Hepatitis C and Cigarette Smoking Behavior: Themes From Focus Groups.

INTRODUCTION: People with chronic hepatitis C virus (HCV; PWHC) use cigarettes at a much higher prevalence than other individuals, and smoking can exacerbate the harms specifically related to HCV (eg, hepatocellular carcinoma). Little is known about factors related to cigarette use among PWHC. AIMS AND METHODS: This study examined focus group data to explore beliefs and behaviors related to cigarette use among PWHC. Qualitative data from two focus groups of PWHC reporting current cigarette smoking (n = 15, 60% male) were collected using a semi-structured interview guide. Participants were asked about reasons for smoking, barriers to quitting smoking, and the relationship of HCV to smoking. Focus groups were transcribed verbatim and coded in NVivo 12. Four coders examined themes that arose in the focus groups. Common themes are described and supported with quotes. RESULTS: Reasons for smoking included addiction to cigarettes, stress, substituting cigarettes for other drugs, and social norms, while reasons for quitting included health and being free from the use of all drugs. Barriers to quitting included concerns about coping with stress, weight gain, and having a lack of support for and education about quitting. Many participants believed there was a link between smoking and HCV and discussed smoking in relation to the stress of an HCV diagnosis. CONCLUSIONS: Participants identified both HCV-related and non-HCV-related aspects of cigarette smoking and cessation-related behaviors that could be targeted in cessation treatment. More research is needed to identify the best treatment approaches that reduce the significant medical consequences of cigarette use among PWHC. IMPLICATIONS: People with chronic hepatitis C virus (HCV; PWHC) smoke cigarettes at a high prevalence, yet little is known about their smoking behaviors. Moreover, there are no cessation treatments targeting PWHC. This is the first study to collect focus group data from PWHC who smoke in order to identify reasons for cigarette use (HCV-related and non-HCV-related), and motivators and barriers to quitting cigarettes. PWHC reports using cigarettes to cope with the stress of an HCV diagnosis and to celebrate HCV cure. These findings suggest there are specific times during the HCV care continuum where providers can aid with cessation efforts.

Changes in Inflammatory Cytokines After Chronic Hepatitis C Treatment Among People Living With HIV.

We aimed to evaluate the effect of hepatitis C virus cure on serum inflammatory markers among people with HIV. Among 127 people with HIV, serum alanine aminotransferase, soluble tumor necrosis factor receptor 1, and inflammatory index score were significantly lower at the 24-week time point in patients who achieved sustained virologic response as compared with those who did not.

Nonadherence to Ledipasvir/Sofosbuvir Did Not Predict Sustained Virologic Response in a Randomized Controlled Trial of Human Immunodeficiency Virus/Hepatitis C Virus Coinfected Persons Who Use Drugs.

BACKGROUND: Eliminating hepatitis C virus (HCV) will require effective treatment delivery to persons with substance use disorders (SUDs). We evaluated the relationship between ledipasvir/sofosbuvir treatment persistence (receiving 84 tablets), adherence, and sustained virologic response (SVR) in persons with human immunodeficiency virus (HIV)/HCV coinfection. METHODS: Of the 144 participants with HIV/HCV and SUDs, 110 initiated a 12-week treatment course under 1 of 3 conditions (usual care, peer mentors, and cash incentives). We used self-report, pharmacy pill counts, and expected date of refill to examine adherence. Persistent participants were categorized as high adherence (taking ≥90% of doses) or low adherence (taking <90% of doses). RESULTS: Most participants persisted on treatment after initiation (n = 105), with 95% (n = 100) achieving SVR. One third (34%) of participants had moderate/heavy alcohol use by the biomarker phosphatidylethanol ([Peth] ≥50 ng/mL), and 44% had urine toxicology positive for cocaine or heroin at enrollment. The proportion of persons with high adherence was 72% (n = 76), and the proportion of persons with low adherence was 28%. Although low adherence was associated with moderate/heavy alcohol use by PEth (relative risk = 2.77; 95% confidence interval, 1.50-5.12), SVR did not vary according to adherence (P = .702), and most participants (97%) with low adherence achieved SVR. CONCLUSIONS: Treatment persistence led to high SVR rates among persons with HIV/HCV, despite imperfect adherence and SUDs.

Breast MRI during Neoadjuvant Chemotherapy: Lack of Background Parenchymal Enhancement Suppression and Inferior Treatment Response.

Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response. Materials and Methods A retrospective review was performed for women with menopausal status data who were treated for breast cancer by one of 10 drug arms (standard NAC with or without experimental agents) between May 2010 and November 2016 in the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2 TRIAL (NCT01042379). Patients underwent MRI at four points: before treatment (T0), early treatment (T1), interregimen (T2), and before surgery (T3). BPE was quantitatively measured by using automated fibroglandular tissue segmentation. To test the hypothesis effectively, a subset of examinations with BPE with high-quality segmentation was selected. BPE change from T0 was defined as suppressed or nonsuppressed for each point. The Fisher exact test and the Z tests of proportions with Yates continuity correction were used to examine the relationship between BPE suppression and pathologic complete response (pCR) in hormone receptor (HR)-positive and HR-negative cohorts. Results A total of 3528 MRI scans from 882 patients (mean age, 48 years ± 10 [standard deviation]) were reviewed and the subset of patients with high-quality BPE segmentation was determined (T1, 433 patients; T2, 396 patients; T3, 380 patients). In the HR-positive cohort, an association between lack of BPE suppression and lower pCR rate was detected at T2 (nonsuppressed vs suppressed, 11.8% [six of 51] vs 28.9% [50 of 173]; difference, 17.1% [95% CI: 4.7, 29.5]; P = .02) and T3 (nonsuppressed vs suppressed, 5.3% [two of 38] vs 27.4% [48 of 175]; difference, 22.2% [95% CI: 10.9, 33.5]; P = .003). In the HR-negative cohort, patients with nonsuppressed BPE had lower estimated pCR rate at all points, but the P values for the association were all greater than .05. Conclusions In hormone receptor-positive breast cancer, lack of background parenchymal enhancement suppression may indicate inferior treatment response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

Predicting breast cancer response to neoadjuvant treatment using multi-feature MRI: results from the I-SPY 2 TRIAL.

Dynamic contrast-enhanced (DCE) MRI provides both morphological and functional information regarding breast tumor response to neoadjuvant chemotherapy (NAC). The purpose of this retrospective study is to test if prediction models combining multiple MRI features outperform models with single features. Four features were quantitatively calculated in each MRI exam: functional tumor volume, longest diameter, sphericity, and contralateral background parenchymal enhancement. Logistic regression analysis was used to study the relationship between MRI variables and pathologic complete response (pCR). Predictive performance was estimated using the area under the receiver operating characteristic curve (AUC). The full cohort was stratified by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status (positive or negative). A total of 384 patients (median age: 49 y/o) were included. Results showed analysis with combined features achieved higher AUCs than analysis with any feature alone. AUCs estimated for the combined versus highest AUCs among single features were 0.81 (95% confidence interval [CI]: 0.76, 0.86) versus 0.79 (95% CI: 0.73, 0.85) in the full cohort, 0.83 (95% CI: 0.77, 0.92) versus 0.73 (95% CI: 0.61, 0.84) in HR-positive/HER2-negative, 0.88 (95% CI: 0.79, 0.97) versus 0.78 (95% CI: 0.63, 0.89) in HR-positive/HER2-positive, 0.83 (95% CI not available) versus 0.75 (95% CI: 0.46, 0.81) in HR-negative/HER2-positive, and 0.82 (95% CI: 0.74, 0.91) versus 0.75 (95% CI: 0.64, 0.83) in triple negatives. Multi-feature MRI analysis improved pCR prediction over analysis of any individual feature that we examined. Additionally, the improvements in prediction were more notable when analysis was conducted according to cancer subtype.

Single hepatocytes show persistence and transcriptional inactivity of hepatitis B.

There is no cure for the more than 270 million people chronically infected with HBV. Nucleos(t)ide analogs (NUCs), the mainstay of anti-HBV treatment, block HBV reverse transcription. NUCs do not eliminate the intranuclear covalently closed circular DNA (cccDNA), from which viral RNAs, including pregenomic RNA (pgRNA), are transcribed. A key gap in designing a cure is understanding how NUCs affect HBV replication and transcription because serum markers yield an incomplete view of intrahepatic HBV. We applied single-cell laser capture microdissection and droplet digital PCR to paired liver biopsies collected from 5 HBV/HIV-coinfected persons who took NUCs over 2-4 years. From biopsy 1 to 2, proportions of HBV-infected hepatocytes declined with adherence to NUC treatment (P < 0.05); we extrapolated that eradication of HBV will take over 10 decades with NUCs in these participants. In individual hepatocytes, pgRNA levels diminished 28- to 73-fold during NUC treatment, corresponding with decreased tissue HBV core antigen staining (P < 0.01). In 4 out of 5 participants, hepatocytes with cccDNA but undetectable pgRNA (transcriptionally inactive) were present, and these were enriched in 3 participants during NUC treatment. Further work to unravel mechanisms of cccDNA transcriptional inactivation may lead to therapies that can achieve this in all hepatocytes, resulting in a functional cure.

Maxillofacial prosthodontics practice profile: a survey of non-United States prosthodontists.

BACKGROUND: This study surveyed non-United States maxillofacial prosthodontists (MFP) to determine their practice profile and rationale for pursuing an MFP career. METHODS: Email addresses for the MFP were obtained from the International Society for Maxillofacial Rehabilitation, American Academy of Maxillofacial Prosthetics, and International Academy for Oral Facial Rehabilitation. Emails with a link to the electronic survey program were sent to each participant. Chi-square and Mann-Whitney-U tests were used to investigate the influence of formal MFP training on professional activities and type of treatments provided. RESULTS: One hundred twelve respondents (response rate 39%) from 33 nationalities returned the survey. The top three reasons for pursuing an MFP career were personal satisfaction, prosthodontics residency exposure, and mentorship. The predominant employment setting was affiliation with a university (77%). There were significant differences between respondents with and without formal MFP training regarding provision of surgical treatments (P = 0.021) and dental oncology (P = 0.017). Most treatments were done together with otolaryngology, oral surgery (68%) and head and neck surgery (61%). Practitioners not affiliated with a university spent significantly more time in clinical practice (P = 0.002), whereas respondents affiliated with universities spent significantly more time in teaching/training (P = 0.008) and funded research (P = 0.015). CONCLUSIONS: Personal satisfaction is the most important factor in a decision to choose an MFP career. Most of the MFPs work at a university and within a multidisciplinary setting. There were differences regarding type of treatments provided by respondents with and without formal MFP training.

Biopsy versus conservative management of sonographically benign-appearing solid breast masses in adolescents.

OBJECTIVES: To determine whether the size of palpable solid breast masses in adolescents at initial sonography and their growth at follow-up sonography could be used to decide between conservative management and tissue biopsy. METHODS: This retrospective study included 37 adolescent female patients with 45 palpable benign-appearing solid breast masses on initial sonography. They were grouped as follows: group I, masses undergoing follow-up sonography with subsequent biopsy (n = 9); group II, masses undergoing biopsy without follow-up sonography (n = 13); and group III, masses undergoing follow-up sonography without biopsy (n = 23). The largest dimension, volume, volume change per month, and change in the sonographic appearance were analyzed to predict the need for biopsy. A combination of a largest dimension greater than 3 cm and volume change per month greater than 16% was used to assess the need for biopsy. Sonograms of 22 masses were correlated with histopathologic diagnoses. RESULTS: None of the masses that underwent follow-up sonography showed changes in their sonographic appearance. All masses that underwent biopsy were benign on histopathologic analysis. There was no significant difference in the largest dimension among the groups at initial sonography or between groups I and III at follow-up sonography. The volume change was smaller for fibroadenomas (n = 7; mean, 22.67%) than benign phyllodes tumors (n = 2; mean, 45.30%) in group I, but the difference was not significant (P = .384). However, the volume change for groups I and III showed a significant difference (P = .026). Neither size greater than 3 cm nor volume change greater than 16% predicted pathologic outcomes. CONCLUSIONS: If the combined criteria for assessing benignity of palpable breast masses had been used, biopsy could have been reduced by 89% in group I and deemed not necessary in 96% of group III breast masses.

A bioactive probe for glutathione-dependent antioxidant capacity in breast cancer patients: implications in measuring biological effects of arsenic compounds.

INTRODUCTION: Glutathione, a major cellular non-protein thiol (NPSH), serves a central role in repairing damage induced by cancer drugs, pollutants and radiation and in the detoxification of several cancer chemotherapeutic drugs and toxins. Current methods measure glutathione levels only, which require cellular extraction, rather than the glutathione recycling dependent antioxidant activity in intact cells. Here, we present a novel method using a bioactive probe of the oxidative pentose phosphate cycle, termed the OxPhos™ test, to quantify glutathione recycling dependent antioxidant activity in whole blood and intact human and rodent cells without the need for the isolation and cytoplasm extraction of cells. METHODS: OxPhos™ test kit (Rockland Immunochemicals, USA), which uses hydroxyethyldisulfide (HEDS) as a probe for the oxidative pentose phosphate cycle, was used in these studies. The results with OxPhos™ test kit in human blood and intact cells were compared with total thiol and high pressure liquid chromatography/electrochemical detection of HEDS metabolism. RESULTS: The OxPhos™ test measured glutathione-dependent antioxidant activity both in intact human and rodent cells and breast cancer patient's blood with a better correlation coefficient and biological variability than the thiol assay. Additionally, human blood and mammalian cells treated with various arsenicals showed a concentration-dependent decrease in activity. DISCUSSION: The results demonstrate the application of this test for measuring the antioxidant capacity of blood and the effects of environmental pollutants/toxins. It opens up new avenues for an easy and reliable assessment of glutathione-dependent antioxidant capacity in various diseases such as stroke, blood borne diseases, infection, cardiovascular disease and other oxidative stress related diseases and as a prognostic indicator of chemotherapy response and toxicity. The use of this approach in pharmacology/toxicology including screening drugs that improve the glutathione-dependent antioxidant capacity and not just the glutathione level is clinically relevant since mammalian cells require glutathione dependent pathways for antioxidant activity.

A bioactive probe of the oxidative pentose phosphate cycle: novel strategy to reverse radioresistance in glucose deprived human colon cancer cells.

The specific effects of glucose deprivation on oxidative pentose phosphate cycle (OPPC) function, thiol homeostasis, protein function and cell survival remain unclear due to lack of a glucose-sensitive chemical probe. Using p53 wild type and mutant human colon cells, we determined the effects of hydroxyethyl disulfide (HEDS) on NADPH, GSH, GSSG, total glutathione, total non-protein and protein thiol levels, the function of the DNA repair protein Ku, and the susceptibility to radiation-induced free radicals under normal glucose or glucose-deprived conditions. HEDS is rapidly detoxified in normal glucose but triggered a p53-independent metabolic stress in glucose depleted state that caused loss of NADPH, protein and non-protein thiol homeostasis and Ku function, and enhanced sensitivity of both p53 wild type and mutant cells to radiation induced oxidative stress. Additionally, high concentration of HEDS alone induced cell death in p53 wild type cells without significant effect on p53 mutant cells. HEDS offers a useful tool to gain insights into how glucose metabolism affects OPPC dependent stress-induced cellular functions and injury, including in tumor cells, where our findings imply a novel therapeutic approach to target glucose deprived tumor. Our work introduces a novel probe to address cancer metabolism and ischemic pathology.

Hydroxyethyl disulfide as an efficient metabolic assay for cell viability in vitro.

Cell viability assays have a variety of well known practical and technical limitations. All the available approaches have disadvantages, such as non-linearity, high background and cumbersome protocols. Several commonly used tetrazolium chemicals rely upon generation of a colored formazan product formed by mitochondrial reduction of these compounds via phenazine methosulfate (PMS). However, sensitivity is inherently limited because their reduction relies on mitochondrial bioreduction and cellular transport of PMS, as well as accessibility to tetrazolium chemicals. In this study, we identify hydroxethyldisulfide (HEDS) as an inexpensive probe that can measure cellular metabolic activity without the need of PMS. In tissue culture medium, HEDS accurately quantitated metabolically active live cells in a linear manner superior to tetrazolium based and other assays. Cell toxicity produced by chemotherapeutics (cisplatin, etoposide), oxidants (hydrogen peroxide, acetaminophen), toxins (phenyl arsine oxide, arsenite) or ionizing radiation was rapidly determined by the HEDS assay. We found that HEDS was superior to other commonly used assays for cell viability determinations in its solubility, membrane permeability, and intracellular conversion to a metabolic reporter that is readily transported into the extracellular medium. Our findings establish the use of HEDS in a simple, rapid and low cost assay to accurately quantify viable cells.

Glucose deprivation increases nuclear DNA repair protein Ku and resistance to radiation induced oxidative stress in human cancer cells.

Recent studies have indicated that nutrient deprivation particularly glucose may play a major role in tumor cell tolerance to a generally oxidative stress environment in solid tumors. Here, we studied the impact of glucose deprivation on the response of human colon (HT29) and prostate (DU145) cancer cells to gamma radiation. A significant decrease in intracellular glucose level was observed in glucose deprived cells as measured by bioreductive assay. The survival of HT29 and DU145 were increased by 30 and 100% respectively when these cells were exposed to gamma radiation in the absence of glucose compared to that in the presence of glucose. In glucose depleted medium, glutathione (GSH), a free radical scavenger, content remained the same, and showed no correlation with the radiation resistance induced by glucose deprivation. Glucose regulated protein78 (GRP78), a stress response survival protein, was not significantly increased in cells deprived of glucose for 4 h compared to those cells in glucose. DNA repair protein Ku, which is known to play a major role in cellular resistance to radiation, was significantly increased in glucose deprived cancer cells that showed enhanced radiation resistance. These results have demonstrated, for the first time, that glucose deprivation mediated stress increased the expression of nuclear Ku and resistance to radiation induced oxidative stress in human cancer cells. The additional resistance caused by glucose deprivation in cancer cells has clinical significance since solid tumors are known to have low level of glucose due to diffusion limited blood supply and higher metabolic activity.

Malignant-appearing microcalcifications at the lumpectomy site with the use of FloSeal hemostatic sealant.

OBJECTIVE: The aim of this article is to describe the benign mammographic calcifications that occur at the lumpectomy site after the use of a topical hemostatic sealant (FloSeal Matrix Hemostatic Sealant). These calcifications can have an appearance similar to that of recurrent carcinoma. CONCLUSION: Application of FloSeal hemostatic sealant in the lumpectomy cavity results in benign mammographic microcalcifications that could be misinterpreted as malignant.

Role of breast sonography in imaging of adolescents with palpable solid breast masses.

OBJECTIVE: The purpose of this study was to assess the role of sonography in the diagnosis and management of palpable solid breast masses in adolescents and to correlate the sonographic findings with the histopathologic findings and clinical outcome. MATERIALS AND METHODS: A retrospective study was conducted with the breast sonograms of 20 adolescent girls 13-19 years old who presented with palpable breast masses found to be solid at breast sonography. The Stavros sonographic criteria were used to assess the benignity or malignancy of solid breast masses. All sonographic findings were correlated with histopathologic or clinical follow-up findings. RESULTS: Sonography showed 21 solid masses in 20 patients (one patient had bilateral solid breast masses). All but six solid masses were presumed benign according to the Stavros sonographic criteria. All solid masses were proved benign at histopathologic or clinical follow-up examination. CONCLUSION: Sonography was not useful for predicting the histologic diagnosis of all solid benign breast masses in adolescent patients. The Stavros sonographic criteria, however, were useful for predicting benignity in 65% of the breast masses on which histopathologic examination was performed. Tissue biopsy may be performed on solid breast masses that do not meet the criteria for benign masses according to the Stavros sonographic criteria.

Sonographic appearance of ruptured ovarian cyst in the neonatal period.

Rupture is a rare complication of ovarian cysts diagnosed during the prenatal period. We present a case that focuses on the postnatal sonographic appearance of rupture of an ovarian cyst after vaginal delivery. Histopathologic correlation is provided. The main sonographic features include complicated ascites and a collapsed cystic structure in the abdomen. Ruptured ovarian cyst should be included in the differential diagnosis of unexplained ascites in a newborn girl.

Economic profiling of physician specialists: use of outlier treatment and episode attribution rules.

This paper examines the influence of episode attribution methodology and cost outlier methodology on the accuracy of physicians' economic profiles. Four years of claims data from a mixed model HMO were processed using the leading episode grouper software. Episode grouped results then were applied to construct input distributions for a simulation model. For each of four specialties (cardiology, family practice, general surgery, and neurology), we employed sets of 18 simulations to investigate the effects of three alternative episode attribution methodologies and six alternative cost outlier methodologies on sensitivity, specificity, and positive predictive error in classifying cost-efficient and cost-inefficient physicians. For identification of cost-efficient physicians, the most accurate profiling results were obtained when Winsorizing outliers at 2% and 98% of episode-type cost distributions, and attributing responsibility for episode costs to physicians who accounted for at least 30% of associated professional and prescribing fees. No consistent combination of outlier methodology and episode attribution rule was found to be superior for identifying cost-inefficient physicians.