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7 pages, 669 KiB  
Case Report
Pathologically Confirmed Dual Coronavirus Disease 2019-Associated Tracheobronchial Aspergillosis and Pulmonary Mucormycosis in a Non-Endemic Region: A Case Report
by Keon Oh, Sung-Yeon Cho, Dong-Gun Lee, Dukhee Nho, Dong Young Kim, Hye Min Kweon, Minseung Song and Raeseok Lee
J. Clin. Med. 2025, 14(15), 5526; https://doi.org/10.3390/jcm14155526 - 5 Aug 2025
Abstract
Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and [...] Read more.
Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article
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12 pages, 1302 KiB  
Article
Exploring the Relationship Between Insulin Resistance, Liver Health, and Restrictive Lung Diseases in Type 2 Diabetes
by Mani Roshan, Christian Mudrack, Alba Sulaj, Ekaterina von Rauchhaupt, Thomas Fleming, Lukas Schimpfle, Lukas Seebauer, Viktoria Flegka, Valter D. Longo, Elisabeth Kliemank, Stephan Herzig, Anna Hohneck, Zoltan Kender, Julia Szendroedi and Stefan Kopf
J. Pers. Med. 2025, 15(8), 340; https://doi.org/10.3390/jpm15080340 - 1 Aug 2025
Viewed by 163
Abstract
Background: Restrictive lung disease (RLD) is a potential complication in type 2 diabetes (T2D), but its relationship with insulin resistance and liver-related metabolic dysfunction remains unclear. This study evaluated the association between lung function and metabolic markers in T2D and retrospectively assessed [...] Read more.
Background: Restrictive lung disease (RLD) is a potential complication in type 2 diabetes (T2D), but its relationship with insulin resistance and liver-related metabolic dysfunction remains unclear. This study evaluated the association between lung function and metabolic markers in T2D and retrospectively assessed whether metabolic improvements from dietary intervention were accompanied by changes in lung function. Methods: This cross-sectional analysis included 184 individuals (101 with T2D, 33 with prediabetes, and 50 glucose-tolerant individuals). Lung function parameters—vital capacity (VC), total lung capacity by plethysmography (TLC-B), and diffusion capacity for carbon monoxide (TLCO)—were assessed alongside metabolic markers including HOMA2-IR, fatty liver index (FLI), NAFLD score, and Fibrosis-4 index (FIB-4). In a subset of 54 T2D participants, lung function was reassessed after six months following either a fasting-mimicking diet (FMD, n = 14), Mediterranean diet (n = 13), or no dietary intervention (n = 27). Results: T2D participants had significantly lower VC and TLC-B compared to glucose-tolerant and prediabetic individuals, with 18–21% falling below clinical thresholds for RLD. Lung volumes were negatively correlated with HOMA2-IR, FLI, NAFLD score, and FIB-4 across the cohort and within the T2D group. Although the FMD intervention led to significant improvements in HOMA2-IR and FLI, no corresponding changes in lung function were observed over the six-month period. Conclusions: Restrictive lung impairment in T2D is associated with insulin resistance and markers of liver steatosis and fibrosis. While short-term dietary interventions can improve metabolic parameters, their effect on lung function may require a longer duration or additional interventions and targeted follow-up. These findings highlight the relevance of pulmonary assessment in individuals with metabolic dysfunction. Full article
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11 pages, 245 KiB  
Review
The Impact of Insulin Resistance on Lung Volume Through Right Ventricular Dysfunction in Diabetic Patients—Literature Review
by Daniel Radu, Oana-Andreea Parlițeanu, Andra-Elena Nica, Cristiana Voineag, Octavian-Sabin Alexe, Alexandra Maria Cristea, Livia Georgescu, Roxana Maria Nemeș, Andreea Taisia Tiron and Alexandra Floriana Nemeș
J. Pers. Med. 2025, 15(8), 336; https://doi.org/10.3390/jpm15080336 - 1 Aug 2025
Viewed by 200
Abstract
Insulin resistance (IR), a core component in the development of type 2 diabetes mellitus (T2DM), is increasingly recognized for its role in cardiovascular and pulmonary complications. This review explores the relationship between IR, right ventricular dysfunction (RVD), and decreased lung volume in patients [...] Read more.
Insulin resistance (IR), a core component in the development of type 2 diabetes mellitus (T2DM), is increasingly recognized for its role in cardiovascular and pulmonary complications. This review explores the relationship between IR, right ventricular dysfunction (RVD), and decreased lung volume in patients with T2DM. Emerging evidence suggests that IR contributes to early structural and functional alterations in the right ventricle, independent of overt cardiovascular disease. The mechanisms involved include oxidative stress, inflammation, dyslipidemia, and obesity—factors commonly found in metabolic syndrome and T2DM. These pathophysiological changes compromise right ventricular contractility, leading to reduced pulmonary perfusion and respiratory capacity. RVD has been associated with chronic lung disease, pulmonary hypertension, and obstructive sleep apnea, all of which are prevalent in the diabetic population. As RVD progresses, it can result in impaired gas exchange, interstitial pulmonary edema, and exercise intolerance—highlighting the importance of early recognition and management. Therapeutic strategies should aim to improve insulin sensitivity and cardiac function through lifestyle interventions, pharmacological agents such as SGLT2 inhibitors and GLP-1/GIP analogs, and routine cardiac monitoring. These approaches may help slow the progression of RVD and its respiratory consequences. Considering the global burden of diabetes and obesity, and the growing incidence of related complications, further research is warranted to clarify the mechanisms linking IR, RVD, and respiratory dysfunction. Understanding this triad will be crucial for developing targeted interventions that improve outcomes and quality of life in affected patients. Full article
(This article belongs to the Section Mechanisms of Diseases)
18 pages, 955 KiB  
Article
Unequal Burdens: Exploring Racial Disparities in Cardiovascular and SLE Outcomes Using National Inpatient Database 2016–2021
by Freya Shah, Siddharth Pravin Agrawal, Darshilkumar Maheta, Jatin Thukral and Syeda Sayeed
Rheumato 2025, 5(3), 10; https://doi.org/10.3390/rheumato5030010 - 30 Jul 2025
Viewed by 291
Abstract
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with significant racial and ethnic disparities in prevalence, disease severity, and outcomes. Cardiovascular complications, including pericarditis, myocarditis, valvular disease, and conduction abnormalities, contribute to increased morbidity and mortality in SLE patients. This study [...] Read more.
Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with significant racial and ethnic disparities in prevalence, disease severity, and outcomes. Cardiovascular complications, including pericarditis, myocarditis, valvular disease, and conduction abnormalities, contribute to increased morbidity and mortality in SLE patients. This study examines racial and ethnic disparities in cardiovascular outcomes among hospitalized SLE patients in the United States. Methods: This retrospective study utilized the National Inpatient Sample (NIS) database from 2016 to 2021 to analyze hospitalizations of adult patients (≥18 years) with a primary or secondary diagnosis of SLE. Patients were stratified into racial/ethnic groups: White, Black, Hispanic, Asian, Native American, and Other. Primary outcomes include major adverse cardiovascular events (MACEs), which are a composite of in-hospital mortality, myocardial infarction (MI), sudden cardiac death, and other SLE-related outcomes including cardiac, pulmonary, and renal involvement. Statistical analyses included multivariable logistic regression models adjusted for demographic, socioeconomic, and hospital-related factors to assess racial disparities. Results: The study included 514,750 White, 321,395 Black, and 146,600 Hispanic patients, with smaller proportions of Asian, Native American, and Other racial groups. Black patients had significantly higher odds of in-hospital mortality (OR = 1.17, 95% CI = 1.08–1.26, p < 0.001) and sudden cardiac death (OR = 1.64, 95% CI = 1.46–1.85, p < 0.001) compared to White patients. Asian patients also exhibited increased mortality risk (OR = 1.37, 95% CI = 1.14–1.63, p = 0.001) as compared to Whites. Conversely, Black (OR = 0.90, 95% CI = 0.85–0.96, p = 0.01) and Hispanic (OR = 0.87, 95% CI = 0.80–0.96, p = 0.03) patients had lower odds of MI. Racial disparities in access to care, socioeconomic status, and comorbidity burden may contribute to these differences. Conclusion: Significant racial and ethnic disparities exist in cardiovascular outcomes among hospitalized SLE patients. Black and Asian individuals face higher in-hospital all-causes mortality and sudden cardiac death risks, while Black and Hispanic patients exhibit lower MI rates. Addressing social determinants of health, improving access to specialized care, and implementing targeted interventions may reduce disparities and improve outcomes in minority populations with SLE. Full article
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13 pages, 777 KiB  
Article
Nomogram Development and Feature Selection Strategy Comparison for Predicting Surgical Site Infection After Lower Extremity Fracture Surgery
by Humam Baki and Atilla Sancar Parmaksızoğlu
Medicina 2025, 61(8), 1378; https://doi.org/10.3390/medicina61081378 - 30 Jul 2025
Viewed by 192
Abstract
Background and Objectives: Surgical site infections (SSIs) are a frequent complication after lower extremity fracture surgery, yet tools for individualized risk prediction remain limited. This study aimed to develop and internally validate a nomogram for individualized SSI risk prediction based on perioperative [...] Read more.
Background and Objectives: Surgical site infections (SSIs) are a frequent complication after lower extremity fracture surgery, yet tools for individualized risk prediction remain limited. This study aimed to develop and internally validate a nomogram for individualized SSI risk prediction based on perioperative clinical parameters. Materials and Methods: This retrospective cohort study included adults who underwent lower extremity fracture surgery between 2022 and 2025 at a tertiary care center. Thirty candidate predictors were evaluated. Feature selection was performed using six strategies, and the final model was developed with logistic regression based on bootstrap inclusion frequency. Model performance was assessed by area under the curve, calibration slope, Brier score, sensitivity, and specificity. Results: Among 638 patients undergoing lower extremity fracture surgery, 76 (11.9%) developed SSIs. Of six feature selection strategies compared, bootstrap inclusion frequency identified seven predictors: red blood cell count, preoperative C-reactive protein, chronic kidney disease, operative time, chronic obstructive pulmonary disease, body mass index, and blood transfusion. The final model demonstrated an AUROC of 0.924 (95% CI, 0.876–0.973), a calibration slope of 1.03, and a Brier score of 0.0602. Sensitivity was 86.2% (95% CI, 69.4–94.5) and specificity was 89.5% (95% CI, 83.8–93.3). Chronic kidney disease (OR, 88.75; 95% CI, 5.51–1428.80) and blood transfusion (OR, 85.07; 95% CI, 11.69–619.09) were the strongest predictors of infection. Conclusions: The developed nomogram demonstrates strong predictive performance and may support personalized SSI risk assessment in patients undergoing lower extremity fracture surgery. Full article
(This article belongs to the Special Issue Evaluation, Management, and Outcomes in Perioperative Medicine)
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11 pages, 556 KiB  
Article
Added Value of SPECT/CT in Radio-Guided Occult Localization (ROLL) of Non-Palpable Pulmonary Nodules Treated with Uniportal Video-Assisted Thoracoscopy
by Demetrio Aricò, Lucia Motta, Giulia Giacoppo, Michelangelo Bambaci, Paolo Macrì, Stefania Maria, Francesco Barbagallo, Nicola Ricottone, Lorenza Marino, Gianmarco Motta, Giorgia Leone, Carlo Carnaghi, Vittorio Gebbia, Domenica Caponnetto and Laura Evangelista
J. Clin. Med. 2025, 14(15), 5337; https://doi.org/10.3390/jcm14155337 - 29 Jul 2025
Viewed by 246
Abstract
Background/Objectives: The extensive use of computed tomography (CT) has led to a significant increase in the detection of small and non-palpable pulmonary nodules, necessitating the use of invasive methods for definitive diagnosis. Video-assisted thoracoscopic surgery (VATS) has become the preferred procedure for nodule [...] Read more.
Background/Objectives: The extensive use of computed tomography (CT) has led to a significant increase in the detection of small and non-palpable pulmonary nodules, necessitating the use of invasive methods for definitive diagnosis. Video-assisted thoracoscopic surgery (VATS) has become the preferred procedure for nodule resections; however, intraoperative localization remains challenging, especially for deep or subsolid lesions. This study explores whether SPECT/CT improves the technical and clinical outcomes of radio-guided occult lesion localization (ROLL) before uniportal video-assisted thoracoscopic surgery (u-VATS). Methods: This is a retrospective study involving consecutive patients referred for the resection of pulmonary nodules who underwent CT-guided ROLL followed by u-VATS between September 2017 and December 2024. From January 2023, SPECT/CT was systematically added after planar imaging. The cohort was divided into a planar group and a planar + SPECT/CT group. The inclusion criteria involved nodules sized ≤ 2 cm, with ground glass or solid characteristics, located at a depth of <6 cm from the pleural surface. 99mTc-MAA injected activity, timing, the classification of planar and SPECT/CT image findings (focal uptake, multisite with focal uptake, multisite without focal uptake), spillage, and post-procedure complications were evaluated. Statistical analysis was performed, with continuous data expressed as the median and categorical data as the number. Comparisons were made using chi-square tests for categorical variables and the Mann–Whitney U test for procedural duration. Cohen’s kappa coefficient was calculated to assess agreement between imaging modalities. Results: In total, 125 patients were selected for CT-guided radiotracer injection followed by uniportal-VATS. The planar group and planar + SPECT/CT group comprised 60 and 65 patients, respectively. Focal uptake was detected in 68 (54%), multisite with focal uptake in 46 (36.8%), and multisite without focal uptake in 11 patients (8.8%). In comparative analyses between planar and SPECT/CT imaging in 65 patients, 91% exhibited focal uptake, revealing significant differences in classification for 40% of the patients. SPECT/CT corrected the classification of 23 patients initially categorized as multisite with focal uptake to focal uptake, improving localization accuracy. The mean procedure duration was 39 min with SPECT/CT. Pneumothorax was more frequently detected with SPECT/CT (43% vs. 1.6%). The intraoperative localization success rate was 96%. Conclusions: SPECT/CT imaging in the ROLL procedure for detecting pulmonary nodules before u-VATs demonstrates a significant advantage in reclassifying radiotracer positioning compared to planar imaging. Considering its limited impact on surgical success rates and additional procedural time, SPECT/CT should be reserved for technically challenging cases. Larger sample sizes, multicentric and prospective randomized studies, and formal cost–utility analyses are warranted. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
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14 pages, 1906 KiB  
Article
Integrating CT-Based Lung Fibrosis and MRI-Derived Right Ventricular Function for the Detection of Pulmonary Hypertension in Interstitial Lung Disease
by Kenichi Ito, Shingo Kato, Naofumi Yasuda, Shungo Sawamura, Kazuki Fukui, Tae Iwasawa, Takashi Ogura and Daisuke Utsunomiya
J. Clin. Med. 2025, 14(15), 5329; https://doi.org/10.3390/jcm14155329 - 28 Jul 2025
Viewed by 382
Abstract
Background/Objectives: Interstitial lung disease (ILD) is frequently complicated by pulmonary hypertension (PH), which is associated with reduced exercise capacity and poor prognosis. Early and accurate non-invasive detection of PH remains a clinical challenge. This study evaluated whether combining quantitative CT analysis of [...] Read more.
Background/Objectives: Interstitial lung disease (ILD) is frequently complicated by pulmonary hypertension (PH), which is associated with reduced exercise capacity and poor prognosis. Early and accurate non-invasive detection of PH remains a clinical challenge. This study evaluated whether combining quantitative CT analysis of lung fibrosis with cardiac MRI-derived measures of right ventricular (RV) function improves the diagnostic accuracy of PH in patients with ILD. Methods: We retrospectively analyzed 72 ILD patients who underwent chest CT, cardiac MRI, and right heart catheterization (RHC). Lung fibrosis was quantified using a Gaussian Histogram Normalized Correlation (GHNC) software that computed the proportions of diseased lung, ground-glass opacity (GGO), honeycombing, reticulation, consolidation, and emphysema. MRI was used to assess RV end-systolic volume (RVESV), ejection fraction, and RV longitudinal strain. PH was defined as a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg and pulmonary vascular resistance ≥ 3 Wood units on RHC. Results: Compared to patients without PH, those with PH (n = 21) showed significantly reduced RV strain (−13.4 ± 5.1% vs. −16.4 ± 5.2%, p = 0.026) and elevated RVESV (74.2 ± 18.3 mL vs. 59.5 ± 14.2 mL, p = 0.003). CT-derived indices also differed significantly: diseased lung area (56.4 ± 17.2% vs. 38.4 ± 12.5%, p < 0.001), GGO (11.8 ± 3.6% vs. 8.65 ± 4.3%, p = 0.005), and honeycombing (17.7 ± 4.9% vs. 12.8 ± 6.4%, p = 0.0027) were all more prominent in the PH group. In receiver operating characteristic curve analysis, diseased lung area demonstrated an area under the curve of 0.778 for detecting PH. This increased to 0.847 with the addition of RVESV, and further to 0.854 when RV strain was included. Combined models showed significant improvement in risk reclassification: net reclassification improvement was 0.700 (p = 0.002) with RVESV and 0.684 (p = 0.004) with RV strain; corresponding IDI values were 0.0887 (p = 0.03) and 0.1222 (p = 0.01), respectively. Conclusions: Combining CT-based fibrosis quantification with cardiac MRI-derived RV functional assessment enhances the non-invasive diagnosis of PH in ILD patients. This integrated imaging approach significantly improves diagnostic precision and may facilitate earlier, more targeted interventions in the management of ILD-associated PH. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
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13 pages, 309 KiB  
Article
Sex Disparities Among Lithuanian Ischemic Stroke Patients According to Laboratory Findings; Comorbidities, Including COVID-19; Acute In-Hospital Complications; and Outcomes
by Erika Jasukaitienė, Šarūnas Augustis, Lolita Šileikienė, Abdonas Tamošiūnas, Dalia Lukšienė, Gintarė Šakalytė, Diana Žaliaduonytė, Karolina Marcinkevičienė, Daina Krančiukaitė-Butylkinienė and Ričardas Radišauskas
Medicina 2025, 61(8), 1367; https://doi.org/10.3390/medicina61081367 - 28 Jul 2025
Viewed by 178
Abstract
Background and Objectives: Ischemic stroke (IS) is a critical health issue, affecting individuals of all ages, sexes, and backgrounds. Mounting evidence suggests that sex indeed could play some distinct role in shaping the incidence, outcomes, and treatment of IS. In the context [...] Read more.
Background and Objectives: Ischemic stroke (IS) is a critical health issue, affecting individuals of all ages, sexes, and backgrounds. Mounting evidence suggests that sex indeed could play some distinct role in shaping the incidence, outcomes, and treatment of IS. In the context of the COVID-19 pandemic, contradictory findings from previous studies that also addressed sex differences in cerebrovascular diseases demonstrate the need for further focused research. This study aimed to evaluate the sex discrepancies in the clinical presentation of IS and its outcomes in patients admitted to Kaunas Hospital of the Lithuanian University of Health Sciences (LUHS), Lithuania. Materials and Methods: This is a retrospective record-based single-center study. All the study patients—727 men and 1082 women—enrolled between 1 January 2020, and 27 February 2022; suffered from acute IS; and had absolute contraindications against interventional IS treatment. These patients received a conservative non-interventional IS treatment at the neurological department of the LUHS’s Kaunas Hospital. The sociodemographic data; laboratory findings; comorbidities, including COVID-19; in-hospital complications; and outcome factors were obtained from the patients’ medical records and evaluated by deploying appropriate statistical tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by the Cox proportional hazards regression for in-hospital lethality. Results: The mean age of IS patients was significantly higher in women compared to men (p < 0.001), as was the proportion of in-hospital deaths (19.10% and 15.36%, respectively; p < 0.05). The mean total number of in-hospital complications was again significantly higher in the group of women compared to men (p < 0.05). The prevalence of COVID-19 was higher in men compared to women (p < 0.05). COVID-19 diagnosis (HR = 1.53; p = 0.02) and acute in-hospital pulmonary complications (HR = 1.91; p = 0.008) significantly increased the risk of in-hospital lethality in men. The risk of in-hospital lethality was significantly higher in women with comorbid diabetes mellitus type 2 (DM) compared to those with comorbid isolated arterial hypertension (AH) (HR = 2.25, p = 0.007). Increased C-reactive protein elevated the risk of in-hospital lethality by more than twice in both men and women (HR = 2.46; p < 0.001 and HR = 2.28; p < 0.001, respectively). Conclusions: The following differences between men and women with IS were determined: Acute in-hospital pulmonary complications, including COVID-19, significantly increased the risk of in-hospital lethality in the male group, but not in women. However, women suffering from DM had a significantly increased risk of in-hospital lethality compared with those women IS patients with AH or chronic ischemic heart disease (IHD). Increased C-reactive protein was associated with an elevated risk of in-hospital lethality both in male and female groups. Full article
(This article belongs to the Section Epidemiology & Public Health)
8 pages, 855 KiB  
Case Report
Severe Malaria Due to Plasmodium falciparum in an Immunocompetent Young Adult: Rapid Progression to Multiorgan Failure
by Valeria Sanclemente-Cardoza, Harold Andrés Payán-Salcedo and Jose Luis Estela-Zape
Life 2025, 15(8), 1201; https://doi.org/10.3390/life15081201 - 28 Jul 2025
Viewed by 273
Abstract
Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation [...] Read more.
Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation below 75%, necessitating orotracheal intubation. During the procedure, he developed pulseless electrical activity cardiac arrest, achieving return of spontaneous circulation after advanced resuscitation. Diagnosis was confirmed by thick blood smear, demonstrating P. falciparum infection. The patient progressed to multiorgan failure, including acute respiratory distress syndrome with capillary leak pulmonary edema, refractory distributive shock, acute kidney injury with severe hyperkalemia, and consumptive thrombocytopenia. Management included invasive mechanical ventilation, vasopressor support, sedation-analgesia, neuromuscular blockade, methylene blue, unsuccessful hemodialysis due to hemorrhagic complications, and platelet transfusions. Despite these interventions, the patient experienced a second cardiac arrest and died. This case highlights the severity and rapid progression of severe malaria with multisystem involvement, underscoring the critical importance of early diagnosis and intensive multidisciplinary management. It also emphasizes the need for preventive strategies for travelers to endemic areas and the development of clinical protocols to improve outcomes in complicated malaria. Full article
(This article belongs to the Section Medical Research)
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11 pages, 924 KiB  
Article
Radial-Probe Endobronchial Ultrasound as Part of Different Navigational Bronchoscopy Modalities in Combination with Cryobiopsy Could Be More than a Confirmation Tool: A Case Series
by Nevenka Piskac Zivkovic, Maja Karaman Ilic, Suncana Divosevic, Hrvoje Feljan, Igor Nikolic, Zrinka Juros, Ana-Marija Sola, Sven Seiwerth, Dragan Schwarz and Ivica Mazuranic
Diagnostics 2025, 15(15), 1884; https://doi.org/10.3390/diagnostics15151884 - 27 Jul 2025
Viewed by 310
Abstract
Background: As part of different navigational bronchoscopy (NVB) modalities, radial-probe endobronchial ultrasound (rEBUS) is used to confirm the peribronchial localization of peripheral pulmonary nodules (PPNs) immediately before collecting samples for histopathological analysis. Methods: This retrospective case series study presents the results [...] Read more.
Background: As part of different navigational bronchoscopy (NVB) modalities, radial-probe endobronchial ultrasound (rEBUS) is used to confirm the peribronchial localization of peripheral pulmonary nodules (PPNs) immediately before collecting samples for histopathological analysis. Methods: This retrospective case series study presents the results of en bloc cryobiopsy of PPNs using a flexible 1.1-mm cryoprobe with different NVB modalities. For PPNs classified as adjacent or eccentric lesions by rEBUS (ES-rEBUS), the cryoprobe’s position was adjusted by 90–180° in relation to the ultrasound image of the lesion during the first and second biopsies. Results: All patients with a final histopathologically confirmed diagnosis of PPNs had positive rEBUS findings, regardless of the navigation modality, eccentric (18/42 patients, 43%) and concentric (24/42 patients, 57%) rEBUS view. In 5 out of 6 patients without a histopathological diagnosis, PPNs were not visualized by radial ultrasound. In the (ES-rEBUS) group of patients, 4 out of 18 had fewer than three biopsy samples collected per procedure, which means only an adjusted probe position has been applied, although diagnostic outcomes were achieved. Common Terminology Criteria for Adverse Events (CTCAE) grade 2 complications were reported in 10.4% of the patients, and grade 3 complications in 2% of the patients. Conclusions: Confirming the localization of nodules by rEBUS and properly adjusting the cryoprobe immediately before cryobiopsy of PPNs resulted in a diagnostic yield meeting the literature standards. Full article
(This article belongs to the Special Issue New Advances in Diagnostic Bronchoscopy)
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13 pages, 1542 KiB  
Case Report
Reclassification of Seronegative Rheumatoid Arthritis as Anti-PL-12 Antisynthetase Syndrome with Interstitial Lung Disease and Joint Involvement–Case Report
by Diana Elena Cosău, Alexandru Dan Costache, Irina Iuliana Costache Enache, Ionela Lăcrămioara Șerban, Luiza Andreea Petrariu, Cristina Pomîrleanu, Mara Russu, Vladia Lăpuște and Codrina Ancuța
Reports 2025, 8(3), 123; https://doi.org/10.3390/reports8030123 - 26 Jul 2025
Viewed by 372
Abstract
Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include [...] Read more.
Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include Raynaud’s phenomenon and “mechanic’s hands”. Among antisynthetase antibodies, anti-PL-12 is notably associated with predominant or isolated ILD and may occur in the absence of clinically evident myositis, thereby complicating timely diagnosis. Case Presentation: We are presenting a 45-year-old non-smoking female patient with a prior diagnosis of seronegative rheumatoid arthritis (RA) who developed progressive dyspnea, dry cough, and sicca symptoms. High-resolution computed tomography revealed a nonspecific interstitial pneumonia (NSIP) pattern. Despite normal creatine kinase and lactate dehydrogenase levels, serological work-up revealed positive anti-PL-12 and anti-Ro52 antibodies, supporting a diagnosis of antisynthetase syndrome without myositis, fulfilling the diagnostic criteria for ASyS per Connors and Solomon. Treatment with corticosteroids and cyclophosphamide induced clinical and functional respiratory improvement, while azathioprine was initiated for maintenance. Conclusions: This case underscores the clinical heterogeneity of antisynthetase syndrome and highlights the diagnostic challenge posed by anti-PL-12–associated ILD in the absence of myositis. Importantly, it demonstrates that in patients with pre-existing rheumatologic diagnoses, the emergence of atypical pulmonary manifestations warrants repeat serologic evaluation to assess ASyS and other autoimmune conditions. Early diagnosis and immunosuppressive treatment are essential to optimize outcomes. Full article
(This article belongs to the Section Critical Care/Emergency Medicine/Pulmonary)
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22 pages, 3902 KiB  
Article
Comparative Immunomodulatory Efficacy of Secukinumab and Honokiol in Experimental Asthma and Acute Lung Injury
by Andrei Gheorghe Vicovan, Diana Cezarina Petrescu, Lacramioara Ochiuz, Petru Cianga, Daniela Constantinescu, Elena Iftimi, Mariana Pavel-Tanasa, Codrina Mihaela Ancuta, Cezar-Cătălin Caratașu, Mihai Glod, Carmen Solcan and Cristina Mihaela Ghiciuc
Pharmaceuticals 2025, 18(8), 1108; https://doi.org/10.3390/ph18081108 - 25 Jul 2025
Viewed by 182
Abstract
Background: The study evaluates the immunomodulatory potential of secukinumab (SECU) and honokiol (HONK) in a murine model of allergic asthma complicated by acute lung injury (ALI), with an emphasis on modulating key inflammatory pathways. The rationale is driven by the necessity to attenuate [...] Read more.
Background: The study evaluates the immunomodulatory potential of secukinumab (SECU) and honokiol (HONK) in a murine model of allergic asthma complicated by acute lung injury (ALI), with an emphasis on modulating key inflammatory pathways. The rationale is driven by the necessity to attenuate Th17-mediated cytokine cascades, wherein IL-17 plays a critical role, as well as to explore the adjunctive anti-inflammatory effects of HONK on Th1 cytokine production, including IL-6, TNF-α, and Th2 cytokines. Methods: Mice were sensitized and challenged with ovalbumin (OVA) and lipopolysaccharide (LPS) was administrated to exacerbate pulmonary pathology, followed by administration of SECU, HONK (98% purity, C18H18O2), or their combination. Quantitative analyses incorporated OVA-specific IgE measurements, differential cell counts in bronchoalveolar lavage fluid (BALF), and extensive cytokine profiling in both BALF and lung tissue homogenates, utilizing precise immunoassays and histopathological scoring systems. Results: Both SECU and HONK, when used alone or in combination, display significant immunomodulatory effects in a murine model of allergic asthma concomitant with ALI. The combined therapy synergistically reduced pro-inflammatory mediators, notably Th1 cytokines, such as TNF-α and IL-6, as measured in both BALF and lung tissue homogenates. Conclusions: The combined therapy showed a synergistic attenuation of pro-inflammatory mediators, a reduction in goblet cell hyperplasia, and an overall improvement in lung histoarchitecture. While the data robustly support the merit of a combinatorial approach targeting multiple inflammatory mediators, the study acknowledges limitations in cytokine diffusion and the murine model’s translational fidelity, thereby underscoring the need for further research to optimize clinical protocols for severe respiratory inflammatory disorders. Full article
(This article belongs to the Section Pharmacology)
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19 pages, 925 KiB  
Review
Muscle Wasting and Treatment of Dyslipidemia in COPD: Implications for Patient Management
by Andrea Bianco, Raffaella Pagliaro, Angela Schiattarella, Domenica Francesca Mariniello, Vito D’Agnano, Roberta Cianci, Ersilia Nigro, Aurora Daniele, Filippo Scialò and Fabio Perrotta
Biomedicines 2025, 13(8), 1817; https://doi.org/10.3390/biomedicines13081817 - 24 Jul 2025
Viewed by 437
Abstract
Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial condition associated with significant systemic complications such as cardiovascular disease (CVD), metabolic disorders, muscle wasting, and sarcopenia. While Body Mass Index (BMI) is a well-established indicator of obesity and has prognostic value in COPD, its [...] Read more.
Chronic Obstructive Pulmonary Disease (COPD) is a multifactorial condition associated with significant systemic complications such as cardiovascular disease (CVD), metabolic disorders, muscle wasting, and sarcopenia. While Body Mass Index (BMI) is a well-established indicator of obesity and has prognostic value in COPD, its role in predicting disease outcomes is complex. Muscle wasting is prevalent in COPD patients and exacerbates disease severity, contributing to poor physical performance, reduced quality of life, and increased mortality. Additionally, COPD is linked to metabolic disorders, such as dyslipidemia and diabetes, which contribute to systemic inflammation and worse prognosis and, therefore, should be treated. The systemic inflammatory response plays a central role in the development of sarcopenia. In this review, we highlight the mixed efficacy of statins in managing dyslipidemia in COPD, considering side effects, including muscle toxicity in such a frail population. Alternative lipid-lowering therapies and nutraceuticals, in addition to standard treatment, have the potential to target hypercholesterolemia, which is a coexisting condition present in more than 50% of all COPD patients, without worsening muscle wasting. The interference between adipose tissue and lung, and particularly the potential protective role of adiponectin, an adipocytokine with anti-inflammatory properties, is also reviewed. Respiratory, metabolic and muscular health in COPD is comprehensively assessed. Identifying and managing dyslipidemia and paying attention to other relevant COPD comorbidities, such as sarcopenia and muscle wasting, is important to improve the quality of life and to reduce the clinical burden of COPD patients. Future research should focus on understanding the relationships between these intimate mechanisms to facilitate specific treatment for systemic involvement of COPD. Full article
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14 pages, 701 KiB  
Article
COVID-19 Organ Injury Pathology and D-Dimer Expression Patterns: A Retrospective Analysis
by Raluca Dumache, Camelia Oana Muresan, Sorina Maria Denisa Laitin, Nina Ivanovic, Adina Chisalita, Alexandra Herlo, Adelina Marinescu, Elena Voichita Lazureanu and Talida Georgiana Cut
Diagnostics 2025, 15(15), 1860; https://doi.org/10.3390/diagnostics15151860 - 24 Jul 2025
Viewed by 281
Abstract
Background and Objectives: Coronavirus Disease 2019 (COVID-19) may cause extensive multi-organ pathology, particularly in the lungs, heart, kidneys, and liver. While hypercoagulability—often signaled by elevated D-dimer—has been thoroughly investigated, the concurrent pathological findings across organs and their interrelation with distinct D-dimer levels remain [...] Read more.
Background and Objectives: Coronavirus Disease 2019 (COVID-19) may cause extensive multi-organ pathology, particularly in the lungs, heart, kidneys, and liver. While hypercoagulability—often signaled by elevated D-dimer—has been thoroughly investigated, the concurrent pathological findings across organs and their interrelation with distinct D-dimer levels remain incompletely characterized. This study aimed to evaluate the pathological changes observed in autopsied or deceased COVID-19 patients, focusing on the prevalence of organ-specific lesions, and to perform subgroup analyses based on three D-dimer categories. Methods: We conducted a retrospective review of 69 COVID-19 patients from a Romanian-language dataset, translating all clinical and pathological descriptions into English. Pathological findings (pulmonary microthrombi, bronchopneumonia, myocardial fibrosis, hepatic steatosis, and renal tubular necrosis) were cataloged. Patients were grouped into three categories by admission D-dimer: <500 ng/mL, 500–2000 ng/mL, and ≥2000 ng/mL. Laboratory parameters (C-reactive protein, fibrinogen, and erythrocyte sedimentation rate) and clinical outcomes (intensive care unit [ICU] admission, mechanical ventilation, and mortality) were also recorded. Intergroup comparisons were performed with chi-square tests for categorical data and one-way ANOVA or the Kruskal–Wallis test for continuous data. Results: Marked organ pathology was significantly more frequent in the highest D-dimer group (≥2000 ng/mL). Pulmonary microthrombi and bronchopneumonia increased stepwise across ascending D-dimer strata (p < 0.05). Myocardial and renal lesions similarly showed higher prevalence in patients with elevated D-dimer. Correlation analysis revealed that severe lung and heart pathologies were strongly associated with high inflammatory markers and a greater risk of ICU admission and mortality. Conclusions: Our findings underscore that COVID-19-related organ damage is magnified in patients with significantly elevated D-dimer. By integrating pathology reports with clinical and laboratory data, we highlight the prognostic role of hypercoagulability and systemic inflammation in the pathogenesis of multi-organ complications. Stratifying patients by D-dimer may inform more tailored management strategies, particularly in those at highest risk of severe pathology and adverse clinical outcomes. Full article
(This article belongs to the Special Issue Respiratory Diseases: Diagnosis and Management)
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20 pages, 2796 KiB  
Systematic Review
Comparative Efficacy and Safety Profile of the Combination of Pulmonary Surfactant and Budesonide vs. Surfactant Alone in the Management of Neonatal Respiratory Distress Syndrome: An Updated Meta-Analysis
by Urooj Fatima, Naveera Naveed, Zahra Riaz, Emaan Khalid, Aemon Qamer, Shehmeen Baig, Roshaan Fatima, Asawir Hussain, Zoya Mustunsar, Ayesha Khan, Sadia Mangan, Mehak Kumari, Soban Ali Qasim, Ali Hasan and Raheel Ahmed
Medicina 2025, 61(8), 1329; https://doi.org/10.3390/medicina61081329 - 23 Jul 2025
Viewed by 295
Abstract
Background and Objectives: Neonatal respiratory distress syndrome (NRDS), resulting from a deficiency of pulmonary surfactant (PS), can cause alveoli to collapse. Glucocorticoids reduce inflammation and are effective in reducing pulmonary swelling. This study aims to assess the effectiveness of the combination of PS [...] Read more.
Background and Objectives: Neonatal respiratory distress syndrome (NRDS), resulting from a deficiency of pulmonary surfactant (PS), can cause alveoli to collapse. Glucocorticoids reduce inflammation and are effective in reducing pulmonary swelling. This study aims to assess the effectiveness of the combination of PS and budesonide in the management of NRDS. Materials and Methods: Publications between 21 May and 24 November were screened through PubMed, Cochrane and Embase. Data analysis was performed on RevMan 5.3 software. Subgroup analysis was performed to evaluate the routes of administrations. Results: The use of budesonide along with pulmonary surfactant for treating NRDS revealed the following results: (1) a reduced duration of invasive mechanical ventilation (standardized mean difference (SMD) = −1.06, 95% confidence interval (CI) = −1.55 to −0.56, p < 0.0001); (2) reduced rate of bronchopulmonary dysplasia (BPD) occurrence (relative risk (RR) = 0.72, 95% CI = 0.60 to 0.86, p = 0.0003); (3) reduced duration for hospital admittance (SMD = −0.38, 95% CI = −0.64 to −0.11, p = 0.005). The occurrence of complications, i.e., sepsis, pneumothorax, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), rate of mortality, hyperglycemia and intraventricular hemorrhage (IVH), was not significantly different among the intervention and comparison group except for patent ductus arteriosus (PDA) and pulmonary hemorrhage, with their incidence being higher in the control group (p = 0.002 and p = 0.05, respectively). Conclusions: The combination of pulmonary surfactant and budesonide decreases the occurrence of BPD, duration of mechanical ventilation, length of hospital stay and risk of pulmonary hemorrhage and PDA. It does not increase the risk of complications and death and is clinically safe. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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