Laryngeal features in Lipoid proteinosis: a systematic review and meta-analysis of individual participant data.

PURPOSE: Lipoid proteinosis (LP) or Urbach-Wiethe disease (OMIM 247100) is a rare syndrome characterised by early vocal folds infiltration and subsequent multi-organ involvement. LP is often unrecognised and its associated hoarseness is overlooked. The main objective of the study was to investigate hoarseness in LP and implement a diagnosis among otolaryngologists. METHODS: PubMed/MEDLINE and OMIM databases were systematically searched. Authors concentrated the search on published articles starting from the discovery of the pathogenesis of LP by Hamada et al. in 2002. Only cases in which a diagnosis was reported both clinically and through biopsy and/or genetic molecular testing were included. Characteristics of the LP cases were extracted from each included study. Results were obtained through Generalized Estimating Equations. RESULTS: The search strategy yielded 217 articles, of which 74 (34.1%) met the selection criteria. A total of 154 cases were included. Hoarseness was described in all LP cases and clearly stated as the onset symptom in 68.8%. The onset was on average at 19 months of age (CI: 3.00-20.00), while the mean age at diagnosis was 15 years (CI: 10.00-30.00). Therefore, the diagnostic delay amounted to 13.42 years (CI: 8.00-23.83). Hoarseness alone was responsible for an LP diagnosis in only 14.3% of cases. In 43.5% of cases, genetic analysis of the ECM1 gene was performed and exon 6 was the most frequently altered portion. CONCLUSION: Analysing the largest number of published cases, the study underlined that hoarseness is the key symptom for diagnosing LP since early childhood, though frequently overlooked.

Accuracy of Dysphagia Standard Assessment (DSA®) bedside screening test: a flowchart for patient eligibility.

BACKGROUND: Oropharyngeal dysphagia (OD) screening tests have improved patient management; however, the complex applicability and high percentage of false negatives do not allow these tests to be considered completely reliable if not supported by an instrumental investigation. The aim of the present study is to evaluate an OD screening test, the Dysphagia Standard Assessment (DSA®) with different volumes and viscosities. MATERIALS AND METHODS: Prospective study of 72 patients evaluated for suspected OD through a double-blind methodology conducted by two operators. All patients underwent fiberoptic endoscopic evaluation of swallowing (FEES) as a reference test and a separate DSA® test. DSA® was performed by administering boluses with different viscosities, with the signal of interruption of the test being: onset of the cough reflex, wet voice after swallowing, and/or desaturation of O2 ≥ 5%. The Penetration-Aspiration Scale (PAS) was evaluated by FEES. The cut-off identified to diagnose OD was PAS ≥ 3. RESULTS: The test showed an accuracy of 82%, a sensitivity of 0.93 (95% C.I. 0.84-0.97), and a specificity of 0.78 (95% C.I. 0.67-0.87); positive predictive value 0.55 (95% C.I. 0.43-0.67); negative predictive value 0.97 (95% C.I. 0.90-0.99), positive likelihood ratio 4.37 (95% C.I. 3.6-5.2); likelihood negative ratio 0.08 (95% C.I. 0.06-0.09). CONCLUSIONS: According to the preliminary results, the test showed good outcomes in determining the presence or absence of OD with a wide spectrum of applicability with some limitations that could be overcome by the selection of a target population. For this reason, a flowchart to address patient eligibility was developed.

Progression of Oropharyngeal Dysphagia in Amyotrophic Lateral Sclerosis: A Retrospective Cohort Study.

Little is known regarding the optimal timing of dysphagia assessment and PEG indication in amyotrophic lateral sclerosis (ALS). The study aims to investigate the progression of dysphagia in a cohort of ALS patients and to analyse whether there are variables linked to a faster progression of dysphagia and faster indication of PEG placement. A retrospective cohort study in 108 individuals with ALS. Fiberoptic endoscopic evaluation of swallowing was performed 6 monthly until PEG indication or death. Dysphagia severity and PEG indication were assessed using Penetration Aspiration Scale. Progression Index (PI) analysed the risk of disease progression (fast/slow) in relation to dysphagia onset and PEG indication. Patients were grouped based on ALS onset and PI. Person-time incidence rates were computed considering dysphagia onset and PEG indication from ALS symptoms during the entire observation period and have been reported as monthly and 6-month rates. Cox regression survival analysis assessed dysphagia and PEG risk factors depending on onset. Person-time incidence rates of dysphagia progression and PEG risk were increased based on type of ALS onset and PI. Patients with a fast progressing disease and with bulbar onset (BO) show statistically significant increased risk of dysphagia (BO 178.10% hazard ratio (HR) = 2.781 P < 0.01; fast 181.10% HR 2.811 P < 0.01). Regarding PEG risk, fast patients and patients with BO had a statistically significant increased risk (fast 147.40% HR 2.474 P < 0.01, BO 165.40% HR 2.654 P < 0.01). Fast PI predicts the likelihood of faster progression of dysphagia and PEG indication and should be included in multidisciplinary assessments and considered in the design of future guidelines regarding dysphagia management in ALS patients.Level of Evidence Level IV.

Phase 2 study of NAB-paclitaxel in SensiTivE and refractory relapsed small cell lung cancer (SCLC) (NABSTER TRIAL).

BACKGROUND: Despite sensitivity to first-line chemotherapy, most small-cell lung cancer (SCLC) patients relapse. In this setting, topotecan demonstrated modest activity with significant toxicity. Paclitaxel was also active. This study was designed to evaluate activity and safety of nab-paclitaxel in relapsed SCLC. METHODS: In this multicentre prospective Phase 2 trial, patients with refractory or sensitive SCLC progressed to first-line platinum-based chemotherapy received nab-paclitaxel 100 mg/smq on days 1, 8, 15 every 4 weeks up to six cycles, progressive disease or intolerable toxicity. Primary endpoint was investigator-assessed objective tumour response. Secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). RESULTS: Of the 68 patients treated, partial response was 8% in the refractory cohort and 14% in the sensitive cohort. Most common toxicities of any grade were fatigue (54%), anaemia (38%), neutropenia (29%), leukopenia (26%) and diarrhoea (21%). Median PFS was similar in both refractory (1.8 months) and sensitive cohorts (1.9 months), while median OS was longer in sensitive one (6.6 versus 3.6 months). CONCLUSIONS: Although nab-paclitaxel has shown some modest anti-tumour activity in relapsed SCLC, associated with a favourable toxicity profile, the primary end-point of the study was not met. CLINICAL TRIAL REGISTRATION: Clinical Trial registration number is ClinicalTrials.gov Identifier: NCT03219762.

The Italian consensus conference on the role of rehabilitation for children and adolescents with leukemia, central nervous system, and bone tumors, part 1: Review of the conference and presentation of consensus statements on rehabilitative evaluation of motor aspects.

Because of increasing survival rates in pediatric oncology, attention is focusing on cancer and its treatment-related side effects. Rehabilitation may reduce their impact. However, the literature does not provide strong evidence regarding rehabilitation pathways. Therefore, the Italian Association of Pediatric Hematology and Oncology organized a consensus conference on the role of rehabilitation of motor impairments in children/adolescents affected by leukemia, central nervous system, and bone tumors to define recommendations for daily practice. The grading of recommendation assessment, developing and evaluation (GRADE) method was used in order to formulate questions, select outcomes, evaluate evidence, and create recommendations. This paper includes the results on the rehabilitation assessment.

Voice Parameter Changes in Professional Musician-Singers Singing with and without an Instrument: The Effect of Body Posture.

BACKGROUND AND AIM: The impact of body posture on vocal emission is well known. Postural changes may increase muscular resistance in tracts of the phono-articulatory apparatus and lead to voice disorders. This work aimed to assess whether and to which extent body posture during singing and playing a musical instrument impacts voice performance in professional musicians. SUBJECTS AND METHODS: Voice signals were recorded from 17 professional musicians (pianists and guitarists) while they were singing and while they were singing and playing a musical instrument simultaneously. Metrics were extracted from their voice spectrogram using the Multi-Dimensional Voice Program (MDVP) and included jitter, shift in fundamental voice frequency (sF0), shimmer, change in peak amplitude, noise to harmonic ratio, Voice Turbulence Index, Soft Phonation Index (SPI), Frequency Tremor Intensity Index, Amplitude Tremor Intensity Index, and maximum phonatory time (MPT). Statistical analysis was performed using two-tailed t tests, one-way ANOVA, and χ2 tests. Subjects' body posture was visually assessed following the recommendations of the Italian Society of Audiology and Phoniatrics. Thirty-seven voice signals were collected, 17 during singing and 20 during singing and playing a musical instrument. RESULTS: Data showed that playing an instrument while singing led to an impairment of the "singer formant" and to a decrease in jitter, sF0, shimmer, SPI, and MPT. However, statistical analysis showed that none of the MDVP metrics changed significantly when subjects played an instrument compared to when they did not. Shoulder and back position affected voice features as measured by the MDVP metrics, while head and neck position did not. In particular, playing the guitar decreased the amplitude of the "singer formant" and increased noise, causing a typical "raucous rock voice." CONCLUSIONS: Voice features may be affected by the use of the instrument the musicians play while they sing. Body posture selected by the musician while playing the instrument may affect expiration and phonation.

Phosphoinositide-specific phospholipase C in normal human liver and in alcohol abuse.

The phosphoinositide (PI) signal transduction pathway participates in liver metabolism. Abnormal activity or expression of PI-specific phospholipase C (PLC) enzymes has been described in different liver diseases. We resume the role of the PI metabolism in liver and PLC abnormalities in different liver diseases. Moreover, we present the results of PLC analyses in a normal human liver and an alcohol-damaged liver. PLC enzymes and the expression of the corresponding genes in liver biopsies from individuals deceased for complications of the alcoholic liver disease (ALD) at different stages compared with normal controls (deceased individuals with histologically normal livers without alcohol addiction anamnesis) were analyzed by using immunohistochemistry and molecular biology techniques. The expression panel of PLCs was described in normal and alcohol abuse liver. Our observations suggest that the regulation of PLC expression might be due to posttranscriptional events and that alcohol affects the epigenetic control of PLC expression belonging to PI signaling. We also describe the alternate expression of PLCB1 and PLCH1 genes in liver. Our results corroborate literature data suggesting that PLC enzymes are differently expressed in normal versus pathological liver, playing a role in the histopathogenesis of liver tissue damage. The expression and/or localization of selected PLC isoforms is especially affected in alcohol-related liver tissue histopathology. Our present observations confirm that the modulation of protein synthesis plays a role in the regulation of PLC enzymes. We also suggest that this modulation might act at the transcription level. Further studies are required to investigate related epigenetic mechanisms.

Somatic Tinnitus.

Modulation of tinnitus characteristics such as pitch and loudness has been extensively described following movements of the head, neck and limbs, vertical or horizontal eye gaze, pressure on myofascial trigger points, cutaneous stimulation of the hands, electrical stimulation of the median nerve, and transcranial direct current stimulation. Modulation of tinnitus follows complex interactions between auditory and somatosensory afferents and can be favored by underlying somatic disorders. When tinnitus appears to be preceded or strictly linked to a somatic disorder, and therefore related to problems of the musculoskeletal system rather than of the ear, it is defined somatic tinnitus. A correct diagnosis and treatment of somatic disorders underlying tinnitus play a central role for a correct management of somatic tinnitus. However, the identification of somatic tinnitus may be complex in some cases. In this paper, after a general review of the current evidences for somatic tinnitus available in the literature, we present and discuss some cases of patients in which somatic modulation of tinnitus played a role-although different from case to case-in their tinnitus, describing the diagnostic and therapeutic approaches followed in each individual case and the results obtained, also highlighting unexpected findings and pitfalls that may be encountered when approaching somatic tinnitus patients.

Vestibular Schwannoma and Ipsilateral Endolymphatic Hydrops: An Unusual Association.

Vestibular schwannoma and endolymphatic hydrops are two conditions that may present with similar audio-vestibular symptoms. The association of the two in the same patient represents an unusual finding that may lead clinicians to errors and delays in diagnosis and clinical management of affected subjects. We discuss the case of a patient with an intrameatal vestibular schwannoma reporting symptoms suggestive for ipsilateral endolymphatic hydrops. The patient presented with fluctuating hearing loss, tinnitus, and acute rotatory vertigo episodes, and underwent a full audiological evaluation and imaging of the brain with contrast-enhanced Magnetic Resonance Imaging. Clinical audio-vestibular and radiological examination confirmed the presence of coexisting vestibular schwannoma and endolymphatic hydrops. Hydrops was treated pharmacologically; vestibular schwannoma was monitored over time with a wait and scan protocol through conventional MRI. The association of vestibular schwannoma and endolymphatic hydrops is rare, but represents a possible finding in clinical practice. It is therefore recommended investigating the presence of inner ear disorders in patients with vestibular schwannoma and, similarly, to exclude the presence of this condition in patients with symptoms typical of inner ear disorders.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia syndrome.

The term diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) may be used to describe a clinico-pathological syndrome, as well as an incidental finding on histological examination, although there are obvious differences between these two scenarios. According to the World Health Organization, the definition of DIPNECH is purely histological. However, DIPNECH encompasses symptomatic patients with airway disease, as well as asymptomatic patients with neuroendocrine cell hyperplasia associated with multiple tumourlets/carcinoid tumours. DIPNECH is also considered a pre-neoplastic lesion in the spectrum of pulmonary neuroendocrine tumours, because it is commonly found in patients with peripheral carcinoid tumours.In this review, we summarise clinical, physiological, radiological and histological features of DIPNECH and critically discuss recently proposed diagnostic criteria. In addition, we propose that the term "DIPNECH syndrome" be used to indicate a sufficiently distinct patient subgroup characterised by respiratory symptoms, airflow obstruction, mosaic attenuation with air trapping on chest imaging and constrictive obliterative bronchiolitis, often with nodular proliferation of neuroendocrine cells with/without tumourlets/carcinoid tumours on histology. Surgical lung biopsy is the diagnostic gold standard. However, in the appropriate clinical and radiological setting, transbronchial lung biopsy may also allow a confident diagnosis of DIPNECH syndrome.

Detection of fraudulent addition of bovine whey in water buffalo ricotta cheese by isoelectric focusing.

BACKGROUND: Prevention of food fraud in the dairy field is a difficult issue for researchers, industries and policy makers, both for commercial and health reasons. Currently, no analytical method allows detection of the addition of bovine whey to water buffalo ricotta, so this fraudulent practice cannot be prevented. The authors' aim was to develop such a method. RESULTS: The conditions for extraction and purification of denatured ricotta whey proteins, which are unfolded and coagulated by heating during the production process, were optimized. The optimal composition of the polyacrylamide gel (pH range, type and concentration of chemical separator) was first evaluated and then the best conditions to perform the separation by isoelectric focusing were established. The performance of the method (precision, selectivity, robustness, sensibility) was determined. CONCLUSIONS: The method was shown to be reliable and robust for detection of the presence of bovine whey added to water buffalo Ricotta at percentages above 5% (v/v). The results suggest that the differences observed between bovine and water buffalo electrophoretic profiles are due to bovine ß-lactoglobulin isoform A, which is never detected in water buffalo samples.

Looking for an Objective Parameter to Identify Early Vocal Dysfunctions in Healthy Perceived Singers.

The finding of minimal laryngeal dysfunctions in professional voice users is essential to prevent the onset of organic vocal pathologies. The purpose of this study is to identify an objective parameter that supports the phoniatric evaluation in detecting minimal laryngeal dysfunctions in singers. 54 professional and non-professional singers have been evaluated with laryngostroboscopy, Multi-Dimensional Voice Program (MDVP), Dysphonia Severity Index (DSI), maximum phonation time (TMF), minimum intensity of sound emission (I-min), maximum frequency (F-max), voice handicap index (VHI), singing voice handicap index (SVHI), manual phonogram and audiometric examination. The SVHI of all the "healthy" singers was on average 23.7 ± 22.5, while that of the "dysfunctional" 20.9 ± 18. No statistically significant difference was found between the SVHI scores of the total of healthy singers compared to the scores of the dysfunctional ones on the VSL (p = 0.6). The between-group comparison of the means of individual parameter values of DSI, TMF, F-max, Jitter, Shimmer, NHR, and SPI was not statistically significant (respectively p = 0.315, 0.2, 0.18, 0.09, 0.2, 0.08, 0.3). The only parameter analyzed that was statistically significant was the I-min (p < 0.05). SVHI is a valid instrument for the evaluation after a therapy but in our experience, it is not useful in distinguishing healthy from dysfunctional patients. The minimum intensity of sound emission measured with the sound level meter (I-low2) resulted a reliable parameter to identify minimal laryngeal dysfunctions and a useful tool in supporting the phoniatric diagnostic-therapeutic process in singers.

Reinke's Edema: New Insights into Voice Analysis, a Retrospective Study.

PURPOSE: Reinke's edema (RE) is a pathological condition involving increased volume of the vocal folds and resulting in significant impact on speech, fundamental frequency, and vocal range. Literature reports few studies which analyze vocal features according to the severity of RE. The aims of this study were to investigate the aerodynamics, acoustic characteristics, and sound spectrograms of a group of RE patients and to assess whether there was any correlation with their endoscopic grading. METHODS: A total of 98 patients were included in the study, 49 patients with RE and 49 healthy volunteers (HV). Multidimensional Voice Program was used to perform objective voice assessment. Maximum phonation time (MPT) and Voice Handicap Index (VHI) questionnaire were collected. The spectrograms of the vowel /a/ and of the word /aiuole/, which contains the five Italian vowels, of each patient were analyzed according to the classification of Yanaghiara modified by Ricci Maccarini and De Colle. Laryngological assessment was used to record vocal folds morphology according to Yonekawa's classification. Univariate analysis was used to compare group outcomes. Bivariate analysis was used to compare endoscopic grading and voice analysis results. RESULTS: Univariate analysis of the HV and RE groups revealed statistically significant differences (P < 0.05) for the following parameters: jitter%, shimmer%, harmonic-to-noise ratio (NHR), voice turbulence index (VTI), MPT, VHI except for soft phonation index. Spearman's rank correlation showed a positive correlation between vocal parameters such as jitter%, shimmer%, NHR, VTI, and RE gradings. A negative correlation was found between MPT and RE gradings. Bivariate analysis indicated a strong positive correlation between RE grading and the spectrogram classification performed both with the vowel / a / (Rho 0.86; P = 0.0001) and with the word / aiuole / (Rho 0.81; P = 0.0001). CONCLUSION: The present study demonstrates that patients with RE have different voice characteristics compared to HV. In particular, the voice analysis highlighted acoustic parameters that correlated to differing degrees of RE. In addition, spectrogram analysis should be considered for acoustic assessments before and after medical and surgical therapy and also in forensic medicine.

Complex post-traumatic stress disorder (cPTSD) and suicide risk: A multigroup mediation analysis exploring the role of post-traumatic symptomatology on hopelessness.

Complex post-traumatic stress disorder (cPTSD) is a clinical condition that features not only PTSD symptoms, but also disturbances in self-organization. Patients with cPTSD have a higher incidence of psychiatric comorbidities, including suicidality. A key construct tightly related to suicidality is hopelessness, described as a feeling of despair, with a state of mind giving low or negative expectancies regarding one's future. Since there is a paucity of studies investigating the link between cPTSD and hopelessness as a risk factor for suicidality, the aim of this study was to examine the role of post-traumatic symptomatology as the primary driver of suicidality, as measured by hopelessness. 211 patients were enrolled and divided into two groups: PTSD (143 patients) and cPTSD (78 patients). A set of standardized measures was administered to study post-traumatic symptomatology, depression, and hopelessness. The results showed that compared to PTSD, cPTSD patients experienced more severe symptoms in all clinical outcomes (p < 0.001). The mediation analysis revealed a significant positive association between post-traumatic symptomatology and hopelessness in the cPTSD group, which was not significant in the PTSD group. Among PTSD patients, depression mediated 43.37% of the impact of post-traumatic symptomatology on suicidal ideation. Our results contribute to a better understanding of complex post-traumatic symptomatology, further highlighting its role in the pathogenesis of suicidality. Hence, these findings have important clinical implications, suggesting that targeted, trauma-focused interventions might effectively prevent hopelessness and therefore suicide risk in patients with cPTSD.

Acoustic analysis in stuttering: a machine-learning study.

Background: Stuttering is a childhood-onset neurodevelopmental disorder affecting speech fluency. The diagnosis and clinical management of stuttering is currently based on perceptual examination and clinical scales. Standardized techniques for acoustic analysis have prompted promising results for the objective assessment of dysfluency in people with stuttering (PWS). Objective: We assessed objectively and automatically voice in stuttering, through artificial intelligence (i.e., the support vector machine - SVM classifier). We also investigated the age-related changes affecting voice in stutterers, and verified the relevance of specific speech tasks for the objective and automatic assessment of stuttering. Methods: Fifty-three PWS (20 children, 33 younger adults) and 71 age-/gender-matched controls (31 children, 40 younger adults) were recruited. Clinical data were assessed through clinical scales. The voluntary and sustained emission of a vowel and two sentences were recorded through smartphones. Audio samples were analyzed using a dedicated machine-learning algorithm, the SVM to compare PWS and controls, both children and younger adults. The receiver operating characteristic (ROC) curves were calculated for a description of the accuracy, for all comparisons. The likelihood ratio (LR), was calculated for each PWS during all speech tasks, for clinical-instrumental correlations, by using an artificial neural network (ANN). Results: Acoustic analysis based on machine-learning algorithm objectively and automatically discriminated between the overall cohort of PWS and controls with high accuracy (88%). Also, physiologic ageing crucially influenced stuttering as demonstrated by the high accuracy (92%) of machine-learning analysis when classifying children and younger adults PWS. The diagnostic accuracies achieved by machine-learning analysis were comparable for each speech task. The significant clinical-instrumental correlations between LRs and clinical scales supported the biological plausibility of our findings. Conclusion: Acoustic analysis based on artificial intelligence (SVM) represents a reliable tool for the objective and automatic recognition of stuttering and its relationship with physiologic ageing. The accuracy of the automatic classification is high and independent of the speech task. Machine-learning analysis would help clinicians in the objective diagnosis and clinical management of stuttering. The digital collection of audio samples here achieved through smartphones would promote the future application of the technique in a telemedicine context (home environment).

Impact of influenza vaccination on survival of patients with advanced cancer receiving immune checkpoint inhibitors (INVIDIa-2): final results of the multicentre, prospective, observational study.

Background: The prospective multicentre observational INVIDIa-2 study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving immune checkpoint inhibitors (ICI). In this secondary analysis of the original trial, we aimed to assess the outcomes of patients to immunotherapy based on vaccine administration. Methods: The original study enrolled patients with advanced solid tumours receiving ICI at 82 Italian Oncology Units from Oct 1, 2019, to Jan 31, 2020. The trial's primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020, the results of which were reported previously. Secondary endpoints (data cut-off Jan 31, 2022) included the outcomes of patients to immunotherapy based on vaccine administration, for which the final results are reported herein. A propensity score matching by age, sex, performance status, primary tumour site, comorbidities, and smoking habits was planned for the present analysis. Only patients with available data for these variables were included. The outcomes of interest were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease-control rate (DCR). Findings: The original study population consisted of 1188 evaluable patients. After a propensity score matching, 1004 patients were considered (502 vaccinated and 502 unvaccinated), and 986 of them were evaluable for overall survival (OS). At the median follow-up of 20 months, the influenza vaccination demonstrated a favourable impact on the outcome receiving ICI in terms of median OS [27.0 months (CI 19.5-34.6) in vaccinated vs. 20.9 months (16.6-25.2) in unvaccinated, p = 0.003], median progression-free survival [12.5 months (CI 10.4-14.6) vs. 9.6 months (CI 7.9-11.4), p = 0.049], and disease-control rate (74.7% vs. 66.5%, p = 0.005). The multivariable analyses confirmed the favourable impact of influenza vaccination in terms of OS (HR 0.75, 95% C.I. 0.62-0.92; p = 0.005) and DCR (OR 1.47, 95% C.I. 1.11-1.96; p = 0.007). Interpretation: The INVIDIa-2 study results suggest a favourable immunological impact of influenza vaccination on the outcome of cancer patients receiving ICI immunotherapy, further encouraging the vaccine recommendation in this population and supporting translational investigations about the possible synergy between antiviral and antitumour immunity. Funding: The Federation of Italian Cooperative Oncology Groups (FICOG), Roche S.p.A., and Seqirus.

Is there a Link between Non Melanoma Skin Cancer and Hydrochlorothiazide?

AIMS: Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BACKGROUND: Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability. OBJECTIVE: To evaluate the statistically significant difference (P<0.05) in the development of NMSC between HCTZ users and non-users and the correlation (P<0.05) between HCTZ use and NMSC. METHODS: We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression. RESULTS: We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC. CONCLUSION: In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.

Multicenter Observational Study on Metastatic Non-Small Cell Lung Cancer Harboring BRAF Mutations: Focus on Clinical Characteristics and Treatment Outcome of V600E and Non-V600E Subgroups.

INTRODUCTION: BRAF mutation involved 2-4% of lung adenocarcinoma. Differences in clinicopathologic features and patient outcome exist between V600E and non-V600E BRAF mutated NSCLC. Thus, we sought to assess the frequency and clinical relevance of BRAF mutations in a real-life population of advanced-NSCLC, investigating the potential prognostic significance of distinct genetic alterations. MATERIALS AND METHODS: The present multicenter Italian retrospective study involved advanced BRAF mutant NSCLC. Complete clinicopathologic data were evaluated for BRAF V600E and non-V600E patients. RESULTS: A total of 44 BRAFmut NSCLC patients were included (V600E, n = 23; non-V600E, n = 21). No significant differences in survival outcome and treatment response were documented, according to V600E vs. non-V600E mutations, although a trend towards prolonged PFS was observed in the V600E subgroup (median PFS = 11.3 vs. 6.0 months in non-V600E). In the overall population, ECOG PS and age significantly impacted on OS, while bone lesions were associated with shorter PFS. Compared to immunotherapy, first-line chemotherapy was associated with longer OS in the overall population, and especially in the BRAF V600E subtype. CONCLUSIONS: Here, we report on real-life data from a retrospective cohort of advanced-NSCLC harboring BRAF alterations. Our study offers relevant clues on survival outcome, therapeutic response, and clinicopathologic correlations of BRAF-mutant NSCLC.