A case of lung and fungus ball lesions associated with Cladosporium Subcinereum A48 in a diabetic patient.

This study reports the first case of lung and fungus ball lesions caused by Cladosporium subcinereum A48. A rural diabetic woman infected by C. subcinereum A48, presented with fever and hemoptysis. CT scans, bronchoalveolar lavage, culture and molecular methods were used to evaluate and confirm the disease. Our patient had not taken insulin during the last few months of her life which probably caused acidosis and a decrease in the patient's immunity level, resulting in penetration and formation of a fungal in the lung.

We report a case of a rare lung disease caused by the fungus Cladosporium subcinereum A48. The patient had diabetes and a weak immune system. The patient went to the hospital because of a fever and bloody sputum. In the last months of their life, they did not use the medication that they have to lower their blood sugar. This would probably have led to a decrease in immunity and allowed the penetration and growth of fungus in their lungs. At first, doctors diagnosed the patient with lung cancer, but closer examination revealed no definitive proof supporting the presence of cancer.

The lung in inborn errors of immunity.

The lungs are integral to immune defense, and inborn errors of immunity (IEI) often manifest as lung disease. Lung complications of IEI can involve the airways, alveolar spaces, interstitium, vasculature, and pleura. Accurate identification of these lung disease patterns requires a thorough clinical history, physical examination, and high-resolution computed tomography (HRCT), as lung imaging patterns guide further respiratory and immunological evaluations. Respiratory assessment may also include pulmonary function tests, bronchoscopy with bronchoalveolar lavage, and, in some cases, lung biopsy. Additionally, molecular diagnosis of underlying immune defects, typically through comprehensive clinical phenotyping, functional immune studies, and genetic testing, is crucial for informing patient management and guiding targeted therapies. Importantly, given the complexity of IEI, a multidisciplinary approach is necessary. Furthermore, ongoing research is required to refine therapies and improve outcomes for lung complications.

Development and validation of a predictive model for pulmonary infection risk in patients with traumatic brain injury in the ICU: a retrospective cohort study based on MIMIC-IV.

OBJECTIVE: To develop a nomogram for predicting occurrence of secondary pulmonary infection in patients with critically traumatic brain injury (TBI) during their stay in the intensive care unit, to further optimise personalised treatment for patients and support the development of effective, evidence-based prevention and intervention strategies. DATA SOURCE: This study used patient data from the publicly available MIMIC-IV (Medical Information Mart for Intensive Care IV) database. DESIGN: A population-based retrospective cohort study. METHODS: In this retrospective cohort study, 1780 patients with TBI were included and randomly divided into a training set (n=1246) and a development set (n=534). The impact of pulmonary infection on survival was analysed using Kaplan-Meier curves. A univariate logistic regression model was built in training set to identify potential factors for pulmonary infection, and independent risk factors were determined in a multivariate logistic regression model to build nomogram model. Nomogram performance was assessed with receiver operating characteristic (ROC) curves, calibration curves and Hosmer-Lemeshow test, and predictive value was assessed by decision curve analysis (DCA). RESULT: This study included a total of 1780 patients with TBI, of which 186 patients (approximately 10%) developed secondary lung infections, and 21 patients died during hospitalisation. Among the 1594 patients who did not develop lung infections, only 85 patients died (accounting for 5.3%). The survival curves indicated a significant survival disadvantage for patients with TBI with pulmonary infection at 7 and 14 days after intensive care unit admission (p<0.001). Both univariate and multivariate logistic regression analyses showed that factors such as race other than white or black, respiratory rate, temperature, mechanical ventilation, antibiotics and congestive heart failure were independent risk factors for pulmonary infection in patients with TBI (OR>1, p<0.05). Based on these factors, along with Glasgow Coma Scale and international normalised ratio variables, a training set model was constructed to predict the risk of pulmonary infection in patients with TBI, with an area under the ROC curve of 0.800 in the training set and 0.768 in the validation set. The calibration curve demonstrated the model's good calibration and consistency with actual observations, while DCA indicated the practical utility of the predictive model in clinical practice. CONCLUSION: This study established a predictive model for pulmonary infections in patients with TBI, which may help clinical doctors identify high-risk patients early and prevent occurrence of pulmonary infections.

The gut-lung axis: the impact of the gut mycobiome on pulmonary diseases and infections.

The gastrointestinal tract contains a diverse microbiome consisting of bacteria, fungi, viruses and archaea. Although these microbes usually reside as commensal organisms, it is now well established that higher abundance of specific bacterial or fungal species, or loss of diversity in the microbiome can significantly affect development, progression and outcomes in disease. Studies have mainly focused on the effects of bacteria, however, the impact of other microbes, such as fungi, has received increased attention in the last few years. Fungi only represent around 0.1% of the total gut microbial population. However, key fungal taxa such as Candida, Aspergillus and Wallemia have been shown to significantly impact health and disease. The composition of the gut mycobiome has been shown to affect immunity at distal sites, such as the heart, lung, brain, pancreas, and liver. In the case of the lung this phenomenon is referred to as the 'gut-lung axis'. Recent studies have begun to explore and unveil the relationship between gut fungi and lung immunity in diseases such as asthma and lung cancer, and lung infections caused by viruses, bacteria and fungi. In this review we will summarize the current, rapidly growing, literature describing the impact of the gut mycobiome on respiratory disease and infection.

The role of airways microbiota on local and systemic diseases: a rationale for probiotics delivery to the respiratory tract.

INTRODUCTION: Recent discoveries in the field of lung microbiota have enabled the investigation of new therapeutic interventions involving the use of inhaled probiotics. AREAS COVERED: This review provides an overview of what is known about the correlation between airway dysbiosis and the development of local and systemic diseases, and how this knowledge can be exploited for therapeutic interventions. In particular, the review focused on attempts to formulate probiotics that can be deposited directly on the airways. EXPERT OPINION: Despite considerable progress since the emergence of respiratory microbiota restoration as a new research field, numerous clinical implications and benefits remain to be determined. In the case of local diseases, once the pathophysiology is understood, manipulating the lung microbiota through probiotic administration is an approach that can be exploited. In contrast, the effect of pulmonary dysbiosis on systemic diseases remains to be clarified; however, this approach could represent a turning point in their treatment.

Chronic granulomatous disease: A single-center experience in Central Anatolia.

BACKGROUND: Chronic granulomatous disease (CGD), one of the phagocytic cell defects, is the primary immunodeficiency caused by dysfunction of the NADPH oxidase complex in neutrophils. METHODS: The clinical, demographic and laboratory findings of 17 CGD patients who were followed-up between 2002 and 2021 were obtained retrospectively from the records of the patients. RESULTS: The number of male and female patients was 10/7. The median age at diagnosis was 5.3 months (range 4-120) for 3 patients with X-CGD, and 42.4 months (range 8-350) for 14 patients with AR-CGD. We have investigated rare CYBA exon 3-6 deletion in 7 patients and hotspot mutation with delGT at the beginning of exon 2 of NCF1 in 5 patients. The most common clinical findings were pneumonia and lymphadenitis with recurrent fever, respectively (41.2%, 35.3%). A total of 154 microbial infections requiring hospital admission (27 in 3 XL and 127 in 14 AR patients) were detected in the follow-up of the patients and median infection number for a patient was 9 in both groups. Eight of 17 patients had stem cell transplantation and the survival rate was 87.5%. CONCLUSIONS: X-CGD patients are more rapidly recognized by family history and severe infections than those with AR-CGD and early prophylaxis may decrease infectious episodes. We have investigated the large deletion suggesting a possible founder effect for CYBA exon 3-6 deletion in Central Anatolia. Additionally, HSCT transplantation leads to a high survival rate for the patients with CGD.

Targeted treatment for biofilm-based infections using PEGylated tobramycin.

Chronic infections often involve biofilm-based bacteria, in which the biofilm results in significant resistance against antimicrobial agents and prevents eradication of the infection. The physicochemical barrier presented by the biofilm matrix is a major impediment to the delivery of many antibiotics. Previously, PEGylation has been shown to improve antibiotic penetration into biofilms in vitro. In these studies, PEGylating tobramycin was investigated both in vitro and in vivo. Two distinct PEGylated tobramycin molecules were synthesized (mPEG-SA-Tob and mPEG-AA-Tob). Then, in a P. aeruginosa biofilm in vitro model, we found that mPEG-SA-Tob can operate as a prodrug and showed 7 times more effectiveness than tobramycin (MIC80: 14 µM vs.100 µM). This improved biofilm eradication is attributable to the fact that mPEG-SA-Tob can aid tobramycin to penetrate through the biofilm and overcome the alginate-mediated antibiotic resistance. Finally, we used an in vivo biofilm-based chronic pulmonary infection rat model to confirm the therapeutic impact of mPEG-SA-Tob on biofilm-based chronic lung infection. mPEG-SA-Tob has a better therapeutic impact than tobramycin in that it cannot only stop P. aeruginosa from multiplying in the lungs but can also reduce inflammation caused by infections and prevent a recurrence infection. Overall, our findings show that PEGylated tobramycin is an effective treatment for biofilm-based chronic lung infections.

Dry powder inhalation containing muco-inert ciprofloxacin and colistin co-loaded liposomes for pulmonary P. Aeruginosa biofilm eradication.

Pseudomonas aeruginosa (PA), a predominant pathogen in lung infections, poses significant challenges due to its biofilm formation, which is the primary cause of chronic and recalcitrant pulmonary infections. Bacteria within these biofilms exhibit heightened resistance to antibiotics compared to their planktonic counterparts, and their secreted toxins exacerbate lung infections. Diverging from traditional antibacterial therapy for biofilm eradication, this study introduces a novel dry powder inhalation containing muco-inert ciprofloxacin and colistin co-encapsulated liposomes (Cipro-Col-Lips) prepared using ultrasonic spray freeze drying (USFD) technique. This USFD dry powder is designed to efficiently deliver muco-inert Cipro-Col-Lips to the lungs. Once deposited, the liposomes rapidly diffuse into the airway mucus, reaching the biofilm sites. The muco-inert Cipro-Col-Lips neutralize the biofilm-secreted toxins and simultaneously trigger the release of their therapeutic payload, exerting a synergistic antibiofilm effect. Our results demonstrated that the optimal USFD liposomal dry powder formulation exhibited satisfactory in vitro aerosol performance in terms of fine particle fraction (FPF) of 44.44 ± 0.78 %, mass median aerodynamic diameter (MMAD) of 4.27 ± 0.21 µm, and emitted dose (ED) of 99.31 ± 3.31 %. The muco-inert Cipro-Col-Lips effectively penetrate the airway mucus and accumulate at the biofilm site, neutralizing toxins and safeguarding lung cells. The triggered release of ciprofloxacin and colistin works synergistically to reduce the biofilm's antibiotic resistance, impede the development of antibiotic resistance, and eliminate 99.99 % of biofilm-embedded bacteria, including persister bacteria. Using a PA-beads induced biofilm-associated lung infection mouse model, the in vivo efficacy of this liposomal dry powder aerosol was tested, and the results demonstrated that this liposomal dry powder aerosol achieved a 99.7 % reduction in bacterial colonization, and significantly mitigated inflammation and pulmonary fibrosis. The USFD dry powder inhalation containing muco-inert Cipro-Col-Lips emerges as a promising therapeutic strategy for treating PA biofilm-associated lung infections.

Determinants of multidrug-resistant tuberculosis among adults undergoing treatment for tuberculosis in Tigray Region, Ethiopia: a case-control study.

BACKGROUND: Multidrug-resistant tuberculosis is a type of tuberculosis that is resistant to at least the first-line antituberculosis drugs namely, rifampicin and isoniazid. However, most of these studies were limited only to a single hospital. Therefore, this study aimed to identify the determinants of multidrug-resistant tuberculosis among adults undergoing treatment for tuberculosis in the Tigray region of Ethiopia. METHODS: Hospital-based unmatched case-control study was conducted from 1 April 2019 to 30 June 2019. A simple random sampling method was used to select the required sample size. Variables at a p value less than 0.25 in bivariate analysis were entered into a multivariable analysis to identify the determinant factors of multidrug-resistant tuberculosis. Finally, the level of significance was declared at p<0.05. RESULTS: Rural residence (adjusted OR (AOR) 2.54; 95% CI 1.34 to 4.83), HIV (AOR 4.5; 95% CI 1.4 to 14.2), relapse (AOR 3.86; 95% CI 1.98 to 7.5), return after lost follow-up (AOR 6.29; 95% CI 1.64 to 24.2), treatment failure (AOR 5.87; 95% CI 1.39 to 24.8) were among the determinants of multidrug-resistant tuberculosis. CONCLUSION: Rural residence, HIV, relapses, return after lost follow-up and treatment failure were the identified determinant factors of multidrug-resistance tuberculosis.

The prevalence of pneumothorax in human immunodeficiency virus patients. A single center study.

OBJECTIVES: To assess the prevalence, risk factors, and associated complications of pneumothorax that are present in patients with human immunodeficiency virus (HIV) at our institution and to provide an updated local study addressing the association between pneumothorax and HIV. METHODS: This retrospective cohort study examined 161 patients who were admitted with a diagnosis of HIV from June 2017 to May 2022. They were divided into 2 groups depending on the presence of pneumothorax during their stay. Multiple variables were studied, including age, gender, tuberculosis infection, pneumocystis jiroveci pneumonia (PJP)infection, bacterial pneumonia, and pneumothorax type and treatment course. RESULTS: There were 11 patients diagnosed with pneumothorax (prevalence rate: 6.8%). Bacterial lung infection was found in 9 (81.8%) of these patients, while fungal infection was found in 6 (54.5%) (p<0.001, 0.010). The MTB was found in 3 (27.3%) patients (p=0.728), while none were infected with PJP. Intercostal tube insertion was attempted in 9 (81.8%) patients, the mean duration of tube stay was 39.3±30.7 days, and the mortality rate was 72.7% (p=0.007). CONCLUSION: Pneumothorax in patients with HIV is a manifestation of the progression of the disease and its poor outcome. It has a complicated treatment course and a high mortality rate.