Management and treatment of Magnusiomyces capitatus (Geotrichum capitatum) pleural infection in a non-neutropenic patient with posaconazole. A new therapeutic opportunity?

Magnusiomyces capitatus may cause uncommon yet severe infections, especially in patients with haematologic disorders. Diagnosis may be difficult and time-consuming and newer approaches are required including the MALDI-TOF technique implemented with the detection of fungal antigens in the body fluids. The recommended treatment includes amphotericin B alone or in combination with flucytosine. We describe a case of a non-neutropenic patient with M. capitatus pleural infection, as identified by MALDI-TOF, positivity for galactomannan antigen in the BAL fluid, and successfully treated with oral posaconazole in single therapy.

Genetic variation and population structure in the endangered Hermann's tortoise: the roles of geography and human-mediated processes.

The Hermann's tortoise (Testudo hermanni) is an endangered land tortoise distributed in disjoint populations across Mediterranean Europe. We investigated its genetic variation by typing 1 mitochondrial locus and 9 nuclear microsatellites in approximately 300 individuals from 22 localities. Our goal was to understand the relative impact of natural and human-mediated processes in shaping the genetic structure and to identify the genetic priorities for the conservation of this species. We found that 1) all geographic areas are highly differentiated, mainly as a function of their distance but with a clear genetic discontinuity (F st values larger than 0.4) between the Eastern and the Western subspecies; 2) the contact zone between subspecies is located farthest to the west than previously believed, and it probably coincides with the delta of the largest Italian river; 3) extinction events due to climatic conditions in the Upper Palaeolithic and subsequent human-mediated translocations in the Neolithic possibly explain the unexpected similarity among Spain, Sicily, and Corsica. For conservation purposes, the large majority of genetic pools appears native although hybridization among subspecies, related to extensive 20th century trade of tortoises across Europe, is observed in Spain and some Italian samples. Most populations do not seem at immediate risk of low genetic variation, except the French population, which has very low nuclear genetic diversity (heterozygosity = 0.25) and where 50 out of 51 sampled animals shared the same mitochondrial sequence. In general, restocking and reintroduction plans should carefully consider the genetic background of the individuals.

Correlation between collateral ventilation and interlobar lung fissures.

BACKGROUND: New bronchoscopic techniques for end-stage emphysema treatment are nowadays available; the presence of interlobar collateral ventilation (CV) and interlobar lung fissures (ILF) is crucial for patient selection. OBJECTIVES: Assessment of these variables has been reported previously, but it has never been anatomically validated in vivo. This is the purpose of our study. METHODS: Twenty-one patients undergoing lung resection for lung cancer were prospectively enrolled in this study. At operation, CV was assessed by the Chartis catheter system. ILF completeness at high-resolution computed tomography (HRCT) was retrospectively reviewed. The ILF status at HRCT and at surgery was compared; furthermore, the relationship between CV and ILF status was assessed. RESULTS: At HRCT, ILF were incomplete in 18 cases; at catheter evaluation, CV was present in 11 cases; 15 patients had incomplete ILF at operation. HRCT specificity, sensitivity and accuracy were 33, 93 and 76% compared with ILF status at surgery. HRCT accuracy was 90% on the right and 63% on the left. We demonstrated a high grade of probability of CV presence and incomplete ILF at surgery (odds ratio = 10.0). CONCLUSIONS: There is a correlation between ILF status and CV. Both catheter evaluation of CV and HRCT assessment of ILF show some limitations. However, the cumulative information provided by these techniques allows to reliably assess the anatomical ILF status.

Malignant Solitary Fibrous Tumours of the Pleura Are Not All the Same: Analysis of Long-Term Outcomes and Evaluation of Risk Stratification Models in a Large Single-Centre Series.

Introduction: Malignant solitary fibrous tumours of the pleura (mSFTP) are extremely rare diseases (<5% of all pleural neoplasms) with unpredictable behaviour. Surgery remains the standard of care for these tumours; however, estimating patient prognosis and planning follow-up remain challenging. Several risk stratification models have been proposed, but a classification with diagnostic and prognostic potential has not been well standardised yet. The aim of this study was to analyse the clinicopathological data of mSFTP to investigate their prognostic features and to compare the performance of three risk stratification models proposed in the literature. Methods: Observational retrospective cohort study on all proven cases of mSFTP surgically resected with radical intent between 2000 and 2019 in a single centre. Demographic, surgical and pathological data were examined. All patients were risk-stratified by using three prediction models: modified Demicco, De Perrot and Tapias. Overall survival (OS) and disease-free survival (DFS) were analysed. Results: There were 21 men and 13 women (median age, 67 years, range, 23-83 years). Twenty-one patients (62%) were symptomatic. The median follow-up was 111 months (range, 6-258 months). The 5-year OS and DFS were 81.2% and 77.4%, respectively. Nine patients (26.5%) experimented recurrences. At univariate analysis, the presence of necrosis (p = 0.019), nuclear atypia (p = 0.006), dimension greater than 11.5 cm (median value of our cohort) (p = 0.037) and relapse/disease progression (p = 0.001) were independent prognostic factor of worse OS. The administration of adjuvant treatment was a protective independent factor for survival (p = 0.001). Radicality of resection (p = 0.005); tumour dimension (p = 0.013), presence of necrosis (p = 0.041) and nuclear atypia (p = 0.007) and pleural pattern (p = 0.011) were independent prognostic factors of worse DFS. Analysing the three risk stratification models, the Tapias score was revealed as the best index to predict both OS (p = 0.002) and DFS (p = 0.047) in patients with mSFTP. Conclusions: Using the risk stratification model proposed by Tapias, patients with the highest risk of recurrence could be identified at the time of surgery to establish a more frequent imaging surveillance and longer follow-up. The role of adjuvant treatment in mSFTP therapy has not been established yet, but further analysis on patients with a high risk of recurrence, stratified according to risk models, along with biomolecular panels may tailor future post-surgical therapies.

Effective Mechanical Properties of AlSi7Mg Additively Manufactured Cubic Lattice Structures.

Lattice structures, whose manufacturing has been enabled by additive technologies, are gaining growing popularity in all the fields where lightweighting is imperative. Since the complexity of the lattice geometries stretches the technological boundaries even of additive processes, the manufactured structures can be significantly different from the nominal ones, in terms of expected dimensions but also of defects. Therefore, the successful use of lattices needs the combined optimization of their design, structural modeling, build orientation, and setup. The article reports the results of quasi-static compression tests performed on BCCxyz lattices manufactured in a AlSi7Mg alloy using additive manufacturing. The results are compared with numerical simulations using two different approaches. The findings show the influence of the relative density on stiffness, strength, and on the energy absorption properties of the lattice. The correlation with the technological feasibility points out credible improvements in the choice of a unit cell with fewer manufacturing issues, lower density, and possibly equal mechanical properties.

Which Surgery for Stage II-III Empyema Patients? Observational Single-Center Cohort Study of 719 Consecutive Patients.

OBJECTIVE: Recent guidelines support the use of thoracoscopic surgery in stage II-III empyema; however, there is still debate regarding the best surgical approach. The aim of our study is to compare postoperative outcomes of VATS and open surgical approaches for the treatment of post-pneumonic empyema. METHODS: Observational cohort study on prospectively collected cases of post-pneumonic empyema surgically treated in a single center (2000-2020). Patients were divided into an open group (OT, posterolateral muscle sparing thoracotomy) and VATS group (VT, 2 or 3 port ± utility incision). The primary outcome of the study was empyema resolution, assessed by the recurrence rate. Secondary outcomes were mortality, complications, pain and return to daily life. All patients were followed up at 1, 3 and 6 months after surgery in the outpatient clinic with a chest radiograph/CT scan. RESULTS: In total, 719 consecutive patients were surgically treated for stage II-III empyema, with 644 belonging to the VT group and 75 to the OT group. All patients had a clinical history of pneumonia lasting no more than 6 months before surgery, and 553 (76.9%) had stage II empyema. Operative time was 92.7 ± 6.8 min for the OT group and 112.2 ± 7.4 for the VT group. The conversion rate was 8.4% (46/545) for stage II and 19.2% (19/99) for stage III. Twelve patients (1.86%) in the VT group and four patients (5.3%) in the OT group underwent additional surgery for bleeding. Postoperative mortality was 1.25% (9/719): 5.3% (4/75) in OT and 0.77% (5/644) in VT. Postoperative stay was 10 ± 6.5 days in OT and 8 ± 2.4 in VT. Overall morbidity was 14.7% (106/719): 21.3% (16/75) in OT and 13.9% (90/644) in VT. In VT, six patients (0.93%) showed recurrent empyema: five were treated with chest drainage and one with additional open surgery. CONCLUSIONS: Our findings suggest that the VATS approach, showing a 99% success rate, shorter length of stay and lower postoperative morbidity, should be considered the treatment of choice for thoracic empyema.

Coaxial Drainage versus Standard Chest Tube after Pulmonary Lobectomy: A Randomized Controlled Study.

Chest tubes are routinely inserted after thoracic surgery procedures in different sizes and numbers. The aim of this study is to assess the efficacy of Smart Drain Coaxial drainage compared with two standard chest tubes in patients undergoing thoracotomy for pulmonary lobectomy. Ninety-eight patients (57 males and 41 females, mean age 68.3 ± 7.4 years) with lung cancer undergoing open pulmonary lobectomy were randomized in two groups: 50 received one upper 28-Fr and one lower 32-Fr standard chest tube (ST group) and 48 received one 28-Fr Smart Drain Coaxial tube (SDC group). Hospitalization, quantity of fluid output, air leaks, radiograph findings, pain control and costs were assessed. SDC group showed shorter hospitalization (7.3 vs. 6.1 days, p = 0.02), lower pain in postoperative day-1 (p = 0.02) and a lower use of analgesic drugs (p = 0.04). Pleural effusion drainage was lower in SDC group in the first postoperative day (median 400.0 ± 200.0 mL vs. 450.0 ± 193.8 mL, p = 0.04) and as a mean of first three PODs (median 325.0 ± 137.5 mL vs. 362.5 ± 96.7 mL, p = 0.01). No difference in terms of fluid retention, residual pleural space, subcutaneous emphysema and complications after chest tubes removal was found. In conclusion, Smart Drain Coaxial chest tube seems a feasible option after thoracotomy for pulmonary lobectomy. The SDC group showed a shorter hospitalization and decreased analgesic drugs use and, thus, a reduction of costs.

Role of radiomics in predicting lung cancer spread through air spaces in a heterogeneous dataset.

Background: Spread through air spaces (STAS) has been reported as a negative prognostic factor in patients with lung cancer undergoing sublobar resection. Radiomics has been recently proposed to predict STAS using preoperative computed tomography (CT). However, limitations of previous studies included the strict selection of imaging acquisition protocols, leading to results hardly applicable to daily clinical practice. The aim of this study is to test a radiomics-based prediction model of STAS in a practice-based dataset. Methods: A training cohort of 99 consecutive patients (65 STAS+ and 34 STAS-) with resected lung adenocarcinoma (ADC) was retrospectively collected. Preoperative CT images were collected from different centers regardless model and scanner manufacture, acquisition and reconstruction protocol, contrast phase and pixel size. Radiomics features were selected according to separation power and P value stability within different preprocessing setups and bootstrapping resampling. A prospective cohort of 50 patients (33 STAS+ and 17 STAS-) was enrolled for the external validation. Results: Only the five features with the highest stability were considered for the prediction model building. Radiomics, radiological and mixed radiomics-radiological prediction models were created, showing an accuracy of 0.66±0.02 after internal validation and reaching an accuracy of 0.78 in the external validation. Conclusions: Radiomics-based prediction models of STAS may be useful to properly plan surgical treatment and avoid oncological ineffective sublobar resections. This study supports a possible application of radiomics-based models on data with high variance in acquisition, reconstruction and preprocessing, opening a new chance for the use of radiomics in the prediction of STAS. Trial Registration: ClinicalTrials.gov identifier: NCT04893200.

Prognostic impact of spread through air spaces in lung adenocarcinoma.

OBJECTIVE: Spread through air spaces (STAS) is a pattern of invasion present in some adenocarcinomas (ADC). The goal of this study was to assess the impact of STAS in patients treated with different types of surgical resections and on the clinical outcome in patients with ADC of different diameters and with different degrees of nodal involvement. METHODS: A total of 109 patients were reviewed. Complete surgical resection with systematic nodal dissection was achieved in all patients. The median follow-up was 65 months (3-90 months). RESULTS: STAS was observed in 70 cases (64.2%); 13 patients (18.5%) had lymph node involvement (N1 and N2). Overall survival and progression-free survival were higher in patients without STAS (P = 0.042; P = 0.027). The presence of STAS in tumours ≤2 cm was a predictor of worse progression-free survival following sublobar resection compared to major resections (P = 0.011). Sublobar resection of N0 STAS-positive tumours was associated with worse long-term survival compared to a major resection (P = 0.04). Statistical analyses showed that age >70 years and recurrence were independent variables for survival; smoking pack-years >20, sublobar resection and nodal involvement were independent variables for recurrence; and smoking pack-years >20 were independent variables for a history of cancer and pleural invasion for local recurrence. CONCLUSIONS: STAS seems to play a role in long-term survival, particularly for patients with N0 and tumours smaller than 2 cm. Further studies are necessary to validate this hypothesis.

Left uniportal VATS for lung decortication after chemical pleurodesis under spontaneous breathing in patient with lymphangiomyomatosis.

Pneumothorax can be the first symptom of lymphangioleiomyomatosis. Patients with lymphangioleiomyomatosis have a higher risk of recurrence of pneumothorax. Chemical pleurodesis is a viable option to treat the recurrence, but in rare cases, it is not the solution. We present the case of a patient with lymphangioleiomyomatosis undergoing a talc poudrage via video-assisted thoracoscopic surgery for pneumothorax that failed to reexpand the lung. We proposed to the patient a surgical approach to debride the lung parenchyma with the patient under deep sedation with spontaneous breathing. The patient was discharged on the 5th postoperative day. The chest computed tomography scan showed complete lung reexpansion.    We advocate that video-assisted thoracoscopic surgery in patients who are awake is a feasible surgical option that permits the restoration of physiological lung expansion in selected patients who underwent chemical pleurodesis and minimizes the risk of one-lung ventilation.

Thymomectomy plus total thymectomy versus simple thymomectomy for early-stage thymoma without myasthenia gravis: a European Society of Thoracic Surgeons Thymic Working Group Study.

OBJECTIVES: Resection of thymic tumours including the removal of both the tumour and the thymus gland (thymothymectomy; TT) is the procedure of choice and is recommended in most relevant articles in the literature. Nevertheless, in recent years, some authors have suggested that resection of the tumour (simple thymomectomy; ST) may suffice from an oncological standpoint in patients with early-stage thymoma who do not have myasthenia gravis (MG) (non-MG). The goal of our study was to compare the short- and long-term outcomes of ST versus TT in non-MG early-stage thymomas using the European Society of Thoracic Surgeons thymic database. METHODS: A total of 498 non-MG patients with pathological stage I thymoma were included in the study. TT was performed in 466 (93.6%) of 498 patients who had surgery with curative intent; ST was done in 32 (6.4%). The completeness of resection, the rate of complications, the 30-day mortality, the overall recurrence and the freedom from recurrence were compared. We performed crude and propensity score-adjusted comparisons by surgical approach (ST vs TT). RESULTS: TT showed the same rate of postoperative complications, 30-day mortality and postoperative length of stay as ST. The 5-year overall survival rate was 89% in the TT group and 55% in the ST group. The 5-year freedom from recurrence was 96% in the TT group and 79% in the ST group. CONCLUSION: Patients with early-stage thymoma without MG who have a TT show significantly better freedom from recurrence than those who have an ST, without an increase in postoperative morbidity rate.

Technological Feasibility of Lattice Materials by Laser-Based Powder Bed Fusion of A357.0.

Lattice materials represent one of the utmost applications of additive manufacturing. The promising synergy between additive processes and topology optimization finds full development in achieving components that comprise bulky and hollow areas, as well as intermediate zones. Yet, the potential to design innovative shapes can be hindered by technological limits. The article tackles the manufacturability by laser-based powder bed fusion (L-PBF) of aluminum-based lattice materials by varying the beam diameter and thus the relative density. The printing accuracy is evaluated against the distinctive building phenomena in L-PBF of metals. The main finding consists in identification of a feasibility window that can be used for development of lightweight industrial components. A relative density of 20% compared with fully solid material (aluminum alloy A357.0) is found as the lowest boundary for a 3-mm cell dimension for a body-centered cubic structure with struts along the cube edges (BCCXYZ) and built with the vertical edges parallel to the growth direction to account for the worst-case scenario. Lighter structures of this kind, even if theoretically compliant with technical specifications of the machine, result in unstable frameworks.

Left main bronchial sleeve resection with total lung parenchymal preservation: a tailored surgical approach.

Bronchial sleeve resection is an uncommon thoracic surgical procedure. Under specific conditions, patients can be selected to undergo a sleeve resection of the main bronchus with complete parenchymal preservation. The left main bronchus is longer than the contralateral bronchus, therefore left endobronchial tumours can be localized at the proximal end of the bronchus or distally, near the secondary carina. Bronchial anastomosis in these 2 situations requires different approaches. We present the surgical technique of left main bronchus resection with complete preservation of lung parenchyma through a hemi-clamshell incision (proximal tumour) or posterolateral thoracotomy (distal tumour).

Comparison of preoperative scores predicting outcome in elderly undergoing lung malignancies resection.

BACKGROUND: Increased age of cancer patients is not an absolute contraindication to pulmonary resection. Different scores have been developed to determine the risk of morbidity and mortality. We have compared four scores in a series of elderly patients with primary or metastatic lung neoplasms who underwent pulmonary resection. METHODS: Data from 150 patients with an age equal or more than 75 years were reviewed. Mean age was 78.3 (range, 75-86) years. Based on medical history and preoperative tests 4 predicting scores were calculated. Statistical analysis was performed to identify which score correlates better with postoperative morbidity and mortality. RESULTS: Mortality at 30 days was observed in 3 patients (2%). Postoperative morbidity was observed in 38 patients (25.3%). Univariate analysis showed that risk factors significantly predicting the onset of postoperative complications were type of resection (P=0.02), American Society of Anesthesiology (ASA) score (P<0.001) and Glasgow Prognostic Score (GPS) (P=0.02). At multivariate analysis smoking and type of resection were significant prognostic factors for both overall and pulmonary morbidity; the ASA score and GPS showed an impact only on overall morbidity. The Cox regression showed significant results for GPS greater than zero and cancer-related death. Age above 80 years was not a negative prognostic factor. A significant difference in terms of 1-year survival was noted in ASA I-II vs. ASA III-IV (90% vs. 78%; P=0.022) and GPS 0 vs. GPS 1 or 2 (90% vs. 77%; P=0.02). CONCLUSIONS: Prognostic scores are useful to predict postoperative morbidity and mortality and GPS seems to correlate better with them.

Use of Ceftazidime-Avibactam and Ceftolozane-Tazobactam After Lung Transplantation.

INTRODUCTION: After lung transplantation (LTx), infections caused by multidrug-resistant (MDR) bacteria are frequent and difficult to treat. Some new antibiotics seem to be effective in treating these infections. MATERIAL AND METHODS: We describe our experience in treatment of Klebsiella pneumoniae MDR and Pseudomonas aeruginosa MDR infections with ceftazidime-avibactam (CEF-AVI) and ceftazidime-tazobactam (CEFT-TAZ) in patients who underwent LTx. RESULTS: In 3 patients who underwent double LTx and in 4 patients who underwent single LTx, strains of K. pneumoniae and P. aeruginosa were isolated from bronchoalveolar lavage. All patients showed worsening of respiratory functions, increasing in inflammation indexes, and, in some cases, onset of pulmonary consolidation. P. aeruginosa was treated with CEFT-TAZ for 10 days average (7-15 days) and K. pneumoniae with CEF-AVI for 14 days average (4-24 days). One patient developed a septic state caused by K. pneumoniae, requiring 24 days of therapy. None had shown side effects caused by drugs administration. One patient died after 15 days from lung transplant owing to primary graft dysfunction. CONCLUSIONS: CEF-AVI and CEFT-TAZ seems to be effective in treatment of infections caused by MDR bacteria after lung transplant.

Inflammatory Myofibroblastic Tumor After Lung Transplant-A Rare and Aggressive Complication: A Case Report.

INTRODUCTION: Malignant diseases are well-known complications after lung transplantation (LT). Among these, inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with a not well-known and often aggressive biological behavior. MATERIAL AND METHODS: We hereby describe 2 cases of cystic fibrosis patients who underwent bilateral sequential LT (BSLT) complicated by IMT. RESULTS: A 26-year-old man presented a right endobronchial lesion 6 months after BSLT. Two consecutive fiber bronchoscopic biopsies showed granulation tissue. For the persistent lesion growth, the patient underwent a transthoracic biopsy showing histologic diagnosis of IMT. Therefore, he underwent to right pneumonectomy that was unfortunately complicated after 6 months with a late bronchopleural fistula and empyema with exitus 6 months later. A 31-year-old woman 1 year after BSLT presented with a left voluminous pleural-parenchymal lesion; the histologic examination after biopsy revealed an IMT. She underwent a removal of the lesion with a macroscopic R0 resection. Histologic, immunophenotypic, and cytogenetic examinations showed a strong overexpression of anaplastic lymphoma kinase requiring biological adjuvant therapies; however, the patient refused it. Four years later, she presented a recurrence treated with debulking procedure and adjuvant radiotherapy. At last follow-up, the patient was alive with stable disease and optimal graft function. CONCLUSIONS: Although IMT is a rare complication after lung transplant, to obtain a careful diagnosis, an early and aggressive treatment is mandatory.