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.

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.

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.

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.

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.

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.

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.

Six-month smell and taste recovery rates in coronavirus disease 2019 patients: a prospective psychophysical study.

BACKGROUND: The long-term recovery rate for coronavirus disease 2019 related chemosensory disturbances has not yet been clarified. METHODS: Olfactory and gustatory functions were assessed with psychophysical tests in patients in the first seven days from coronavirus disease 2019 onset and one, two, three and six months after the first evaluation. RESULTS: A total of 300 patients completed the study. The improvement in olfactory function was significant at the two-month follow up. At the end of the observation period, 27 per cent of the patients still experienced a persistent olfactory disturbance, including anosmia in 5 per cent of cases. As for taste, the improvement in the psychophysical scores was significant only between the baseline and the 30-day control. At the 6-month evaluation, 10 per cent of the patients presented with a persistent gustatory disturbance with an incidence of complete ageusia of 1 per cent. CONCLUSION: Six months after the onset of coronavirus disease 2019, about 6 per cent of patients still had a severe persistent olfactory or gustatory disturbance.

Post-operative outcomes of different surgical approaches to oropharyngeal squamous cell cancer: a case-matched study.

OBJECTIVE: To compare the post-operative outcomes of transoral laser microsurgery, lateral pharyngotomy and transmandibular surgery in oropharyngeal cancer management. METHODS: Records of 162 patients treated with transmandibular surgery, transoral laser microsurgery or lateral pharyngotomy were reviewed. The transoral laser microsurgery cohort was matched with the lateral pharyngotomy and transmandibular surgery cohorts for tumour stage, tumour subsite and human papilloma virus status, and the intra- and post-operative outcomes were compared. RESULTS: Duration of surgery and hospital stay were significantly longer for transmandibular surgery. Tracheostomy and nasogastric feeding tube rates were similar, but time to decannulation and to oral feeding were longer in the transmandibular surgery group. Transmandibular surgery more frequently required flap reconstruction and had a greater complication rate. Negative margins were fewer in the lateral pharyngotomy group than in the transoral laser microsurgery and transmandibular surgery groups. CONCLUSION: In comparison with transmandibular surgery, transoral laser microsurgery and lateral pharyngotomy were associated with fewer complications and faster functional recovery. Lateral pharyngotomy had a higher rate of positive margins than transoral laser microsurgery, with a consequently greater need for adjuvant therapy. Many patients are nonetheless unsuitable for transoral surgery. All these factors should be considered when deciding on oropharyngeal cancer surgical treatment.

Extranodal extension in head and neck squamous cell cancer: is there a role for further stratification?

To investigate the prognostic significance of the stratification of extranodal extension (ENE) into ENE minor (ENEmi, up to 2mm) and ENE major (ENEma, over 2mm) in non-HPV-related squamous cell cancers of the head and neck, we retrospectively reviewed microscopic slides from neck dissection specimens of ENE-positive patients and subcategorised them into ENEmi and ENEma. We then compared the two groups in terms of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). Forty-four patients with pathologically positive necks had ENE in the histological report. Twenty-six had ENEmi and 18 ENEma. The three-year OS was 46% in the ENEmi group and 38.9% in the ENEma group. DSS and DFS were 80.8% and 80.8%, respectively, in the ENEmi group and 61.1% and 77.8%, respectively, in the ENEma group. None of the comparisons revealed any statistically significant difference. The results of our survival analysis seem to show a trend towards better survival rates in the ENEmi group, particularly regarding OS. Nonetheless, extension of the tumour outside the lymph node capsule by more than 2mm was not found to be significantly associated with any of the explored survival outcomes.

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.

Smell and taste recovery in coronavirus disease 2019 patients: a 60-day objective and prospective study.

BACKGROUND: The long-term recovery rate of chemosensitive functions in coronavirus disease 2019 patients has not yet been determined. METHOD: A multicentre prospective study on 138 coronavirus disease 2019 patients was conducted. Olfactory and gustatory functions were prospectively evaluated for 60 days. RESULTS: Within the first 4 days of coronavirus disease 2019, 84.8 per cent of patients had chemosensitive dysfunction that gradually improved over the observation period. The most significant increase in chemosensitive scores occurred in the first 10 days for taste and between 10 and 20 days for smell. At the end of the observation period (60 days after symptom onset), 7.2 per cent of the patients still had severe dysfunctions. The risk of developing a long-lasting disorder becomes significant at 10 days for taste (odds ratio = 40.2, 95 per cent confidence interval = 2.204-733.2, p = 0.013) and 20 days for smell (odds ratio = 58.5, 95 per cent confidence interval = 3.278-1043.5, p = 0.005). CONCLUSION: Chemosensitive disturbances persisted in 7.2 per cent of patients 60 days after clinical onset. Specific therapies should be initiated in patients with severe olfactory and gustatory disturbances 20 days after disease onset.

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.

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.

Real-world outcomes according to treatment strategies in ALK-rearranged non-small-cell lung cancer (NSCLC) patients: an Italian retrospective study.

PURPOSE: Anaplastic lymphoma kinase (ALK) rearrangement confers sensitivity to ALK inhibitors (ALKis) in non-small-cell lung cancer (NSCLC). Although several drugs provided an impressive outcome benefit, the most effective sequential strategy is still unknown. We describe outcomes of real-life patients according to the treatment strategy received. PATIENTS: We retrospectively collected 290 ALK rearranged advanced NSCLC diagnosed between 2011 and 2017 in 23 Italian institutions. RESULTS: After a median follow-up of 26 months, PFS for crizotinib and a new generation ALKis were 9.4 [CI 95% 7.9-11.2] and 11.1 months [CI 95% 9.2-13.8], respectively, while TTF were 10.2 [CI 95% 8.5-12.6] and 11.9 months [CI 95% 9.7-17.4], respectively, being consistent across the different settings. The composed outcomes (the sum of PFS or TTF) in patients treated with crizotinib followed by a new generation ALKis were 27.8 months [CI 95% 24.3-33.7] in PFS and 30.4 months [CI 95% 24.7-34.9] in TTF. The median OS from the diagnosis of advanced disease was 39 months [CI 95% 31.8-54.5]. Patients receiving crizotinib followed by a new generation ALKis showed a higher median OS [57 months (CI 95% 42.0-73.8)] compared to those that did not receive crizotinib [38 months (CI 95% 18.6-NR)] and those who performed only crizotinib as target agent [15 months (CI 95% 11.3-34.0)] (P < 0.0001). CONCLUSION: The sequential administration of crizotinib and a new generation ALKis provided a remarkable clinical benefit in this real-life population, being an interesting option to consider in selected patients.

Metronomic oral vinorelbine for the treatment of advanced non-small cell lung cancer: a multicenter international retrospective analysis.

PURPOSE: Metronomic oral vinorelbine (MOV) could be a treatment option for unfit patients with advanced non-small cell lung cancer (NSCLC) based on its safety profile and high patient compliance. METHODS: We retrospectively collected data on 270 patients [median age 76 (range 48-92) years, M/F 204/66, PS 0 (27)/1 (110)/≥ 2 (133), median of 3 serious comorbidities] with stage IIIB-IV NSCLC treated with MOV as first (T1) (67%), second (T2) (19%) or subsequent (T3) (14%) line. Schedules consisted of vinorelbine 50 mg (138), 40 mg (68) or 30 mg (64) three times a week continuously. RESULTS: Patients received an overall median of 6 (range 1-25) cycles with a total of 1253 cycles delivered. The overall response rate was 17.8% with 46 partial and 2 complete responses and 119 patients (44.1%) experienced stable disease > 12 weeks with an overall disease control rate of 61.9%. Median overall time to progression was 5 (range 1-21) months [T1 7 (1-21), T2 5.5 (1-19) and T3 4 (1-19) months] and median overall survival 9 (range 1-36) months [T1 10 (1-31), T2 8 (1-36) and T3 6.5 (2-29) months]. Treatment was extremely well tolerated with 2% (25/1253) G3/4 toxicity (mainly G3 fatigue and anemia) and no toxic deaths. We observed the longer OS 14 (range 7-36) months in a subset of squamous NSCLC patients receiving immunotherapy after metronomic oral vinorelbine. CONCLUSION: We confirmed MOV as an extremely safe treatment in a large real world population of advanced NSCLC with an interesting activity mainly consisting of long-term disease stabilization. We speculate the possibility of a synergistic effect with subsequent immunotherapy.