CD8 T cells play a major role in antiviral immune responses. Their importance for progression to chronic hepatitis C and response to treatment are still unclear. To address these issues, hepatitis C virus (HCV)-specific CD8 T-cell responses were monitored, at the single-cell level, using HLA class I pentamers specific for HCV core and HCV NS3 epitopes, in 23 chronically infected patients during treatment with pegylated alpha interferon and ribavirin. Patients who presented a sustained-response to therapy had stronger HCV-specific CD8 T-cell responses at all time points studied. Moreover, there were clear differences in the phenotypes of these cells during therapy: in responder patients, terminally differentiated effector cells increased more rapidly, and their frequency was always higher than in nonresponder patients. Sustained-responder patients also showed a higher frequency of HCV-specific CD8 T cells producing cytotoxic factors. Overall, a late and inefficient differentiation process of HCV-specific CD8 T cells might be associated with lack of response to treatment. A better knowledge of the mechanisms underlying this impairment may be important for the development of new therapeutic strategies to maintain, restore, or increase CD8 T-cell effectiveness in chronic HCV infection.

No abstract

To compare a physically active lifestyle or structured exercise program to physically inactive lifestyle or control groups on telomere length (TL). Method: We searched PubMed, EMBASE, Cochrane Library, and Open Gray databases up to March 31, 2020. We calculated standardized mean differences (SMD) with 95% confidence intervals (CI) of TL comparing physically active to physically inactive individuals and exercise intervention to control groups. Risk of bias was judged using the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS) for physical activity (PA) studies and the Cochrane risk-of-bias (RoB2) for exercise intervention studies. Certainty of evidence was judged using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results:We included 30 studies (24 assessing the effects of PA and 6 assessing the effects of exercise interventions) comprising 7418 individuals. Physically active individuals had longer telomeres (SMD = 0.70, 95% CI 0.12-1.28, verylow certainty), especially in middle-aged individuals (SMD = 0.90, 95% CI 0.08-1.72, very-low certainty) and when considering only athletes (SMD = 0.54, 95% CI 0.18-0.90, very-low certainty). Trim-and-fill analyses revealed that most of See related Editorial by Pignolo et al. in this issue.

Mucormycosis is an emergent and threatening invasive fungal invasion underdiagnosed by clinicians due to lack of awareness and aspecific clinical picture. The authors describe a clinical case of a diabetic and cirrhotic patient who developed rhino-orbital-cerebral and pulmonary mucormycosis, non-responsive to treatment. Typical gaps in the management of this deadly disease are addressed. There is a strong need for novel therapies and an expectation that sponsors will recognize the critical need for randomized clinical trials.

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Objective: To evaluate if patient-derived organoids (PDOs) may predict response to neoadjuvant (NAT) chemotherapy in patients with pancreatic adenocarcinoma. Background: PDOs have been explored as a biomarker of therapy response and for personalized therapeutics in patients with pancreatic cancer. Methods: During 2017–2021, patients were enrolled into an IRB-approved protocol and PDO cultures were established. PDOs of interest were analyzed through a translational pipeline incorporating molecular profiling and drug sensitivity testing. Results: One hundred thirty-six samples, including both surgical resections and fine needle aspiration/biopsy from 117 patients with pancreatic cancer were collected. This biobank included diversity in stage, sex, age, and race, with minority populations representing 1/3 of collected cases (16% Black, 9% Asian, 7% Hispanic/Latino). Among surgical specimens, PDO generation was successful in 71% (15 of 21) of patients who had received NAT prior to sample collection and in 76% (39 of 51) of patients who were untreated with chemotherapy or radiation at the time of collection. Pathological response to NAT correlated with PDO chemotherapy response, particularly oxaliplatin. We demonstrated the feasibility of a rapid PDO drug screen and generated data within 7 days of tissue resection. Conclusion: Herein we report a large single-institution organoid biobank, including ethnic minority samples. The ability to establish PDOs from chemotherapy-naive and post-NAT tissue enables longitudinal PDO generation to assess dynamic chemotherapy sensitivity profiling. PDOs can be rapidly screened and further development of rapid screening may aid in the initial stratification of patients to the most active NAT regimen.

Screening mammography is associated with decreased stage at diagnosis and receipt of less-extensive treatment. This was evident in all groups, including the 40-49 years age group, where controversy exists on whether screening is even necessary.

Conflicting data in the literature concern possible differences in the immunochemical measurement of cardiac troponins, either in plasma or in serum. In order to address this specific point, 96 serum and heparin-plasma pairs were obtained for cardiac marker measurement [cardiac troponin T (cTnT); myoglobin (Myo) and creatine kinase-MB isoenzyme (CK-MB)]; 29 additional "common" analytes were measured in 77 such samples. The cardiac markers were measured by electrochemiluminescence (Elecsys 2010, Roche); the other analytes by established automated methods (Modular, Roche). Mean plasma/serum ratios for cTnT (0.95), creatine kinase-MB (1.01) and myoglobin (0.99) were comparable with those of the 29 common analytes (interval of means 0.83-1.05). The distribution of the plasma-serum differences also showed similarities between cardiac markers and other analytes. A few outlier plasma-serum differences (3-5%) were measured for both categories of analytes. Addition of heparin to serum (51 samples) caused decreased cTnT (mean ratio 0.92). In 3 of 51 such samples the cTnT decrease was more marked, but in a second sample from the same subjects (1 week later) such a prominent, heparin-induced loss of cTnT no longer appeared. In conclusion, plasma-serum differences in immuno-reactive cTnT compare with those observed for other analytes. In occasional heparin-plasma samples immunochemical measurement of cTnT may give exceptionally low values. However, in our sample group of 96 patients (cTnT lower or higher than the cut-off in, respectively, 24 and 72 patients), no misclassification occurred if plasma instead of serum cTnT values were considered.