Systemic air embolism as a complication of percutaneous computed tomography guided transthoracic lung biopsy.

A 57-year-old man underwent prone position computed tomography (CT) guided percutaneous transthoracic lung biopsy. After removal of the 18-gauge biopsy needle, the patient lost consciousness and developed shock. CT showed signs of air embolism in descending aorta and left atrium. Cardiopulmonary resuscitation was unsuccessful. A postmortem CT scan confirmed a massive air embolism in the descending aorta, left ventricle and brain. Systemic air embolism occurs in around 0.001-0.003% of lung biopsy procedures. Recommendations to reduce the risk include requesting the patient to stop breathing during the procedure and preventing the exposure of the outer cannula of a coaxial biopsy needle to the atmosphere.

Leukocyte telomere length in patients with schizophrenia: A meta-analysis.

Schizophrenia has been suggested as a syndrome of accelerated aging. Telomere length (TL) decrease is considered one biological marker associated with age and can be accelerated by pathological characteristics present in schizophrenia. Several studies evaluated TL in schizophrenia, but the results are still controversial. The aim of this study was to conduct a meta-analysis of the existing results of TL in leukocytes of individuals with schizophrenia compared to healthy controls. A search was performed in PubMed, using the keywords 'telomere schizophrenia' and 'telomere psychosis'. We included data from original articles that measured TL in leukocytes of human patients with schizophrenia and healthy control subjects. 45 articles were found, but only 7 met our criteria. Telomere length of controls was not statistically different from that of patients with schizophrenia (p=0.07). Crossvalidation with the leave-one-out method resulted in a significant model (p=0.03) in which TL of individuals with schizophrenia is smaller than control (SMD=0.38; 95% CI=[0.05, 0.72]). We also propose a biological pathway through which schizophrenia could promote telomere erosion and how antipsychotics might compensate this loss. There are few studies made on this subject with diverse methodology and heterogeneous sample. Some articles did not consider other possible influences on TL. Overall our results suggest that TL is decreased in schizophrenia. Although this is consistent with the idea of accelerated aging, schizophrenia is a complex disease and there are several factors that influence TL that should be controlled in future studies.

[The longsurvivors for non-small cell lung cancer: remarks on the present and in perspective]. / Le lungosopravvivenze nel carcinoma broncogeno non-microcitoma: riflessioni criticamente "obbligate" sul presente e in prospettiva.

The Authors fully share cricitisms voiced in international literature to NSCLC longsurvivors, in particular those remarkes related to advanced disease patients following various anti-tumor treatments ( mostly multimodal). To this point, even the NCCN version 3.2014 guidelines prove inadequate as they mostly focus on longsurvivors post-NSCLC early stage surgical resection. Although AIOM Working Group's recommendations for follow-up seem to be more adequate, still they lack depth with respect to advanced-stage bronchogenic carcinoma. The Authors quote a number of case report related to advanced disease longsurvivors, and draws his attention on the peculiar role of pneumologists in the follow-up for such patients: in particular, as regards respiratory pathologies prior or subsequent to different anti-tumor treatments (i.e., BPCO, interstitial lung diseases, pulmonary thromboembolism, etc.).

[On adjuvant therapy after limited resections for NSCLC Stage IA in patients with high risk of recurrence: waiting for the announced 8th Edition 2017 of TNM Staging System]. / Sulla terapia adiuvante dopo resezioni limitate per NSCLC Stadio IA in pazienti ad alto rischio di recidiva: in attesa della annunciata 8a edizione 2017 del TNM Staging System.

The adjuvant therapy in NSCLC Stage IA still remains a controversial issue even in the interdisciplinary decision making after limited resections of the neoplasm as an alternative to lobectomy. The Authors accept from literature that this mainly concerns specific sub-group of patients, the istopathological post-resection diagnosis of whom highlights linfovascular o perineural as well as visceral pleura invasion. There is confidence that the presently depersonalizing rigidity in the guidelines implementation is overcome in the presence of clear istological signs of invasion. As a consequence the interdisciplinary team should reasonably consider as correct the adjuvant treatment.

Efficacy and safety of fibrin sealant patch in the treatment of air leakage in thoracic surgery.

AIM: Air leakage represents a major problem in lung surgery. Absorbable fibrin sealant patch (AFSP), a collagen sponge coated with human fibrinogen and thrombin, can be used as an adjunct to primary stapling or suturing. This study compared the efficacy of AFSP with manual suturing after primary stapling. METHODS: This was a prospective, multicenter, randomized study. Patients undergoing lobectomy, bilobectomy, anatomical segmentectomy for lung cancer or wedge resection for pulmonary metastasis with air leakage grade 1 or 2 according to Macchiarini scale after stapler suture were randomized to receive AFSP or standard surgical treatment (ST). The primary endpoint was the reduction of intraoperative air leakage intensity. Duration of postoperative air leakage and number of days until removal of last chest drain were secondary endpoints. Safety was recorded for all patients. RESULTS: A total of 346 patients were enrolled in 14 centres, 179 of whom received AFSP and 167 ST. Intraoperative air leak intensity was reduced in 90.5% of AFSP patients and 82% of ST patients (P=0.03). A significant reduction in postoperative air leakage duration was observed in the AFSP group (P=0.0437). The median number of days until removal of last drainage was 6 (3-37) in the AFSP group and 7 (2-27) in the ST (P=0.38). Occurrence of adverse events was comparable in both groups. CONCLUSION: AFSP was more efficacious than standard ST as an adjunct to primary stapling in reducing intraoperative air leakage intensity and duration of postoperative air leakage in patients undergoing pulmonary surgery. AFSP was well tolerated.

Role of combined 18F-FDG-PET/CT for predicting the WHO malignancy grade of thymic epithelial tumors: a multicenter analysis.

INTRODUCTION: To investigate the performance of combined (18)F-FDG-PET/CT as a predictor of the WHO-classification based malignancy grade in thymic epithelial tumors. METHODS: From 05/06 to 02/12, the data of 47 patients with thymic epithelial tumors assessed by (18)F-FDG-PET/CT before being surgically treated were collected in 3 centers and retrospectively reviewed for the purposes of this study. The SUVmax and the SUVmax/T index (the ratio tumor-SUVmax to tumor-size) have been matched with specific subgroups of the WHO-classification: low-risk thymomas (types A-AB-B1), high-risk thymomas (types B2-B3) and thymic carcinomas (type C). RESULTS: There were 22 men and 25 women (age range: 31-84 yrs). Mean tumor size was 44.7 ± 19.0 mm. The WHO-classification was: type-A #2, type-AB #11, type-B1 #9, type-B2 #9, type-B3 #9 and type-C #7. The SUVmax and the SUVmax/T were found to be predictive factors useful to distinguish thymomas from thymic carcinomas (SUVmax: area under ROC-curve: 0.955, p = 0.0045; SUVmax/T-size: area under ROC-curve: 0.927, p = 0.0022). Moreover, both parameters were found to be correlated with the WHO malignancy grade (low-risk thymomas; high-risk thymomas; thymic carcinoma), Spearman correlation coefficients being 0.56 (p < 0.0001) and 0.76 (p < 0.0001), respectively for the SUVmax and for the SUVmax/T index. In addition, the SUVmax is also significantly correlated with Masaoka stage (Spearman correlation coefficient: 0.30, p = 0.0436) CONCLUSIONS: A significant relationship was observed between (18)F-FDG-PET/CT findings and histologic WHO-classification for this cohort of thymic epithelial tumors. Thus, on the basis of these evidences, we infer that (18)F-FDG-PET/CT may be useful to predict histology and the WHO classes of risk.

Short-term safety of thoracoscopic talc pleurodesis for recurrent primary spontaneous pneumothorax: a prospective European multicentre study.

The safety of talc pleurodesis is under dispute following reports of talc-induced acute respiratory distress syndrome (ARDS) and death. We investigated the safety of large-particle talc for thoracoscopic pleurodesis to prevent recurrence of primary spontaneous pneumothorax (PSP). 418 patients with recurrent PSP were enrolled between 2002 and 2008 in nine centres in Europe and South Africa. The main exclusion criteria were infection, heart disease and coagulation disorders. Serious adverse events (ARDS, death or other) were recorded up to 30 days after the procedure. Oxygen saturation, supplemental oxygen use and temperature were recorded daily at baseline and after thoracoscopic pleurodesis (2 g graded talc). During the 30-day observation period following talc poudrage, no ARDS (95% CI 0.0-0.9%), intensive care unit admission or death were recorded. Seven patients presented with minor complications (1.7%, 95% CI 0.7-3.4%). After pleurodesis, mean body temperature increased by 0.41°C (95% CI 0.33-0.48°C; p<0.001) at day 1 and returned to baseline value at day 5. Pleural drains were removed after day 4 in 80% of patients. Serious adverse events, including ARDS or death, did not occur in this large, multicentre cohort. Thoracoscopic talc poudrage using larger particle talc to prevent recurrence of PSPS can be considered safe.

Epidemiology and a novel procedure for large scale analysis of CFTR rearrangements in classic and atypical CF patients: a multicentric Italian study.

BACKGROUND: Mutation epidemiology in each ethnic group is a crucial step of strategies for cystic fibrosis (CF) diagnosis and counselling. To date, the scanning of the whole coding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene permits to identify about 90% of alleles from patients bearing CF and a lower percentage in patients bearing atypical CF. CFTR rearrangements in heterozygosis elude current techniques for molecular analysis, and some of them have been reported with a frequency up to 6% in various ethnic groups. METHODS: Using quantitative PCR analysis of all coding regions, we assessed the occurrence of CFTR rearrangements in 130 alleles from classic CF patients and in 198 alleles from atypical CF patients (all unrelated and from Italian descent) bearing unidentified mutations after the scanning of CFTR. RESULTS: Seven rearrangements (i.e., dele1, dele2, dele2_3, dele 14b_17b, dele17a_18, dele22_23, and dele22_24) were identified in 34/131 (26.0%) CF alleles bearing undetected mutations (which means about 2.5% of all CF alleles) and in none of the 198 alleles from atypical CF. The CFTR haplotype and the sequence analysis of the breakpoints confirmed the common origin of all the rearrangements. Thus, we set up a novel duplex PCR assay for the large-scale analysis of the seven rearrangements. The procedure was rapid (all PCR amplifications were obtained under the same conditions), costless and repeatable. CONCLUSIONS: It is useful to select the CFTR rearrangements more frequent in specific ethnic groups and to set up procedures for large-scale analysis. Their study can be performed in cases in which a high detection rate is required (i.e., partners of CF carriers/patients). On the contrary, the analysis of rearrangement is useless in atypical CF patients.

Molecular epidemiology of phenylalanine hydroxylase deficiency in Southern Italy: a 96% detection rate with ten novel mutations.

Hyperphenylalaninemia (HPA) comprises a group of autosomal recessive disorders mainly caused by phenylalanine hydroxylase (PAH) gene mutations. We investigated PAH mutations in 126 HPA patients from Southern Italy who were identified in a neonatal screening program. The promoter, coding and exon-flanking intronic sequences of the PAH gene were amplified and sequenced. Mutations were identified in 240/249 alleles (detection rate: 96.4%). We found 60 gene variants; the most frequent were p.R261Q (15.7% of alleles), p.A403V (11.6% of alleles) and c.1066-11G > A (8.8% of alleles). The remaining mutations were rare, and ten are novel. This mutation epidemiology differs from that reported for Northern Italy and other European countries. We also identified several discordant genotype/phenotype correlations. About two-thirds of all mild phenylketonuria patients showed at least one tetrahydrobiopterin (BH4)-responsive mutation, and are thus candidates for a customized therapeutic approach.

Unusual amino acids: synthesis and introduction into naturally occurring peptides and biologically active analogues.

This review covers our recent advances in the synthesis of unusual amino acids in optically pure form, and their introduction into naturally occurring peptides with specific biological properties, or into modified bioactive peptides, aiming to obtain analogues displaying enhanced performances in term of activity, bioavailability and resistance to enzymatic hydrolysis.

Long-term follow-up of video-assisted talc pleurodesis in malignant recurrent pleural effusions.

OBJECTIVE: Recurrent pleural effusion is a common condition and often presents a challenge for treatment. The aim of this report is to evaluate the long-term follow-up of thoracoscopic management of malignant recurrent pleural effusions. METHODS: From July 1st, 1992 to February 28th, 2001, out of 2311 VATS procedures performed at our Institution, 690 patients (29.85%) underwent videothoracoscopy (VATS) for recurrent pleural effusion. Of these 611 (88.55%) were treated for a malignant pleural effusion. There were 374 male and 237 female, with a mean age of 61.2 years. In all patients VATS was performed under general anaesthesia. The pleural effusion was carefully aspirated; fibrinous adhesions were taken down while dense fibrous adhesions were selectively divided; some limited decortications were also performed. Multiple pleural biopsies were always performed. Pleurodesis was performed with 5 g of sterile purified talc insufflated through a talc atomizer. One chest tube was left in situ for 3-5 days. RESULTS: Operative mortality was 0.81% (five cases). Postoperative complications occurred in 19 cases (3.1%). Specific histologic diagnosis was obtained in all patients. Follow-up was available for 602 patients (98.5%). After a median follow-up of 64 months (range 5-105 months), talc pleurodesis was successful in controlling recurrence of effusion in 92.7% (558 out of 602) of patients. The success rate did not show any statistically significant difference between patients who underwent postoperative adjuvant therapy and patients who did not. In two patients with failure of talc pleurodesis a redo-VATS was performed. CONCLUSIONS: VATS represents the method of choice for both diagnosis and treatment of malignant recurrent pleural effusions. Talc poudrage is safe and effective in obtaining pleurodesis.

Neurotrophins and neurotrophin receptors in human lung cancer.

The expression of neurotrophins (NTs) and related high- and low-affinity receptors was studied in surgical samples of histologically diagnosed human tumors of the lower respiratory tract. The experiment was conducted with 30 non-small cell lung cancer specimens and in eight small cell lung cancer specimens by Western blot analysis and immunohistochemistry to assess expression and distribution of NT and NT receptor proteins in tissues examined. Immunoblots of homogenates from human tumors displayed binding of anti-nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and NT-3 antibodies as well as of anti-tyrosine-specific protein kinase (Trk) A, TrkB, and TrkC receptor antibodies, with similar migration characteristics than those displayed by human beta-NGF and proteins from rat brain. A specific immunoreactivity for NTs and NT receptors was demonstrated in vessel walls, stromal fibroblasts, immune cells, and sometimes within neoplastic cell bodies. Approximately 33% of bronchioloalveolar carcinomas exhibited a strong membrane NGF and TrkA immunoreactivity, whereas 46% adenocarcinomas expressed an intense TrkA immunoreactivity but a weak immunostaining for NGF within tumor cells. Moreover, squamous cell carcinomas developed an intense TrkA immunoreactivity only within stroma surrounding neoplastic cells. A faint BDNF and TrkB immunoreactivity was documented in adenocarcinomas, squamous cell carcinomas, and small cell lung cancers. NT-3 and its corresponding TrkC receptor were found in a small number of squamous cell carcinomas within large-size tumor cells. No expression of low-affinity p75 receptor protein was found in tumor cells. The detection of NTs and NT receptor proteins in tumors of the lower respiratory tract suggests that NTs may be involved in controlling growth and differentiation of human lung cancer and/or influencing tumor behavior.

NMR investigations on boron complexes in the conjugate addition on alpha,beta-unsaturated imides.

[reaction: see text]. The 1,4-addition of O-benzylhydroxylamine to alpha,beta-unsaturated imide 1 in the presence of BF3.Et2O proceeds with the preferential attack of the nucleophile on the Cbeta-re face. To explain this unexpected reactivity 1H, 13C, and 11B NMR investigations have been carried out on the boron-imide complex, which show the presence of an S-cis imide chain conformation.

Recurrences following videothoracoscopic treatment of primary spontaneous pneumothorax: the role of redo-videothoracoscopy.

OBJECTIVE: There is very little experience regarding recurrences following videothoracoscopic (VATS) treatment of primary spontaneous pneumothorax. We report our experience with 19 patients who underwent redo-VATS to evaluate the feasibility of such surgical approach. METHODS: From July 1, 1992 to September 1, 2000, out of 2136 VATS procedures performed at our institution, 597 patients (27.94%) underwent VATS treatment of primary spontaneous pneumothorax with a recurrence rate of 3.85% (23 cases). Primary VATS treatment in these patients was: talc poudrage, three cases; subtotal pleurectomy, three cases; ligation of the bullae + subtotal pleurectomy, 12 cases; stapling of the bullae + subtotal pleurectomy, two cases; ligation of the bullae + talc poudrage, one case; stapling of the bullae + talc poudrage, one case. Treatment of the 23 recurrences included: 15 redo-VATS, four standard thoracotomy, three pleural drainage, one bed rest. Four additional redo-VATS were also performed in four patients operated on in different institutions. Redo-VATS showed residual bullae in nine cases and a minimal leaking area in one patient; in the remaining nine patients no lesion was found. Redo-VATS treatment was: stapling of the bullae + talc poudrage in nine patients; suture of the leaking area with a no-knife stapler + talc poudrage in one patient; isolated talc poudrage in the remaining nine patients with no-evidence of bullae or blebs. RESULTS: No mortality was reported; no major complications occurred. The conversion rate in the group of redo-VATS was 5.2% (one patient). At a mean follow-up of 32 months no patient showed recurrent pneumothorax. CONCLUSIONS: In the light of our initial experience, redo-VATS seems to be a promising tool for the surgical therapy of recurrences following VATS treatment of primary spontaneous pneumothorax.

Chest wall invasion in non-small cell lung carcinoma: a rationale for en bloc resection.

OBJECTIVE: The choice of surgical approach to non-small cell lung cancer invading the chest wall, extrapleural resection versus en bloc chest wall resection, is much more related to the experience of the surgeon than to objective criteria. The aim of the present study is to help to establish a rationale for en bloc chest wall resection in lung cancer invading the chest wall. METHODS: From January 1990 to June 1999, of 1855 patients having major pulmonary resections for non-small cell lung carcinoma, 104 (5.6%) patients with neoplasms involving the chest wall underwent en bloc chest wall and lung resection plus radical mediastinal lymphadenectomy. RESULTS: All patients underwent complete resection with microscopically disease-free tissue margins. Depth of invasion was into the parietal pleura only in 28 (26.92%), into the pleura and soft tissue in 36 (34.62%), and into the pleura, soft tissue, and bone in 40 (38.46%). No operative mortality was reported. Follow-up was completed in 96 patients. One patient had a local recurrence. The overall 5-year estimated survival was 61.4%. Survival in the subsets T3 N0 and T3 N2 were, respectively, 67.3% and 17.9% (P =.007). The 5-year survival was 79.1% in involvement of parietal pleura only and 54.0% in involvement of soft tissue with or without bone invasion (P =.014). Five-year survival was 53.0% in adenocarcinoma versus 71.8% in squamous cell carcinoma (P =.329) and 74.1% in patients who did undergo radiation therapy versus 46.7% in patients who did not undergo radiation therapy (P =.023). CONCLUSIONS: En bloc resection of the chest wall and lung is the procedure of choice to obtain complete resection in lung carcinoma invading the chest wall. Survival is highly dependent on the completeness of resection, nodal involvement, and depth of chest wall invasion.

A new selective synthesis of the Ile-allo-Thr-Gly tripeptide fragment of lysobactin.

[formula: see text] trans-Aziridine-2-carboxylic acid derivatives are useful intermediates for the synthesis of threonine or allo-threonine through ring expansion and SN2 displacement, respectively. We describe here the preparation of the Ile-allo-Thr-Gly 11 fragment of Lysobactin via the aziridine 9 intermediate.

Videothoracoscopic treatment of primary spontaneous pneumothorax: a 6-year experience.

BACKGROUND: Timing and surgical approach in the treatment of primary spontaneous pneumothorax (PSP) are not well defined. The objective of this study is to propose a treatment protocol by videothoracoscopy (VATS) in PSP. METHODS: From July 1992 to May 1998, 432 patients underwent VATS treatment of PSP. Indications were: recurrent ipsilateral pneumothorax: 322 cases; persistent air leak following a first episode: 93 patients; recurrence following VATS: 16 cases; recurrence following thoracotomy: 1 patient. Vanderschueren's classification was used for staging. Surgical indications were: stages I and II, subtotal pleurectomy or talc poudrage; stages III and IV, stapling or ligation of the bullae and subtotal pleurectomy or talc poudrage. Differences in recurrence rates were calculated to compare the specific procedures. RESULTS: No postoperative deaths occurred. Complication rate was 4.16%. Conversion rate was 2.3%. Mean follow-up was 38 months (2 to 72 months). Overall recurrence rate was 4.4%. Specific recurrence rates following stapling and talc poudrage were, respectively, 1.27% and 1.79%. Talc poudrage and stapling of the bullae are respectively superior to subtotal pleurectomy (p < 0.0001) and ligation (p < 0.0001). CONCLUSIONS: Stapling of the bullae and talc poudrage by VATS represent the treatment of choice of PSP.

Localized (solitary) fibrous tumors of the pleura: an analysis of 55 patients.

BACKGROUND: Localized (solitary) fibrous tumors (LFTPs) of the pleura are rare, slow-growing neoplasms thought to originate from submesothelial connective tissue. The aim of this article is to present 55 new cases of LFTP, and to discuss the treatment of choice and the clinical behavior of such neoplasms. METHODS: From July 1990 to November 1999, 55 patients (32 male, 23 female) with an LFTP were surgically treated at our Institution. Neoplasms were considered to be malignant if one or more of the following histologic features were present: high cellularity with crowding and overlapping of nuclei; high mitotic activity; or mild, moderate, or marked pleomorphism. RESULTS: No operative mortality was reported. Forty-eight of the cases arose from the visceral pleura and seven arose from the parietal pleura. A local removal of the neoplasm with free surgical margins was accomplished by video-assisted thoracic surgery in 39 patients and by standard thoracotomy in 10 patients. Four patients underwent formal lung resections, 1 had thymectomy, and 1 had en bloc chest wall resection. Four malignant variants were identified. One patient developed local recurrence and underwent redo surgery with chest wall resection. One patient died of unrelated disease. The remaining patients are alive and disease free at a median follow-up of 53.2 months. CONCLUSIONS: LFTPs show a benign outcome in most of the cases. Video-assisted thoracic surgery, with intraoperative assessment of the surgical margins, represents the treatment of choice.