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Background: The gene AK2 encodes the phosphotransferase adenylate kinase 2 (AK2). Human variants in AK2 cause reticular dysgenesis, a severe combined immunodeficiency with agranulocytosis, lymphopenia, and sensorineural deafness that requires hematopoietic stem cell transplantation for survival., Objective: We investigated the mechanisms underlying recurrent sinopulmonary infections and hypogammaglobulinemia in 15 patients, ranging from 3 to 34 years of age, from 9 kindreds. Only 2 patients, both of whom had mildly impaired T-cell proliferation, each had a single clinically significant opportunistic infection., Methods: Patient cells were studied with next-generation DNA sequencing, tandem mass spectrometry, and assays of lymphocyte and mitochondrial function., Results: We identified 2 different homozygous variants in AK2. AK2 G100S and AK2 A182D permit residual protein expression, enzymatic activity, and normal numbers of neutrophils and lymphocytes. All but 1 patient had intact hearing. The patients' B cells had severely impaired proliferation and in vitro immunoglobulin secretion. With activation, the patients' B cells exhibited defective mitochondrial respiration and impaired regulation of mitochondrial membrane potential and quality. Although activated T cells from the patients with opportunistic infections demonstrated impaired mitochondrial function, the mitochondrial quality in T cells was preserved. Consistent with the capacity of activated T cells to utilize nonmitochondrial metabolism, these findings revealed a less strict cellular dependence of T-cell function on AK2 activity. Chemical inhibition of ATP synthesis in control T and B cells similarly demonstrated the greater dependency of B cells on mitochondrial function., Conclusions: Our patients demonstrate the in vivo sequelae of the cell-specific requirements for the functions of AK2 and mitochondria, particularly in B-cell activation and antibody production., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: To evaluate the early and long-term postoperative results of malabsorptive surgery in morbidly obese patients., Methods: Between 2000 and 2007, 102 morbidly obese patients were referred to the Department of Surgery "Pietro Valdoni", "Sapienza" University of Rome, Policlinico "Umberto I°", Rome, Italy for malabsorptive surgery. All patients underwent derivative biliodigestive surgery after they had been reviewed by a team of surgeons, physicians, dieticians, and psychologists., Results: There were no intra-operative complications, but two patients suffered postoperative pulmonary embolisms, which resolved with medical treatment. The mean postoperative hospital stay was 7 days, with no early or late mortality. Maximum weight loss was reached 12-24 months after surgery, while the mean percentage excess weight loss at 3-5 years ranged from 45 to 64 %. Specific postoperative complications in the first 2 years after surgery were abdominal abscess (n = 2), gastroduodenal reflux (n = 4), and incisional hernia (n = 6). Diabetes resolved in 98 % of the diabetic patients within a few weeks after surgery and blood pressure normalised in 86.4 % of those who had had hypertension preoperatively. Obstructive sleep apnoea and obesity hypoventilation syndrome also improved significantly in 92 % of the patients., Conclusions: Morbidly obese patients can undergo biliodigestive surgery safely with good long-term weight loss and quality of life expectancy.

Aim: Considerable controversy surrounds mortality from non-neoplastic diseases during the postoperative follow-up of patients with non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD). This study investigated the incidence of mortality from cardiovascular and respiratory (CVR) causes in patients with COPD submitted to follow-up after lung resection for NSCLC, and identified preoperative and postoperative risk factors., Methods: A total of 398 patients with mild or moderate COPD were followed up in our department after lung resection for NSCLC (median follow-up 61 months). Statistical analysis of the data was carried out to determine the incidence and the prognostic factors of postoperative death from CVR causes., Results: Of the 398 resected patients, 186 survived without tumor recurrence; 24/186 (12.9%) died of CVR causes (acute respiratory failure, pneumonia, pulmonary embolism, acute pulmonary edema, acute myocardial ischemia or stroke). These 24 patients had a higher frequency of pre-existing coronary artery disease or heart failure (P=0.0003), predicted postoperative FEV1 <1000 mL (P=0.0008), exertional dyspnea (P=0.0000), and 30-day operative cardiopulmonary complications (P=0.001). Protective features were young age (<40 years), early stage disease, and minor resection (lobectomy). Independently significant adverse prognostic factors were stage III-IV disease (cumulative CVR death rate 47% at 5-10 years; P=0.028 vs. stage I-II) and completion pneumonectomy or partial resection of the other lung for a second primary tumor (cumulative CVR death rate 50% and 57%, respectively, at 5-10 years; P=0.0016 vs. all other resections). Older age and tumor histology were significant risk factors only in patients with advanced stage disease., Conclusion: The findings suggest that postoperative CVR death may be expected in patients with COPD and advanced stage NSCLC or in those undergoing completion pneumonectomy or partial resection of the other lung for a second primary tumor. Other risk factors are previous coronary artery disease and/or heart failure, exertional dyspnea and predicted postoperative FEV1 <1000 mL.

Background: Bronchioloalveolar carcinoma (BAC) remains one of the most controversial of lung cancer subtypes., Methods: From 1980 to 1998, 374 resected patients for NSCLC were followed up in our department. Of the 147 cases histologically defined as adenocarcinoma, 34 were pure BAC. The records of these 34 patients were retrospectively reviewed in order to evaluate patient and tumor characteristics and to identify which variables had a prognostic impact on survival and recurrence rate., Results: Patient age, sex, smoking habits and symptoms were not differentiating characteristics when related to radiographic presentation or to natural history. Mucinous cell-type (23.6% of cases) was more frequent with non-smokers, presence of a single nodule or mass and stage I. Favorable characteristics were: a) the prevalence of stage I and N0 cases (59% and 76.7% of cases, respectively) with a mean survival time of 66 and 77 months, respectively; and b) the radiographic presentation of a solitary pulmonary nodule or mass (76.4% of cases), that, independently of nodal involvement, showed a higher mean survival time (62 months). Independently significant adverse prognostic factors were: stage II-IV, lymph node involvement, and patient age over sixty years. The radiographic presence of multiple or satellite nodules was related to a significantly adverse prognosis (mean survival time: 18 months) by univariate analysis; this was not confirmed by multivariate analysis., Conclusions: In our experience BAC was the NSCLC subtype more frequently associated with a good outcome after resection; surgery should not to be denied also in patients with multiple nodules, when under sixty years of age and no lymph node involvement.

Treatment of NSCLC invading the chest wall (T3) remains controversial. Surgery is undoubtedly the only chance for these neoplasms, but its role regarding the T3N2 tumors is highly questionable. Between 1975 and 1994, 710 NSCLC patients underwent surgery in our department. Of these, 38 with tumor involvement of the chest wall underwent curative resection: en bloc resection or extrapleural resection, and 31 of these patients (19 with T3N0 tumors and 12 with T3N1-N2 tumors) were available for estimating long-term survival. The overall survival was 20.5% at 5 years and 15.4% at 10 years. Patients without lymph-node involvement had a survival rate of 26.2% at 5 years and 19.27% at 10 years. No patient with T3N2 tumor was alive 5 years after surgery. Patients with T3N1 tumor had a survival rate of 16.7% at both 5 and 10 years. The difference between T3N0 and T3N2 tumors was statistically significant. Neither histologic type nor depth of chest wall involvement had a significant impact on survival. En bloc or extrapleural resection, if curative, can be effective in T3N0-N1 tumors. Surgery is inadequate for the treatment of T3N2 tumors with chest wall involvement.

Pericardial cysts are an uncommon benign disease. Their treatment, in the past, was based on excision by thoracotomy or, in selected cases, on percutaneous aspiration. The progress of video-assisted thoracoscopy gave new possibilities, but most surgeons still consider the thoracotomic approach as the treatment of choice. The aim of this study is to report our experience and to discuss the role of different therapeutic procedures in the management of pericardial cysts. Between 1970 and 1996, 24 patients with pericardial cysts were treated at the first Department of Surgery of the University of Rome <>. Of 24 cysts, six were located in the right cardiophrenic angle, three in the left cardiophrenic angle, two in the subcarenal areas, one in the paracardiac area and one on the posterior mediastinum. Ten patients were asymptomatic. Diagnosis was performed preoperatively only in patients with cysts typically located in the cardiophrenic angle. Twenty-three patients were surgically treated by a standard posterolateral thoracotomy or limited thoracotomy with sparing of muscles. One patient underwent CT-guided transparietal fine-needle aspiration. There were no cases of operative mortality. Morbidity was 12.5% and consisted of retained secretions, moderate hypoxemia and partial atelectasis. All patients were submitted to a long-term follow-up and no cyst recurrences were found. We conclude that excision via thoracotomy is an optimal treatment for pericardial cysts. Limited thoracotomy with sparing muscles offers a good cosmetic result and a rapid functional respiratory recovery. Percutaneous cyst aspiration may be, in selected patients, an attractive alternative to surgery.

From 1976 to 1993, nine patients (5 men, 4 women) with pericardial cysts were treated in Authors' Department. Of the nine cysts, six were located in the right cardiophrenic angle, one in the subcarinal site, one in the right tracheobronchial angle, and one in the para-auricular site just above the diaphragm. Four patients were asymptomatic. A correct diagnosis was possible preoperatively only in patients with cysts typically located in the cardiophrenic angle. Eight patients were surgically treated by a standard posterolateral or axillary thoracotomy. One patient with a large pericardial cyst underwent needle percutaneous aspiration and CT-guided drainage of the cyst with a positive outcome. There was no operative morbidity or mortality.