Search

Abstract Background Most scales that assess the presence and severity of psychotic symptoms often measure a broad range of experiences and behaviours, something that restricts the detailed measurement of specific symptoms such as delusions or hallucinations. The Psychotic Symptom Rating Scales (PSYRATS) is a clinical assessment tool that focuses on the detailed measurement of these core symptoms. The goal of this study was to examine the psychometric properties of the French version of the PSYRATS. Methods A sample of 103 outpatients suffering from schizophrenia or schizoaffective disorders and presenting persistent psychotic symptoms over the previous three months was assessed using the PSYRATS. Seventy-five sample participants were also assessed with the Positive And Negative Syndrome Scale (PANSS). Results ICCs were superior to .90 for all items of the PSYRATS. Factor analysis replicated the factorial structure of the original version of the delusions scale. Similar to previous replications, the factor structure of the hallucinations scale was partially replicated. Convergent validity indicated that some specific PSYRATS items do not correlate with the PANSS delusions or hallucinations. The distress items of the PSYRATS are negatively correlated with the grandiosity scale of the PANSS. Conclusions The results of this study are limited by the relatively small sample size as well as the selection of participants with persistent symptoms. The French version of the PSYRATS partially replicates previously published results. Differences in factor structure of the hallucinations scale might be explained by greater variability of its elements. The future development of the scale should take into account the presence of grandiosity in order to better capture details of the psychotic experience.

Abstract Background The risk of influenza infection depends on biological characteristics, individual or collective behaviors and the environmental context. The Cohorts for Pandemic Influenza (CoPanFlu) France study was set up in 2009 after the identification of the novel swine-origin A/H1N1 pandemic influenza virus. This cohort of 601 households (1450 subjects) representative for the general population aims at using an integrative approach to study the risk and characteristics of influenza infection as a complex combination of data collected from questionnaires regarding sociodemographic, medical, behavioral characteristics of subjects and indoor environment, using biological samples or environmental databases. Methods/Design Households were included between December 2009 and July 2010. The design of this study relies on systematic follow-up visits between influenza seasons and additional visits during influenza seasons, when an influenza-like illness is detected in a household via an active surveillance system. During systematic visits, a nurse collects individual and environmental data on questionnaires and obtains blood samples from all members of the household. When an influenza-like-illness is detected, a nurse visits the household three times during the 12 following days, and collects data on questionnaires regarding exposure and symptoms, and biological samples (including nasal swabs) from all subjects in the household. The end of the follow-up period is expected in fall 2012. Discussion The large amount of data collected throughout the follow-up will permit a multidisciplinary study of influenza infections. Additional data is being collected and analyzed in this ongoing cohort. The longitudinal analysis of these households will permit integrative analyses of complex phenomena such as individual, collective and environmental risk factors of infection, routes of transmission, or determinants of the immune response to infection or vaccination.

Abstract Background Kabuki syndrome (Niikawa-Kuroki syndrome) is a rare, multiple congenital anomalies/mental retardation syndrome characterized by a peculiar face, short stature, skeletal, visceral and dermatoglyphic abnormalities, cardiac anomalies, and immunological defects. Recently mutations in the histone methyl transferase MLL2 gene have been identified as its underlying cause. Methods Genomic DNAs were extracted from 62 index patients clinically diagnosed as affected by Kabuki syndrome. Sanger sequencing was performed to analyze the whole coding region of the MLL2 gene including intron-exon junctions. The putative causal and possible functional effect of each nucleotide variant identified was estimated by in silico prediction tools. Results We identified 45 patients with MLL2 nucleotide variants. 38 out of the 42 variants were never described before. Consistently with previous reports, the majority are nonsense or frameshift mutations predicted to generate a truncated polypeptide. We also identified 3 indel, 7 missense and 3 splice site. Conclusions This study emphasizes the relevance of mutational screening of the MLL2 gene among patients diagnosed with Kabuki syndrome. The identification of a large spectrum of MLL2 mutations possibly offers the opportunity to improve the actual knowledge on the clinical basis of this multiple congenital anomalies/mental retardation syndrome, design functional studies to understand the molecular mechanisms underlying this disease, establish genotype-phenotype correlations and improve clinical management.

Background The Ouabain and Adducin for Specific Intervention on Sodium in Hypertension (OASIS-HT) Trial was a phase-2 dose-finding study of rostafuroxin, a digitoxygenin derivative, which selectively antagonizes the effects of endogenous ouabain (EO) on Na+,K+-ATPase and mutated adducin. Rostafuroxin lowered blood pressure (BP) in some animal models and in humans. Methods OASIS-HT consisted of 5 concurrently running double-blind cross-over studies. After 4 weeks without treatment, 435 patients with uncomplicated systolic hypertension (140-169 mm Hg) were randomized to rostafuroxin (0.05, 0.15, 0.5, 1.5 or 5.0 mg/d) or matching placebo, each treatment period lasting 5 weeks. The primary endpoint was the reduction in systolic office BP. Among the secondary endpoints were diastolic office BP, 24-h ambulatory BP, plasma EO concentration and renin activity, 24-h urinary sodium and aldosterone excretion, and safety. ANOVA considered treatment sequence (fixed effect), subjects nested within sequence (random), period (fixed), and treatment (fixed). Results Among 410 analyzable patients (40.5% women; mean age, 48.4 years), the differences in the primary endpoint (rostafuroxin minus placebo) ranged from -0.18 mm Hg (P = 0.90) on 0.15 mg/d rostafuroxin to 2.72 mm Hg (P = 0.04) on 0.05 mg/d. In the 5 dosage arms combined, the treatment effects averaged 1.30 mm Hg (P = 0.03) for systolic office BP; 0.70 mm Hg (P = 0.08) for diastolic office BP; 0.36 mm Hg (P = 0.49) for 24-h systolic BP; and 0.05 mm Hg (P = 0.88) for 24-h diastolic BP. In the 2 treatment groups combined, systolic (-1.36 mm Hg) and diastolic (-0.97 mm Hg) office BPs decreased from week 5 to 10 (P for period effect ≤0.028), but carry-over effects were not significant (P ≥ 0.11). All other endpoints were not different on rostafuroxin and placebo. Minor side-effects occurred with similarly low frequency on rostafuroxin and placebo. Conclusions In 5 concurrently running double-blind cross-over studies rostafuroxin did not reduce BP at any dose. Trial Registration ClinicalTrials (NCT): NCT00415038

Abstract Background The main hypothesis of this study is that Oxpentifylline administration will effectively treat erythropoietin- or darbepoietin-resistant anaemia in chronic kidney disease patients. Methods/design Inclusion criteria are adult patients with stage 4 or 5 chronic kidney disease (including dialysis patients) with significant anaemia (haemoglobin ≤ 110 g/L) for at least 3 months for which there is no clear identifiable cause and that is unresponsive to large doses of either erythropoietin (≥ 200 IU/kg/week) or darbepoetin (≥ 1 μg/kg/week). Patients will be randomized 1:1 to receive either placebo (1 tablet daily) or oxpentifylline (400 mg daily) per os for a period of 4 months. During this 4 month study period, haemoglobin measurements will be performed monthly. The primary outcome measure will be the difference in haemoglobin level between the 2 groups at the end of the 4 month study period, adjusted for baseline values. Secondary outcome measures will include erythropoiesis stimulating agent dosage, Key's index (erythropoiesis stimulating agent dosage divided by haemoglobin concentration), and blood transfusion requirement. Discussion This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their chronic kidney disease patients determine whether oxpentifylline represents a safe and effective strategy for treating erythropoiesis stimulating agent resistance in chronic kidney disease. Trial Registration Australian New Zealand Clinical Trials Registry Number ACTRN12608000199314.

Abstract Background In breast cancer current guidelines do not recommend the routine use of serum tumour markers. Differently, we observed that CEA-TPA-CA15.3 (carcinoembryonic (CEA) tissue polypeptide (TPA) and cancer associated 115D8/DF3 (CA15.3) antigens) panel permits early detection and treatment for most relapsing patients. As high sensitivity and specificity and different cut-off values have been reported for mucin-like carcinoma associated antigen (MCA), we compared MCA with the above mentioned tumour markers and MCA-CA15.3 with the CEA-TPA-CA15.3 panel. Methods In 289 breast cancer patients submitted to an intensive post-operative follow-up with tumour markers, we compared MCA (cut-off values, ≥ 11 and ≥ 15 U/mL) with CEA or CA15.3 or TPA for detection of relapse. In addition, we compared the MCA-CA15.3 and CEA-TPA-CA15.3 tumour marker panels. Results Distant metastases occurred 19 times in 18 (6.7%) of the 268 patients who were disease-free at the beginning of the study. MCA sensitivity with both cut-off values was higher than that of CEA or TPA or CA15.3 (68% vs 10%, 26%, 32% and 53% vs 16%, 42%, 32% respectively). With cut-off ≥ 11 U/mL, MCA showed the lowest specificity (42%); with cut-off ≥ 15 U/mL, MCA specificity was similar to TPA (73% vs 72%) and lower than that of CEA and CA15.3 (96% and 97% respectively). With ≥ 15 U/mL MCA cut-off, MCA sensitivity increased from 53% to 58% after its association with CA15.3. Sensitivity of CEA-TPA-CA15.3 panel was 74% (14 of 19 recurrences). Eight of the 14 recurrences early detected with CEA-TPA-CA15.3 presented as a single lesion (oligometastatic disease) (5) or were confined to bony skeleton (3) (26% and 16% respectively of the 19 relapses). With ≥ 11 U/mL MCA cut-off, MCA-CA15.3 association showed higher sensitivity but lower specificity, accuracy and positive predictive value than the CEA-TPA-CA15.3 panel. Conclusion At both the evaluated cut-off values serum MCA sensitivity is higher than that of CEA, TPA or CA15.3 but its specificity is similar to or lower than that of TPA. Overall, CEA-TPA-CA15.3 panel is more accurate than MCA-CA15.3 association and can "early" detect a few relapsed patients with limited metastatic disease and more favourable prognosis. These findings further support the need for prospective randomised clinical trial to assess whether an intensive post-operative follow-up with an appropriate use of serum tumour markers can significantly improve clinical outcome of early detected relapsing patients.

Background: Tracheobronchial injury is a life-threatening condition with a considerable missed diagnosis rate. The larger the tracheal lesion the more difficult it is to heal. Both conservative and non-conservative treatments are used to treat tracheal injury. This article reports a clinical scenario in which conservative treatment was successfully used to manage a severe tracheal tear., Case Description: We present the case of a 63-year-old male with a cough for over a year who suffered from a 4-cm tracheobronchial injury (level IIIA, Cardillo classification) after endotracheal intubation for right lower bilobectomy. This injury showed full-layer tissue tearing of the tracheal wall, without esophageal injury or mediastinitis. The tracheal tear was discovered during the bronchoscopy examination on postoperative day one. The patient's vital signs were almost stable, including body temperature, blood pressure, heart rate, and oxygen saturation. We adopted a conservative treatment approach, including oxygen administration, painkillers, broad-spectrum antibiotics therapy, and nutritional support. Using this treatment, the 4-cm long tracheal rupture healed within four weeks. No tracheal tear was found in the bronchoscopy re-examination. The computed tomography scan showed that the mediastinal and subcutaneous emphysema had disappeared entirely. The patient fully recovered well without any complaints of discomfort., Conclusions: Conservative treatment provides a valuable strategy for treating patients with massive tracheal lesions, representing an effective approach, especially in older patients with underlying diseases whose conditions are not suitable for operative treatments., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1288/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: Radical resection of isolated lung metastases (LM) from colorectal cancer (CRC) is debated. Like Fong's criteria in liver metastases, our study was meant to assign a clinical prognostic score in patients with LM from CRC, aiming for better surgery selection., Methods: We retrospectively analyzed data from 260 CRC patients who underwent curative LM resection from December 2002 to January 2022, verifying the impact of different clinicopathological features on the overall survival (OS)., Results: At the univariate analysis: higher baseline CEA levels (p = 0.0001), disease-free survival less than or equal to 12 months (m) (p = 0.0043), LM size larger than 2 cm (p = 0.0187), multiple resectable nodules (p = 0.0083), and positive nodal status of the primary tumor (p = 0.0011) were associated with worse prognosis. In a Cox regression model, these characteristics retained their independent role for OS (p < 0.0001) and were chosen as criteria to be assigned one point each for clinical risk score. The 5-year survival rate in patients with 0 points was 88%, while no patients with a 5-point score survived at 2 years. Based on the 0-1 vs. 2-5 score range, we obtained a significant difference in median OS: not reached vs. 40.8 months (95 %CI 36 to 87.5), respectively (p < 0.0001) stratifying patients into good and poor prognosis. The prognostic role of the score was also confirmed in terms of median RFS: not reached in 0-1 scored patients vs. 30.5 months (95 %CI 19.4 to 42) in patients with 2-5 scores (p = 0.0006)., Conclusions: When LM from CRC is resectable, the Meta-Lung Score provides valuable prognostic information. Indeed, while upfront surgery should be considered in patients with scores of 0 to 1, it should be cautiously suggested in patients with scores of 2 to 5, for whom a prognosis comparison between preventive surgery and other treatments should be investigated in prospective randomized clinical trials., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

An uncommon clinical case of an adult woman who was referred to the hospital with severe symptoms attributable to cystic echinococcosis (CE) is described in this report. According to a questionnaire, the subject was exposed to a high risk of infection since she was employed on a farm about 20 years before diagnosis. She lived close to several animal species and handled vegetables in inadequate hygienic conditions. Medical and laboratory investigations confirmed the presence of massive echinococcal cystic lesions in each lung and in the liver. Given the peculiarity of the case, pharmacological and surgical treatments were the only conceivable option. The association of pharmacological treatment, surgery, and interventional radiology procedure represented a reliable and effective way to handle a complex case of human hydatidosis. A multi-disciplinary approach was mandatory, resulting in a clear and conclusive diagnosis of CE caused by the zoonotic parasite E. granulosus sensu stricto of the G1 genotype.

Introduction: Exhaled breath condensate (EBC) sampling has been suggested as a less-invasive and cost-effective method to detect biological macromolecules, including miRNA. To explore the feasibility of its use as a biomarker of early effects of asbestos exposure, we conducted a preliminary test on male volunteers by comparing the miRNA profile in the EBC and the plasma using 2 different sequencing platforms., Methods: Six male volunteers, all retired and unexposed to dust or fumes, participated in the test. RNA was extracted from 200 μL EBC samples and same-size plasma samples. Sample aliquots were processed in 2 laboratories using 2 different sequencing platforms: a MiSeq Illumina ® platform and a more performing HiSeq Illumina ® platform., Results: The HiSeq3000 ® sequencing platform identified twice as many unique molecular indexes (UMI)-validated miRNA as the MiSeq ® platform. The Spearman's correlation coefficient between EBC counts and plasma counts was significant in 5/6 subjects with either platform (MiSeq ®  = 0.128-0.508, P  = .026-<.001; HiSeq ®  = 0.156-0.412, P  = .001-<.001). The intraclass correlation coefficient confirmed the consistency of the miRNA profile over the 6 participants with both biospecimens. Exploring the agreement between the EBC and plasma samples with Bland-Altman plots showed that using the HiSeq3000 ® platform substantially improved the EBC miRNA detection rate., Conclusion: Our preliminary study confirms that, when using the HiSeq ® sequencing platform, EBC sampling is a suitable, non-invasive method to detect the miRNA profile in healthy subjects., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Mediastinal hemangiomas are rare, and their etiology remains unclear. Most patients affected have no pathognomonic clinical symptoms, and the diagnosis is often incidental. Due to the paucity of the available literature regarding the management of this disease, the choice and timing of treatment remains controversial., Case Presentation: Herein, we report the case of a hemangioma of the azygos vein arch in a 66-year-old woman who presented with dyspnea, chest discomfort, dysphagia, and weight loss. A simultaneous right chylothorax refractory to conservative management was found. A CT-guided biopsy of the mass was performed, and it confirmed the vascular nature of the lesion. Therefore, the patient underwent an angiography followed by endo-vascular embolization. Three days later, thoracoscopic surgical resection of the mass and the repair of the chyle leakage were performed safely. The patient was discharged uneventfully on postoperative day seven, with complete resolution of all the presenting symptoms., Conclusions: Treatment of symptomatic mediastinal hemangiomas could be mandatory, but a thorough multidisciplinary approach to these rare malformations is essential. Despite the risk of intraoperative bleeding, selective endovascular embolization followed by thoracoscopic surgery allowed for a complete and safe resection with a good outcome.

Background: Uniportal video-assisted thoracic surgery (VATS) basal segmentectomy is technically challenging and requires a deep understanding of the segmental anatomy of the lung. This report describes the uniportal VATS segmentectomy of basal segments using a single-direction approach., Methods: A total of 49 patients who underwent uniportal VATS basal segmentectomy between April 2019 and April 2021 were included in this retrospective study. All the surgeries were conducted using a single-direction approach. The resections of segments 7-8 were mainly performed using the interlobar fissure approach, while the resections of segments 9-10 were performed using the inferior pulmonary ligament approach., Results: A total of 33 patients underwent a single basal segmentectomy and 16 patients underwent combined basal segmentectomy/sub-segmentectomy. The median operative time was 120 min (range, 60-180 min), and the median blood loss was 20 mL (range, 10-100 mL). The median chest tube duration was 2 days (range, 1-5 days), and the median hospital stay after surgery was 4 days (range, 2-15 days). The morbidity rate after surgery was 6.1% (3/49). There were no perioperative deaths. The pathological examinations revealed 3 cases of adenocarcinoma in situ (AIS), 33 cases of minimally invasive adenocarcinoma, and 13 cases of lepidic-predominant invasive adenocarcinoma. No recrudescence or mortality was reported during the median follow-up time of 7 months (range, 2-25 months)., Conclusions: Uniportal VATS basal segmentectomy is a feasible and reliable technique based on our experience. This single-direction method allows the uniportal VATS basal segmentectomy to be performed in an easy manner with the targeted segmental bronchi and vessels exposed from superficial to deep in order of their appearance while avoiding the repeated turnover of the lung., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-22-651/coif). The authors have no conflicts of interest to declare., (2022 Translational Lung Cancer Research. All rights reserved.)

Background: According to the international guidelines, patients affected by interstitial lung disease with unusual clinical presentation and radiological findings that are not classic for usual interstitial pneumonia end up meeting criteria for surgical lung biopsy, preferably performed with video-assisted thoracic surgery. The growing appeal of non-intubated thoracic surgery has shown the benefits in several different procedures, but the strict selection criteria of candidates are often considered a limitation to this approach. Although several authors define obesity as a contraindication for non-intubated thoracoscopic surgery, the assessment of obesity as a dominant risk factor represents a topic of debate when minor tubeless procedures such as lung biopsy are considered. Our study aims to investigate the impact of obesity on morbidity and mortality in non-intubated lung biopsy patients with interstitial lung disease, analyzing the efficacy and safeness of this procedure., Materials and Methods: The study group of 40 obese patients consecutively collected from 202 patients who underwent non-intubated lung biopsy was compared with overweight and normal-weight patients, according to their body mass index. Post-operative complications were identified as the primary endpoint. The other outcomes explored were the early 30-day mortality rate and intraoperative complications, length of surgery, post-operative hospitalization, patient's pain feedback, and diagnostic yield., Results: The overall median age of the patients was 67.4 years (60, 73.5). No 30-day mortality or significant differences in terms of post-operative complications ( P = 0.93) were noted between the groups. The length of the surgery was moderately longer in the group of obese patients ( P = 0.02). The post-operative pain rating scale was comparable among the three groups ( P = 0.45), as well as the post-operative length of stay ( P = 0.96). The diagnosis was achieved in 99% of patients without significant difference between groups ( P = 0.38)., Conclusion: Our analysis showed the safety and efficacy of surgical lung biopsy with a non-intubated approach in patients affected by lung interstitiopathy. In the context of perioperative risk stratification, obesity would not seem to affect the morbidity compared to normal-weight and overweight patients undergoing this kind of diagnostic surgical procedure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cherchi, Ferrari, Guerrera, Grimaldi, Pinna-Susnik, Murenu, Rosboch, Lybéris, Ibba, Balsamo, Saderi, Fois, Ruffini and Sotgiu.)

Background: Non-Intubated Thoracic Surgery (NITS) is becoming increasingly adopted all over the world. Although it is mainly used for pleural operations,, non-intubated parenchymal lung surgery has been less frequently reported. Recently, NITS utilization seems to be increased also in Italy, albeit there are no multi-center studies confirming this finding. The objective of this survey is to assess quantitatively and qualitatively the performance of NITS in Italy., Methods: In 2018 a web-based national survey on Non-Intubated management including both thoracic surgeons and anesthesiologists was carried out. Reference centers have been asked to answer 32 questions. Replies were collected from June 26 to November 31, 2019., Results: We raised feedbacks from 95% (55/58) of Italian centers. Seventy-eight percent of the respondents perform NITS but only 38% of them used this strategy for parenchymal surgery. These procedures are more frequently carried out in patients with severe comorbidities and/or with poor lung function. Several issues as obesity, previous non-invasive ventilation and/or oxygen therapy are considered contraindications to NITS. The regional anesthesia technique most used to provide intra- and postoperative analgesia was the paravertebral block (37%). Conversion to general anesthesia is not anecdotal (31% of answerers). More than half of the centers believed that NITS may reduce postoperative intensive care unit admissions. Approximately a quarter of the centers are conducting trials on NITS and, three quarters of the respondent suppose that the number of these procedures will increase in the future., Conclusions: There is a growing interest in Italy for NITS and this survey provides a clear view of the national management framework of these procedures., (© 2021. The Author(s).)

The progress of the SARS-CoV-2 pandemic requires the design of large-scale, cost-effective testing programs. Pooling samples provides a solution if the tests are sensitive enough. In this regard, the use of the gold standard, RT-qPCR, raises some concerns. Recently, droplet digital PCR (ddPCR) was shown to be 10-100 times more sensitive than RT-qPCR, making it more suitable for pooling. Furthermore, ddPCR quantifies the RNA content directly, a feature that, as we show, can be used to identify nonviable samples in pools. Cost-effective strategies require the definition of efficient deconvolution and re-testing procedures. In this paper we analyze the practical implementation of an efficient hierarchical pooling strategy for which we have recently derived the optimal, determining the best ways to proceed when there are impediments for the use of the absolute optimum or when multiple pools are tested simultaneously and there are restrictions on the throughput time. We also show how the ddPCR RNA quantification and the nested nature of the strategy can be combined to perform self-consistency tests for a better identification of infected individuals and nonviable samples. The studies are useful to those considering pool testing for the identification of infected individuals., (© 2021. The Author(s).)

Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/tlcr-21-663). Wenhua L serves as an unpaid Associate Editor-in-Chief of Translational Lung Cancer Research. The other authors have no conflicts of interest to declare.

Background: Surgical lung biopsy for interstitial lung disease (ILD) is traditionally performed through video-assisted thoracic surgery (VATS) and general anesthesia (GA). The mortality and morbidity rates associated with this procedure are not negligible, especially in patients with significant risk factors and respiratory impairment. Based on these considerations, our center evaluated a safe non-intubated VATS approach for lung biopsy performed in ILD subjects., Methods: Ninety-nine patients affected by undetermined ILD were enrolled in a retrospective cohort study. In all instances, lung biopsies were performed using a non-intubated VATS technique, in spontaneously breathing patients, with or without intercostal nerve blockage. The primary end-point was the diagnostic yield, while surgical and global operating room times, post-operative length of stay (pLOS), numeric pain rating scale (NPRS) after surgery and early mortality were considered as secondary outcomes., Results: All the procedures were carried out without conversion to GA. The pathological diagnosis was achieved in 97 patients with a diagnostic yield of 98%. The mean operating room length-of-stay and operating time were 73.7 and 42.5 min, respectively. Mean pLOS was 1.3 days with a low readmissions rate (3%). No mortality in the first 30 days due to acute exacerbation of ILD occurred. Both analgesia methods resulted in optimal feasibility with a mean NPRS score of 1.13., Conclusions: In undetermined ILD patients, surgical lung biopsy with a non-intubated VATS approach and spontaneous ventilation anesthesia appears to be both a practical and safe technique with an excellent diagnostic yield and high level of patient satisfaction., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-1551). The authors have no conflicts of interest to declare., (2020 Journal of Thoracic Disease. All rights reserved.)

Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: ICU patients must be kept conscious, calm, and cooperative even during the critical phases of illness. Enteral administration of sedative drugs might avoid over sedation, and would be as adequate as intravenous administration in patients who are awake, with fewer side effects and lower costs. This study compares two sedation strategies, for early achievement and maintenance of the target light sedation., Methods: This was a multicenter, single-blind, randomized and controlled trial carried out in 12 Italian ICUs, involving patients with expected mechanical ventilation duration > 72 h at ICU admission and predicted mortality > 12% (Simplified Acute Physiology Score II > 32 points) during the first 24 h on ICU. Patients were randomly assigned to receive intravenous (midazolam, propofol) or enteral (hydroxyzine, lorazepam, and melatonin) sedation. The primary outcome was percentage of work shifts with the patient having an observed Richmond Agitation-Sedation Scale (RASS) = target RASS ±1. Secondary outcomes were feasibility, delirium-free and coma-free days, costs of drugs, length of ICU and hospital stay, and ICU, hospital, and one-year mortality., Results: There were 348 patients enrolled. There were no differences in the primary outcome: enteral 89.8% (74.1-100), intravenous 94.4% (78-100), p = 0.20. Enteral-treated patients had more protocol violations: n = 81 (46.6%) vs 7 (4.2%), p < 0.01; more self-extubations: n = 14 (8.1%) vs 4 (2.4%), p = 0.03; a lighter sedative target (RASS = 0): 93% (71-100) vs 83% (61-100), p < 0.01; and lower total drug costs: 2.39 (0.75-9.78) vs 4.15 (1.20-20.19) €/day with mechanical ventilation (p = 0.01)., Conclusions: Although enteral sedation of critically ill patients is cheaper and permits a lighter sedation target, it is not superior to intravenous sedation for reaching the RASS target., Trial Registration: ClinicalTrials.gov, NCT01360346 . Registered on 25 March 2011.

Background: Human pulmonary dirofilariasis is a rare zoonosis caused by the dog worm Dirofilaria spp., a parasite transmitted by mosquitos and resulting in peripheral lung nodules. The filarial nematode enters the subcutaneous tissue, travels to the right ventricle and dies causing a small pulmonary infarction that may embolize through the pulmonary vessels and may appear as a solitary nodule. These nodules are usually incidentally identified in asymptomatic patients undergoing chest imaging studies, and are generally interpreted to be malignant., Case Presentation: We present the case report of a human dirofilariasis in a patient with multiple pulmonary nodules resected using video-assisted thoracic surgery (VATS). According to our literature review, this is the first case with double synchronous lung nodules reported in Italy., Conclusions: Minimally invasive resection with histologic examination may be the best approach for the diagnosis and treatment of pulmonary dirofilariasis. Polymerase Chain Reaction testing may provide a more accurate etiological diagnosis in case of an inconclusive pathology result.

[This corrects the article DOI: 10.21037/jtd.2017.06.12.].

Background: VATS lobectomy is an established option for the treatment of early-stage NSCLC. Complete lymph node dissection (CD), systematic sampling (SS) or resecting a specific number of lymph nodes (LNs) and stations are possible intra-operative LN management strategies., Methods: All VATS lobectomies from the "Italian VATS Group" prospective database were retrospectively reviewed. The type of surgical approach (CD or SS), number of LN resected (RN), the positive/resected LN ratio (LNR) and the number and types of positive LN stations were recorded. The rates of nodal upstaging were assessed based on different LN management strategies., Results: CD was the most frequent approach (72.3%). Nodal upstaging rates were 6.03% (N0-to-N1), 5.45% (N0-to-N2), and 0.58% (N1-to-N2). There was no difference in N1 or N2 upstaging rates between CD and SS. The number of resected nodes was correlated with both N1 (OR =1.02; CI, 1.01-1.04; P=0.03) and N2 (OR =1.02; CI, 1.01-1.05; P=0.001) upstaging. Resecting 12 nodes had the best ability to predict upstaging (6 N1 LN or 7 N2 LN). The finding of two positive LN stations best predicted N2 upstaging [area under the curve (AUC) of receiver operating characteristic (ROC) =0.98]., Conclusions: Nodal upstaging (and, indirectly, the effectiveness of intra-operative nodal management) cannot be predicted based on the surgical technique (CD or SS). A quantitative assessment of intra-operative LN management may be a more appropriate and measurable approach to justify the extension of LN resection during VATS lobectomy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Video-assisted thoracic surgery (VATS) is currently considered a 'gold standard' approach for pulmonary lobectomy in patients with early-stage lung cancer, displaying equal or superior results compared with an open traditional approach. In patients with limited pulmonary function, VATS lobectomy may reduce the impact of surgery and allow outcomes similar to patients with normal pulmonary function. The preliminary analysis of our initial, single center series of VATS lobectomy showed less complications and shorter postoperative length of stay compared with a historical series of open lobectomy patients. Patients with reduced predicted preoperative FEV1% (ppoFEV1%) who underwent VATS lobectomy had similar outcomes compared with patients with normal ppoFEV1, but longer postoperative length of stay.

This article focuses on a statistical tool for dependence analysis in scientific research. Starting from a recent index of concordance for a multiple linear regression model, a coefficient suitable in catching any monotonic dependence relationship between a dependent variable and an independent variable is derived and discussed. Given its interpretation in terms of monotonic dependence, it is called monotonic dependence coefficient (MDC). It is appropriate to all contexts where the dependent variable is quantitative (continuous or discrete) and the independent variable is at least of ordinal nature; tied data are also allowed. MDC's adequacy is validated through Monte Carlo simulations led by taking into account different scenarios of dependence. Finally, an application to real data is provided to stress MDC's capability of detecting dependence relationships between two variables, even if some pieces of information about original data are lost.

Background and Objectives: Some intracranial procedures are achievable with patients awake, however, there are challenges ranging from patient compliance to homeostasis. The aim of this study is to present a case of intracranial surgery for removal of a tumor in the left parietal lobe with the patient awake during the procedure., Case Report: After patient selection and psychological preparation, the proposed excision of the left parietal lobe lesion in the waking state was clarified and accepted. Continuous infusion of propofol and remifentanil was administered to maintain a Ramsay score of 2-3. The bilateral scalp blockade was performed with ropivacaine. The Mayfield head fixation device was installed and drapes adjusted to maintain the airway and eyes accessible for mapping with electrical stimulation and tumor excision. For dura mater incision, a pad with 2% lidocaine was applied for 3 minutes. The surgery was uneventful. The patient was discharged on the seventh day of hospitalization without presenting complication., Conclusion: Although the maintenance of analgesia and hemodynamic stability was a challenge with the patient awake, the target-controlled infusion of propofol provided the desired level of consciousness, remifentanil titrated analgesia and sedation without drug accumulation, and the blockade with ropivacaine provided satisfactory analgesia. We conclude that the anesthetic technique was satisfactory for our patient., (Copyright © 2013 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

The increasing use of ordinal variables in different fields has led to the introduction of new statistical methods for their analysis. The performance of these methods needs to be investigated under a number of experimental conditions. Procedures to simulate from ordinal variables are then required. In this article, we deal with simulation from multivariate ordinal random variables. We propose a new procedure for generating samples from ordinal random variables with a prespecified correlation matrix and marginal distributions. Its features are examined and compared with those of its main competitors. A software implementation in R is also provided along with examples of its application.

Hypothyroidism has been frequently reported in systemic sclerosis (SSc), but whether SSc itself increases the risk of thyroid dysfunction is still controversial. The aim of the present study was to determine whether routine thyroid function screening in SSc should be warranted. Serum levels of free triiodothyronine, free thyroxine, and thyroid-stimulating hormone, and the presence of thyroid-specific autoantibodies (antithyroid peroxidase and antithyreoglobulin) were measured in 79 women with SSc and 81 age-matched women with osteoarthritis (OA) serving as controls. Hyperthyroidism was found in 2 of 79 (2.5%) SSc and in 4 of 81 (5%) OA cases. Hypothyroidism was found in 16 of 79 (20%) patients with SSc (subclinical in 14/16 cases) and in 9 of 81 (11%) patients with OA (subclinical in all cases; P = 0.131). Antithyreoglobulin antibodies were present in 14% versus 13% patients (SSc versus OA, P = NS), whereas antithyroid peroxidase antibodies were present in 23% versus 11% patients (SSc versus OA, P = 0.057). The risk of hypothyroidism was significantly higher in antithyroid peroxidase-positive patients (P < 0.0001), irrespective of the primary diagnosis, and greater in women with OA (OR = 24.6, 95% CI 4.3-141.9, P < 0.0001) than SSc (OR = 4.2, 95% CI 1.2-14.3, P = 0.035). SSc is not independently associated with an increased risk of thyroid dysfunction, but antithyroid peroxidase antibodies may identify a subset of patients at risk of developing thyroid dysfunction.

We study the competition interface between two clusters growing over a random vacant sector of the plane in a simple setup which allows us to perform formal computations and obtain analytical solutions. We demonstrate that a phase transition occurs for the asymptotic inclination of this interface when the final macroscopic shape goes from curved to noncurved. In the first case it is random while in the second one it is deterministic. We also show that the flat case (stationary growth) is a critical point for the fluctuations: for curved and flat final profiles the fluctuations are in the Kardar-Parisi-Zhang (KPZ) scale (2/3); for noncurve final profile the fluctuations are in the same scale of the fluctuations of the initial conditions, which in our model are Gaussian (1/2).

Objective: To verify some of the previous findings of venous valves described in the literature, their pathophysiological significance and clinical implications., Materials and Methods: The elementary components of 65 proximal valves of the long saphenous vein and their interrelationships were subjected to histopathological examination. Valves were taken from patients subjected to long saphenous vein surgical removal for varicose veins of the lower limbs. Measurements and morphological evaluations were performed by optical microscopy., Results: The valvular sinus, agger and proximal portion of the cusp underwent parallel variations of thickness. Thickening of the proximal portion of cusp was related to increase in smooth muscle cells in the agger and to elastic layer dissociation. Thickening of the distal portion of cusp depended on the collagen component; sometimes it was shortened, crumpled and led to the formation of a thickened border. The vein wall in a commissural aneurysm was usually thinner than in the valvular sinus. Alterations in the intima, in the elastic membrane and in the media were found in the 98% of the valvular annulus. Ectasis and asymmetry of the venous wall were mainly related to the muscular hypoplasia of the media., Conclusions: The development of primary venous insufficiency seems to be due to the following tissue alterations: dilatation of the valvular annulus and hypotrophy of the cusp. The hemodynamic mechanical injury increases the tissue damages of both annulus and cusps. This pathophysiologic interpretation of venous insufficiency suggests the need for detailed diagnostic procedures before reparative surgery of valves.

In 103 patients with peripheral arterial disease (PAD) of the lower limbs, coagulation and fibrinolytic parameters were evaluated to identify hemostatic abnormalities characteristic of this patient population. PAD was defined as clinically stable Leriche stage 2 (based on clinical history, peripheral pulses, ankle-arm index, and treadmill test) for at least 3 months, walking distance > 100 m, and no other major illnesses, rest pain, or trophic lesions. Defibrotide, a polydeoxyribonucleotide derivative with vascular effects, was administered to the patients as part of a multicenter trial. The PAD patients exhibited a prothrombotic state as evidenced by high D-dimer in all but 24% of the patients (average 797 +/- 802 vs. 163 +/- 54 ng/mL normal population; p < 0.001) and high thrombin-antithrombin III complex (TAT) levels (10.2 +/- 8.9 vs. 2.5 + 1.5 ng/mL; p < 0.001) with low to normal levels of protein C (86 +/- 25 vs. 102 +/- 18%; p < 0.01) and plasminogen activator inhibitor-1 (PAI-1) antigen (5.9 +/- 4.5 vs. 1.3 + 0.7 ng/mL; p < 0.001) were elevated in 79% of the patients. These results suggest that there is ongoing thrombosis in the majority of PAD patients. Differences from normal controls were observed for t-PA, PAI-1, protein C, and protein S; however, it is not certain that the thrombosis in patients with PAD is due to these factors.

The analysis of the combined effects of nutritional factors with other putative disease determinants in log-linear or logistic models is methodologically complicated by the strong multicollinearity between nutritional factors, resulting in poor precision in estimating the parameters. Furthermore, the generally used multiplicative structure is not always the most appropriate for describing the resulting joint effect of two or more factors on the disease risk. The authors addressed such problems in a case-control study assessing the interactions between alcohol intake, chronic hepatitis C virus (HCV) infection, and nutrient intake on the risk of liver cirrhosis. During the period from November 1989 to May 1990, 282 patients admitted to the medical departments of the hospitals of the Province of L'Aquila (central Italy) were enrolled: 115 cirrhotic patients aged 24-82 years (78 of whom were males) hospitalized because of liver decompensation, and 167 control patients aged 25-84 years (100 of whom were males) admitted to the same hospitals for acute diseases unrelated to alcohol intake, infection with hepatotropic viruses, and nutrition. No dose-effect relation was found between the intake of any nutrient and the risk of cirrhosis using classical methods. The analysis of principal components showed, however, that a pattern of higher lipid but lower protein and carbohydrate intakes was significantly associated with the risk of cirrhosis. The Breslow and Storer parametric family of relative risk functions showed that a multiplicative structure was the most adequate to describe the joint effect of nutritional pattern with alcohol intake and/or chronic HCV infection, whereas an additive structure best described the joint effect of chronic HCV infection and alcohol intake. In conclusion, the analysis of principal components and the Breslow and Storer family are useful tools to explore the role of diet on disease risk when precise pathogenic knowledge is not available. As an original finding, the authors suggest that a higher lipid intake, combined with lower protein and carbohydrate intakes, modifies multiplicatively the risk of cirrhosis associated with alcohol intake and/or chronic HCV infection.

Nonulcer dyspepsia remains to this date a clinical disease entity that is diagnosed and treated empirically by considering such patients potential ulcer carriers and treating them accordingly with H2 antagonists. The purpose of this study was to assess the therapeutic effectiveness of sulglycotide in patients with nonulcer dyspepsia in a random double-blind trial vs sucralfate. One hundred and eighty-seven consecutive patients with nonulcer dyspepsia were treated with sulglycotide (oral, 200 mg t.i.d. for 6 weeks, n = 93) or with sucralfate (oral, 1 g t.i.d. for the same length of time, n = 94). Drug effectiveness was evaluated in terms of apparent clinical symptom modifications, fiberoptic endoscopy findings and histological aspects of biopsy specimens. Both treatments resulted in prompt abatement of the clinical complaints of nonulcer dyspepsia and the improvement of macroscopic gastritis at endoscopy. These results confirm the usefulness of cytoprotective drugs in nonulcer dyspepsia characterized by gastroduodenal inflammation.

The developmental capabilities of the iris rudiment in the chicken embryo, as well as the role of tissue interactions in the differentiation of the iris, were investigated in vitro. Sectors of the intact iris from 7 1/2- through 9-day embryos (stages 32 through 35) lost their morphological organization in vitro, but were capable of normal histodifferentiation. The pigmentation of the epithelium increased, and muscle differentiation occurred. Developing muscle was identified using immunocytochemistry with antiserum against chicken muscle myosin; this procedure permitted positive identification of myoblasts, myotubes, and muscle fibres in cultures in which histological features alone were equivocal. The proportion of irideal explants which developed muscle increased with the age of the embryo, and correlated with the incidence of epithelial buds and epithelial cells in the stroma. Irideal mesenchyme from stage-32 through stage-35 embryos was already populated with stromal epithelial cells when isolated, but growth and muscle differentiation in these cultures compared poorly with that in the intact iris in vitro. Isolated irideal epithelium (stages 32 through 37) demonstrated even more limited muscle differentiation in vitro, suggesting reciprocal interaction between irideal epithelium and mesenchyme during development. Irideal epithelium was also cultured in direct association with non-irideal mesenchyme from various embryonic organ rudiments, but muscle differentiation was not enhanced.

The development of the iris was studied in chicken embryos from 4 days of incubation through hatching and in chicks up to 17 days posthatching. Serial sections of the eye were stained routinely or by immunocytochemical methods using myosin antiserum to enhance detection of differentiating muscle by light microscopy. Eyes from embryos at each stage were also examined by scanning electron microscopy. Outgrowth of the iris occurs in a sequential pattern around the eye, beginning at 6 1/2 days of incubation in the region temporal to the choroid fissure and proceeding around the eye. Since differentiation of the iris follows the same pattern, similar areas of the iris were compared at each stage of development. At 6 1/2 days of incubation, pigment granules can be seen in the anterior epithelium at the root of the iris, but it is not until 8 days of incubation that pigment is identified in the same area of the posterior epithelium. As development proceeds, the pigmentation of both epithelial layers progresses from the root of the iris to the pupillary margin. Early features of the development of the sphincter muscle can first be recognized in the 7-day embryo, when epithelial buds form from the anterior epithelium adjacent to the pupillary margin. Cells from these buds detach from the epithelium and populate the entire irideal stroma; these cells are the precursors of the sphincter muscle. The epithelial buds increase in size and distribution, and coalesce into a continuous ridge of cells around the iris by 10 days of incubation. The first muscle cells differentiate at 11 days of incubation when striated fibres can be identified by immunocytochemistry. The first striated fibres of the dilator muscle are seen in the 13-day embryo. Differentiation of the dilator muscle begins near the root of the iris and proceeds toward the pupillary margin, ultimately arising from the entire anterior epithelium except near the pupillary margin. Further differentiation of the sphincter and dilator muscles continues throughout incubation and for several weeks beyond hatching.