Protease inhibitors-based therapy induces acquired spherocytic-like anemia and ineffective erythropoiesis in chronic HCV patients

Background & Aims: The addition of protease inhibitors, boceprevir (BOC)or telaprevir (TRV), to peg-interferon and ribavirin (PR) increases the incidenceof anaemia in patients with chronic hepatitis C virus (HCV) infection.Although genetic variants in inosine triphosphatase (ITPA) gene have beenlinked to the haemolytic anaemia induced by PR, the mechanism sustainingsevere anaemia during triple therapy is still unknown. This study aims to elucidatethe molecular mechanisms underlying anaemia in chronic HCVpatients with combined therapy. Methods: We studied 59 patients withchronic HCV genotype-1: 29 treated with TRV/PR and 30 with BOC/PR. Weevaluated biochemical and haematological parameters, red cell index at baseline,4, 12, 16 and 24 weeks of treatment; in a subgroup, we performed functionalstudies: osmotic fragility, red cell membrane protein separation, massspectrometry analysis, quantification of erythroid microparticles release.IL28B and ITPA polymorphisms were also evaluated. Results: We foundearly acute normochromic normocytic haemolytic anaemia (4\u20138 weeks) followedby a late macrocytic hypo-regenerative anaemia with inappropriatelow reticulocyte count (12\u201324 weeks). Studies on red cells revealed: (i) presenceof spherocytes; (ii) increased osmotic fragility; (iii) abnormalities in redcell membrane protein composition; (iv) reduced membrane-cytoskeletonstability; (v) increased release of erythroid microparticles. ITPA polymorphismsimpacted only the early phase of anaemia. Conclusions: The bimodalpattern of anaemia in chronic HCV patients on triple therapy might bebecause of acquired spherocytic-like anaemia in the early phase, followed byhyporegenerative anaemia, most likely related to the combined effects of PRand TRV or BOC on erythropoiesis

Olfactory and Gustatory Outcomes in COVID-19: A Prospective Evaluation in Nonhospitalized Subjects

Objective: To prospectively assess the rate and timing of recovery of olfactory (OD) and gustatory (GD) dysfunction in patients affected by COVID-19. Study Design: Cohort study. Setting: Population-based evaluation in a COVID-19 high-prevalence region. Subjects and Methods: We analyzed the clinical course of OD and GD in a cohort of home-quarantined SARS-CoV-2–positive patients from Northern Italy. Physicians administered a survey-based questionnaire at recruitment (T0). During follow-up, patients responded to online dedicated surveys modulated according to symptoms at T0. Results: A total of 151 patients completed the follow-up survey. OD and/or GD were observed in 83% and 89% of subjects, respectively. Resolution rates of OD and GD at 30 days from onset were 87% and 82%, respectively. Risk factors for late resolution were grade of dysfunction at onset (total vs partial), gender, and presence of nasal congestion. Three (2%) patients previously reporting complete resolution of symptoms complained of subsequent recurrence of OD and/or GD after a mean of 19 days from resolution of the previous episode. Conclusion: COVID-19–related OD and GD had high rate of resolution in the first month from onset of symptoms. However, in 10% to 15% of patients, these symptoms showed only partial improvement after this period

Intestinal type adenocarcinoma of the ethmoid: Outcomes of a treatment regimen based on endoscopic surgery with or without radiotherapy.

Background The objective of this study was to assess survival, prognostic factors, and complications in a cohort of patients with intestinal-type adenocarcinoma (ITAC) treated with transnasal endoscopic surgery (ES) ± radiotherapy [RT]. Methods Patients with ITAC who underwent ES ± RT at two tertiary centers were retrospectively reviewed. Overall (OS) and event-free (EFS) survivals were calculated, and statistically significant variables were entered in a multivariate Cox regression model. Complications were also analyzed. Results One-hundred-sixty-nine patients were included. Major complications occurred in 9.5% of patients. Adjuvant RT was delivered in 58.6% of patients. Five-year OS and EFS were 68.9% and 63.6%, respectively. Advanced pT classification, high grade, and positive surgical margins were independently predictive of poor survival. Conclusions ES ± RT is a valid treatment option in most cases of ITAC. When compared with series based on external surgery, our results support a definitive paradigm shift in the management of ITAC

Protease inhibitors-based therapy induces acquired spherocytic-like anaemia and ineffective erythropoiesis in chronic hepatitis C virus patients.

Abstract BACKGROUND & AIMS: The addition of protease inhibitors, boceprevir (BOC) or telaprevir (TRV), to peg-interferon and ribavirin (PR) increases the incidence of anaemia in patients with chronic hepatitis C virus (HCV) infection. Although genetic variants in inosine triphosphatase (ITPA) gene have been linked to the haemolytic anaemia induced by PR, the mechanism sustaining severe anaemia during triple therapy is still unknown. This study aims to elucidate the molecular mechanisms underlying anaemia in chronic HCV patients with combined therapy. METHODS: We studied 59 patients with chronic HCV genotype-1: 29 treated with TRV/PR and 30 with BOC/PR. We evaluated biochemical and haematological parameters, red cell index at baseline, 4, 12, 16 and 24 weeks of treatment; in a subgroup, we performed functional studies: osmotic fragility, red cell membrane protein separation, mass spectrometry analysis, quantification of erythroid microparticles release. IL28B and ITPA polymorphisms were also evaluated. RESULTS: We found early acute normochromic normocytic haemolytic anaemia (4-8 weeks) followed by a late macrocytic hypo-regenerative anaemia with inappropriate low reticulocyte count (12-24 weeks). Studies on red cells revealed: (i) presence of spherocytes; (ii) increased osmotic fragility; (iii) abnormalities in red cell membrane protein composition; (iv) reduced membrane-cytoskeleton stability; (v) increased release of erythroid microparticles. ITPA polymorphisms impacted only the early phase of anaemia. CONCLUSIONS: The bimodal pattern of anaemia in chronic HCV patients on triple therapy might be because of acquired spherocytic-like anaemia in the early phase, followed by hyporegenerative anaemia, most likely related to the combined effects of PR and TRV or BOC on erythropoiesis

The impact of nodal status in major salivary gland carcinoma: A multicenter experience and proposal of a novel N-classification

Objectives: Despite differences in oncological behavior, the 8th edition of AJCC TNM staging currently proposes the same N-classification for major salivary glands (MSG) carcinoma and squamous cell carcinoma of the upper aerodigestive tract. The present study aims to investigate a more reliable definition of N-categories for MSG carcinoma. Materials and methods: A retrospective multicenter study was performed, including 307 patients treated for primary MSG carcinoma from 1995 to 2019. Outcome measures included overall survival (OS), disease specific survival, and local, regional, and distant recurrence. Survival analysis was performed using log-rank test and Cox proportional-hazards model. Overall number (ON) and largest diameter (LD) of nodal metastases, including intra-parotid metastases, were considered to develop three novel proposals of N-classification; their performance were compared with the current TNM staging using Akaike information criterion (AIC), Bayesian information criterion (BIC), and Nagelkerke pseudo-R2. Results: Intra-parotid nodes, ON and LD of nodal metastases emerged as major prognosticators for OS, while extra-nodal extension did not impact on any survival. The current N-classification did not show a satisfactory OS stratification. Three novel N-classifications were developed according to number of metastatic nodes (0 vs 1\u20133 vs 65 4) and/or their maximum diameter (<20 mm vs 65 20 mm). They all showed better accuracy in OS stratification, and achieved better AIC, BIC and Nagelkerke pseudo-R2 indices when compared to current N-classification. Conclusion: All the proposed N-classifications improved OS stratification and could help in defining a specific N-classification for MSG carcinoma. Their validation and assessment in an external cohort is needed

Salvage surgery in recurrent sinonasal cancers: Proposal for a prognostic model based on clinicopathologic and treatment-related parameters

Background: Evidence on survival and major prognosticators after salvage surgery in recurrent sinonasal cancers (SNC) is limited. Methods: A retrospective, single-center study of recurrent SNC treated with salvage surgery between 1997 and 2019 was conducted. Univariate and multivariable analyses were performed to define a prognostic score for overall survival (OS). Results: One hundred and eighteen patients were included. Recurrent SNC originated mostly in the naso-ethmoidal box (67.8%) and were mainly epithelial (76.2%), high-grade (49.2%), and locally advanced (rpT4, 60.1%) malignancies. Negative margins were achieved in 56.6% of cases. Two- and 5-year OS were 71.7% and 56%, respectively. The prognostic model included treatment modality for primary tumor, histology, rpT class, margin status, perineural invasion, and adjuvant radiotherapy and stratified patients into three prognostic groups (5-year OS: 84.4%, 44.9%, and 0%, respectively). Conclusions: Treatment of recurrent SNC can result in good long-term survival estimates with limited morbidity. Our score can provide excellent prognostic stratification

Survival in HIV-Infected Patients after a Cancer Diagnosis in the cART Era: Results of an Italian Multicenter Study.

OBJECTIVES: We studied survival and associated risk factors in an Italian nationwide cohort of HIV-infected individuals after an AIDS-defining cancer (ADC) or non-AIDS-defining cancer (NADC) diagnosis in the modern cART era. METHODS: Multi-center, retrospective, observational study of HIV patients included in the MASTER Italian Cohort with a cancer diagnosis from January 1998 to September 2012. Malignancies were divided into ADC or NADC on the basis of the Centre for Disease Control-1993 classification. Recurrence of cancer and metastases were excluded. Survivals were estimated according to the Kaplan-Meier method and compared according to the log-rank test. Statistically significant variables at univariate analysis were entered in a multivariate Cox regression model. RESULTS: Eight hundred and sixty-six cancer diagnoses were recorded among 13,388 subjects in the MASTER Database after 1998: 435 (51%) were ADCs and 431 (49%) were NADCs. Survival was more favorable after an ADC diagnosis than a NADC diagnosis (10-year survival: 62.7%±2.9% vs. 46%±4.2%; p = 0.017). Non-Hodgkin lymphoma had lower survival rates than patients with Kaposi sarcoma or cervical cancer (10-year survival: 48.2%±4.3% vs. 72.8%±4.0% vs. 78.5%±9.9%; p<0.001). Regarding NADCs, breast cancer showed better survival (10-year survival: 65.1%±14%) than lung cancer (1-year survival: 28%±8.7%), liver cancer (5-year survival: 31.9%±6.4%) or Hodgkin lymphoma (10-year survival: 24.8%±11.2%). Lower CD4+ count and intravenous drug use were significantly associated with decreased survival after ADCs or NADCs diagnosis. Exposure to cART was found to be associated with prolonged survival only in the case of ADCs. CONCLUSIONS: cART has improved survival in patients with an ADC diagnosis, whereas the prognosis after a diagnosis of NADCs is poor. Low CD4+ counts and intravenous drug use are risk factors for survival following a diagnosis of ADCs and Hodgkin lymphoma in the NADC groupObjectives: We studied survival and associated risk factors in an Italian nationwide cohort of HIV-infected individuals after an AIDS-defining cancer (ADC) or non-AIDS-defining cancer (NADC) diagnosis in the modern cART era. Methods: Multi-center, retrospective, observational study of HIV patients included in the MASTER Italian Cohort with a cancer diagnosis from January 1998 to September 2012. Malignancies were divided into ADC or NADC on the basis of the Centre for Disease Control-1993 classification. Recurrence of cancer and metastases were excluded. Survivals were estimated according to the Kaplan-Meier method and compared according to the log-rank test. Statistically significant variables at univariate analysis were entered in a multivariate Cox regression model. Results: Eight hundred and sixty-six cancer diagnoses were recorded among 13,388 subjects in the MASTER Database after 1998: 435 (51%) were ADCs and 431 (49%) were NADCs. Survival was more favorable after an ADC diagnosis than a NADC diagnosis (10-year survival: 62.7%±2.9% vs. 46%±4.2%; p = 0.017). Non-Hodgkin lymphoma had lower survival rates than patients with Kaposi sarcoma or cervical cancer (10-year survival: 48.2%±4.3% vs. 72.8%±4.0% vs. 78.5%±9.9%; p<0.001). Regarding NADCs, breast cancer showed better survival (10-year survival: 65.1%±14%) than lung cancer (1-year survival: 28%±8.7%), liver cancer (5-year survival: 31.9%±6.4%) or Hodgkin lymphoma (10-year survival: 24.8%±11.2%). Lower CD4+ count and intravenous drug use were significantly associated with decreased survival after ADCs or NADCs diagnosis. Exposure to cART was found to be associated with prolonged survival only in the case of ADCs. Conclusions: cART has improved survival in patients with an ADC diagnosis, whereas the prognosis after a diagnosis of NADCs is poor. Low CD4+ counts and intravenous drug use are risk factors for survival following a diagnosis of ADCs and Hodgkin lymphoma in the NADC group. © 2014 Gotti et al