Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Lipomatous Hypertrophy: An Accidental Finding in Heart.

Lipomatous hypertrophy is an uncommon benign lesion of the atrium, generally asymptomatic, characterized by unencapsulated accumulation of adipose tissue entrapping cardiomyocytes. This pathology generally remains unnoticed and often emerges as an occasional finding. Here, we report two cases from our hospital including a review of the available literature.

Pleuroparenchymal fibroelastosis (PPFE) associated with giant cell arteritis: A coincidence or a novel phenotype?

Pleuroparenchymal fibroelastosis (PPFE) is a rare interstitial lung disease characterized by the fibrotic thickening of subpleural and parenchymal areas of the upper lobes. It may be both idiopathic or secondary to infections, interstitial lung diseases and/or drug exposure. Often PPFE patients report recurrent lower respiratory tract infections, suggesting that repeated inflammatory alterations induced by pulmonary infections may contribute to the development/progression of PPFE. Here, we report for the first time the case of a patient affected by Giant cell Arteritis with histologically proven PPFE. The lung involvement in GCA is rare and interstitial lung diseases are usually reported as an uncommon clinical manifestation of GCA. Our patient is probably the first case presenting PPFE associated with GCA and we wonder if this is a real associative disease or a coincidence perhaps, secondary to drug effects.

Cyto-histological and morpho-physiological responses of common duckweed (Lemna minor L.) to chromium.

Along with cadmium, lead, mercury and other heavy metals, chromium is an important environmental pollutant, mainly concentrated in areas of intense anthropogenic pressure. The effect of potassium dichromate on Lemna minor populations was tested using the growth inhibition test. Cyto-histological and physiological analyses were also conducted to aid in understanding the strategies used by plants during exposure to chromium. Treatment with potassium dichromate caused a reduction in growth rate and frond size in all treated plants and especially at the highest concentrations. At these concentrations the photosynthetic pathway was also altered as shown by the decrease of maximum quantum yield of photosystem II and the chlorophyll b content and by the chloroplast ultrastructural modifications. Starch storage was also investigated by microscopic observations. It was the highest at the high concentrations of the pollutant. The data suggested a correlation between starch storage and reduced growth; there was greater inhibition of plant growth than inhibition of photosynthesis, resulting in a surplus of carbohydrates that may be stored as starch. The investigation helps to understand the mechanism related to heavy metal tolerance of Lemna minor and supplies information about the behavior of this species widely used as a biomarker.

Steroid resistance in nasal polyposis: role of glucocorticoid receptor and TGF-beta1.

BACKGROUND: Glucocorticoids (GCs) are considered drugs of choice for treating nasal polyps (NPs). However, a subset of patients shows a limited clinical response even to high doses of GCs. Altered expression of glucocorticoid receptors (GRs), namely GR-alpha; and GR-beta;, is a potential mechanism underlying GC insensitivity. GCs modulate the expression of several cytokines, including transforming growth factor-beta (TGF-beta), which may contribute to cellular proliferation in NPs. The study investigates some biomolecular features of GC-resistant NPs, and examines possible differences from normal mucosa (NM). METHODOLOGY: Radioligand binding assay (binding) was used to determine GR-alpha; binding capacity; Western blotting was used to evaluate GR-alpha;, GR-beta;, and TGF-beta; expression and GR-alpha; subcellular distribution. NPs were sampled in 32 patients during ethmoidectomy; NM was taken from 15 healthy patients during rhinoplasty. RESULTS: GR-alpha; was present in NPs and NM, with lower affinity for the ligand in NPs. GR-alpha; was prevalent in the cytosol of NPs that were GR-alpha-negative to the binding assay. GR-beta was expressed in NPs and absent in the majority of NM. TGF-beta1 expression was higher in NPs than in NM. CONCLUSIONS: GR-beta and TGF-beta1 might be involved in NP pathogenesis, but their role in modulating GC sensitivity is still unclear.

Multiparametric statistical correlations between paranasal sinus anatomic variations and chronic rhinosinusitis.

Improvements in functional endoscopic sinus surgery (FESS) and computed tomography (CT) have concurrently increased interest in the anatomy of the paranasal region. Common anatomical variations are not rare in patients with chronic paranasal sinusitis. The aim of this retrospective study was to analyze the incidence of anatomic variations of the lateral nasal wall in a series of 200 patients with persistent symptoms of rhinosinusitis, after failure of medical therapies, and their correlation with paranasal sinus disease. A detailed analysis of CT scans showed that 140 of 200 (70%) patients had anatomic variations. In particular, 122 patients (87%) were affected by common anatomic variations, and 18 patients (13%) with uncommon variations. There were 85 (60.7%) male and 55 (39.3%) females with ages ranging from 13 to 77 years (mean 45.5 years). The maxillary sinus was most commonly involved, followed by the anterior ethmoid, frontal sinus, posterior ethmoid and sphenoid sinus. Statistically significant association was found between the presence of common anatomic variations - septal deviation, bilateral concha bullosa, medial deviation of uncinate process, Haller cell, ethmoidal bulla hypertrophic, agger nasi cell - and the presence of sinus mucosal disease (p < 0.05). There was no significant correlation between other common and uncommon anatomic variations and mucosal pathologies. The associations were evaluated using the Fisher's exact test, and compared with those reported in the literature. Considering the results obtained, we believe that some anatomic variations may increase the risk of sinus mucosal disease. We therefore emphasize the importance of a careful evaluation of CT study in patients with persistent symptoms and recurrent chronic rhinosinusitis in order to identify those with anatomical variations that may have an increased risk of developing rhinosinusitis.

Overdose of Vinblastine in place of Vinorelbine during IGEV chemotherapy.

Any class of drugs is susceptible to errors, in case of antineoplastic agents the medication errors may cause severe and life-threatening toxicity due to very limited therapeutic index with toxic events even at therapeutic dosage, to complexity of regimens and the particular vulnerable population. We report herein a case of Vinblastine (VBL) accidental overdose, the cause of mistake, the toxic effect and the salvage therapy adopted in a young lady suffering of Hodgkin relapse during IGEV chemotherapy.

Hyalinizing trabecular tumor of the thyroid: a case report.

Hyalinizing trabecular tumor (HTT) of the thyroid is a rare neoplasm that was first described by Carney in 1987. It is a tumor of follicular derivation with peculiar nuclear, architectural, histochemical, and immunohistochemical features. We report a case of HTT in a 69-year-old woman with a mutinodular goiter. Since the clinical and ultrasonographic features were nonspecific, fine needle aspiration biopsy (FNAB) of the left lobe-dominant node was performed that resulted in an indeterminate cytologic diagnosis (category THY-3). The patient underwent total thyroidectomy, with a histologic diagnosis of HTT. We discuss the clinical and diagnostic approach, including the role of FNAB, and the pathologic features of HTT with special reference to the possible differential diagnosis. Total thyroidectomy or hemithyroidectomy represent adequate treatments, while radioiodine ablation is not standard. Although rare cases of malignant HTT have been documented, this tumor should be considered a benign neoplasm or, at most, a neoplasm of extremely low malignant potential. As a consequence, once this diagnosis is rendered, clinical management should be conservative, which may include a precautionary annual follow-up in order to exclude the very rare possibility of recurrence, as exceptionally reported.

Post-transplant lymphoproliferative disorders in liver transplanted patients: a single-centre experience.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication after solid organ transplantation. Reduction of immunosuppression (RI) is accepted as a first step treatment with a long-term complete response rate observed in 23-50% of patients. Chemotherapy for diseases refractory to RI is based on small cohorts treated with different regimens. This paper reports on 10 consecutive cases of PTLD after liver transplantation. The median time from transplantation to PTLD diagnosis was 5 years. PTLD was frequently extranodal involving the transplanted liver. Seven monomorphic PTLD, 2 polymorphic and one Hodgkin disease were observed. Epstein Barr virus was present in tumour tissue only in one case. Initial therapy included RI in all patients. Chemotherapy was used in eight patients. No treatment-related mortality was observed and no patient developed graft rejection during chemotherapy. At a median follow-up period of 25 months, 6 of the 10 patients were alive and without evidence of disease.

Acute cellular rejection and Epstein-Barr virus-related post-transplant lymphoproliferative disorder in a pediatric lung transplant with low viral load.

We report the case of an 18-year-old male who underwent bilateral lung transplantation for end-stage cystic fibrosis. No Epstein-Barr virus (EBV) or cytomegalovirus serology mismatch was detected on pre-transplant evaluation (donor and recipient were both positive). Two months after lung transplantation a computed tomography scan showed multiple nodules throughout both lungs. At that time a low EBV DNA blood level was detected (<300 copies/100,000 lymphomonocytes). Scheduled follow-up transbronchial biopsy (TBB) revealed a prevalent finding characterized by perivascular lymphoid infiltrates with endothelitis. Extensive tissue coagulative necrosis with peripheral areas of dense aggregates of larger lymphoid cells were detected in the trans-thoracic fine needle core biopsy (FNCB) performed on the largest nodule. The immunophenotypic profile characterized the perivascular lymphoid cells in TBB as mainly composed of T lymphocytes (CD3 positive) while the larger number of lymphocytes in FNCB as B cells (CD20 positive). In situ hybridization for EBV (EBER mRNA) was negative in TBB while it was positive in many lymphocytes of the FNCB. Real-time polymerase chain reaction (PCR) for EBV was performed on paraffin-embedded FNCB and detected a high quantity of EBV genomes (1260 copies/cell). IgH gene rearrangement using a fragment size PCR technique revealed a monoclonal B-cell population in FNCB. Morphological and molecular findings suggest a final diagnosis of acute cellular rejection and a post-transplant lymphoproliferative disorder (PTLD) EBV-related in a lung transplant recipient with a low EBV DNA blood level. A possible coexistence of PTLD and acute rejection should be considered both for diagnosis and treatment. EBV PCR in the peripheral blood is a useful screening tool in transplant recipients; however, rare cases with PTLD may not have detectable levels of EBV DNA. This aspect should be taken into consideration to avoid false negatives.

[A case of Kaposi's sarcoma in the rapamycin era]. / Un caso di sarcoma di Kaposi nell'era della Rapamicina.

We report a case of Kaposi's sarcoma in a patient who received a double kidney transplant in 2005. Immunosuppression was induced with rapamycin and antilymphocyte serum while maintenance therapy consisted of rapamycin, corticosteroids and mycophenolic acid. The patient developed delayed graft function but no rejection. In November 2006 and March 2007 two graft biopsies were taken because of a significant rise in serum creatinine; they revealed chronic allograft nephropathy and polyomavirus infection. Meanwhile a skin biopsy of the leg was performed to determine the nature of a discolored lesion. The morphohistological diagnosis was Kaposi's sarcoma. For this reason rapamycin was stopped and steroid treatment gradually reduced. Specific therapy with doxorubicin was started; radiological and endoscopic examination excluded disseminated disease while serological tests were positive for antibodies to HHV-8, a virus known to cause Kaposi's sarcoma. Unfortunately, withdrawal of antirejection therapy caused loss of the graft, so the patient had to start dialysis. In this report we stress the possible development of malignancy in transplanted patients who are given rapamycin. Rapamycin is known to be an antirejection drug and to have antineoplastic activity; the major risk of malignancy is probably related to immunosuppression rather than the type of drugs used to obtain it.

Nasal and lung function in competitive swimmers.

Nasal and sinusal complaints are considered common among swimmers. Aim of the present study was to evaluate the nasal and bronchial functions, before and after swimming, and the relationship between nasal resistances and FEV1 in competitive swimmers. A group of 30 competitive swimmers were examined: spirometry and nasal respiratory tests were carried out before and after swimming. Moreover, both the competitive swimmers and the 150 visitors of a swimming pool were asked to complete a specific questionnaire. In this questionnaire, 18% of the population reported nasal-sinusal symptoms after swimming. The differences between nasal volumes and resistances before and after swimming were not statistically significant. Nasal patency increased or remained unchanged in 21/30 athletes. The variations in FEV1 were not statistically significant. In conclusion, results showed that swimming is able to increase nasal patency or to leave it unchanged. Temporary worsening of the nasal patency was observed in only a few hyper-reactive patients. In the whole group, no variations, at bronchial level, were found.

Post-transplant lymphoproliferative disorders after heart or kidney transplantation at a single centre: presentation and response to treatment.

Post-transplant lymphoproliferative disorders (PTLD) is a serious complication after solid organ transplantation. Reduction of immunosuppression (RI) alone is not able to control the disease. We report a prospective analysis of 30 patients with PTLD after heart or kidney transplantation. Only 5 of 30 patients, treated solely with RI, obtained a complete response. Five patients were treated heterogeneously; in the remaining 20, the efficacy and safety of a weekly anthracycline-based chemotherapy were assessed. Sixteen patients obtained a complete remission. One death was related to treatment. With a median follow-up of 36 months, 3-year overall survival was 63.3% and 57% for the entire group and the chemotherapy-treated group, respectively. Moreover, 4 second neoplasms were observed in the chemotherapeutic group. In this study, we demonstrated that most PTLD need other treatment than RI and a weekly regimen is manageable and has a favourable impact on long-term survival.

Adeno-tonsillar surgery in Italy.

Indications to surgery for adeno-tonsillar inflammatory disorders and analysis of the effectiveness of surgical treatment, compared with watchful waiting strategy, continue to be the subject of scientific debate. The present investigation focuses on the surgical activity of 14 Italian Otorhinolaryngological Units between 1999 and 2004. Surgical interventions (adeno-tonsillectomy, adenoidectomy, tonsillectomy) on 26915 children (age range: 2-11 years) were considered. Data on adeno-tonsillar interventions were analysed in relation to other interventions of ENT interest, performed in the same units and in the same period. Adeno-tonsillar interventions accounted for 35.4% of all operations of ENT interest. Adeno-tonsillectomy accounted for 56.6% of overall adeno-tonsillar operations, adenoidectomy 31.6%, tonsillectomy 11.8%. The percentage for the three interventions was homogeneous in the period of the study and in the recruited units. The percentage of children who underwent adeno-tonsillar surgery in paediatric units was higher as compared to general units, as far as concerns the overall number of operations performed. In southern Italy, the number of adeno-tonsillar interventions, in general, and of adeno-tonsillectomy, in particular, was higher compared to that in northern Italy. Results of the present study suggest that environmental factors, cultural issues and local health demands, may influence indications and, therefore, the different incidence of the operations under consideration in the units taking part in the investigation.

Upfront high-dose sequential therapy (HDS) versus VACOP-B with or without HDS in aggressive non-Hodgkin's lymphoma: long-term results by the NHLCSG.

BACKGROUND: There is not univocal concordance for using high-dose sequential therapy (HDS) as first-line treatment for aggressive non-Hodgkin's lymphoma (NHL). We designed this study to evaluate the usefulness of HDS followed by high-dose therapy (HDT) with autologous stem cell transplantation as front-line treatment in different subsets of aggressive NHL. PATIENTS AND METHODS: Among 223 patients aged 15-60 years with aggressive, advanced stage NHL, 106 patients were randomized to VACOP-B (etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, bleomycin) for 12 weeks (plus HDS/HDT in case of persistent disease) (arm A), and 117 patients to VACOP-B for 8 weeks plus upfront HDS/HDT (arm B). RESULTS: According to the intention-to-treat analysis, the complete response rate was 75% for arm A and 72.6% for arm B. With a median follow-up of 62 months there was no difference in 7-year probability of survival (60% and 57.8%; P = 0.5), disease-free survival (DFS) (62% and 71%; P = 0.2) and progression-free survival (PFS) (44.9% and 40.9%; P = 0.7) between the two arms. Subgroup analyses confirmed that the best results in terms of survival, DFS and PFS were achieved by patients with large B-cell NHL without bone marrow (BM) involvement, independently of the treatment arm. Results were poorer in other categories of patients and poorest in patients with BM involvement. CONCLUSIONS: Aggressive NHL patients do not benefit from upfront HDS/HDT.

Collecting duct carcinoma of kidney producing alpha-fetoprotein.

AIM: A case of a collecting duct carcinoma (CDC) of the kidney alpha-fetoprotein producing is reported. Serum elevation of alpha-fetoprotein (AFP) is a common marker for hepatocellular carcinoma, although some extrahepatic carcinomas, also of the kidney, with elevated AFP levels have also been reported in the literature. CASE REPORT: A 62-year-old man with a collecting duct carcinoma of the kidney presenting as a mediastinal mass and supra-clavicular lymph node enlargement, and with a serum alpha-fetoprotein (AFP) level of 102.8 microg/L. RESULTS AND CONCLUSIONS: CDC of the kidney is associated with an aggressive course and extremely poor prognosis. There are no standard treatment regimens, and neither immunotherapy nor chemotherapy has been found to be effective. In the present case, nephrectomy followed by a chemotherapeutic association of carboplatin and gemcitabine gave promising results, with lessening of the patient's symptoms.

Vinorelbine and prednisone in frail elderly patients with intermediate-high grade non-Hodgkin's lymphomas.

BACKGROUND: Frail patients with non-Hodgkin's lymphoma (NHL) are generally excluded from clinical trials and not even treated. The aim of this study was to evaluate the efficacy and tolerability of vinorelbine and prednisone in frail elderly patients with NHL. PATIENTS AND METHODS: Thirty consecutive frail elderly patients were entered in a phase II study with vinorelbine 25 mg/m2 i.v. on days 1 and 8 and oral prednisone 30 mg total dose on days 1-8 for six cycles. Criteria of frailty were age > or =80 years, or age > or =70 years and three or more comorbidities of grade 3 or at least one comorbidity of grade 4 according to the Cumulative Illness Rating Scale (CIRS), or not self-sufficient or the presence of one or more geriatric syndromes. RESULTS: Of 30 evaluable patients, three (10.0%) achieved a complete response (CR), nine (30.0%) showed a partial response (PR), while 10 presented with stable disease and eight with progressive disease. The median duration of CR was 29 months (range 5-36 months), and the median duration of PR was 1 month (range 1-22 months). Three patients had grade 3 neutropenia and one had grade 4. One grade 4 neurotoxicity was observed. Three patients died because of heart failure within 28 days of therapy, and one patient died after 4 days because of rapid progression. The median overall survival was only 10 months. CONCLUSION: Vinorelbine and prednisone is a relatively non-toxic combination with modest activity in frail patients with NHL. If initial aggressive chemotherapy has been excluded, this combination could be tried to obtain a temporary palliation.

Galectin-3: presurgical marker of thyroid follicular epithelial cell-derived carcinomas.

Preoperative follicular lesion characterisation represents an unsolved diagnostic problem in thyroid nodular disease. Although fine-needle aspiration biopsy is the most reliable preoperative diagnostic procedure, it shows inherent limitations in differentiating adenoma from follicular carcinoma and, sometimes, follicular variants of papillary carcinoma. Galectin-3 cytoplasmic neoexpression has been proposed as a peculiar feature of thyroid malignant cells, easily detectable in cytological and histological samples. The aim of this study was to re-evaluate the galectin-3 expression in a large sample of thyroid lesions using an immunohistocytochemical biotin-free detection system and a specific anti-human-galectin-3 monoclonal antibody in order to avoid the interference of technical factors, a cause of conflicting results recently reported by some authors. We analysed galectin-3 expression of 39 follicular carcinomas, 26 papillary carcinomas, and 105 adenomas in both cell-block samples and their histological counterparts. All cell-block and histological papillary carcinoma samples showed high levels of galectin-3 immunoreactivity. Thirty-four follicular carcinomas were positive, whereas 5 were negative in cell-blocks but positive in their histological counterparts. Twelve out of 105 adenomas expressed galectin-3 in cell-blocks and histological samples. The diagnostic accuracy of preoperative galectin-3 evaluation in adenomas vs follicular carcinomas was 90.0%. Galectin-3 expression was also investigated in 22 minimally-invasive follicular carcinomas. All of them showed galectin-3 immunoreactivity in both cytological and histological specimens with the exception of two cases, where galectin-3 positivity was observed only in the surgical material. The routine correct use of galectin-3, by increasing the diagnostic accuracy of conventional cytology, improves the management of thyroid nodules and can lead to a sensitive reduction of useless thyroid surgeries.