Safety and efficacy of direct-acting antivirals for the treatment of chronic hepatitis C in a real-world population aged 65 years and older.

The availability of direct-acting antiviral agents (DAA) regimens has expanded the pool of patients eligible for treatment. However, data on the virologic response and tolerability of DAAs in elderly patients are lacking. We evaluated the efficacy and safety of DAAs in patients with advanced fibrosis/cirrhosis in real-life practice with the focus on those aged ≥65 years. Between January and December 2015, all consecutive patients with HCV-related advanced fibrosis/cirrhosis treated with DAA at eleven tertiary referral centres in Emilia Romagna (Italy) were enrolled. Regimen choice was based on viral genotype and stage of disease, according to guidelines. The primary end point was sustained virologic response 12 weeks after the end of treatment (SVR12). Overall, 282 of 556 (50.7%) patients evaluated were elderly, most of them with cirrhosis. Antiviral therapy was stopped prematurely in four (1.4%) patients. Two patients, both with cirrhosis, died during treatment due to worsening of liver/renal function. SVR12 was achieved by 94.7% and was comparable to that obtained in patients aged <65 (P=.074). Similar data were also reported in subgroup of patients aged ≥75 years. All patients with advanced fibrosis achieved virologic response. SVR12 was 80.8% in Child-Pugh-Turcotte (CTP)-B cirrhosis and 95.4% in CTP-A (P=.013). According to genotype, the SVR12 was achieved in 172 of 181 (95%) with genotype 1b cirrhosis and in 44 of 48 (91.7%) with genotype 2 cirrhosis. In conclusions, in a real-world setting, DAAs are safe and effective in elderly patients with HCV-related advanced fibrosis/cirrhosis, but SVR12 is lower with worsening CTP class.

Lack of efficacy of long-term, low-dose azithromycin in chronic rhinosinusitis: a randomized controlled trial.

BACKGROUND: In persistent chronic rhinosinusitis (CRS), conventional treatment is often insufficient. Long-term, low-dose administration of macrolides has been suggested as a treatment option. The MACS (Macrolides in chronic rhinosinusitis) study is a randomized placebo-controlled trial evaluating the efficacy of azithromycin (AZM) in CRS. METHODS: We describe a group of patients with recalcitrant CRS with and without nasal polyps unresponsive to optimal medical and (in 92% also) surgical treatment. Patients were treated with AZM or placebo. AZM was given for 3 days at 500 mg during the first week, followed by 500 mg per week for the next 11 weeks. Patients were monitored until 3 months post-therapy. The assessments included Sino-Nasal Outcome Test-22 (SNOT-22), a Patient Response Rating Scale, Visual Analogue Scale (VAS), Short Form-36 (SF-36), rigid nasal endoscopy, peak nasal inspiratory flow (PNIF), Sniffin' Sticks smell tests and endoscopically guided middle meatus cultures. RESULTS: Sixty patients with a median age of 49 years were included. Fifty per cent had asthma and 58% had undergone revision sinus surgery. In the SNOT-22, Patient Response Rating Scale, VAS scores and SF-36, no significant difference between the AZM and the placebo groups was demonstrated. Nasal endoscopic findings, PNIF results, smell tests and microbiology showed no relevant significant differences between the groups either. CONCLUSION: At the investigated dose of AZM over 3 months, no significant benefit was found over placebo. Possible reasons could be disease severity in the investigated group, under-dosage of AZM and under-powering of the study. Therefore, more research is urgently required.

Nasal saline irrigations for the symptoms of chronic rhinosinusitis.

BACKGROUND: The use of nasal irrigation for the treatment of nose and sinus complaints has its foundations in yogic and homeopathic traditions. There has been increasing use of saline irrigation, douches, sprays and rinsing as an adjunct to the medical management of chronic rhinosinusitis. Treatment strategies often include the use of topical saline from once to more than four times a day. Considerable patient effort is often involved. Any additional benefit has been difficult to discern from other treatments. OBJECTIVES: To evaluate the effectiveness and safety of topical saline in the management of chronic rhinosinusitis. SEARCH STRATEGY: Our search included the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4 2006), MEDLINE (1950 to 2006) and EMBASE (1974 to 2006). The date of the last search was November 2006. SELECTION CRITERIA: Randomised controlled trials in which saline was evaluated in comparison with either no treatment, a placebo, as an adjunct to other treatments or against treatments. The comparison of hypertonic versus isotonic solutions was also compared. DATA COLLECTION AND ANALYSIS: Trials were graded for methodological quality using the Cochrane approach (modification of Chalmers 1990). Only symptom scores from saline versus no treatment and symptom and radiological scores from the hypertonic versus isotonic group could be pooled for statistical analysis. A narrative overview of the remaining results is presented. MAIN RESULTS: Eight trials were identified that satisfied the inclusion criteria. Three studies compared topical saline against no treatment, one against placebo, one as an adjunct to and one against an intranasal steroid spray. Two studies compared different hypertonic solutions against isotonic saline. There is evidence that saline is beneficial in the treatment of the symptoms of chronic rhinosinusitis when used as the sole modality of treatment. Evidence also exists in favour of saline as a treatment adjunct. No superiority was seen when saline was compared against a reflexology 'placebo'. Saline is not as effective as an intranasal steroid. Some evidence suggests that hypertonic solutions improve objective measures but the impact on symptoms is less clear. AUTHORS' CONCLUSIONS: Saline irrigations are well tolerated. Although minor side effects are common, the beneficial effect of saline appears to outweigh these drawbacks for the majority of patients. The use of topical saline could be included as a treatment adjunct for the symptoms of chronic rhinosinusitis.

Prophylactic vs postoperative antibiotic use in complex septorhinoplasty surgery: a prospective, randomized, single-blind trial comparing efficacy.

OBJECTIVE: To compare the efficacy of prophylactic vs postoperative antibiotic use in complex septorhinoplasty and strengthen the evidence base for antibiotic use in nasal surgery. DESIGN: A randomized, prospective, single-blinded trial. One hundred sixty-four patients requiring complex septorhinoplasty surgery were recruited sequentially from the waiting lists of the 2 senior authors. Power was calculated at 80% at the 5% significance level. Patients randomized to the prophylactic arm of the study received three 1200-mg intravenous doses of amoxicillin-clavulanate, given at induction of anesthesia and at 6 and 12 hours postoperatively. Patients in the postoperative antibiotic arm received a 7-day course of 375 mg of amoxicillin-clavulanate 3 times a day. Patients allergic to penicillin were given erythromycin. Clinical and microbiological evidence of infection on the 10th postoperative day was categorized as either minor (vestibulitis) or major (nasal or septal cellulitis, septal abscess, secondary hemorrhage, or donor-site infection) infections. RESULTS: At follow-up, 6 (7%) of 82 patients in the prophylactic arm and 9 (11%) of 82 of patients in the postoperative arm showed evidence of infection. Most (80%) of infections were minor. There was no significant difference in infection rates between the prophylactic and postoperative arms on chi2 analysis (P = .42). All 164 patients completed the study on an intention-to-treat basis. CONCLUSION: We recommend the use of prophylactic antibiotics rather than empirical postoperative antibiotics for patients undergoing complex septorhinoplasty.

Recombinant X chromosome in a prenatal diagnosis.

The prenatal cytogenetic study of an amniotic fluid sample of a 39-year-old female showed one X chromosome with a fragment of extra material in the short arm. The G-band pattern suggested that the extra material could be the long arm of an X chromosome. Several complementary studies were performed in order to better clarify the origin of the material. These studies included parental karyotypes, microsatellite typing and comparative genomic hybridization (CGH). The results obtained allowed us to conclude that the derivative chromosome arose de novo as a recombinant X chromosome with duplication of Xq and partial deletion of Xp. Once informed, the parents decided to continue with the pregnancy, after which a healthy girl was born with no apparent disorders.

A randomized trial of Rapid Rhino Riemann and Telfa nasal packs following endoscopic sinus surgery.

OBJECTIVES: To compare Telfa with the Rapid Rhino Riemann nasal pack for use following endoscopic sinus surgery. DESIGN: Prospective, randomized, double-blind, paired trial. SETTING: Tertiary otolaryngology hospital. PARTICIPANTS: Forty-five adult patients undergoing bilateral endoscopic sinus surgery for either chronic rhinosinusitis or nasal polyps. MAIN OUTCOME MEASURES: A visual analogue scale was used to assess discomfort caused by the presence of the packs in the nose and by their removal. The amount of bleeding was noted with the packs in place and following their removal. Crusting and adhesions were assessed 2 and 6 weeks following surgery. RESULTS: Both packs performed well giving good haemostasis and causing little bleeding on removal. Both packs caused only mild discomfort while in the nose. On the visual analogue scale of 0-10 cm the mean visual analogue score for Rapid Rhino Riemann pack was 1.7 and for Telfa 2.0 (P = 0.371). The Rapid Rhino Riemann pack caused significantly less pain on removal compared with the Telfa pack with a mean visual analogue score of 2.0 in comparison with 3.7 for Telfa (P = 0.001). There were less adhesions with the Rapid Rhino Riemann than Telfa pack but this was not statistically significant (P = 0.102). CONCLUSIONS: Both Telfa and Rapid Rhino Riemann packs can be recommended as packs that control postoperative haemorrhage, do not cause bleeding on removal and cause little discomfort while in the nose. The Rapid Rhino Riemann pack has the advantage of causing significantly less pain on removal.

Trisomy rescue by postzygotic unbalanced (X;14) translocation in a girl with dysmorphic features.

In this report we present the clinical features and molecular and cytogenetic findings in a female with partial trisomy 14q. Molecular and cytogenetic studies allowed us to determine that the extra 14q material (of paternal origin) was translocated postzygotically onto the maternal X chromosome. Consequently, only the derivative X chromosome was inactivated, although inactivation apparently did not spread over the entire chromosome 14q. This partial inactivation makes the present case unusual, giving rise to phenotypic features absent in other patients with partial trisomy 14q, typically restricted to the distal part of the chromosome.

The effect of laser assisted uvulopalatoplasty on the sense of smell and taste.

AIM: To assess the effect, if any, of Laser Assisted Uvulo Palatoplasty (LAUP) on the sense of smell and taste. MATERIALS AND METHODS: A prospective study examined 33 patients undergoing LAUP for snoring. Significant sinonasal pathology was excluded in all patients by a complete examination including rigid nasal endoscopy. None of the cases had any systemic illness or drug history that was likely to affect the sense of smell or taste. Twenty-eight patients were male and five female. The mean age was 44 years (range, 25-67). Twelve patients (36%) were regular smokers, and eight patients (24%) were ex-smokers all of whom reported a change in smell and taste after stopping. Preoperative assessment utilised a visual analogue score of smell and taste perception, the University of Pennsylvania Smell Identification Test (UPSIT) for the assessment of olfaction (maximum score of 40), and whole mouth testing for solutions of NaCl, sucrose, quinine, citric acid and acetic acid. LAUP technique was standardised for each case and reassessment was performed 3 months postoperatively. RESULTS: Three patients failed to complete the study and were excluded. The mean values for visual analogue score pre and post surgery were 9.1 and 8.9 respectively, which was not significant using Wilcoxon Rank test (P = 0.257). The mean value of the UPSIT scores before surgery were 32.3 (+4.0), range, 24-39, and after surgery 31.2 (+4.3), range 20-37. There was no significant difference in pre and post UPSIT scores (p = 0.068). Whole mouth taste testing had a preoperative mean value of 4.1 and a postoperative value of 4.2. The difference was not statistically significant, Wilcoxon Rank test (p = 0.317). CONCLUSION: In this study there was no significant change in the patients' perception of smell and taste or in their objective measurement following a standardised Laser Assisted Uvulopalatoplasty.

Primary spontaneous cerebrospinal fluid rhinorrhea and obesity.

The objective of this paper is to determine whether there is a relationship among obesity, gender, and the risk of development of primary spontaneous cerebrospinal fluid (CSF) rhinorrhea. A retrospective case review of all the patients with CSF rhinorrhea treated at our unit over a 10-year period is presented. From a series of 20 patients, we studied 9 cases of primary spontaneous CSF rhinorrhea; 6 patients were female (mean age 50 +/- 10 years) and 3 male (mean age 61 +/- 7 years). All the female patients were clinically obese, i.e., they had a body mass index >30 kg/m2. All the male patients had a body mass index within normal parameters. We review the postulated etiologic factors of this uncommon condition and study the pathophysiologic basis for obese patients to have CSF rhinorrhea. This study suggests a relationship between obese females and the risk of developing a primary spontaneous CSF rhinorrhea.

Topical corticosteroids in nasal polyposis.

Nasal polyps are the common end-point of a number of conditions characterised by inflammation and are rarely 'curable' in its true sense. After consideration of the underlying aetiology and confirmation of the diagnosis, they are normally managed by a combination of medical and surgical interventions. Of these, topical corticosteroids have proved to be the medical treatment of choice. The objectives of the medical management are to eliminate or reduce the size of polyps, re-establish nasal airway and nasal breathing, improve or restore the sense of smell, and prevent recurrence of nasal polyps. The mechanism of action of corticosteroids may be by a multifactorial effect on various aspects of the inflammatory reaction, the effect being initiated by their binding to a specific cytoplasmic glucocorticoid receptor. At a cellular level, there is a reduction in the number of antigen-presenting cells, in the number and activation of T cells, in the number of mast cells, and in the number and activation of eosinophils. When polyps are large (grade 3) topical medication is difficult to instil in a very blocked nose and surgery or short term systemic corticosteroids may be required. Topical corticosteroids are of use in the primary treatment of nasal polyps when they are of a small or medium size (grades 1 and 2) and in the maintenance of any therapeutic improvement. The efficacy of topical corticosteroids such as betamethasone sodium phosphate nose drops, beclomethasone dipropionate, fluticasone propionate and budesonide nasal sprays in reducing polyp size and rhinitis symptoms has been demonstrated in several randomised, placebo-controlled trials. Beclomethasone dipropionate, flunisolide and budesonide sprays have also been shown to delay the recurrence of polyps after surgery. Placebo-controlled studies of agents that have shown a significant clinical effect in the management of nasal polyposis are reviewed.

Dilated pupil during endoscopic sinus surgery: what does it mean?

Endoscopic sinus surgery has become the standard of care for the surgical management of chronic sinus disease. Sinus disease and its surgical treatment carry the risk of orbital complications, irrespective of the approach. Orbital complications associated with sinus surgery include nasolacrimal duct damage, extraocular muscle injury, intraorbital hemorrhage/emphysema, and direct optic nerve damage, resulting in blindness. The finding of an unequal pupil at the end of a procedure would be a cause of considerable concern, but it is most likely due to the topical contamination of the eye with a mydriatic pharmacological agent commonly used in endoscopic sinus surgery.

A case of rhinoscleroma treated with ciprofloxacin.

Respiratory scleroma (often termed 'rhinoscleroma') is a chronic inflammatory condition in which deforming masses of tissue distend the nasal cavity. Klebsiella rhinoscleromatis is the causative agent of this infection and the Mikulicz cell is specific to the lesion being a large macrophage with clear cytoplasm containing the bacilli. Antibiotic therapy has traditionally consisted of streptomycin and tetracycline long-term but this presents problems with adverse side-effects and poor patient compliance. We report on a young patient with nasal rhinoscleroma who achieved resolution after treatment with oral ciprofloxacin. As mentioned in a review of patients with rhinoscleroma at the Mayo clinic in 1993, the fluoroquinolones deserve further study as potentially highly effective agents for this condition. Ciprofloxacin is convenient for oral administration and has few adverse effects. It achieves good tissue penetration, is concentrated in macrophages and may prove to be useful in the therapy of rhinoscleroma.

Primary chordoma of the ethmoid sinus.

Primary chordoma of the paranasal sinuses are extremely rare tumours, with only a small number of cases verified and published in the literature. It appears that only five of these cases involved the ethmoid sinuses either as a primary or by local invasion, and of these documented cases only one other has been found to solely involve the ethmoid sinus. We present a case of primary ethmoid sinus chordoma treated by wide local surgical excision and present a review of the literature with regard to prevalence and treatment rationale.

Chromosome 11 abnormalities in myelodysplastic syndromes.

Cytogenetic studies were performed in 140 patients with myelodysplastic syndrome (MDS) at diagnosis. Chromosome 11 anomalies were found in 7 cases (5%); 2 of these patients had refractory anemia (RA), 2 had refractory anemia with excess of blasts (RAEB), 1 had RAEB in transformation (RAEB-t), and 2 had chronic myelomonocytic leukemia (CMMoL) according to the French-American-British (FAB) Cooperative Group criteria. The chromosome 11 abnormalities comprised trisomy 11 (2 patients), monosomy 11 (1 patient), del(11)(q23) (2 patients), add(11)(p15) (1 patient), and der(11) t(3;11)(p21;q23) (1 patient). Abnormalities involving band q23 of chromosome 11 occurred in 3 cases and were the most common alteration. However, specific chromosomal alterations were not associated with any FAB classification group. These findings and their implications in the biology of MDS are discussed.

Indicaciones y resultados del trasplante hepático con donante vivo relacionado en el tratamiento de la insuficiencia hepática aguda / Indications and results of hepatic transplatation using living-related donor in the treatment of acute hepatic insufficiency

La técnica de trasplante hepático(TH)con donante vivo relacionado(DVR)es un recurso valioso para resolver la escacez de donantes y la aplicabilidad del TH en niños con insuficiencia hepática aguda(IHA)Se analizan las indicaciones y resultados del TH con DVR en niñops con IHA y hepatopatía crónica severa(HCS)Entre junio de 1995 y Junio de 1998 se realizaron en nuestro centro 107 TH en 104 pacientes(77 adultos y 27 niños)De los 27 pacientes pediátricos 13(48 por ciento)fueron transplantados con DVR.La edad media fue de 38 meses con un rango de 7 meses a 9 años.De los 13 pacientes transplantados con DVR,4 presentaron complicaciones postrasplante:trombosis arterial que requirió postrsplante en un caso,fístula biliar y absceso abdominal que requirió reexploración en otro y estenosis de la anstomosis billiar tratados con dilatación percutánea en dos casos.Dos pacientes fallecieron,uno de ellos a los 18 meses del trasplante.La curva de sobrevida actuarial al año de todos los niños trasplantados con DVR(Kaplan-Meier) fue de 90 por ciento u para los 14 con DC fue del 88 por ciento

Indicaciones y resultados del trasplante hepático con donante vivo relacionado en el tratamiento de la insuficiencia hepática aguda / Indications and results of hepatic transplatation using living-related donor in the treatment of acute hepatic insufficiency

La técnica de trasplante hepático(TH)con donante vivo relacionado(DVR)es un recurso valioso para resolver la escacez de donantes y la aplicabilidad del TH en niños con insuficiencia hepática aguda(IHA)Se analizan las indicaciones y resultados del TH con DVR en niñops con IHA y hepatopatía crónica severa(HCS)Entre junio de 1995 y Junio de 1998 se realizaron en nuestro centro 107 TH en 104 pacientes(77 adultos y 27 niños)De los 27 pacientes pediátricos 13(48 por ciento)fueron transplantados con DVR.La edad media fue de 38 meses con un rango de 7 meses a 9 años.De los 13 pacientes transplantados con DVR,4 presentaron complicaciones postrasplante:trombosis arterial que requirió postrsplante en un caso,fístula biliar y absceso abdominal que requirió reexploración en otro y estenosis de la anstomosis billiar tratados con dilatación percutánea en dos casos.Dos pacientes fallecieron,uno de ellos a los 18 meses del trasplante.La curva de sobrevida actuarial al año de todos los niños trasplantados con DVR(Kaplan-Meier) fue de 90 por ciento u para los 14 con DC fue del 88 por ciento

A novel TP53 germ-line mutation identified in a girl with a primitive neuroectodermal tumor and her father.

A search of TP53 mutations was undertaken in a series of 51 pediatric brain tumors. The only germ-line mutation was detected in a 9-year-old girl with a PNET. Her family history was unremarkable for neoplastic disease, except for the paternal grandfather, who died of a gallbladder carcinoma at an advanced age. The mutation was a thymine deletion at the first base of codon 241, leading to termination codon at position 246 that has not previously been reported. This mutation was found to be inherited from the proband's father, who was healthy at age 40. In the tumoral sample, loss of heterozygosity in several 17p markers was found, the only TP53 allele preserved in the tumor was the mutated one. The presence of two short tandem repeats and two different palindromic sequences spanning the deletion lead us to propose the predisposition of this region to forming a complex secondary structure during replication. Consequently, it could have facilitated the present deletion. Furthermore, six other short deletions affecting--partially or totally--the region implicated in the folding model that we propose have been described in the literature. These findings confirm that this sequence represents a hotspot of deletion in the TP53 gene.

Pediatric brain tumors: loss of heterozygosity at 17p and TP53 gene mutations.

Cytogenetic and molecular analyses of primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) have demonstrated material losses of 17p, the region that contains the TP53 gene, as the most frequent abnormality. Mutations in the TP53 gene are, however, very rare in these tumors. These findings strongly suggest that another, as yet unidentified, gene on 17p may be involved. We performed a search for loss of heterozygosity (LOH) on 17p by microsatellite markers on 26 childhood CNS tumors as well as TP53 gene mutations (exons 5-8) by single-strand conformational polymorphism analysis on 41 pediatric brain tumor samples of distinct histologic types. LOH was detected in 10 cases: 7 PNET, 2 astrocytomas, and 1 glioblastoma multiforme. In 4 of the PNETs the losses were limited to more distal markers. On the other hand, TP53 mutations were detected in 6 of 41 samples studied. Our results not only confirm the low penetrance of the TP53 gene on pediatric CNS tumors, but also provide further evidence of a putative tumor suppressor gene distal to TP53, between markers (D17S938, D17S926) and 17pter, specifically taking part in the development of PNET.

Heterotopic pleomorphic adenoma of the external nose.

Pleomorphic adenomas arising from sites other than the major or minor salivary glands are uncommon. We describe a case of pleomorphic adenoma in the subcutaneous tissue of the nasomaxillary crease. An identical tumour was previously excised from the right nasal cavity. The possible aetiology of these heterotopic salivary gland tumours is discussed.