Comparison of diuretic strategies in diuretic-resistant acute heart failure: a systematic review and network meta-analysis.

OBJECTIVE: Up to 50% of patients hospitalized for acute heart failure (AHF) show resistance to diuretics. This condition contributes to a prolonged hospital length of stay and a higher risk of death. This review aimed to investigate whether a diuretic therapeutic approach more effective than furosemide alone exists for patients with diuretic-resistant AHF. MATERIALS AND METHODS: We identified all randomized controlled trials (RCTs) evaluating diuretic therapy in patients with diuretic-resistant AHF. We searched Pubmed, BioMed Central, and Cochrane CENTRAL databases. RESULTS: Six RCTs were identified, involving a total of 845 patients. The P-score ranges from 0.6663 for furosemide to 0.2294 for the tolvaptan-furosemide. We found no significant differences in efficacy for any drug comparison. CONCLUSIONS: None of the diuretics considered in RCTs performed to date (tolvaptan, metolazone, hydrochlorothiazide, indapamide) appear to be more effective than furosemide therapy alone for the treatment of patients with diuretic-resistant AHF.

[Periconceptional supplementation with folic acid for the primary prevention of congenital malformations]. / La supplementazione con acido folico nel periodo periconcezionale: un intervento di prevenzione primaria delle malformazioni congenite.

Most international trials support the recommendation that all women planning or at risk of pregnancy take a daily multivitamin supplement containing folic acid, beginning one month before conception and continuing through the first trimester for primary prevention of neural tube defects and other congenital malformations. Recently an intervention project started also in Italy, in order to support and maintain the periconceptional supplementation and to evaluate the efficacy of a national preventive campaign on parents' behaviour.

[Respiratory diseases in infants hospitalized during the 1st 2 years of life for viral lower respiratory tract infections: a one-year follow-up]. / Patologia respiratoria in bambini ospedalizzati nei primi due anni di vita per infezioni virali delle basse vie respiratorie: 1 anno di follow-up.

BACKGROUND: Epidemiologic data suggest strong links between hospitalisation with bronchiolitis in infancy and subsequent higher risk of developing lower respiratory tract infections (LRTI) and/or hyperreactive airway diseases. The aim of this study was to evaluate in an Italian population the natural history of respiratory diseases in children hospitalised for LRTI when they were <2 years. METHODS: An observational, perspective, longitudinal study was performed through telephone interviews. Nine pediatric tertiary care centres participated to the study evaluating a population of 187 children, hospitalised in the previous year (November 1999-April 2000) for bronchiolitis or pneumonia when they were <2 years of age and participated to a previous study on the prevalence of infant LRTI in Italy (RADAR). RESULTS: Twenty-three (12.3%) children had a gestational age <36 weeks. In the 12 months following the first hospitalisation, an elevated frequency of respiratory symptoms was found. Indeed, 152 (81.3%) children suffered from not-requiring-hospital-admission respiratory infections and 21 (11.2%) were hospitalized again for LRTI: 11.6% had bronchiolitis, 23.5% bronchitis and 35.2% pneumonia. In addition, 1.2% had gs;3 infectious episodes and 21.4% gs;6: 68 (36.4%) showed wheezy bronchitis and 17 (9.1%) were reported to have asthma; 132 children (71%) took antibiotics during the last year, 19.4% >3 times; 111 (59.4%) bronchodilators and 49 (26.2%) oral corticosteroids. One year after the first hospitalisation, 19 subjects (10.2%) were found to be positive to at least one class of allergens by prick test or RAST. CONCLUSIONS: Thus, the demonstration of a high morbidity rate for LRTI, wheezing and asthma in this study group during the first year follow-up after hospital admission further support the need for prophylactic interventions to reduce the morbidity and severity of sequelae of LRTI, in particularly in premature children and/or with additional risk factors.

Pulmonary artery leiomyosarcoma with thyroid metastases.

Primary pulmonary artery sarcomas are uncommon and usually fatal tumours. The diagnosis of these tumours is delayed in most cases as they are mistaken for pulmonary thromboembolism. We present a fatal case of a woman referred to us five months after a primary diagnosis of pulmonary thromboembolism, due to an increase in dyspnea and presence of hemoptysis despite having undergone anticoagulant treatment. On the basis of the findings obtained by computed tomography, echocardiogram and MRI, a mass arising from the pulmonary trunk was evidenced, that suggested other diagnostic hypotheses. The worsening of patient's conditions did not allow an endovascular catheter biopsy and diagnosis was made at autopsy. The mass was a leiomyosarcoma of the pulmonary artery with thyroid metastases, which is an uncommon findings.

Prognostic significance of primary-tumor extension, stage and grade of nuclear differentiation in patients with renal cell carcinoma.

Surgery remains the preferred therapy for renal cell carcinoma. The various adjunctive or complementary therapies currently yield disappointing results. Identifying reliable prognostic factors could help in selecting patients most likely to benefit from postoperative adjuvant therapies. We reviewed the surgical records of 78 patients who had undergone radical nephrectomy with lymphadenectomy for renal cell carcinoma, matched for type of operation and histology. According to staging (TNM), 5.1% of the patients were classified as stage I, 51.3% as stage II, 29.5% as stage III and 14.5% as stage IV. Of the 78 patients 40 were T2N0 and 21 T3aN0. Tumor grading showed that 39.7% of the patients had well-differentiated tumors(G1), 41.1% moderately-differentiated (G2), and 19.2% poorly-differentiated tumors (G3). Overall actuarial survival at 5 and 10 years was 100% for stage 1; 91.3% at 5 years and 83.1% at 10 years for stage II; 45.5% and 34.1% for stage III; and 29.1% and nil for stage IV (stage II vs stage III p = 0.0001). Patients with tumors confined to the kidney (pT2N0) had better 5- and 10-year survival rates than patients with tumors infiltrating the perirenal fat (pT3aN0) (p = 0.000006). Survival differed according to nuclear grading (G1 vs G3 ; p = 0.000005; G2 vs G3; p = 0.0009). In conclusion our review identified tumor stage, primary-tumor extension, and the grade of nuclear differentiation as reliable prognostic factors in patients with renal cell carcinomas.

Bronchioloalveolar carcinoma: clinical, radiographic, and pathological findings. Surgical results.

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.

Renal biopsy and pregnancy.

OBJECTIVE: Our aim was to review our experience with renal biopsy in pregnancy. STUDY DESIGN: We reviewed 18 renal biopsies performed during pregnancy or in the immediate postpartum period at the University of North Carolina. Indications, histopathologic findings, complications, and neonatal outcome were reviewed for each case. RESULTS: Fifteen patients underwent biopsy during the antepartum period and 3 in the postpartum period. Only 5 patients had the classic histopathologic preeclamptic lesion glomeruloendotheliosis confirmed. There were 7 identifiable renal hematomas after biopsy; 2 patients required blood transfusion. There were 4 intrauterine fetal deaths in this series; it is presumed that none were a result of the biopsy. CONCLUSION: Renal biopsy in pregnancy is a morbid procedure and should be considered only if it offers the opportunity to make a diagnosis other than severe preeclampsia in a patient remote from term.

Cervical stroma apoptosis in pregnancy.

OBJECTIVE: To determine whether the percentage of apoptotic nuclei is different in cervical stroma of pregnant laboring women compared with nonpregnant women and pregnant nonlaboring women. METHODS: We took cervical stromal biopsies during cesarean delivery at the level of the lower uterine segment from ten women in active labor and 13 women before labor. In addition, we took biopsies of cervical stroma at the level of the internal cervical os from hysterectomy specimens in ten reproductive-aged women. Cryosections were then analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining. Tissue specimens were analyzed with ligation-mediated polymerase chain reaction to visualize nucleosomal ladders characteristic of apoptosis. To detect a 10% difference in the percentage of apoptotic cells per subject between study groups assuming a power of 0.90, an alpha of.05 in approximately ten subjects per group was needed. RESULTS: The median percentage of apoptotic nuclei was 0.7 (interquartile range 0.4, 1.4) for the nonpregnant group, 7.5 (interquartile range 6.6, 11.2) for the pregnant nonlaboring group, and 11.6 (interquartile range 8.3, 16.7) for the pregnant laboring group (P <.001). The percentage of apoptotic nuclei differed significantly across the three study groups. Using ligation-mediated polymerase chain reaction, nucleosomal ladders were seen in the specimens from pregnant women but not in the specimens from nonpregnant women, confirming the increase in stromal apoptosis seen with pregnancy. CONCLUSION: Apoptosis of cervical stromal cells may play a role in the remodeling of the cervix during pregnancy and contribute to cervical changes during labor.

Clinical behavior of solitary fibrous tumors of the pleura. An immunohistochemical study.

Localized fibrous tumors of the pleura are uncommon, generally asymptomatic and usually have a benign behavior even if in a few cases a malignant variant can be observed. We report 11 cases of localized pleural neoplasms submitted to surgical resection during the period 1987-1996. The differentiation between the localized fibrous as well as the less frequent localized malignant mesothelioma has been researched employing cyto-histopathologic and immunohistochemical assays. For the purpose of identifying solitary fibrous tumors of pleura that will behave in malignant manner, we applied the more recent criteria of specific immunohistochemical stains, microvessel density and proliferation mdex. All solitary fibrous tumors resulted positive for Vimentin and negative for Cytokeratin. Among these forms, high cellularity and microvessel density, high expression of Ki 67 and CD31 and negativity of CD34 prognostic factors for a poor prognosis.

Technetium-99m tetrofosmin single photon emission computed tomography in the evaluation of suspected lung cancer.

Technetium-99m-tetrofosmin is a radiopharmaceutical employed for myocardial imaging, which has recently emerged as useful in the visualization of tumors. In this study technetium-99m-tetrofosmin was evaluated for its accuracy in differentiating malignant from benign pulmonary lesions, and in detecting mediastinal node metastasis due to lung cancer. Eighty-one patients with a solitary lung lesion on the chest radiograph and/or CT scan were submitted to chest single photon emission computed tomography after technetium-99m-tetrofosmin injection (740 MBq i.v.). The scintigraphic findings were correlated to the final histopathological diagnosis, demonstrating abnormal tracer accumulation in 51 of 54 malignant lesions (sensitivity 94%) and in 4 out of 27 benign conditions (specificity 85%), yielding an accuracy of 91%. Mediastinal lymph-node involvement was evaluated in 35 patients with non small cell lung cancer who underwent mediastinoscopy and/or surgery. Tetrofosmin accuracy (89%) was significantly higher than that of CT (69%, p < 0.05); the false negative scintigraphic results were in nodes sized less than 1 cm. In conclusion, technetium-99m-tetrofosmin imaging is useful in distinguishing malignant from benign pulmonary lesions, and in non-invasively assessing mediastinal node metastases from non small cell lung cancer, especially in patients with enlarged nodes by CT scan.

Hemodynamic and pulmonary changes during and after laparoscopic cholecystectomy. A comparison with traditional surgery.

BACKGROUND: The cardiopulmonary changes experienced by patients who undergo laparoscopic cholecystectomy (LC) and the prognostic value of patient characteristics are not well understood. METHODS: Cardiorespiratory changes were investigated in 120 patients undergoing LC or open cholecystectomy (OC). The results and their relation to patient variables were statistically evaluated. RESULTS: The most significant cardiorespiratory changes were (A-a)PO2 increase during OC; decrease of pH and compliance and increase of peak airway pressure during LC; impairment of arterial blood gas mean values and respiratory muscle strength; atelectasis and pneumonia (five cases) after OC; and lamellar atelectasis (two cases) after LC. Significant adverse prognostic factors related to intra- and postoperative LC cardiorespiratory changes were ASA class greater than I, FEF75-85% < 900 ml, and PaO2 < 10.4 kPa (PPV, 71.4% and 46.6%, respectively). CONCLUSIONS: LC carries no significant cardiorespiratory changes provided that intraoperative monitoring of hemodynamics and respiratory parameters is done for the study of blood gas values in all patients at risk.

Ventilation-perfusion mismatching as prognostic factor of respiratory failure after pulmonary resection.

This paper reports the results of a retrospective study undertaken to assess the reliability of regional ventilation-perfusion pulmonary scanning in predicting the remaining respiratory function (pFEV1), and the early and long-term outcome of 33 patients with chronic airways disease, submitted to pulmonary resection at the 1st Department of Surgery. All patients had been diagnosed as resectable with the traditional tools and had a traditional pFEV1 (tpFEV1) greater than 800 ml. All pFEV1 were re-calculated (npFEV1) with our new formula which also includes as lost for function all lung areas not to be resected with V/Q mismatching. Normal perfusion and ventilation distribution was found in 24.2% of patients in the lesion area and in 33.3% in the remaining pulmonary areas. An impairment of perfusion was observed in the lesion area in 72.7% of patients, in the remaining areas in 48.4%. An impairment of ventilation was observed in the same regions in 66.6% and 48.5% of patients, respectively. Abnormality in ventilation/perfusion matching occurred in the lesion area in 15.2% of cases, in the ipsilateral lung areas in 18.2%, in the contralateral lung in 48.4% of cases. In predicting postoperative FEV1, and early and long-term mortality among our resectable patients, the tpFEV1 showed an accuracy of 91%, an index of resectability of 93.7%, of unresectability of 0%. Our npFEV1 reached an accuracy of 94.4%, an index of resectability of 100% and an index of unresectability of 66.7%.

Lung cancer surgery in elderly patients.

AIMS AND BACKGROUND: Bronchogenic carcinoma is the major cancer-related cause of death in patients aged 70 years and over, and its incidence is rising. The aim of our study was to compare the incidence and the prognostic effect of the parameters characterizing resected patients with non-small-cell lung cancer (NSCLC) when stratified by age. Of 283 NSCLC patients candidates to a long-term follow-up program and who underwent pulmonary resection in our Unit, 34 (12%) were older than 70 years. METHODS: All patients had been preoperatively selected to exclude those with severe or multiple organ system disease and staged in accordance with the UICC classification. RESULTS: When univariate and multivariate analyses were performed within the elderly group, exclusively epidermoid carcinoma and multiple tumor nodules emerged as independent poor prognostic factors (hazard risk, 5.77 and 7.33, respectively). In comparing the older and younger groups, a higher incidence of previous primary neoplastic disease (P = 0.001), epidermoid carcinoma (P < 0.05) and multiple tumor nodules (P < 0.001) was observed in the elderly. Postoperative death was similar (3% vs 4.8%) in the two age groups, as was survival expectancy when stratified by stage. However, univariate analysis showed that epidermoid carcinoma (P = 0.001) and pneumonectomy (P = 0.00001) had a worse outcome in the older early stage subset than in the younger group. When multivariate analysis was performed in all early stage patients, only lymph node involvement and multiple tumor nodules were independently related to survival (hazard risk, 1.82 and 3.76, respectively) and had a poor prognosis. In more advanced disease, elderly and younger patients had a similar outcome. CONCLUSIONS: Our results confirm that a patient's advanced age is not a risk factor in deciding on pulmonary resection, at least for stage I and II NSCLC, and suggest that in all patients, irrespective of age, stage and histologic cell type, the presence of multiple tumor nodules is the only true prognostic factor with a very low survival rate.

Lung cancer in young patients.

Despite the increasing frequency of lung cancer, the percentage occurring in young patients is very low (1.3-5.5% of all lung cancers). In 1992, of the 78,124 cases observed in Italy, 2.8% involved patients under 40 years of age. We reviewed a series of 800 patients with histologically proven lung cancer, candidates to a long-term follow-up. Of these, 23 (2.9%) were under 40 years of age, with a low male/female ratio (1.87:1). Fifty-two percent were smokers and 82.6% presented symptoms as the time of diagnosis. The most frequent histologic types were adenocarcinoma and large-cell type, which carried a better outcome (10-year survival of 28.5%) than epidermoid and small-cell types (p = 0.013). These tumors detected in 13% and 17.4% of cases, were unresectable (except for one epidermoid carcinoma), with a survival expectancy of 0% at two years. Considering all patients, resection was possible in nine cases, being curative in seven, with an overall 10-year survival rate of 44.4% (p = 0.002 vs non-resected patients). Stage I-II had the best prognosis with a 10-year survival rate of 80% (p = 0.022 vs resected stage III-IV). Patients undergoing primary chemotherapy and/or radiotherapy had the worst prognosis with no survivors at 30 months. In young patients clinical and pathological parameters had almost the same distribution except for sex and histologic type and offered almost the same survival probability as in patients over 40 years of age. When prognostic findings were tested by univariate analysis, only resectability was found to have an independent favourable impact on survival (hazard risk: 7.47; 95% confidence interval: 1.50-37.14).

Assessment of the accuracy of diagnostic chest CT scanning. Impact on lung cancer management.

To evaluate the reliability of computed tomography (CT) scanning in detecting the locoregional extent of bronchogenic carcinoma, preoperative chest CT findings were compared with surgical and pathological findings (pTN) in 61 patients submitted to pulmonary resection for non-small cell lung carcinoma. Neoplastic disease was misdiagnosed in 3 cases. In the remaining 58 cases, CT showed a sensitivity, specificity and accuracy in delineating T factor of 66.6%, 96.1%, 93.1% for T1; of 84.6%, 68.4%, 79.3% for T2; of 66.6%, 95.9%, 91.3% for T3 and of 50.0%, 94.4%, 91.3% for T4. For N1 and N2 factors, sensitivity was 45.4% and 27.2%; and accuracy was 74.1% and 81.0% respectively. The highest incidence of false positive N1 and false positive N2 was found in tumors classified at CT as T2 and T4 respectively. Overall CT showed a good accuracy in discriminating between resectable tumours with better prognosis (postsurgical pathological stage I-II) and those with less favourable outcome (postsurgical pathological stage III).

Modality of failure following resection of stage I and stage II non-small cell lung cancer.

The pattern and sites of recurrence were studied in 270 patients with resected Stage I (NO) or Stage II (Nl) non-small cell lung cancer (NSCLC). Survival, incidence, and type of intrathoracic locoregional recurrence versus distant extra-thoracic recurrence after surgical excision were analyzed. Prognostic parameters, such as postsurgical stage, histologic type, degree of cellular differentiation, and surgical approach, were examined to discern their influence on tumor recurrence. The total incidence of recurrence in patients with stage I and II tumors was high, with a radical surgical approach often resulting ineffective, because of incomplete locoregional neoplastic extirpation due to micrometastases. Lymph node metastases worsened prognosis, with Nl tumors demonstrating a significantly higher recurrence rate at 5 years (63%) than NO neoplasms (48%) (p < 0.01). Stage I tumors showed an elevated incidence of local recurrence (45%), with tumor T-factor making a significant contribution in such cases. N1-factor combined with an elevated T-factor (Stage II Subclass pT2Nl neoplasms) promoted a higher incidence of distant rather than local recurrence. A shorter disease-free interval was observed in patients with N tumors as opposed to NO neoplasms. Histologic type did not play a statistically significant role (p = ns) in the total incidence of recurrence. A similar total incidence of recurrence was observed in Stage I and II tumors treated by lobectomy (51%) or pneumonectomy (56%), with locoregional recurrence appearing more frequently after lobectomy.

Results of surgical treatment of stage IIIA non-small cell lung cancer.

From 1975 to 1993, 665 patients with non-small cell lung carcinoma (NSCLC) were studied in our Unit. Of the 55 stage IIIA patients submitted to resection, 50 were followed-up in order to evaluate the effectiveness of surgery and to identify which variables had a prognostic impact on survival. The expectancy of survival at 3,5 and 10 years was 31.7, 19.5 and 13.7%, respectively. When the analysis was limited to N2 patients, 3,5- and 10-year survival rates were 20.9, 14 and 7%, respectively. Regarding the "TN" factor, the T3N0 subset presented the highest expected survival (24.8 and 18.6% at 5 and 10 years). With regard to the "T3" factor and type of surgery, peripheral tumors submitted to en bloc resection of the chest wall showed the best 5-year survival rate (42.9%), whereas extrapleural resections--even for tumors confined to the parietal pleura--showed a 5-year survival rate of 14.3%. A slightly higher risk of death was observed in tumors originating in the superior sulcus (SST). No patients with mediastinal pleura and pericardium involvement survived more than 34 months. With univariate analysis, "N2" was the variable most significantly associated with a negative prognosis when related to T3 (T3N2 vs T3N0 0.025 < P < 0.05) or non-epidermoid tumor (no survivors at 3 years; N2 epidermoid vs N2 non-epidermoid tumor P < 0.05). Applying multivariate analysis, epidermoid cell type, even if exclusively for N2 tumors, was an independent prognostic factor, showing a favorable impact on survival expectancy (27.8% at 90 months).

Local and/or distant recurrences in T1-2/N0-1 non-small cell lung cancer.

Data from a series of 181 patients subjected to long-term follow-up after surgical resection for non-small cell stage I and II lung cancer were analyzed to evaluate the statistical incidence and the prognostic factors of recurrence. The recurrence rate/year was particularly high in the first 2 years after surgery: the 2-year recurrence rate was 35.1% in stage I tumors and 51.8% in stage II, whereas the 5- and 7-year recurrence rates were 46.1 and 55.9% and 65.8 and 70.7%, respectively, for the same groups. Recurrences were observed more frequently in non-epidermoid carcinomas with multiple nodules (100% at 5 years) and in carcinomas classified as stage II (70.7% at 5-7 years), particularly when defined as adenocarcinoma (100% at 3 years). In the overall recurrence rate we observed no significant difference dependent on the type of resection even though limited segmental or wedge resection appeared to be related to a higher risk rate (true recurrence rate ratio: 0.6). Over two-thirds of the first observed recurrences were located at a distant site, with a slightly higher incidence of non-epidermoid carcinoma (72.5%). Isolated local recurrence mostly occurred in epidermoid carcinoma (47.6%). The most frequent sites of recurrence were the brain, bone and mediastinum. On multivariate analysis, independently significant adverse prognostic factors regarding the recurrence incidence were: tumor size greater than 3 cm, bronchial or hilar lymph node involvement, tumor histologically defined as adenocarcinoma, and the presence of satellite nodules.