Measurement of the 2νßß Decay Rate and Spectral Shape of

Neutrinoless double beta decay (0νßß) is a yet unobserved nuclear process that would demonstrate Lepton number violation, a clear evidence of beyond standard model physics. The process two neutrino double beta decay (2νßß) is allowed by the standard model and has been measured in numerous experiments. In this Letter, we report a measurement of 2νßß decay half-life of ^{100}Mo to the ground state of ^{100}Ru of [7.07±0.02(stat)±0.11(syst)]×10^{18} yr by the CUPID-Mo experiment. With a relative precision of ±1.6% this is the most precise measurement to date of a 2νßß decay rate in ^{100}Mo. In addition, we constrain higher-order corrections to the spectral shape, which provides complementary nuclear structure information. We report a novel measurement of the shape factor ξ_{3,1}=0.45±0.03(stat)±0.05(syst) based on a constraint on the ratio of higher-order terms from theory, which can be reliably calculated. This is compared to theoretical predictions for different nuclear models. We also extract the first value for the effective axial vector coupling constant obtained from a spectral shape study of 2νßß decay.

Determining g_{A}/g_{V} with High-Resolution Spectral Measurements Using a LiInSe_{2} Bolometer.

Neutrinoless double beta decay (0νßß) processes sample a wide range of intermediate forbidden nuclear transitions, which may be impacted by quenching of the axial vector coupling constant (g_{A}/g_{V}), the uncertainty of which plays a pivotal role in determining the sensitivity reach of 0νßß experiments. In this Letter, we present measurements performed on a high-resolution LiInSe_{2} bolometer in a "source=detector" configuration to measure the spectral shape of the fourfold forbidden ß decay of ^{115}In. The value of g_{A}/g_{V} is determined by comparing the spectral shape of theoretical predictions to the experimental ß spectrum taking into account various simulated background components as well as a variety of detector effects. We find evidence of quenching of g_{A}/g_{V} at >5σ with a model-dependent quenching factor of 0.655±0.002 as compared to the free-nucleon value for the interacting shell model. We also measured the ^{115}In half-life to be [5.18±0.06(stat)_{-0.015}^{+0.005}(sys)]×10^{14} yr within the interacting shell model framework. This Letter demonstrates the power of the bolometeric technique to perform precision nuclear physics single-ß decay measurements, which along with improved nuclear modeling can help reduce the uncertainties in the calculation of several decay nuclear matrix elements including those used in 0νßß sensitivity calculations.

First Germanium-Based Constraints on Sub-MeV Dark Matter with the EDELWEISS Experiment.

We present the first Ge-based constraints on sub-MeV/c^{2} dark matter (DM) particles interacting with electrons using a 33.4 g Ge cryogenic detector with a 0.53 electron-hole pair (rms) resolution, operated underground at the Laboratoire Souterrain de Modane. Competitive constraints are set on the DM-electron scattering cross section, as well as on the kinetic mixing parameter of dark photons down to 1 eV/c^{2}. In particular, the most stringent limits are set for dark photon DM in the 6 to 9 eV/c^{2} range. These results demonstrate the high relevance of Ge cryogenic detectors for the search of DM-induced eV-scale electron signals.

Ixodid ticks on wild donkeys in a Mediterranean nature reserve (Asinara National Park): diversity and risk factors.

The Sardinian coloured donkey Equus asinus (Perissodactyla: Equidae) and its albino colour morph represent the wildlife species most typical of the island of Asinara. This Mediterranean island represents a favourable context for ticks and tick-borne diseases; however, knowledge of the tick fauna on Asinara is scarce. A total of 106 Sardinian donkeys were inspected for tick infestation from June to November 2015. All ticks found were collected, classified by stage and sex, and identified to species level. The level of infestation of each donkey was determined; both the overall tick infestation and infestations of each detected species were classified on a scale of 1-3 to give an infestation score (IS). Overall, 256 hard ticks were collected from 60 of 106 donkeys (56.6%). Rhipicephalus bursa, Haemaphysalis punctata and Hyalomma marginatum (all: Ixodida: Ixodidae) infested 26.4%, 28.3% and 6.6% of donkeys, respectively. Different variables affected the IS. With reference to overall tick infestation, a higher IS was observed in donkeys grazing on grassland and Mediterranean shrubland and in albino donkeys compared with coloured donkeys. The collected ticks included species involved in the transmission of pathogens to humans, which highlights the risks for public health in a tourist destination such as Asinara National Park.

Quality of sleep in allergic children and their parents.

BACKGROUND: Quality of sleep is essential for physical and mental health and influences the perception of the patient's well-being during the day. In patients with chronic allergic diseases sleep disorders may increase the severity of the condition, complicate the management and impair their quality of life. When children are concerned, their parents are also affected by the problem. We evaluated the presence of disrupted sleep in parents of children with atopic disorders, and its relationship with clinical features and the presence of disturbed sleep in children. METHODS: Parents of children suffering from allergic diseases were recruited from the Pediatric Allergy Units of Parma University. Evaluation of sleep in parents was based on the Pittsburg Sleep Quality Index (PSQI), while in children it was based on the Sleep Disturbance Scale for Children (SDSC). RESULTS: Of the 102 parents invited, 92 filled in the questionnaire. Only the questionnaires with more than a 95% completion rate were considered for analysis. PSQI mean score in parents was 6.6 (SD 2.6); 75.6% of them had a PSQI ≥ 5, indicating that most parents had a sleep quality perceived as bad. The PSQI ≥ 5 was more common in parents of children with asthma and rhinitis. In children, SDSC mean score was 42.1 (SD: 9.4); 62.3% had a total score ≥ 39. The quality of sleep in parents and children was significantly correlated (p<0.001). CONCLUSION: These findings make it apparent that an alteration of sleep in children can also affect the parents. Such effect further weighs the burden of respiratory allergy and needs to be considered in future studies.

Italian study on buckwheat allergy: prevalence and clinical features of buckwheat-sensitized patients in Italy.

Buckwheat allergy is considered a rare food allergy outside of Asia. In Europe, buckwheat has been described mainly as a hidden allergen. Data on the prevalence of buckwheat hypersensitivity in non-Asian countries is very poor. The aim of this multicenter study was to evaluate the prevalence of buckwheat sensitization and its association with other sensitizations among patients referred to allergy clinics in different geographic areas of Italy. All patients referred to 18 Italian allergy clinics from February through April 2011 were included in the study and evaluated for sensitization to buckwheat and other allergens depending on their clinical history. A total of 1,954 patients were included in the study and 61.3 percent of them were atopic. Mean prevalence of buckwheat sensitization was 3.6 percent with significant difference between Northern (4.5 percent), Central (2.2 percent) and Southern (2.8 percent) regions. This is, to our knowledge, the largest epidemiological survey on buckwheat allergy reported outside of Asia. Buckwheat is an emerging allergen in Italy, being more frequently associated to sensitization in Northern regions.

Allergen immunotherapy: clinical and practical education of Italian trainees in allergy and clinical immunology schools.

We performed a survey, based on a questionnaire including 20 items, submitted anonymously to Italian trainees in Allergology and Clinical Immunology, in order to obtain information about their specific allergen immunotherapy (AIT) practices. The questionnaire was sent to 40 trainees, who had attended the last two years of the training course. Thirty-four subjects (mean age: 27 years, 65% females) adequately completed the survey. The answers to the questionnaire showed that only 60% of the training programs included lectures on AIT. Among the trainees using AIT, only 40% declared being able to prescribe it independently, while 60% were guided by a tutor. Of the trainees who were able to prescribe AIT autonomously, 60% were familiar with both routes of administration, i.e. subcutaneous (SCIT) and sublingual immunotherapy (SLIT), while 25% of these used only SLIT. In 80% of the training institutions involved, the trainees could attend a dedicated AIT outpatient ward for SCIT administration; only 40% administered AIT personally, and in half of these cases, they were guided by a tutor. Only 70% of trainees had experience in the follow-up of patients still under treatment and of patients who had completed treatment. Analysis of the answers obtained for questions on venom immunotherapy (VIT) showed that, in 90% of cases, the trainees attended a dedicated outpatients ward where VIT is administered, but with a role limited to observation/cooperation. Only 30% were involved in the follow-up of patients who were under treatment or who had completed VIT. Only 20% of the trainees felt confident enough about VIT to prescribe this treatment independently, 80% knew there were several administration protocols, and the majority prescribed products from three different manufacturers. These findings suggest that there is significant room for improving the instructions provided regarding allergology and clinical immunology to trainees in Italy with respect to AIT.

Combining Genome Surveillance and Metadata To Characterize the Diversity of Staphylococcus aureus Circulating in an Italian Hospital over a 9-Year Period.

Staphylococcus aureus is an opportunistic pathogen and a leading cause of morbidity and mortality worldwide. Genomic-based surveillance has greatly improved our ability to track the emergence and spread of high-risk clones, but the full potential of genomic data is only reached when used in conjunction with detailed metadata. Here, we demonstrate the utility of an integrated approach by leveraging a curated collection of clinical and epidemiological metadata of S. aureus in the San Matteo Hospital (Italy) through a semisupervised clustering strategy. We sequenced 226 sepsis S. aureus samples, recovered over a period of 9 years. By using existing antibiotic profiling data, we selected strains that capture the full diversity of the population. Genome analysis revealed 49 sequence types, 16 of which are novel. Comparative genomic analyses of hospital- and community-acquired infection ruled out the existence of genomic features differentiating them, while evolutionary analyses of genes and traits of interest highlighted different dynamics of acquisition and loss between antibiotic resistance and virulence genes. Finally, highly resistant clones belonging to clonal complexes (CC) 8 and 22 were found to be responsible for abundant infections and deaths, while the highly virulent CC30 was responsible for rare but deadly episodes of infections. IMPORTANCE Genome sequencing is an important tool in clinical microbiology, as it allows in-depth characterization of isolates of interest and can propel genome-based surveillance studies. Such studies can benefit from ad hoc methods of sample selection to capture the genomic diversity present in a data set. Here, we present an approach based on clustering of antibiotic resistance profiles that allows optimal sample selection for bacterial genomic surveillance. We apply the method to a 9-year collection of Staphylococcus aureus from a large hospital in northern Italy. Our method allows us to sequence the genomes of a large variety of strains of this important pathogen, which we then leverage to characterize the epidemiology in the hospital and to perform evolutionary analyses on genes and traits of interest. These analyses highlight different dynamics of acquisition and loss between antibiotic resistance and virulence genes.

Clinical and morphological features of large-cell neuroendocrine carcinomas and small-cell lung carcinomas expressing the DLL3 and ASCL1 oncoproteins.

Intratumoral similarities and differences between large-cell neuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) are determined partially by the Notch signaling pathway, which controls the switch from neuroendocrine to slight/non-neuroendocrine cell fate. LCNECs are divided into two subgroups according to genomic alterations: type I LCNECs exhibit a neuroendocrine profile characterized by achaete-scute homolog 1 (ASCL1)high/delta-like protein 3 (DLL3)high/NOTCHlow and type II LCNECs show the pattern ASCL1low/DLL3low/NOTCHhigh. Here, we used immunohistochemistry, transmission electron microscopy, and digital analysis to examine the role of the Notch ligand DLL3 as an immunomarker of the neuroendocrine state and ASCL1 as a regulator of cell-cell interactions in SCLCs and LCNECs. High DLL3 and ASCL1 expression was associated with atypical submicroscopic characteristics involving nuclear size, chromatin arrangement, Golgi apparatus, and endoplasmic reticulum, and was characteristic of type I LCNECs with similarity to SCLCs, whereas low DLL3 and ASCL1 expression was found in both SCLCs and type II LCNECs. In patients diagnosed at an early stage who did not have metastasis and who underwent chemotherapy, DLL3high and ASCL1high SCLCs and type I LCNECs were associated with a better prognosis and a lower risk of death. The present findings suggested that DLL3/ASCL1 are potential therapeutic targets and prognostic indicators in patients with SCLCs or LCNECs.

Clinical outcome of Brazilian patients with non-small cell lung cancer in early stage harboring rare mutations in epidermal growth factor receptor.

The common epidermal growth factor receptor (EGFR) mutations, such as the L858R point mutation in exon 21 and the in-frame deletional mutation in exon 19, have been definitively associated with response to EGFR-tyrosine kinase inhibitors (EGFR-TKI). However, the clinical outcome and response to treatment for many other rarer mutations are still unclear. In this study, we report the results of Brazilian patients in stage IB-IIIA non-small cell lung cancer (NSCLC) following complete resection with minimal residual disease and EGFR mutations treated with adjuvant chemotherapy and/or EGFR-TKIs. The frequency of EGFR mutations was investigated in 70 cases of early stage NSCLC. Mutations in exons 18 and 20, uncommon mutations in exons 19 and 21, as well as in exons 3, 7, 14, 16, 22, 27, and 28, and/or the presence of different mutations in a single tumor (complex mutations) are considered rare. EGFR mutations were detected in 23 tumors (32.9%). Fourteen cases carried rare mutations and were treated with platinum-based chemotherapy and two cases were treated with erlotinib. The clinical outcome is described case by case with references to the literature. Notably, we found two rare EGFR mutations and one of them with an unknown response to chemotherapy and/or EGFR-TKIs. We have provided complementary information concerning the clinical outcome and treatment of patients with early stage NSCLC for several rare EGFR mutations not previously or only rarely reported. Description of cases harboring rare mutations can support the decision-making process in this subset of patients.

Concomitant TP53 mutation in early-stage resected EGFR-mutated non-small cell lung cancer: a narrative approach in a genetically admixed Brazilian cohort.

TP53 mutations are frequent in non-small cell lung cancer (NSCLC) and have been associated with poor outcome. The prognostic and predictive relevance of EGFR/TP53 co-mutations in NSCLC is controversial. We analyzed lung tissue specimens from 70 patients with NSCLC using next-generation sequencing to determine EGFR and TP53 status and the association between these status with baseline patient and tumor characteristics, adjuvant treatments, relapse, and progression-free (PFS) and overall survival (OS) after surgical resection. We found the EGFR mutation in 32.9% of patients (20% classical mutations and 12.9% uncommon mutations). TP53 missense mutations occurred in 25.7% and TP53/EGFR co-mutations occurred in 43.5% of patients. Stage after surgical resection was significantly associated with OS (P=0.028). We identified an association between progression-free survival and poor outcome in patients with distant metastases (P=0.007). We found a marginally significant difference in OS between genders (P=0.057) and between mutant and wild type TP53 (P=0.079). In univariate analysis, distant metastases (P=0.027), pathological stage (IIIA-IIIB vs I-II; P=0.028), and TP53 status (borderline significance between wild type and mutant; P=0.079) influenced OS. In multivariable analysis, a significant model for high risk of death and poor OS (P=0.029) selected patients in stage IIIA-IIIB, with relapse and distant metastases, non-responsive to platin-based chemotherapy and erlotinib, with tumors harboring EGFR uncommon mutations, with TP53 mutant, and with EGFR/TP53 co-mutations. Our study suggested that TP53 mutation tends to confer poor survival and a potentially negative predictive effect associated with a non-response to platinum-based chemotherapy and erlotinib in early-stage resected EGFR-mutated NSCLC.

Organotypic human lung bud microarrays identify BMP-dependent SARS-CoV-2 infection in lung cells.

Although lung disease is the primary clinical outcome in COVID-19 patients, how SARS-CoV-2 induces lung pathology remains elusive. Here we describe a high-throughput platform to generate self-organizing and commensurate human lung buds derived from hESCs cultured on micropatterned substrates. Lung buds resemble human fetal lungs and display proximodistal patterning of alveolar and airway tissue directed by KGF. These lung buds are susceptible to infection by SARS-CoV-2 and endemic coronaviruses and can be used to track cell type-specific cytopathic effects in hundreds of lung buds in parallel. Transcriptomic comparisons of infected lung buds and postmortem tissue of COVID-19 patients identified an induction of BMP signaling pathway. BMP activity renders lung cells more susceptible to SARS-CoV-2 infection and its pharmacological inhibition impairs infection by this virus. These data highlight the rapid and scalable access to disease-relevant tissue using lung buds that recapitulate key features of human lung morphogenesis and viral infection biology.

Self-organized stem cell-derived human lung buds with proximo-distal patterning and novel targets of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the global COVID-19 pandemic and the lack of therapeutics hinders pandemic control1-2. Although lung disease is the primary clinical outcome in COVID-19 patients1-3, how SARS-CoV-2 induces tissue pathology in the lung remains elusive. Here we describe a high-throughput platform to generate tens of thousands of self-organizing, nearly identical, and genetically matched human lung buds derived from human pluripotent stem cells (hPSCs) cultured on micropatterned substrates. Strikingly, in vitro-derived human lung buds resemble fetal human lung tissue and display in vivo-like proximo-distal coordination of alveolar and airway tissue differentiation whose 3D epithelial self-organization is directed by the levels of KGF. Single-cell transcriptomics unveiled the cellular identities of airway and alveolar tissue and the differentiation of WNThi cycling alveolar stem cells, a human-specific lung cell type4. These synthetic human lung buds are susceptible to infection by SARS-CoV-2 and endemic coronaviruses and can be used to track cell type-dependent susceptibilities to infection, intercellular transmission and cytopathology in airway and alveolar tissue in individual lung buds. Interestingly, we detected an increased susceptibility to infection in alveolar cells and identified cycling alveolar stem cells as targets of SARS-CoV-2. We used this platform to test neutralizing antibodies isolated from convalescent plasma that efficiently blocked SARS-CoV-2 infection and intercellular transmission. Our platform offers unlimited, rapid and scalable access to disease-relevant lung tissue that recapitulate key hallmarks of human lung development and can be used to track SARS-CoV-2 infection and identify candidate therapeutics for COVID-19.

How much specific is the association between hymenoptera venom allergy and mastocytosis?

BACKGROUND: The preferential association of mastocytosis with hymenoptera sting reactions is well known, but there is no data on the prevalence of clonal mast cell disorders in subjects with severe systemic reactions due to foods or drugs. METHODS: Patients with food- or drug-induced severe systemic reactions, including anaphylaxis, and increased serum tryptase were studied for the presence of mastocytosis, and compared with a population of patients with hymenoptera allergy. The aetiological role of foods or drugs was assessed according to current recommendations. Systemic reactions were graded in severity according to the procedure described by Mueller. Serum tryptase was considered increased if the level was >11.4 ng/ml. Subjects with increased tryptase had dermatological evaluation and Bone marrow(BM) aspirate-biopsy, which included histology/cytology, flow cytometry and detection of KIT mutations. RESULTS: A total of 137 subjects (57 male, mean age 42 years) were studied. Of them, 86 proved positive for drugs and 51 for foods. Overall, out of 137 patients, only nine (6.6%) had a basal tryptase >11.4 ng/ml, and only two (1.5%) were diagnosed with mastocytosis. This was clearly different from patients with hymenoptera allergy, where 13.9% had elevated tryptase and 11.1% had a clonal mast cell disorder. CONCLUSION: The association of clonal mast cell disorders with hymenoptera allergy seems to be more specific than that with food- or drug-induced systemic reactions.

Toxoplasma gondii Antibodies in Bulk Tank Milk Samples of Caprine Dairy Herds.

A major public health issue, Toxoplasma gondii infection can affect humans mainly via the consumption of animal products from certain species, including small ruminants. Therefore, a regular monitoring of the infection in ovine and caprine populations is advisable for the control of human and animal toxoplasmosis. Antibody detection in individual and bulk tank milk (BTM) may represent a valid alternative to serological analysis, in that its collection is easy and does not affect animal welfare. Many serological tools for milk analysis have already been validated for several parasites, including Apicomplexa. Thus, the aim of the present study was to obtain epidemiological data on T. gondii infection through the detection of antibodies in BTM of dairy goat herds from an important area for caprine dairy production (northern Italy). The performance of a commercial ELISA was first evaluated for analysis of caprine milk samples, using a panel of serum-milk pairs of goats naturally infected by T. gondii. The analysis of BTM confirmed the presence of anti- T. gondii antibodies in 59% of the samples. Toxoplasma gondii antibody positivity was more frequently found in goats reared on farms under extensive (64.9%) or semi-intensive systems (68.7%) in comparison with intensive farms (51.1%). Analysis of milk was a valid alternative to serological tests, being easily applied in large-scale epidemiological surveys and for continuous monitoring of T. gondii infection.

Clinical and morphological features of large-cell neuroendocrine carcinomas and small-cell lung carcinomas expressing the DLL3 and ASCL1 oncoproteins

Abstract Intratumoral similarities and differences between large-cell neuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) are determined partially by the Notch signaling pathway, which controls the switch from neuroendocrine to slight/non-neuroendocrine cell fate. LCNECs are divided into two subgroups according to genomic alterations: type I LCNECs exhibit a neuroendocrine profile characterized by achaete‐scute homolog 1 (ASCL1)high/delta-like protein 3 (DLL3)high/NOTCHlow and type II LCNECs show the pattern ASCL1low/DLL3low/NOTCHhigh. Here, we used immunohistochemistry, transmission electron microscopy, and digital analysis to examine the role of the Notch ligand DLL3 as an immunomarker of the neuroendocrine state and ASCL1 as a regulator of cell-cell interactions in SCLCs and LCNECs. High DLL3 and ASCL1 expression was associated with atypical submicroscopic characteristics involving nuclear size, chromatin arrangement, Golgi apparatus, and endoplasmic reticulum, and was characteristic of type I LCNECs with similarity to SCLCs, whereas low DLL3 and ASCL1 expression was found in both SCLCs and type II LCNECs. In patients diagnosed at an early stage who did not have metastasis and who underwent chemotherapy, DLL3high and ASCL1high SCLCs and type I LCNECs were associated with a better prognosis and a lower risk of death. The present findings suggested that DLL3/ASCL1 are potential therapeutic targets and prognostic indicators in patients with SCLCs or LCNECs.

Concomitant TP53 mutation in early-stage resected EGFR-mutated non-small cell lung cancer: a narrative approach in a genetically admixed Brazilian cohort

TP53 mutations are frequent in non-small cell lung cancer (NSCLC) and have been associated with poor outcome. The prognostic and predictive relevance of EGFR/TP53 co-mutations in NSCLC is controversial. We analyzed lung tissue specimens from 70 patients with NSCLC using next-generation sequencing to determine EGFR and TP53 status and the association between these status with baseline patient and tumor characteristics, adjuvant treatments, relapse, and progression-free (PFS) and overall survival (OS) after surgical resection. We found the EGFR mutation in 32.9% of patients (20% classical mutations and 12.9% uncommon mutations). TP53 missense mutations occurred in 25.7% and TP53/EGFR co-mutations occurred in 43.5% of patients. Stage after surgical resection was significantly associated with OS (P=0.028). We identified an association between progression-free survival and poor outcome in patients with distant metastases (P=0.007). We found a marginally significant difference in OS between genders (P=0.057) and between mutant and wild type TP53 (P=0.079). In univariate analysis, distant metastases (P=0.027), pathological stage (IIIA-IIIB vs I-II; P=0.028), and TP53 status (borderline significance between wild type and mutant; P=0.079) influenced OS. In multivariable analysis, a significant model for high risk of death and poor OS (P=0.029) selected patients in stage IIIA-IIIB, with relapse and distant metastases, non-responsive to platin-based chemotherapy and erlotinib, with tumors harboring EGFR uncommon mutations, with TP53 mutant, and with EGFR/TP53 co-mutations. Our study suggested that TP53 mutation tends to confer poor survival and a potentially negative predictive effect associated with a non-response to platinum-based chemotherapy and erlotinib in early-stage resected EGFR-mutated NSCLC.

Tissue alkalosis in cold-ischemia time.

The control of pre-analytical-factors in human biospecimens collected for health research is currently required. Only two previous reports using post-mortem brain samples have tried to address the impact of cold-ischemia on tissue pH. Here we report pH variations according to time (third-order polynomial model) in mice for liver, kidney and lung samples. Tissue alkalosis in cold-ischemia time may be an underlying mechanism of gene expression changes. Therefore, tissue-pH regulation after organ removal may minimize biological stress in human tissue samples.

Clinical outcome of Brazilian patients with non-small cell lung cancer in early stage harboring rare mutations in epidermal growth factor receptor

The common epidermal growth factor receptor (EGFR) mutations, such as the L858R point mutation in exon 21 and the in-frame deletional mutation in exon 19, have been definitively associated with response to EGFR-tyrosine kinase inhibitors (EGFR-TKI). However, the clinical outcome and response to treatment for many other rarer mutations are still unclear. In this study, we report the results of Brazilian patients in stage IB-IIIA non-small cell lung cancer (NSCLC) following complete resection with minimal residual disease and EGFR mutations treated with adjuvant chemotherapy and/or EGFR-TKIs. The frequency of EGFR mutations was investigated in 70 cases of early stage NSCLC. Mutations in exons 18 and 20, uncommon mutations in exons 19 and 21, as well as in exons 3, 7, 14, 16, 22, 27, and 28, and/or the presence of different mutations in a single tumor (complex mutations) are considered rare. EGFR mutations were detected in 23 tumors (32.9%). Fourteen cases carried rare mutations and were treated with platinum-based chemotherapy and two cases were treated with erlotinib. The clinical outcome is described case by case with references to the literature. Notably, we found two rare EGFR mutations and one of them with an unknown response to chemotherapy and/or EGFR-TKIs. We have provided complementary information concerning the clinical outcome and treatment of patients with early stage NSCLC for several rare EGFR mutations not previously or only rarely reported. Description of cases harboring rare mutations can support the decision-making process in this subset of patients.