Prevalence of olfactory dysfunction in D614G, alpha, delta and omicron waves: a psychophysical case-control study.

BACKGROUND: The purpose of this study was to compare the prevalence of olfactory dysfunction (OD) at different stages of the COVID-19 pandemic by evaluating subjects diagnosed with SARS-CoV-2 infection during the Omicron wave with psychophysical tests and comparing the results with those obtained from patients infected during the D614G, Alpha and Delta waves and with those of a control group. METHODOLOGY: The study included adult patients diagnosed with SARS-CoV-2 infection. Depending on the time of diagnosis, the subjects were divided into four study groups: D614G; Alpha, Delta and Omicron variant groups. A group of uninfected individuals was used as control. All subjects underwent psychophysical evaluation of the olfactory function with the Connecticut Chemosensory Clinical Research Center olfactory test (D614G and Alpha groups) or the extended version of the Sniffin'Sticks test (Delta, Omicron and control groups). RESULTS: 372 cases (134 D614G group, 118 Alpha group, 32 in Delta group and 88 Omicron group) were recruited and evaluated within 10 days of infection, alongside 80 controls. Patients self-reported olfactory loss in 72.4% of cases in the D614G group, in 75.4% of cases in the Alpha group, in 65.6% of cases in the Delta group and in 18.1% in the Omicron group. Psychophysical evaluation revealed a prevalence of OD: 80.6%, 83.0%, 65.6% and 36.3% in the D614G, Alpha, Delta and Omicron group respectively. The differences between the D614G, Alpha and Delta groups were not statistically significant. The Omicron group demonstrated a significantly lower prevalence of OD than the other variants but still significantly higher than the controls. CONCLUSIONS: During the Omicron wave OD was less prevalent than during the D614G, Alpha and Delta periods. One-third of patients have reduced olfactory function on psychophysical evaluation during the Omicron wave. Our results should be considered with caution as the VOC has not been determined with certainty.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.

Identification of aroma-active compounds in Cheddar cheese imparted by wood smoke.

Cheddar cheese is the most popular cheese in the United States, and the demand for specialty categories of cheese, such as smoked cheese, are rising. The objective of this study was to characterize the flavor differences among Cheddar cheeses smoked with hickory, cherry, or apple woods, and to identify important aroma-active compounds contributing to these differences. First, the aroma-active compound profiles of hickory, cherry, and apple wood smokes were analyzed by solid-phase microextraction (SPME) gas chromatography-olfactometry (GCO) and gas chromatography-mass spectrometry (GC-MS). Subsequently, commercial Cheddar cheeses smoked with hickory, cherry, or apple woods, as well as an unsmoked control, were evaluated by a trained sensory panel and by SPME GCO and GC-MS to identify aroma-active compounds. Selected compounds were quantified with external standard curves. Seventy-eight aroma-active compounds were identified in wood smokes. Compounds included phenolics, carbonyls, and furans. The trained panel identified distinct sensory attributes and intensities among the 3 cheeses exposed to different wood smokes (P < 0.05). Hickory smoked cheeses had the highest intensities of flavors associated with characteristic "smokiness" including smoke aroma, overall smoke flavor intensity, and meaty, smoky flavor. Cherry wood smoked cheeses were distinguished by the presence of a fruity flavor. Apple wood smoked cheeses were characterized by the presence of a waxy, green flavor. Ninety-nine aroma-active compounds were identified in smoked cheeses. Phenol, guaiacol, 4-methylguaiacol, and syringol were identified as the most important compounds contributing to characteristic "smokiness." Benzyl alcohol contributed to the fruity flavor in cherry wood smoked cheeses, and 2-methyl-2-butenal and 2-ethylfuran were responsible for the waxy, green flavor identified in apple wood smoked cheeses. These smoke flavor compounds, in addition to diacetyl and acetoin, were deemed important to the flavor of cheeses in this study. Results from this study identified volatile aroma-active compounds contributing to differences in sensory perception among Cheddar cheeses smoked with different wood sources.

Discrepancies of SARS-CoV-2 testing results among patients with total laryngectomy.

PURPOSE: Prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is obtained with nasopharyngeal swabs. By the way, there is no consensus regarding sampling in totally laryngectomized subjects (who thus breathe directly by the tracheostomy and, theoretically, may be infected in the trachea). The aim of this study is to evaluate possible differences between swab results in the trachea and in the nasopharynx of this category of patients. METHODS: A retrospective chart review was performed in April 2021 among patients who previously had been operated on for total laryngectomy and who underwent swabs for SARS-CoV-2 research in 3 health-care centers in Northern-Eastern Italy. Data regarding the site of swabbing (trachea or nasopharynx) were analyzed. A comprehensive review of the literature regarding the same topic was then performed. RESULTS: A total of 25 totally laryngectomized subjects underwent swabs. Among them, 5 tested positive in the trachea (1) and in the nasopharynx (4). According to the literature review, 4 more subjects tested positive in the trachea (1) and in the nasopharynx (3). Data were overall divergent and no statistically significant correlations emerged between results of the tests performed in the two sites. CONCLUSION: Due to these discrepancies, both tracheal and nasopharyngeal swabs are recommended in these kinds of patients, to obtain a reliable test and to avoid false negatives.

Consumer perception of smoked Cheddar cheese.

Consumer perception of smoked cheese was evaluated through focus groups, surveys, and central location testing. Three focus groups (n = 29) were conducted with consumers of smoked cheese. Subsequently, 2 online surveys were conducted. The purpose of the first survey (n = 1,195) was to understand types of smoked cheeses consumed and if consumers associated specific wood smokes with smoked cheese. Next, an adaptive choice-based conjoint (n = 367) was designed to evaluate consumer perception of different attributes of smoked cheese. Maximum difference scaling and familiarity questions were also included in the adaptive choice-based conjoint survey. Following the surveys, a central location test (n = 135) was conducted with cheeses smoked with 3 different woods at a low and high intensity (6 cheeses total). Hierarchical Bayesian estimation, 1-way ANOVA, agglomerative hierarchical clustering, and 2-way ANOVA (smoke type × intensity level) were used to interpret the collected data. Results from the focus groups indicated that smoked cheese was perceived as an artisan, high-end product and that appearance and price were strong purchase factors. In general, consumers were not aware of how smoked flavor was imparted to cheese, but when informed of the processes, they preferred cold-smoked cheese to the addition of liquid smoke flavor. Results from both surveys confirmed focus group observations. Consumers perceived flavor differences among different wood smokes and smoked products. Method of smoking, smoke intensity, type of wood, and type of cheese were the most important attributes for purchase of smoked cheese. When tasting, consumers differentiated smoke aroma and flavor among cheeses and preferred cherry wood smoked cheeses over apple wood or hickory smoked cheeses. Understanding consumer perceptions of smoked cheese will give insight into the desired experience that consumers expect when purchasing smoked cheese.

High prevalence of long-term olfactory, gustatory, and chemesthesis dysfunction in post-COVID-19 patients: a matched case-control study with one-year follow-up using a comprehensive psychophysical evaluation.

BACKGROUND: Using an age and gender matched-pair case-control study, we aimed to estimate the long-term prevalence of psychophysical olfactory, gustatory , and chemesthesis impairment at least one year after SARS-CoV-2 infection considering the background of chemosensory dysfunction in non-COVID-19 population. METHODOLOGY: This case-controlled study included 100 patients who were home-isolated for mildly symptomatic COVID-19 between March and April 2020. One control regularly tested for SARS-CoV-2 infection and always tested negative was matched to each case according to gender and age. Chemosensory function was investigated by a comprehensive psychophysical evaluation including ortho- and retronasal olfaction and an extensive assessment of gustatory function. Differences in chemosensory parameters were evaluated through either Fisher’s exact test or Kruskal-Wallis test. RESULTS: The psychophysical assessment of chemosensory function took place after a median of 401 days from the first SARS-CoV-2 positive swab. The evaluation of orthonasal smell identified 46% and 10% of cases and controls, respectively, having olfactory dysfunction, with 7% of COVID-19 cases being functionally anosmic. Testing of gustatory function revealed a 27% of cases versus 10% of controls showing a gustatory impairment. Nasal trigeminal sensitivity was significantly lower in cases compared to controls. Persistent chemosensory impairment was associated with emotional distress and depression. CONCLUSION: More than one year after the onset of COVID-19, cases exhibited an excess of olfactory, gustatory , and chemesthesis disturbances compared to matched-pair controls with these symptoms being associated to emotional distress and depression.

Consumer desires and perceptions of lactose-free milk.

Fluid milk consumption has declined in the United States, but lactose-free dairy milk (LFM) sales have steadily increased. It is important to understand how consumers perceive LFM and what consumers value when purchasing LFM. This study characterized consumer perceptions and preferences for LFM. Three 1.5-h focus groups (n = 25), an online survey (n = 331), trained panel descriptive analysis, and a consumer acceptance taste test (n = 160) were conducted with LFM consumers. Focus groups were evaluated by frequency of responses. From the focus group findings, we found that price was a primary choice driver of LFM. Habit and flavor familiarity with cow milk were a major driver of selection of LFM over plant-based alternatives for consumers. Higher sweetness and lower viscosity were the primary sensory differences between LFM and traditional milk, and were viewed negatively in general. The online survey included Kano questions, maximum difference scaling, and an adaptive choice-based conjoint. The data gathered from these techniques provided insight into the perceptions and purchase habits of consumers. Kano data demonstrated consumer attitudes toward the presence or absence of product attributes. The maximum difference scaling scaled the importance of product attributes to consumers. An adaptive choice-based conjoint provided insight into consumer purchase habits by simulating a purchase decision through an online interface. The attributes evaluated included price, packaging material, package size, lactose removal method, shelf life, sweetness, texture, nutrition claims, and label claims. Survey responses were analyzed by univariate and multivariate statistics. Survey results quantitatively confirmed many focus group observations. Price, texture, sweetness, shelf life, and package size were the most important attributes to LFM consumers. A low price, ultrapasteurized LFM in a half-gallon cardboard package was the ideal LFM. Descriptive analysis of 9 commercial LFM followed by consumer acceptance testing was conducted. External preference mapping was conducted with trained panel and consumer acceptance results. Consumer acceptance testing of commercial LFM revealed 3 consumer clusters with distinct preferences for LFM flavor and texture. High sweet taste was a driver of liking for the overall population, and eggy flavor and viscosity were drivers of disliking. Knowledge of consumer preferences for LFM will provide actionable insights for new product development within the dairy industry for this market segment.

Self-reported alteration of sense of smell or taste in patients with COVID-19: a systematic review and meta-analysis on 3563 patients.

BACKGROUND: Emerging reports suggest that new onset of smell or taste loss are potential early clinical markers of SARS-CoV-2 infection, but it remains unclear as to what extent. Therefore, the purpose of this study is to systematically assess the prevalence of self-reported altered sense of smell or taste in patients with confirmed SARS-CoV-2 infection, overcoming the limitations of individual studies by meta-analysis of pooled data. METHODS: The databases Medline, Embase, Web of Science, Scopus and MedRxiv's set were searched from inception to the 4th May 2020. This study was conducted following the PRISMA checklist. RESULTS: 18 studies met the eligibility criteria out of the 171 initially screened citations. The overall prevalence of alteration of the sense of smell or taste was 47% , but estimates were 31% and 67% in severe and mild-to-moderate symptomatic patients, respec- tively. The loss of smell and taste preceded other symptoms in 20% of cases and it was concomitant in 28%. CONCLUSIONS: Based on this meta-analysis, we recommend self-isolation and testing, where possible, for patients complaining smell or taste impairment during COVID-19 pandemic in order to prevent spread of disease and propose the inclusion of loss of smell and taste as recognized symptoms of SARS-CoV-2 in the World Health Organization and other relevant regulatory body's lists.

Predominance of an altered sense of smell or taste among long-lasting symptoms in patients with mildly symptomatic COVID-19.

There is mounting evidence that a new onset of altered sense of smell or taste is related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In order to allow patients to recognize symptoms indicative of SARS-CoV-2 infection and self-isolate at the earliest opportunity, self-reported loss of smell and taste have greater value in controlling disease transmis- sion than psychophysical testing, which is not widely available outside of highly specialized clinics.

Novel role of the nutraceutical bioactive compound berberine in lectin-like OxLDL receptor 1-mediated endothelial dysfunction in comparison to lovastatin.

BACKGROUND AND AIMS: Oxidized LDL (oxLDL) or pro-inflammatory stimuli lead to increased oxidative stress linked to endothelial dysfunction and atherosclerosis. The oxLDL receptor-1 (LOX1) is elevated within atheromas and cholesterol-lowering statins inhibit LOX1 expression. Berberine (BBR), an alkaloid extracted from plants of gender Berberis, has lipid-lowering and anti-inflammatory activity. However, its role in regulating LOX1-mediated signaling is still unknown. The aim of this study was to investigate the effect of BBR on oxLDL- and TNFα-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs) and to compare it with that of lovastatin (LOVA). METHODS AND RESULTS: Cytotoxicity was determined by lactate dehydrogenase assay. Antioxidant capacity was measured with chemiluminescent and fluorescent method and intracellular ROS levels through a fluorescent dye. Gene and protein expression levels were assayed by qRT-PCR and western blot, respectively. HUVECs exposure to oxLDL (30 µg/ml) or TNFα (10 ng/ml) for 24 h led to a significant increase in LOX1 expression, effect abrogated by BBR (5 µM) and LOVA (5 µM). BBR but not LOVA treatment abolished the TNFα-induced cytotoxicity and restored the activation of Akt signaling. In spite of a low direct antioxidant capacity, both compounds reduced intracellular ROS levels generated by treatment of TNFα but only BBR inhibited NOX2 expression, MAPK/Erk1/2 signaling and subsequent NF-κB target genes VCAM and ICAM expression, induced by TNFα. CONCLUSIONS: These findings demonstrated for the first time that BBR could prevent the oxLDL and TNFα - induced LOX1 expression and oxidative stress, key events that lead to NOX, MAPK/Erk1/2 and NF-κB activation linked to endothelial dysfunction. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Berberine (PubChem CID: 2353); Lovastatin (PubChem CID: 53232).

Infrapatellar branch of the saphenous nerve lesion following tibial nailing: it is possible to avoid it?

BACKGROUND: Iatrogenic injury to the infrapatellar branches of saphenous nerve is a common complication following tibial nailing. This lesion seems to be directly related to the surgical approach adopted for nail insertion. The aim of the present study was to systematically review the current literature in order to assess the eventual superiority of one surgical approach for tibial nailing over the others in limiting the neurological impairment related to infrapatellar branch injury. MATERIALS AND METHODS: The available literature was systematically screened searching papers dealing with iatrogenic injury to the infrapatellar branch of saphenous nerve after intramedullary tibial nailing. The terms "Saphenous" and "Infrapatellar branch" were used in combination with "intramedullary nailing" and "tibial fractures", supplying no limits regarding the publication year. Only publications in English were considered. Case reports, technical notes, instructional course, literature reviews, biomechanical and/ or in vitro studies were all excluded. Coleman methodological score was performed in all the retained articles. RESULTS: Four articles matched the inclusion criteria. There were one original article and three retrospective study. Hypoesthesia and a larger extension of the area of sensory-loss were more frequently observed after vertical incision approach in three out of four articles. A trend towards a lower rate of iatrogenic nerve damage using a transverse incision was found in the remaining one, without any statistical significance. CONCLUSIONS: In order to avoid infrapatellar nerve lesion, horizontal or oblique incisions or percutaneous approaches should be favored, although in some cases a longitudinal incision is required. Limited-extension incisions could minimize the risk and the incidence of this complication.

HLA-dependent autoantibodies against post-translationally modified collagen type II in type 1 diabetes mellitus.

AIMS/HYPOTHESIS: In this study the involvement of oxidative stress in type 1 diabetes mellitus autoimmunity and the possible association with rheumatoid arthritis (RA) was investigated. We tested the hypothesis that oxidative stress induced by chronic hyperglycaemia triggers post-translational modifications and thus the formation of neo-antigens in type 1 diabetes, similar to the ones found in RA. METHODS: Collagen type II (CII), a known autoantigen in RA, was treated with ribose and various reactive oxygen species (ROS). Levels of antibodies specific to native and ROS-modified CII (ROS-CII) were compared in type 1 diabetes, type 2 diabetes and healthy controls, and related to the HLA genotype. RESULTS: Significantly higher binding to ROS-CII vs native CII was observed in type 1 diabetic patients possessing the HLA-DRB1*04 allele irrespective of variables of glucose control (blood glucose or HbA(1c)). Type 1 diabetic patients carrying a DRB1*04 allele with the shared epitope showed the highest risk for ROS-CII autoimmunity, while the DRB1*0301 allele was protective. Conversely, native CII autoimmunity was not associated with any specific DRB1 allele. Positive and inverse seroconversion rates of response to ROS-CII were high in DRB1*04-positive type 1 diabetic patients. CONCLUSION: Hyperglycaemia and oxidative stress may trigger genetically controlled autoimmunity to ROS-CII and may explain the association between type 1 diabetes mellitus and RA.

Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study.

AIMS: Several studies have investigated the effects of metformin treatment in patients with type 1 diabetes mellitus (T1DM). No study has hitherto examined its effects on endothelial function in these patients. In this study we sought to evaluate the effect of metformin on endothelial function in type 1 diabetic patients. METHODS: Forty-two uncomplicated T1DM patients were randomized in a placebo-controlled, double-blind, 6-month trial to treatment with either metformin or placebo. Glycometabolic and clinical parameters as well as flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the right brachial artery were measured at baseline and at the end of the study. Glycaemic variability (GV, calculated from continuous glucose monitoring data) and a biomarker of oxidative stress [urinary 8-iso-prostaglandin F2α (PGF2α)] were also assessed. RESULTS: Baseline data were similar in the two groups. Compared with placebo, metformin significantly reduced body weight [-2.27 kg (95% confidence interval: -3.99; -0.54); p = 0.012] whilst improved FMD [1.32% (0.30; 2.43); p = 0.013] and increased PGF2α [149 pg/mg creatinine (50; 248); p = 0.004]. Notably, the improvement of FMD did not correlate with the decrease of body weight (r(2) < 1%). NMD, haemoglobin A1c, GV, daily insulin dose and other parameters did not significantly change after the treatment comparing the two groups. CONCLUSIONS: Our pilot trial showed that, in uncomplicated type 1 diabetic subjects, metformin improved FMD and increased PGF2α, a marker of oxidative stress, irrespective of its effects on glycaemic control and body weight. Randomized, blinded clinical trials are needed to evaluate the benefits and risks of metformin added to insulin in type 1 diabetes.

Facial ridge management in canal wall down tympanoplasty for middle-ear cholesteatoma.

OBJECTIVE: To estimate whether leaving a high facial ridge during canal wall down tympanoplasty increases the risk of residual cholesteatoma. METHODS: In this retrospective case review, 321 patients treated with primary canal wall down tympanoplasty for middle-ear cholesteatoma were divided into a completely lowered facial ridge group and a non-completely lowered facial ridge group. Factors affecting facial ridge management, residual disease rate and disease-free survival were analysed. RESULTS: Residual disease rates were 10.8 per cent in the non-completely lowered facial ridge group and 16.6 per cent in the completely lowered facial ridge group (p = 0.15). Localisation at sinus tympani, mesotympanum or supratubal recess, pre-operative extracranial complications, and destroyed ossicular chain or fixed platina were associated with a completely lowered facial ridge. Residual disease rates and disease-free survival did not significantly differ between the groups. CONCLUSION: Facial ridge can be managed according to cholesteatoma extension. The facial ridge can be maintained high if the cholesteatoma does not involve sinus tympani, mesotympanum or supratubal recess, without increasing the risk of residual disease.

Myo-inositol may prevent gestational diabetes in PCOS women.

To evaluate retrospectively the prevalence of gestational diabetes (GD) in pregnancies obtained with myo-inositol administration in women with polycystic ovary syndrome. A total of 98 pregnancies in PCOS women obtained in a 3-year period, either with myo-inositol (n. 54), or with metformin (n. 44) were considered. While myo-inositol was assumed through the whole pregnancy, the group of women treated with metformin stopped the drug assumption after pregnancy diagnosis, and was considered as a control group. After having eliminated cases of miscarriages and twin pregnancies, a definitive number of 46 women in the myo-inositol group and 37 in the control group was taken in account to be retrospectively evaluated. The primary outcome measure was GD occurrence in both groups; whereas secondary outcome measures were pregnancy outcomes: hypertensive disorders, pre-term birth, macrosomia and caesarean section occurrence. Prevalence of GD in the myo-inositol group was 17.4% versus 54% in the control group, with a highly significant difference also after adjusting for covariates. Consequently, in the control group the risk of GD occurrence was more than double compared to the myo-inositol group, with an odds ratio 2.4 (confidence interval 95%, 1.3-4.4). There was no difference between the groups in relation to secondary outcome measures. This study suggests a possible effect of myo-inositol in the primary prevention of GD in PCOS women.

Age, Sex, Hypertension and HDL-C Alter Serum BACE1 Activity in Cognitively Normal Subjects: Implications for Alzheimer's Disease.

BACKGROUND: Increasing evidence indicates that ß-secretase 1 (BACE1) activity and concentration in blood are candidate biomarkers for Alzheimer's disease (AD). Investigating potential demographic, biological, and clinical determinants of BACE1 in the blood matrix is the critical step to validate and qualify BACE1 bio-indicators for different contexts-of-use (CoU), such as risk assessment, early detection, diagnosis, prognosis, management of AD, and outcome of amyloid pathway targeted drugs. OBJECTIVES: To evaluate the influence of age, sex, HDL-cholesterol and comorbidities (cardiovascular diseases, hypertension, diabetes) on circulating BACE-1 activity. DESIGN: prospective analysis of serum samples, clinical, biological, and demographic variables. SETTING: Three cohorts: 1) Memory Clinic of the Department of Internal Medicine, S. Anna University Hospital, Ferrara (Italy); 2) outpatients attending the Menopause and Osteoporosis Centre (MOC) of the University of Ferrara (Ferrara, Italy); 3) Prevention Center of the University of Ferrara. PARTICIPANTS: 504 cognitively healthy individuals (median age: 62 years, interquartile range: 51-73) and 175 patients with AD (78 years, 74-82). MEASUREMENTS: serum BACE1 (sBACE1), age, sex, HDL-cholesterol, major comorbidities. RESULTS: Age was the strongest independent predictor of sBACE1 variance (ß=0.425, p<0.0001), followed by sex (ß=0.180, p<0.0001), high density lipoprotein-cholesterol (HDL-C) (ß=-0.168, p<0.0001) and hypertension (ß=0.111, p<0.05) (overall model, R2: 0.232). The probability of having elevated sBACE1 activity increased after 70 years of age, with women being more susceptible to higher sBACE1 activity than men. CONCLUSIONS: We provide evidence about potential clinical and biological determinants of sBACE1 activity with a strong association among biomarker, female sex, and older age.

Functional organ preservation in patients with locoregionally advanced head and neck squamous cell carcinoma treated by platinum-based multidrug induction chemotherapy and concurrent chemoradiotherapy.

BACKGROUND: The objective of this study was to evaluate the feasibility, safety, and efficacy in terms of functional organ preservation of multidrug induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) protocol in patients with locoregionally advanced head and neck squamous cell carcinoma (LA-HNSCC). PATIENTS AND METHODS: Patients with previously untreated, inoperable, histologically proven nonmetastatic stage III or IV HNSCC were eligible. Following one cycle of IC, two cycles of cisplatinum and 5-fluorouracil CCRT with conventional fractionated radiotherapy up to a dose of 66-70 Gy were administrated. RESULTS: Between January 2000 and July 2007, a total of 139 patients were candidates to receive IC-CCRT for LA-HNSCC. Overall, 83% of the patients completed the treatment. Three-year overall survival estimate was 68% [95% confidence interval (CI) 57% to 79%]. Three-year progression-free survival (PFS) estimate was 62% (95% CI 50% to 74%). Three-year functional PFS was 57% (95% CI 44% to 69%). There were no cases of treatment-related deaths. The most frequent severe acute toxicity was pharyngeal mucositis. CONCLUSIONS: Cisplatinum-based multidrug IC-CCRT can result in functional organ preservation and curative treatment in most patients with LA-HNSCC. The toxicity profile and patients' compliance to treatment confirmed the safety and tolerability of this approach.

Simian virus-40 large-T antigen binds p53 in human mesotheliomas.

We found that simian virus 40 (SV40) induces mesotheliomas in hamsters and that 60% of human mesotheliomas contain and express SV40 sequences, results now confirmed by others [ref. 3-5, and presentations by D. Griffiths & R. Weiss, F. Galateau-SallE, and H.I.P. at "Simian virus 40: A possible human polyoma virus," NIH workshop, 27-28 January 1997, Bethesda, MD (transcript available through SAG Corp., Washington, DC 20008)]. Mesothelioma, an aggressive malignancy resistant to therapy, originates from the serosal lining of the pleural, pericardial and peritoneal cavities. The incidence of mesothelioma continues to increase worldwide because of exposure to crocidolite asbestos. However, at least 20% of mesotheliomas in the United States are not associated with asbestos exposure, and only a minority of people exposed to high concentrations of asbestos develop mesothelioma. Thus, other carcinogens may induce mesothelioma in individuals not exposed to asbestos, and/or may render particular individuals more susceptible to the carcinogenic effect of asbestos. We investigated whether the expression of the SV40 large T-antigen (Tag) interferes with the normal expression of the tumor suppressor gene p53 in human mesotheliomas. We found that SV40 Tag retains its ability to bind and to inactivate p53, a cellular protein that when normally expressed plays an important role in suppressing tumor growth and in inducing sensitivity to therapy. Our findings do not establish a cause-and-effect relation, but indicate that the possibility that SV40 contributes to the development of human mesotheliomas should be carefully investigated.