Results and complications of the Baha system (bone-anchored hearing aid).

The aim of this work is to reexamine our experience with the treatment of conductive and mixed hearing loss using the Baha system. The system was implanted in 47 patients (16 adults and 31 children under the age of 14), bilaterally in two cases. The causes of hypoacusis were bilateral congenital aural atresia (31 patients), bilateral chronic otitis media or outcomes of middle-ear surgery (Gillett et al. in J laryngol Otol 120:537-542, 2006), and otosclerosis (Pazzaglia et al. in Acta Orthop Scand 54:574-579, 1983). The following parameters were assessed: mean preoperative air- and bone-conduction thresholds for the frequencies of 500, 1,000, 2,000 and 4,000 Hz; mean postoperative threshold with the Baha; hearing improvement calculated by subtracting the postoperative threshold with the Baha from the preoperative threshold for air conduction in the better ear; speech audiometry test; improvement in the quality of life, calculated using the Glasgow Benefit Inventory for the adult patients and the Glasgow Children's Benefit Inventory for paediatric patients; frequency and type of surgical complications. Follow-up ranged from 6 to 38 months. The audiological results were satisfactory, with air-bone gap closure in 85.1% of cases. In terms of quality of life, assessment using the Glasgow Benefit Inventory showed a clear-cut improvement in health for all the 45 patients that answered to the questionnaires in our study. Out of the 49 operations that were performed, complications were reported in 3 cases (6.1%): 2 cases of skin regrowth around the titanium screw and one in which the abutment was not osseointegrated. The data from this study show that the Baha system offers a high percentage of success, which can significantly improve the patient's quality of life, and a low rate of complications.

Nutraceuticals as immune-stimulating therapy to fight COVID-19. Combination of elements to improve the efficacy.

COVID-19 pandemic has underlined that unknown viral infections, which jump from animals to humans, can be extremely dangerous. In case of new viruses as SARS-CoV2, available drugs can fail to contrast the virus aggressiveness leading patients to death. Long time is necessary to create a vaccine, but immediate solutions are necessary to stop the mortality COVID-19 related. We have learned that the immune-system is the key to reduce the severity of COVID-19 and, through its modulation, it has been possible saving people's life. In this short communication, we discuss the use of nutraceuticals to modulate and stimulate the immune answer for reducing the severity of COVID-19 symptoms. The nutraceuticals are safe and can be administered to all ages. In addition, combination of natural anti-viral elements and immune-stimulating molecules already successfully tested against others upper-respiratory tract infections-could be efficient against SARS-CoV2. We believe that these natural molecules could really be a valid ally against COVID-19, especially in this moment in which a SARS-CoV2 vaccine is still not available.

Autologous haematopoietic stem cell transplantation without CD34+ cell selection in refractory Crohn's disease.

OBJECTIVES: Autologous haematopoietic stem cell transplantation (HSCT) with CD34(+) cell selection has recently been used in the treatment of refractory Crohn's disease, showing good safety and promising efficacy. We investigated the safety and efficacy of HSCT with unselected peripheral blood stem cells (PBSCs) in moderate-severe refractory Crohn's disease. PATIENTS: Four patients (three male, one female; age range 26-45 years) with active moderate-severe Crohn's disease (median Crohn's Disease Activity Index (CDAI) 319, range 272-345), refractory or intolerant to multiple drugs including infliximab, were enrolled. INTERVENTIONS: Unselected PBSCs were collected after mobilisation with cyclophosphamide (CTX) 1.5 g/m2 and granulocyte-colony stimulating factor (G-CSF) 10 microg/kg. The conditioning regimen included CTX 50 mg/kg on days -5 to -2 and rabbit anti-thymocyte globulin (ATG) 2.5 mg/kg on days -4 to -2. MAIN OUTCOME MEASURES: Primary endpoints were toxicity and clinical remission (CDAI<150) at 3 months. Secondary endpoints were clinical and endoscopic response at 3 months and toxicity, clinical and endoscopic remission at 12 months. RESULTS: No improvement or slight deterioration was observed following mobilisation (median CDAI 339, range 258-404). At the third month, the primary endpoint of clinical remission was achieved in all patients, with a median CDAI of 91 (range 56-102), and complete endoscopic remission was achieved in 2/3 patients. After a median follow-up of 16.5 months, 3/4 patients maintained both clinical and endoscopic remission, despite withdrawal of all drugs, and complete fistula closure was observed in all affected patients. No deaths or life-threatening infection occurred. Unexpected adverse events included a perianal abscess after mobilisation in one patient, pleural and pericardial effusions in another and BK virus-related macrohaematuria in another, all rapidly resolved with conservative treatment. CONCLUSION: Autologous HSCT with unselected PBSC appears to be safe and can induce and maintain remission in previously refractory Crohn's disease patients.

The effects of oral supplements with Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (HA122), Arabinogalactans, vitamin D, vitamin E and vitamin C in otitis media with effusion in children: a randomized controlled trial.

OBJECTIVE: To evaluate the ability of oral supplements with immune-stimulating molecules (Sambucus nigra, Zinc, Tyndallized Lactobacillus acidophilus (HA122), Arabinogalactans, vitamin D, vitamin E and vitamin C) to reduce the inflammation of the upper airway tract and improve the outcome of otitis media with effusion (OME) in children. PATIENTS AND METHODS: Randomized controlled trial. One-hundred ninety-eight children (CI 95%: 12-96 months) were divided into four groups. Group 1 (48 subjects) received 10 ml of oral supplements (OS) with immune-stimulating molecules for three months (20 days consecutively, then 10 days of suspension - the therapeutic scheme was repeated three times); Group 2 (54 children) underwent treatment with 10 ml of OS for 90 consecutive days; Group 3 (48 subjects) received 15 ml of OS for 45 consecutive days; a control group (48 children) underwent the standard treatment for rhinitis and OME. Outcome measures included otoscopy, tympanometry, fibroendoscopy, and the pure tone audiometry (PTA) at T0 (before treatment), T1 (45 days after treatment), and T2 (90 days after treatment). RESULTS: All children treated with OS showed a reduction of Upper Airway Infection (UAI) episodes and OME compared to the control group independent of the administration method and posology. The three groups treated with OS showed statistically significant differences between T0 and T2 for otoscopy, tympanometry, fibroendoscopy, and PTA. In Group 2, the otoscopy and the tympanometry scores improved at T1. Group 2 and 3 had better PTA results than Group 1. CONCLUSIONS: OS with immune-stimulating molecules should be considered as a supporting therapy in children affected by recurrent episodes of UAI associated with OME due to their capacity to improve the immune response and reduce the inflammatory phenomena. OS can improve the fibroendoscopic findings by restoring middle ear ventilation, in addition to their ability to reduce inflammation in the middle ear.

Pre-treatment with Melamil Tripto® induces sleep in children undergoing Auditory Brain Response (ABR) testing.

OBJECTIVES: Previous studies have shown that tryptophan and vitamin B6 used in conjunction with melatonin induce sleep more effectively than melatonin alone. This study aims at evaluating the efficacy of different dosages and timings of administration of a solution containing melatonin, tryptophan, and vitamin B6 for inducing sleep in children undergoing ABR testing. METHODS: 294 children scheduled for Auditory Brain Response (ABR) evaluation were administered a solution containing melatonin, tryptophan, and vitamin B6 to induce sleep before the exam. Two different administration timings (pre-treatment and single shot treatment) and three dosages (0.5 ml in pre-treatment, 1.5 ml in pre-treatment, and 3 ml in single shot) were tested. The following parameters were evaluated: time needed for the subject to fall asleep before ABR testing, subject sl'eep features during ABR testing (quality, stability, duration), recorded ABR quality (including presence of abnormalities in amplitude and latency), subject waking up modality, and time needed for the subject to wake up at the end of the ABR exam. RESULTS: Quality of ABR signals was similar across treatments, and subjects responded in a similar manner in terms of time needed to wake-up and wake-up modality. However, pretreatment with the 1.5 ml dose induced sleep faster than the two other dosages, and the length of the induced sleep was longer than that induced by pre-treatment with 0.5 ml. In general, the pre-treatment with 1.5 ml led to a shorter ABR exam, because reduces the time for inducing sleep, allows a long sleeping phase with a good quality, without variation in the wakening up times. CONCLUSIONS: Melamil Tripto® is an alternative to sedative drugs for inducing sleep in pediatric subjects undergoing ABR testing. A pre-medication with 1.5 ml of MT 1 week before ABR testing further improves the strength of the solution.

Stapled hemorrhoidopexy: day surgery or one day surgery?

Hemorrhoidal disease is one of the most common anorectal disorders, from 10% to 20% of all patients admitted at a clinical investigation need to undergo surgery, stapled haemorrhoidopexy is gaining wide acceptance as an interesting, safe and less painful technique, but hemorrhage is one of the most serious early complications and is a severe complication in day surgery. In our day surgery proctology, surgical procedures represent about 32%. Of these, 24% are for hemorrhoidal disease, we present our protocol and experience for early and safe discharge, 6h after stapled hemorrhoidopexy surgery.

Sinuclean Nebules treatment in children suffering from otitis media with effusion.

OBJECTIVE: Otitis media with effusion (OME) is an ear disorder defined by the presence of fluid in the middle ear without signs or symptoms of acute infection. The current randomized, double-blind, controlled study aimed to evaluate whether Sinuclean Nebules treatment, administered by nasal douche (Rinowash), could induce ear healing better than isotonic saline in children with OME. METHODS: The study was randomized, double-blind, and controlled. Group A (30 children) was treated with Sinuclean Nebules 45 and Group B (31 children) was treated with isotonic saline; both compounds were administered by nasal nebulization with Rinowash nasal douche twice/day in the morning and in the evening for 10 days, followed by a one-week suspension, and after by a second course as the first. Tympanogram and audiometry were performed at baseline and after treatment. RESULTS: Considering the global evaluation of the treatment: in Group A, 28 (93.3%) patients had complete resolution and 2 (6.7%) had partial resolution; in Group B, all patients had failure of treatment. There was a significant difference between groups (p < 0.0001). CONCLUSION: The current randomized-controlled study demonstrated that Sinuclean Nebules was effective and in the treatment of children with OME.

Follow-up of permanent hearing impairment in childhood.

Programmes for early childhood childhood hearing impairment identification allows to quickly start the appropriate hearing aid fitting and rehabilitation process; nevertheless, a large number of patients do not join the treatment program. The goal of this article is to present the results of a strategic review of the strengths, weaknesses, opportunities and threats connected with the audiologic/prosthetic/language follow-up process of children with bilateral permanent hearing impairment. Involving small children, the follow-up includes the involvement of specialised professionals of a multidisciplinary team and a complex and prolonged multi-faced management. Within the framework of the Italian Ministry of Health project CCM 2013 "Preventing Communication Disorders: a Regional Program for Early Identification, Intervention and Care of Hearing Impaired Children", the purpose of this analysis was to propose recommendations that can harmonise criteria for outcome evaluation and provide guidance on the most appropriate assessment methods to be used in the follow-up course of children with permanent hearing impairment.

Improving regional universal newborn hearing screening programmes in Italy.

The Universal Newborn Hearing Screening (UNHS) programme aims at achieving early detection of hearing impairment. Subsequent diagnosis and intervention should follow promptly. Within the framework of the Ministry of Health project CCM 2013 "Preventing Communication Disorders: a Regional Program for early Identification, Intervention and Care of Hearing Impaired Children", the limitations and strengths of current UNHS programs in Italy have been analysed by a group of professionals working in tertiary centres involved in regional UNHS programmes, using SWOT analysis and a subsequent TOWS matrix. Coverage and lost-to-follow up rates are issues related to UNHS programmes. Recommendations to improve the effectiveness of the UNHS programme have been identified. The need for homogeneous policies, high-quality information and dissemination of knowledge for operators and families of hearing-impaired children emerged from the discussion.

High-dose therapy and autologous stem-cell transplantation for adult patients with Hodgkin's disease who do not enter remission after induction chemotherapy: results in 175 patients reported to the European Group for Blood and Marrow Transplantation. Lymphoma Working Party.

PURPOSE: To investigate the results of high-dose therapy and autologous stem-cell transplantation (ASCT) in adults with Hodgkin's disease who do not enter remission after induction therapy, to determine overall survival (OS) and progression free survival (PFS), and to identify prognostic factors. PATIENTS AND METHODS: A retrospective analysis of 175 patients reported to the European Group for Blood and Marrow Transplantation between November 1979 and October 1995. One hundred were male and 75 were female, with a median age of 26.5 years. Responses to first-line therapy were defined as progressive disease (PD) in 88 and stable/minimally responsive disease (SD/MR) in 87. Seventy-five patients received ASCT after failure of one induction regimen. Second-line therapy was given to the remaining 100 patients. Response to second-line therapy was PD in 34 and SD/MR in 66. OS and PFS rates were determined, and prognostic factors were investigated using univariate and multivariate analyses. RESULTS: Responses to high-dose therapy and ASCT were complete response (30%), partial response (28%), no response (14%), PD (14%), and toxic death (14%). Actuarial 5-year OS and PFS rates were 36% and 32%, respectively. In univariate analysis for PFS and OS, adverse factors were use of a second-line chemotherapy regimen and interval of more than 18 months between diagnosis and ASCT. In multivariate analysis, the interval between diagnosis and ASCT maintained prognostic significance for OS. Response to the chemotherapy regimen given immediately before ASCT had no predictive value. CONCLUSION: High-dose therapy and ASCT is an effective treatment strategy for patients with Hodgkin's disease for whom induction chemotherapy fails. Outcome was equivalent for those with obvious PD or SD/MR in response to the regimen given immediately before high-dose therapy. Prospective randomized studies are required to compare this approach with conventional-dose salvage therapy.

Idarubicin in the therapy of acute myeloid leukemia: final analysis in 57 previously untreated patients.

Fifty-seven previously untreated adult acute myeloid leukemia patients received idarubicin (IDA) in sequential combination with cytarabine as induction therapy; post-remission treatment included two courses of IDA and cytarabine alternating with two courses of VP-16 and cytarabine. As late intensification, patients received either high-dose cytarabine or, in 10 cases, autologous bone marrow transplantation. Complete remission (CR) was achieved in 48 patients (84.2%), 41 after one induction course and seven after two courses. Median length of disease-free survival (DFS) was 26 months. Univariate analysis did not identify any of the investigated variables as having prognostic significance in predicting DFS. On the other hand, patients achieving CR after one induction course had a better DFS than those requiring two courses. Furthermore, the analysis of DFS slightly favors autologous bone marrow transplantation. In conclusion, the antileukemic activity of the present IDA protocol is testified by the high CR rate and by the possibility of minimizing the role of prognostic factors. The better outcome of patients achieving CR after one induction course further supports the opinion that the intensity of the induction treatment, offered by an agent as potent as IDA, might significantly influence DFS.

Cataracts after total body irradiation and bone marrow transplantation in patients with acute leukemia in complete remission: a study of the European Group for Blood and Marrow Transplantation.

PURPOSE: Advances in bone marrow transplantation (BMT) have consistently improved long-term survival. Therefore, evaluation of late complications such as cataracts is of paramount importance. METHODS AND MATERIALS: We analyzed data of 2149 patients from the EBMT registry. A cohort of 1063 patients were evaluable for survival and ophthalmologic status after transplant for acute leukemia (AL) in first or second complete remission. Conditioning therapy included either single-dose total body irradiation (STBI) or fractionated TBI (FTBI) grouped in different dose rates (low: LDR < or = 0.04 Gy/min; high: HDR > 0.04 Gy/min). RESULTS: The overall 10-year estimated cataract incidence (ECI) was 50%. It was 60% in the STBI group, 43% in the FTBI group < or = 6 fractions, and 7% in the FTBI group > 6 fractions (p < 10(-4)). It was significantly lower (30%) in the LDR than in the HDR groups (59%;p < 10(-4)). Patients receiving heparin for veno-occlusive disease prophylaxis had fewer cataracts than those who did not (10-year ECI: 33% vs. 53%, respectively;p = 0.04). The 10-year ECI was 65% in the allogeneic vs. 46% in the autologous BMT patients (p = 0.0018). Factors independently associated with an increased risk of cataract were an older age (> 23 years), higher dose rate (> 0.04 Gy/min), allogeneic BMT, and steroid administration (> 100 days). The use of FTBI was associated with a decreased risk of cataract. Heparin administration was a protective factor in patients receiving STBI. In terms of cataract surgery, the unfavorable factors for requiring surgery were: age > 23 yr, STBI, dose rate > 0.04 Gy/min, chronic graft-vs.-host disease (cGvHD), and absence of heparin administration. Among the patients who required cataract surgery (111 out of 257), secondary posterior capsular opacification was observed in 15.7%. CONCLUSION: High dose rate and STBI are the main risk factors for cataract development and the need for surgery, and the administration of heparin has a protective role in cataractogenesis.

Cytogenetic and myelodysplastic alterations after autologous hemopoietic stem cell transplantation.

Secondary myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML) are today considered a primary complication of autologous hematopoietic stem cell transplantation. In our Center, 83 autografted patients underwent bone marrow (BM) biopsy and cytogenetic analysis at fixed intervals. Twelve patients developed non-clonal cytogenetic abnormalities and 10 patients clonal abnormalities, five of whom (three - 7, one - 5 and one t(9;11)) developed secondary MDS/AML. MDS was also diagnosed in two patients with a normal karyotype. In brief, seven patients (three males, four females; median age 36 years) developed MDS/AML 12-48 months (median 14) after autografting. The FAB diagnosis was AML-M2 in one, chronic myelomonocytic leukemia in two and refractory anemia with excess of blasts in transformation in four cases. Two patients presented a BM biopsy picture of MDS with fibrosis; none of them experienced leukemic transformation. Four MDS patients died, three of leukemic transformation and one of BM insufficiency; the two remaining patients are still living and untransformed. Our data underline the leukemogenic role of previous treatments, even if it is not possible to exclude that underlying disease and/or conditioning therapy may be involved.

Multiple autoimmune events after autologous bone marrow transplantation.

A 36-year-old woman with RAEB-t and severe bone marrow fibrosis undergoing autologous BMT, developed a histologically documented GVHD-like skin rash. Thereafter, autoimmune thyroiditis, autoimmune thrombocytopenic purpura and autoimmune hemolytic anemia and a lupus anti-coagulant (LAC) were diagnosed. The patient is still alive, symptom-free and in first complete remission (CR); however, all of the autoantibodies are still detectable, with the exception being the anti-erythrocyte antibody. The most outstanding feature of the present case is the polymorphism of the autoimmune events, in the absence of a coexisting systemic autoimmune disease. This patient has achieved long-term disease-free survival (DFS) in first CR despite high-risk MDS and the repeated immunosuppressant therapy required because of the complications described above; a GVL reaction somewhat similar to the autoimmune events may have contributed towards maintaining disease control.

Haematopoietic abnormalities after autologous stem cell transplantation in lymphoma patients.

Haematopoietic reconstitution after autologous stem cell transplantation (ASCT) was evaluated at different times in 26 lymphoma patients. All of the patients showed a significant decrease in the number of both committed (CFU-C) and more primitive progenitor cells (LTC-IC). The expansion of bone marrow progenitor cells in a 'stroma-free' long-term liquid culture system supplemented with SCF, IL-3, IL-6 and GM-CSF from 19 transplanted patients was significantly reduced compared to normal controls. The stromal cell compartment, evaluated by means of a CFU-F assay, was also greatly reduced. The number of haematopoietic and stromal cell progenitors was, nevertheless, very similar to their pre-transplant values. Bone marrow histology, which was evaluated at different times after transplant, showed an increase in reticulin fibres, the dilatation of parenchymal sinusoids and some morphological evidence of trilineage dysplasia in 11 patients; however, the same abnormalities were seen in the majority of pre-transplant samples. No cytogenetic abnormalities were observed in 15 patients before transplant, but four subsequently developed persistent clonal karyotypic alterations and five showed non-clonal abnormalities that generally disappeared over time. Our data suggest that both the stromal and the haematopoietic compartments are somehow damaged after ASCT for lymphoma; however, these defects generally pre-exist the transplant conditioning regimen and seem to become less pronounced over time.

Unrelated mismatched cord blood transplantation in an adult with secondary AML.

Umbilical cord blood (CB) has been widely used for related and unrelated transplants in pediatric patients. We present the case of an adult with secondary AML who received an unrelated, one-antigen mismatched CB transplant due to the lack of a matched donor. The patient was a 26-year-old female (35 kg/bw) who had received an autologous bone marrow transplant for Hodgkin's disease in April 1994 and, 6 months later, developed secondary MDS (RAEB, 46, XX, -7, +mar), which slowly evolved into acute myelogenous leukemia. In May 1995, she was transplanted with a 165 ml CB unit containing a total of 1.6 x 10(9) nucleated cells, 11 x 10(6) CD34+ cells and 7.2 x 10(5) CFU-GM. GVHD prophylaxis consisted of standard CsA and methotrexate. Myeloid engraftment occurred on day +28 (PMN > 500) and full donor chimerism was confirmed twice (on days +33 and +56) by means of cytogenetics and DNA microsatellite analysis. Erythroid and megakaryocytic engraftment was documented by immunohistochemical analysis of a bone marrow biopsy on day +40, showing the presence of erythroblastic islands and isolated CD61+ immature cells. The patient did not develop GVHD but died on day +56 from idiopathic interstitial pneumonia and multiorgan failure. To our knowledge, this is one of the first case reports of unrelated mismatched CB transplantation in an adult.

Treatment of advanced mycosis fungoides by allogeneic stem-cell transplantation with a nonmyeloablative regimen.

SUMMARY: Given the poor prognosis of patients with advanced cutaneous T-cell lymphoma and the high transplant-related mortality associated with conventional allogeneic bone marrow transplantation, we performed nonmyeloablative transplantation of allogeneic stem cells (ASCT) from HLA-identical siblings in three patients with this disease. All patients achieved full donor engraftment, clearance of clonal T cells leading to durable complete remissions but experienced high incidence of infections, which proved fatal in one case. These results suggest that nonmyeloablative ASCT is a novel and potentially curative therapy for patients with advanced T-cell lymphomas who have a histocompatible sibling.

Use of high-dose cytarabine in autologous bone marrow transplantation in acute myeloid leukemia.

Autologous bone marrow transplantation is widely used as late intensification therapy for patients with AML in remission without an HLA identical donor or who are older than 40-45 years. We report our experience in 21 AML patients in 1st or 2nd CR transplanted with a regimen including HD-ARA-C in addition to Cyclophosphamide (CY) and TBI. The median age was 32 years (3-50). Fourteen patients were transplanted in 1st CR and 7 in 2nd CR. In all but one patient BM harvesting and ABMT were done in the same remission status and after at least 3 courses of consolidation therapy. Two patients (9.5%) died from treatment related toxicity on Day +15 and Day +31. The median time to reach 1000 WBC and 50,000 platelets per cmm was 23 (13-55) and 55 (22-790) days respectively. Only 4 (21%) of the 19 evaluable patients (median observation time of 32 months) relapsed, at 3, 8, 18 and 26 months from ABMT. The projected event free survival curve shows survival of 67% at 96 months with a relapse rate of 26%.