8 and 24weeks. Nine tumor necrosis factor (TNF) inhibitor-naïve patients (4 male; mean age 53.2years; 6 UC; 3 CD) and eight TNF inhibitor-experienced patients (7 male; mean age 48years; 3 UC; 5 CD) completed all assessments. No patients developed new features of axial arthritis or features of peripheral SpA (inflammatory oligoarthritis, enthesitis, dactylitis, or psoriasis (nail, body, or scalp)). Both groups demonstrated a good intestinal response. Vedolizumab initiation did not induce new features of axial or peripheral SpA after 24weeks of treatment in TNF inhibitor-experienced or TNF inhibitor-naive patients with IBD.

Plasma neurofilament light chain levels in chemotherapy-induced peripheral neurotoxicity according to type of anticancer drug.

A real-time biomarker in chemotherapy-induced peripheral neurotoxicity (CIPN) would be useful for clinical decision-making during treatment. Neurofilament light chain (NfL) can be detected in blood in the case of neuroaxonal damage. The aim of the study was to compare the levels of plasma NfL (pNfL) according to the type of chemotherapeutic agent and the severity of CIPN. This single-center prospective observational longitudinal study included patients treated with paclitaxel (TX; n = 34), brentuximab vedotin (BV; n = 29), or oxaliplatin (PT; n = 19). All patients were assessed using the Total Neuropathy Score-clinical version and Common Terminology Criteria for Adverse Events before, during, and up to 6-12 months after the end of treatment. Nerve conduction studies (NCS) were performed before and after chemotherapy discontinuation. Consecutive plasma samples were analyzed for NfL levels using a Simoa® analyzer. Changes in pNfL were compared between groups and were eventually correlated with clinical and NCS data. Clinically relevant (CR) CIPN was considered to be grade ≥ 2. Eighty-two patients, mostly women (59.8%), were included. One third of the patients who received TX (29.4%), BV (31%), or PT (36.8%) developed CR-CIPN, respectively, without differences among them (p = 0.854). Although pNfL significantly increased during treatment and decreased throughout the recovery period in all three groups, patients receiving TX showed significantly greater and earlier changes in pNfL levels compared to the other agents (p < 0.001). A variable change in pNfL is observed depending on the type of agent and mechanism of neurotoxicity with comparable CIPN severity, strongly implying the need to identify different cutoff values for each agent.

Role of fibroblast growth factor-23 as an early marker of metabolic bone disease of prematurity

PurposeMetabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3–4 weeks of life in at-risk patients.MethodsA single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05.ResultsIn the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3–4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3–4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation.ConclusionsMBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.

Changes in the Cutaneous Nerve Fiber Staining and Distribution of PGP9.5 in Clinically Uninvolved Skin in Leprosy Patients after Completion of Multidrug Therapy and Assessing PGP9.5 as a Marker of Treatment Response.

Subclinical involvement of nerves may sometimes be present much before the overt clinical manifestations become apparent. Protein gene product (PGP) 9.5, a ubiquitin-C-terminal hydrolase, has been widely used as a marker to study the involvement of peripheral nerve fibers in many diseases. To evaluate the change in cutaneous nerve fiber staining and distribution from pre-treatment and post completion of multidrug therapy through the expression of PGP9.5 and to assess PGP9.5 as a marker of treatment response. In this prospective single-center observational study, skin biopsy was taken in patients with leprosy, having areas of nerve function impairment (NFI), based on findings of nerve conduction studies (NCSs), but not having lesions or impaired tactile or thermal impairment clinically. The thin nerve fiber density in the clinically normal skin in areas supplied by nerve showing changes of sensory neuropathy was evaluated to study the density of the fibers. A second biopsy was taken at the end of treatment from a site near the previous site to assess the changes in intra-epidermal nerve fiber staining and distribution. Thirty-three patients were recruited in the present study (24 males and 9 females). Pre-treatment, 27 patients had abnormal NCSs, while six patients did not have any evidence of neuropathy on NCSs. Staining for nerve fibers using PGP9.5; in the epidermis was positive in five patients pre-treatment and 11 patients post treatment (P = 0.181). Staining in the dermis revealed positivity in 14 pre-treatment, which increased to 18 post treatment (P = 0.342). Adnexae showed positivity in five patients pre-treatment and increased to 17 post treatment (P = 0.005). A reduced PGP9.5 staining in the epidermal, dermal, and adnexal regions was seen in leprosy patients, which improved post treatment. Thus, PGP9.5 may serve as a marker of NFI and treatment response.

Acute Skeletal Muscle Wasting is Associated with Prolonged Hospital Stay in Critical Illness with Brain Injury.

Acute muscle wasting is common in critically ill patients, and this can lead to unfavorable clinical outcomes. The aim of this study was to identify factors associated with muscle wasting and to investigate the association between skeletal muscle wasting and prolonged hospital stay in critically ill patients with acute brain injury. This single-center prospective observational study was conducted in critically ill patients with acute brain injury who stayed in the intensive care unit for at least 1week. The rectus femoris cross-sectional area was measured via ultrasound at baseline and a week after the first assessment. Univariate and multivariate logistic regression analyses were performed to identify factors that predicted prolonged hospital stay. A total of 86 patients were included in the study. Their mean age was 49.4 ± 16.9years, 57% were male, and 46.5% had an admission diagnosis of subarachnoid hemorrhage. The percentage change in the rectus femoris cross-sectional area was 15.8% (95% confidence interval [CI] - 19.8% to - 12.0%; p < 0.001), and 57% of all patients had acute muscle wasting. According to the univariate analysis, there was a significant association between prolonged hospital stay and acute muscle wasting (odds ratio [OR] 3.677; 95% CI 1.487-9.043; p = 0.005), mechanical ventilation status (OR 3.600; 95% CI 1.455-8.904; p = 0.006), and Glasgow Coma Scale score (OR 0.888; 95% CI 0.808-0.976; p = 0.014) at intensive care unit admission. The multivariate analysis demonstrated that acute muscle wasting (OR 3.449; 95% CI 1.344-8.853; p = 0.010) was an independent risk factor for prolonged hospital stay. There was considerable muscle wasting in critically ill patients with brain injuries over a 1-week period. Acute muscle wasting was associated with prolonged hospital stay in critically ill patients with acute brain injury.