Three-Dimensional Imaging-Guided Lung Anatomic Segmentectomy: A Single-Center Preliminary Experiment.

Background and objectives: VATS segmentectomy has been proven to be effective in the treatment of stage I NSCLC, but its technical complexity remains one of the most challenging aspects for thoracic surgeons. Furthermore, 3D-CT reconstruction images can help in planning and performing surgical procedures. In this paper, we present our personal experience of 11 VATS anatomical resections performed after accurate pre-operative planning with 3D reconstructions. Materials and methods: A 3D virtual model of the lungs, airways, and vasculature was obtained, starting from a 1.25 mm 3-phase contrast CT scan, and the original images were used for the semi-automatic segmentation of the lung parenchyma, airways, and tumor. Results: Six males and five females were included in this study. The median diameter of the pulmonary lesion at the pre-operative chest CT scan was 20 mm. The surgical indication was confirmed in seven patients: in three cases, a lobectomy, instead of a segmentectomy, was needed due to intraoperative findings of nodal metastasis. Meanwhile, only in one case, we performed a lobectomy because of inadequate surgical resection margins. Skin-to-skin operative average time was 142 (IQR 1-3 105-182.5) min. The median post-operative stay was 6 (IQR 1-3 3.5-7) days. The mean value of the closest surgical margin was 13.7 mm. Conclusion: Image-guided reconstructions are a useful tool for surgeons to perform complex resections in order to spare healthy parenchyma and to ensure disease-free margins. Nevertheless, human skill and surgeon experience still remain fundamental for the final decisions regarding the proper resection to perform.

Extended criteria donor lung reconditioning with the organ care system lung: a single institution experience.

Lung transplantation is a life-saving procedure limited by donor's availability. Lung reconditioning by ex vivo lung perfusion represents a tool to expand the donor pool. In this study, we describe our experience with the OCS™ Lung to assess and recondition extended criteria lungs. From January 2014 to October 2016, of 86 on-site donors evaluated, eight lungs have been identified as potentially treatable with OCS™ Lung. We analyzed data from these donors and the recipient outcomes after transplantation. All donor lungs improved during OCS perfusion in particular regarding the PaO2 /FiO2 ratio (from 340 mmHg in donor to 537 mmHg in OCS) leading to lung transplantation in all cases. Concerning postoperative results, primary graft dysfunction score 3 at 72 h was observed in one patient, while median mechanical ventilation time, ICU, and hospital stay were 60 h, 14 and 36 days respectively. One in-hospital death was recorded (12.5%), while other two patients died during follow-up leading to 1-year survival of 62.5%. The remaining five patients are alive and in good conditions. This case series demonstrates the feasibility and value of lung reconditioning with the OCS™ Lung; a prospective trial is underway to validate its role to safely increase the number of donor lungs.

Thoracic Ultrasound as an Alternative to Chest X-ray in Thoracic Surgery Patients: A Single-Center Experience.

Background/Objectives: Chest X-ray (CXR) is currently the most used investigation for clinical follow-up after major noncardiac thoracic surgery. This study explores the use of lung ultrasound (LUS) as an alternative to CXR in the postoperative management of patients who undergo major thoracic procedures. Methods: The patients in our cohort were monitored with both a CXR and a lung ultrasonography after surgery and the day after chest drain removal. The LUS was performed by a member of the medical staff of our unit who was blinded to both the images and the radiologist's report of the CXR. Findings were compared between the two methods. Results: In the immediate postoperative evaluation, 280 patients were compared, finding general agreement between the two procedures at 84% (kappa statistic, 0.603). The LUS showed a sensibility of 84.1%, a specificity of 84.3%, a positive predictive value (PPV) of 60.9%, and a negative predictive value (NPV) of 94.8%. We evaluated 219 out of 280 patients in the postdrainage-removal setting due to technical issues. Concordance between the methods in the postdrainage-removal setting was 89% (kappa statistic, 0.761) with the LUS demonstrating an 82.2% sensibility, a 93.2% specificity, a PPV of 85.7%, and an NPV of 91.3%. Conclusions: The results of this study showed a substantial agreement between LUS and CXR, suggesting that the LUS could reduce the number of X rays in certain conditions. The high NPV allows for the exclusion of PNX and pleural effusion without the need to expose patients to radiation. Discrepancies were noted in cases of mild pneumothorax or modest pleural effusion, without altering the clinical approach.

Significance of Spread Through Air Spaces and Vascular Invasion in Early-stage Adenocarcinoma Survival: A Comprehensive Clinicopathologic Study of 427 Patients for Precision Management.

Spread through air spaces (STAS) is a novel invasive pattern of lung cancer associated with poor prognosis in non-small cell cancer (NSCLC). We aimed to investigate the incidence of STAS in a surgical series of adenocarcinomas (ADCs) resected in our thoracic surgery unit and to identify the association of STAS with other clinicopathological characteristics. We retrospectively enrolled patients with stage cT1a-cT2b who underwent resection between 2016 and 2022. For each case, a comprehensive pathologic report was accessible which included histotype, mitoses, pleural invasion, fibrosis, tumor infiltrating lymphocytes, necrosis, inflammation, vascular and perineural invasion, as well as STAS. PD-L1 expression was also investigated. A total of 427 patients with ADCs underwent surgery. Regarding overall survival (OS), no significant difference was observed between the STAS positive (STAS+) and STAS negative (STAS-) groups ( P =0.44). However, vascular invasion (VI) was associated with a poorer survival probability ( P =0.018). STAS+/VI+ patients had tendentially worse survival compared with STAS+/VI- ( P =0.089). ADCs with pathologic evidence of immune system (IS) activation (TILs>10% and PD-L1≥1) demonstrated significantly increased OS compared with ADCs with no IS and VI. In terms of recurrence rate, no statistical differences were found between the STAS+ and STAS- samples ( P =0.2). VI was also linked to a significantly elevated risk of recurrence ( P =0.0048). Our study suggests that in resected early-stage ADCs, STAS+ does not seem to influence recurrence or mortality. VI was instead an adverse pathologic prognostic factor for both survival and recurrence, whereas IS seemed to be protective.

A prospective randomized trial comparing stapler and laser techniques for interlobar fissure completion during pulmonary lobectomy.

Alveolar air leaks, often resulting from lung tissue traumatization during dissection of fissures, still remain a challenging problem in lung surgery. Several tools and techniques have been used to reduce air leakage, but none was judged ideal. This prospective, randomized trial was designed to evaluate the feasibility, safety, and effectiveness of completion of fissures during pulmonary lobectomy by using a laser system. A standard stapler technique was used for comparison; the primary goal was to reach at least a comparable result. Forty-four patients were enrolled, 22 were treated with standard technique by using staplers (S) and 22 underwent laser (L) dissection. Randomization to one of the two groups was intraoperative after evaluating the presence of incomplete fissure (grade 3-4 following Craig's classification). A Thulium laser 2010 nm (Cyber TM, Quanta System, Italy) was used at power of 40 W. Outcome primary measures were the evaluation and duration of intra- and postoperative air leaks, the rate of complications, and the hospital stay. Air leaks (2.1 ± 4.2 vs 3.6 ± 7.2 days; p = 0.98) and chest tube duration (6.4 ± 4.2 vs 7.5 ± 6.3 days, p = 0.44) were lower in L compared with S group even if these were not statistically significant. Complications (36.4 vs 77.3 %; p = 0.006), hospital stay (6.9 ± 3.8 vs 9.9 ± 6.9 days; p = 0.03), hospitalization costs (5,650 vs 8,147 euros; p = 0.01), and procedure costs (77 % of difference; p < 0.0001) were significantly lower for L group, while operative time was longer (197 ± 34 vs 158 ± 41 min; p = 0.004). The use of laser dissection to prevent postoperative air leaks is effective and comparable with stapler technique. Aero-haemostatic laser properties (by sealing of small blood vessels and checking air leaks) allow a safe application during pulmonary lobectomy in interlobar fissure completion avoiding stapler use.

Impact of a standardized protocol for chest tube management after VATS pulmonary resections on post-operative outcomes and complications.

Chest tube management represents a major issue after lung surgery as no protocol is widely accepted and tube management is generally based on local or personal habits. Aim of this study is to evaluate the impact of a standardized protocol for chest tube management after pulmonary resections on the post-operative outcomes. We performed a single center retrospective analysis of all adult patients undergoing thoracoscopic pulmonary resection from January 2020 to December 2021. Starting from January 2021 a standardized protocol of chest tube management was applied after all procedures. Patients were divided into two groups according to the chest tube management strategy. he two groups had similar pre-operative characteristics and the extent of lung resection was comparable. Intervention group had significantly shorter time to chest tube removal (median 1 vs 3 days, p < 0.001) and post-operative length of stay (median 3 vs 4 days, p < 0.001). Despite earlier chest tube removal, there was not an increased incidence of post-removal complications. On multivariable analysis, the new chest drain management strategy was an independent predictor of earlier chest tube removal. A standardized protocol of chest tube management allows for an earlier chest tube removal and a shorter hospital stay, without an increase in post-operative complications.

Sublingual Sufentanil in Pain Management After Pulmonary Resection: A Randomized Prospective Study.

BACKGROUND: Successful postoperative pain management after major lung resection surgery is mostly achieved through intravenous administration of analgesic drugs. This study explored the use of sublingual sufentanil cartridges (Zalviso) as a noninvasive alternative to postoperative analgesia. METHODS: From July 2019 to April 2020, patients who underwent major thoracoscopic lung resection surgery were randomly allocated to receive either intravenous pain management, or patient-controlled analgesia by the Zalviso system. Pain assessment scores were collected for a 72-hour time window, and requests for additional medication due to insufficient pain control were recorded. RESULTS: Of the 80 patients enlisted, 40 were assigned to the Zalviso group and 40 to the control group. The groups were not statistically different from each other. The difference in the mean pain scores reported was statistically significant in the first 24 hours in favor of the Zalviso group (P = .046), and the need for additional pain medication was significantly higher in the control group (P = .004). CONCLUSIONS: Patient-controlled analgesia using sublingual sufentanil cartridges can provide effective pain relief for patients undergoing video-assisted thoracic surgery and can reduce the need for additional medication, offering a noninvasive alternative to traditional intravenous therapy.

Left upper lobectomy with pulmonary artery reconstruction after neoadjuvant therapy in re-VATS.

Video-assisted thoracoscopic surgery (VATS) is considered the gold standard for the treatment of early stage non-small-cell lung cancer. Many studies have demonstrated reduced postoperative pain, hospital stay, and morbidity, while achieving the same oncological results. Indeed, it has become a widespread technique in many countries around the world. VATS can be applied also to challenging surgical procedures, such as plasty of the pulmonary artery, to obtain an oncologically radical resection of the tumor, and in the context of an N2 disease even after a previous operation on the thorax. In this case report, we demonstrate how to  carry out this procedure safely to achieve radical resection of the diseased tissue.

Short- and Long-Term Impact of Smoking Donors in Lung Transplantation: Clinical and Pathological Analysis.

BACKGROUND: The use of smoking donors (SD) is one strategy to increase the organ pool for lung transplantation (LT), but the benefit-to-risk ratio has not been demonstrated. This study aimed to evaluate the impact of SD history on recipient outcomes and graft alterations. METHODS: LTs in 293 patients were retrospectively reviewed and divided into non-SD (n = 225, group I), SD < 20 pack-years (n = 45, group II), and SD ≥ 20 pack-years (n = 23, group III) groups. Moreover, several lung donor biopsies before implantation (equally divided between groups) were evaluated, focusing on smoking-related lesions. Correlations were analyzed between all pathological data and smoking exposure, along with other clinical parameters. RESULTS: Among the three groups, donor and recipient characteristics were comparable, except for higher Oto scores and age in group III. Group III showed a longer intensive care unit (ICU) and hospital stay compared with the other two groups. This finding was confirmed when SD history was considered as a continuous variable. However, survival and other mid- and long-term major outcomes were not affected by smoking history. Finally, morphological lesions did not differ between the three groups. CONCLUSIONS: In our study, SDs were associated with a longer post-operative course, without affecting graft aspects or mid- and long-term outcomes. A definition of pack-years cut-off for organ refusal should be balanced with the other extended criteria donor factors.

Bronchus intermedius sleeve resection through a VATS approach.

In recent years, parenchymal sparing techniques for tumor resection have been developed in order to reduce the amount of lung parenchyma that must be removed in cases of centrally located tumors. These techniques maintain oncological radicality while reducing postoperative complications. At the same time, video-assisted thoracoscopic surgery (VATS) has been shown to offer comparable surgical and oncological outcomes to thoracotomy, even in complex cases that require tracheal and bronchial reconstructions. In this video tutorial, we describe a case of an isolated sleeve resection of the bronchus intermedius performed through a VATS approach for a bronchial paraganglioma.

Two-port intrapericardial left VATS pneumonectomy.

Pneumonectomy is a surgical treatment for locally advanced lung tumors that deeply infiltrate into the pulmonary hilum, and is a major thoracic procedure. An intrapericardial approach may be necessary in cases where it is  impossible to safely deal with the extrapericardial non-invaded sections of the pulmonary vessels. This article describes our technique for intrapericardial left video-assisted thoracoscopic pneumonectomy in a patient with hilar squamous cell carcinoma. The procedure was performed through a two-incision approach and, because of the involvement of the proximal portion of the pulmonary vessels, an intrapericardial isolation and closure of these structures was performed. Radical lymphadenectomy was performed and a pericardial flap was used for coverage of the bronchial stump. This is a complex and challenging procedure, however the patient had an uneventful postoperative course and was discharged on the 7th postoperative day.

Is "lung repair centre" a possible answer to organ shortage?-transplantation of left and right lung at two different centres after ex vivo lung perfusion evaluation and repair: case report.

Ex vivo lung perfusion (EVLP) has become a reality as a technique to evaluate and recondition lungs from marginal donors. We report the first case on the use of EVLP followed by separate transplantation in two different centres. The local organ procurement organization proposed the lungs of a 53-year-old non-smoker donor who died for cerebral haemorrhage. P/F ratio was 294 after lung recruitment manoeuvres. Oto score was 10. Two centres accepted the grafts for two single transplantations under the condition of EVLP evaluation. After usual retrieval, the bi-pulmonary block was transferred to Centre 1 and EVLP was run as previously described. At the end of the procedure the two lungs were evaluated separately and both judged suitable for transplantation. After cooling and storage on ice, the block was separated on the back table. The left lung was transplanted in a patient with pulmonary fibrosis at Centre 1; surgery was complicated by cardiac arrhythmias that required several defibrillations. The right lung was transferred on ice to Centre 2, 250 km away from Centre 1, and transplanted in a patient with idiopathic pulmonary fibrosis. Thirty months after transplantations Patient 1 and Patient 2 are both alive, in good clinical conditions. This is the first report of the separate use of lungs after EVLP for non-urgent recipients in two different centres. This experience opens the door to a new allocation model with great potentials on organ shortage. Actually, we demonstrated that the perspective of a 'lung repair centre' is feasible and effective.

Comparing robotic and trans-sternal thymectomy for early-stage thymoma: a propensity score-matching study.

OBJECTIVES: Minimally invasive techniques seem to be promising alternatives to open approaches in the surgical treatment of early-stage thymoma, although there are controversies because of lack of data on long-term results. The aim of the study was to evaluate the surgical and oncological results after robotic thymectomy for early-stage thymoma compared to median sternotomy. METHODS: Between 1982 and 2017, 164 patients with early-stage thymoma (Masaoka I and II) were operated on by median sternotomy (108 patients) or the robotic approach (56 patients). Duration of surgery, amount of blood loss, complications, duration of chest drainage, postoperative hospital stay, oncological results and total costs were retrospectively evaluated. Data were analysed also after propensity score matching. RESULTS: Compared to the trans-sternal group, robotic thymectomy had significantly longer average operative times (P < 0.001) but less intraoperative blood loss (P = 0.01), less perioperative complications (P = 0.03), shorter time to chest drainage removal and hospital discharge (P < 0.001). The median expense for the trans-sternal approach was significantly higher than the cost of the robotic procedure (P < 0.001), mainly due to longer hospitalization. From an oncological point of view, there were no differences in thymoma recurrence, although follow-up of the trans-sternal group was significantly longer (P < 0.001). Data were confirmed after propensity score matching. CONCLUSIONS: Robotic thymectomy for early-stage thymoma is a technically safe and feasible procedure with low complication rate and shorter hospital stay compared to the trans-sternal approach. Cost analysis revealed lower expenses for the robotic procedure due to the reduced hospital stay. The oncological outcomes seemed comparable, but longer follow-up is needed.

Ex-vivo recruitment and x-ray assessment of donor lungs in a challenging retrieval from a donor supported by lvad using the portable normothermic perfusion system: a case report.

BACKGROUND: Lung transplantation (LTx) is limited by the shortage of suitable donors. To overcome this problem, many programs have begun to use donors with extended criteria (marginal donors). However, brain-dead patients with implanted mechanical circulatory support system have rarely been considered as potential lung donors. This case demonstrates the feasibility of lung transplantations from organ donors supported by a mechanical circulatory support system despite the possible difficulties of lung retrieval. CASE PRESENTATION: Our case presents a successful procurement and bilateral lung transplantation from a donor supported by a left ventricular assist device (LVAD) who experienced an intraoperatively haemodynamic complication. The use of portable normothermic perfusion device let us to reduce ischemic injury and assess these marginal donor lungs helping us to determine the clinical suitability for transplantation. Given our extensive experience with the device instrumentation and management, the EVLP process was uneventful with excellent post-transplant course. CONCLUSIONS: This case report demonstrates the feasibility of lung transplantations from organ donors supported by a mechanical circulatory support system using the portable normothermic perfusion platform to assess and preserve these donor lungs.

Asymptomatic Pulmonary Allograft Kaposi Sarcoma: A Case Report.

Solid-organ transplant recipients are at high risk of developing malignancies. A greater risk of Kaposi sarcoma has been reported in lung recipients in our country, particularly in those from Southern Italy, probably due to the high prevalence of Human herpes virus 8 infection. Kaposi sarcoma affecting only the lung allograft is extremely rare. We describe a case of a lung recipient who developed Kaposi sarcoma only in the graft, 22 months after transplant. The patient, a 65-year-old man from Southern Italy, underwent bilateral lung transplant for idiopathic pulmonary fibrosis in January 2009. He developed mild/moderate acute cellular rejection (≥A2) in 4 of 6 scheduled transbronchial biopsies thus was treated with increased immunosuppressive therapy, shifting from cyclosporine to tacrolimus and mycophenolate mofetil. In July 2010, a high-resolution computed tomography scan showed small bilateral lung nodules, despite a generally good condition. After 2 months, his condition worsened with a severe weight loss. A positron emission tomography scan showed mild metabolic activity in the lesions with no other localizations. In October 2010, a lung biopsy was performed, with results showing typical histologic and immunohistochemical features of Kaposi sarcoma. Molecular tissue evaluations and serologic analyses were positive for Human herpes virus 8. The patient's immunosuppressive therapy was suspended, and he started liposomal doxorubicin treatment; however, after the first cycle, he developed severe respiratory dysfunction. The patient died 27 months after lung transplant for neoplasm. Our report highlights the importance of considering Kaposi sarcoma in the differential diagnosis for lung nodules in lung transplant recipients, even in the absence of any initial specific symptom or cutaneous lesion.

Robotic-assisted thymectomy: current perspectives.

Thymectomy is the cornerstone in the treatment of thymic tumors and an accepted option for the management of myasthenia gravis. Different surgical approaches have been described, but the gold standard is represented by median sternotomy. In the last two decades, the development of minimally invasive surgery has led to an increased acceptance of thymectomy, especially for benign diseases. Robotic thymectomy seems a further step in the development and evolution of minimally invasive approaches. Since its introduction, different authors described their experience with robotic thymectomy, both for nonthymomatous myasthenia gravis and for thymic tumors. Available data show that robotic thymectomy may be considered a safe and feasible operation. In patients with nonthymomatous myasthenia, robotic thymectomy is effective and the long-term results are encouraging. The role of robotic thymectomy in patients affected by thymoma is still under evaluation, but the intermediate results seem promising both in terms of surgical and oncologic outcomes.

A 72-Year-Old Woman With Previous Pulmonary Metastasis and New Peripheral Nodule.

A 72-year-old female nonsmoker was admitted to our Thoracic Surgery Unit in 2013 because of a lesion detected on chest CT scan during oncologic follow-up. Her medical history was significant for the development of a single pulmonary metastasis discovered 1 year after sigmoidectomy for colic adenocarcinoma. At that time, the patient was treated with six cycles of neoadjuvant chemotherapy followed by left lower lobectomy. Histologic examination demonstrated a pulmonary metastasis of colic adenocarcinoma with diffuse necrotic areas. The patient underwent subsequent adjuvant chemotherapy with capecitabine and was followed annually with biohumoral oncologic screening (carcinoembryonic antigen, carbohydrate antigen 19-9), chest-abdomen CT scan, and colonoscopy.

COPD-related adenocarcinoma presents low aggressiveness morphological and molecular features compared to smoker tumours.

OBJECTIVES: Adenocarcinoma comprises a group of diseases with heterogeneous clinical and molecular characteristics. COPD and lung cancer are strictly related; to date it is unknown if COPD-associated cancers have different features from tumours arising in non-COPD patients. Our aim was to study COPD-associated adenocarcinoma phenotypes mainly focusing on morphological and molecular aspects, in comparison to smoke-related cancer without COPD. MATERIALS AND METHODS: From 2010 to 2013, 54 patients with adenocarcinoma (20 COPD and 34 smokers) were prospectively studied. Each patient underwent a complete clinical and instrumental assessment. Morphological studies included analysis of growth pattern, cell proliferation (Ki-67/MIB1 expression) and parameters of intra- and peri-tumoral remodelling (inflammation, fibrosis and necrosis). Genetic analysis of EGFR and KRAS mutations was also performed. RESULTS: The two groups were comparable for the main demographic and biohumoral parameters except for increased blood basophil cell count in the COPD group. Compared to COPD, tumours of smokers presented an increased percentage of solid component (median: 20% vs 5%, p=0.02), a reduced percentage of lepidic pattern (median: 0% vs 10%, p=0.06) and higher Ki-67/MIB1 median value (55% vs 30%, p=0.02). In multivariate analysis lepidic and solid histological pattern were significantly influenced by clinical group (p=0.03 and 0.05, respectively). Concerning EGFR mutation, no differences were found between groups while KRAS mutation presented a trend of higher percentage in smokers compared to COPD (41% vs 20%, p=NS). Adenocarcinoma with KRAS mutation showed a higher value of Ki-67/MIB1 (65% vs 35%, p=0.048) and prevalent solid pattern (35% vs 10%, p=0.019) in comparison to wild-type form. CONCLUSIONS: COPD-related adenocarcinoma presents molecular and morphological features of lower aggressiveness (increased lepidic component, reduced solid pattern, lower cell proliferation and less frequent KRAS mutation) compared to smokers. Different molecular mechanisms could be associated with the development of COPD associated cancer.

Surgical and neurologic outcomes after robotic thymectomy in 100 consecutive patients with myasthenia gravis.

OBJECTIVE: Thymectomy is a well-defined therapeutic option for patients with myasthenia gravis; however, controversies still exist about the surgical approach, indication, and timing for surgery. We reviewed our experience reporting surgical and neurologic results after robotic thymectomy in patients with myasthenia gravis. METHODS: Between 2002 and 2010, 100 patients (74 female and 26 male; median age, 37 years) underwent left-sided robotic thymectomy using the da Vinci robotic system (Intuitive Surgical, Inc, Sunnyvale, Calif). The Myasthenia Gravis Foundation of America classification was adopted for pre- and postoperative evaluation. Preoperative Myasthenia Gravis Foundation of America class was I in 10% of patients, II in 35% of patients, III in 39% of patients, and IV in 16% of patients. RESULTS: Median operative time was 120 (60-300) minutes. No death or intraoperative complications occurred. Postoperative complications were observed in 6 patients (6%) (bleeding requiring blood transfusions in 3, chylothorax in 1, fever in 1, and myasthenic crisis in 1). Median hospital stay was 3 days (range, 2-14 days). Histologic analysis revealed 76 patients (76%) with hyperplasia, 7 patients (7%) with atrophy, 8 patients (8%) with small thymomas, and 9 patients (9%) with normal thymus; ectopic thymic tissue was found in 26 patients (26%). Clinical follow-up showed a 5-year probability of complete stable remission and overall improvement of 28.5% and 87.5%. Remission was significantly associated with preoperative I to II Myasthenia Gravis Foundation of America class (P = .02). A significant improvement rate was found in Myasthenia Gravis Foundation of America class I to II (P = .03) and AbAchR+ (P = .04). A high percentage of patients interrupted or reduced their medications. CONCLUSIONS: Robotic thymectomy is a safe and effective procedure. We observed a neurologic benefit in a great number of patients. A better clinical outcome was obtained in patients with early Myasthenia Gravis Foundation of America class.