Late-Onset Exudative Pleural Effusions Without Concomitant Airway Obstruction or Lung Parenchymal Abnormalities: A Novel Presentation of Chronic Lung Allograft Dysfunction.

Restrictive allograft syndrome (RAS) is an aggressive variant of CLAD characterized by progressive restrictive ventilatory decline and persistent pleuro-parenchymal changes that can be seen on chest CT. We identified four lung transplant recipients with a progressive restrictive ventilatory defect due to lymphocyte-predominant exudative pleural effusions, but no pleuro-parenchymal abnormalities typical of RAS. Using molecular analysis, we also found increased levels of previously described immune markers of RAS, including NFkB, 20S proteasome, lipocalin, TNFα, and TGFß, within the circulating small extracellular vesicles of the remaining living lung transplant recipient. Despite the absence of lung parenchymal changes, these patients had a poor prognosis with rapid deterioration in allograft function and no response to pleural-based interventions such as thoracentesis, decortication, and pleurodesis. We hypothesize that these cases represent a distinct CLAD phenotype characterized by progressive restriction due to pleural inflammation, lymphocyte-predominant pleural effusion, resultant compressive atelectasis, and eventual respiratory failure in the absence of lung parenchymal involvement.

Impact of Blood Sampling Methods on Blood Loss and Transfusion After Pediatric Cardiac Surgery: An Observational Study.

OBJECTIVES: The aims of this study were to assess the impact of the closed-loop sampling method on blood loss and the need for blood transfusion in pediatric patients following cardiac surgery. DESIGN: Retrospective observational study. SETTING: A single tertiary center. PARTICIPANTS: All pediatric patients younger than 4 years old who were admitted to the pediatric intensive care unit (PICU) after cardiac surgery were enrolled. The study included 100 pediatric patients in the conservative (postimplementation) group and 43 pediatric patients in the nonconservative group (preimplementation). INTERVENTIONS: Observational. MEASUREMENTS: The primary outcome was the volume of blood loss during the PICU follow-up period. The secondary outcomes were the requirement for blood transfusion in each group, duration of mechanical ventilation, length of intensive care unit (ICU) stay, length of hospital stay, and mortality. MAIN RESULTS: In the conservative (postimplementation) group, blood loss during the follow-up period was 0.67 (0.33-1.16) mL/kg/d, while it was 0.95 (0.50-2.30) mL/kg/d in the nonconservative (preimplementation) group, demonstrating a significant reduction in blood loss in the conservative group (p = 0.012). The groups showed no significant differences in terms of the required blood transfusion volume postoperatively during the first 24 hours, first 48 hours, or after 48 hours (p = 0.061, 0.536, 0.442, respectively). The frequency of blood transfusion was comparable between the groups during the first 24 hours, first 48 hours, or after 48 hours postoperatively (p = 0.277, 0.639, 0.075, respectively). In addition, the groups did not show significant differences in the duration of mechanical ventilation, length of ICU stay, length of hospital stay, or mortality. CONCLUSIONS: The closed-loop sampling method can be efficient in decreasing blood loss during postoperative PICU follow-up for pediatric patients after cardiac surgeries. However, its application did not reduce the frequency or the volume of blood transfusion in these patients.

Reproducibility of MRI Diagnosis of Female Genital Anomalies.

Purpose: To assess and compare intrareader and interreader reproducibility of magnetic resonance imaging (MRI) diagnosis of female genital anomalies (FGAs) using the American Society for Reproductive Medicine-Mullerian anomalies classification 2021 (ASRM-MAC 2021) and European Society of Human Reproduction and Embryology-European Society for Gynecological Endoscopy (ESHRE-ESGE) 2016 classification. Methods: In this retrospective study, we searched our electronic MRI database from April 2021 to September 2023, selecting MRI studies with FGAs. Seventy-six consecutive studies were included and reviewed by 4 independent radiologists using both classifications. Studies were re-evaluated after 1 month. Reproducibility was assessed using kappa (κ) scores with 95% confidence intervals (CI). Results: Intrareader agreement for MRI diagnosis of FGAs was substantial to excellent, with κ scores ranging from 0.684 (95% CI, 0.534-0.834) to 0.985 (95% CI, 0.963-1.01) using the ASRM-MAC 2021 and from 0.743 (95% CI, 0.621-0.865) to 0.846 (95% CI, 0.719-0.973) using the ESHRE-ESGE 2016 classification. Pairwise interreader agreement was higher with the ASRM-MAC 2021, ranging from moderate (κ = 0.491; 95% CI, 0.341-0.642) to substantial (κ = 0.709; 95% CI, 0.597-0.821), compared to the ESHRE-ESGE 2016 classification, with weak (κ = 0.080; 95% CI, 0.068-0.228) to moderate (κ = 0.511; 95% CI, 0.344-0.678) agreement. Overall interreader agreement was moderate for both classifications (κ = 0.599; 95% CI, 0.562-0.638 for ASRM-MAC 2021 and κ = 0.429; 95% CI, 0.396-0.463 for ESHRE-ESGE 2016 classification), but with significant differences (non-overlapping CIs). Conclusion: The intrareader reproducibility was high for both classifications, whereas the interreader reproducibility was higher using the ASRM-MAC 2021, highlighting the impact of classification criteria on the reproducibility of MRI diagnosis of FGAs.

Effects of obstructive sleep apnea on non-alcoholic fatty liver disease in patients with obesity: a systematic review.

INTRODUCTION: Obesity has been linked to non-alcoholic fatty liver disease (NAFLD), a widespread chronic liver ailment, as well as obstructive sleep apnea (OSA). The development of NAFLD is influenced by repeated intermittent hypoxia, a feature of OSA. METHODS: This systematic review (SR) investigated CENTRAL, PubMed, and EMBASE databases. The endpoint of this SR was to assess which OSA-related indicators could predict the presence of NAFLD and the effect of bariatric metabolic surgery (BMS) on improving OSA and NAFLD over time. RESULTS: Compared to previous SRs published in 2013, 14 new publications were added to our SR, alongside studies conducted prior to 2013. The SR ultimately included 28 studies (18 cross-sectional and 10 cohort trials). In the majority of studies, significant correlations were observed between OSA, OSA-related outcomes, and NAFLD. However, the apnea-hypopnea index (AHI) alone proved to be an inadequate predictor of NAFLD. Instead, respiratory and metabolic changes were found to alleviate oxidative stress induced by hypoxemia. Six studies involved patients who underwent BMS, with one evaluating patients before and after BMS, revealing associations between increased OSA and NAFLD improvement following BMS. Six months after surgery, 100% of patients in the mild-to-moderate OSA group were free from fatty liver, and an 89% reduction was observed in the severe OSA group. CONCLUSION: For the first time, BMS has been tested in treating both OSA and NAFLD pre and postoperative with positive results. Further research, ideally with histological and functional data, is needed to confirm these findings. The SR identified 14 distinct liver outcome tests; however, high heterogeneity and incomplete data precluded a meta-analysis. It is imperative to pay greater attention to the influence of OSA-related factors and uniformity in liver outcomes testing concerning NAFLD. To accomplish this, study designs should be enhanced by incorporating more comprehensive pre- and postoperative evaluations, extending follow-up periods, and employing a more consistent methodology for liver diagnosis in patients with obesity.

The Use of Indocyanine Green and Near-Infrared Fluorescence Imaging Versus Blue Dye in Sentinel Lymph Node Biopsy in Cutaneous Melanoma: A Retrospective, Cohort Study.

BACKGROUND: The use of indocyanine green (ICG) and near-infrared fluorescence imaging is a promising option for sentinel lymph node (SLN) mapping in cutaneous melanoma. The study objective was to compare the performance of ICG and blue dye at detecting SLNs with radioisotope nanocolloid (technetium-99). METHODS: Between April 2018 and June 2022, 293 consecutive patients with cutaneous melanoma (Breslow thickness ≥ 0.8 mm) underwent wide local excision and SLN biopsy. Patients were divided into group A (ICG; n = 122) and group B (blue dye; n = 163). All patients underwent SPECT/CT imaging preoperatively. SLN detection parameters and complications were compared between the groups. RESULTS: A total of 285 patients had complete data and were included in the analysis. The median age was 62.0 (range 10-91) years, and 139 (48.8%) were female patients. The mean Breslow thickness was 2.6 mm, 89 (31.2%) patients had ulceration, and 179 (62.8%) patients had mitosis ≥ 1 mm2. The mean number of SLNs detected per patient in group A was 1.58 and group B was 1.48. In groups A and B, the SLN detection rate was 96.7% versus 89.6% (p = 0.022) and the pathological SLN detection rate was 92.3% versus 97.1% (p = 0.481), respectively. CONCLUSIONS: ICG had a higher SLN detection rate and equal pathological SLN detection rate to blue dye. ICG may not be inferior to blue dye and is a useful adjunct to radioisotope in SLN biopsy in cutaneous melanoma.

Bosniak classification version 2019: a prospective comparison of CT and MRI.

OBJECTIVE: To assess the diagnostic accuracy and agreement of CT and MRI in terms of the Bosniak classification version 2019 (BCv2019). MATERIALS AND METHODS: A prospective multi-institutional study enrolled 63 patients with 67 complicated cystic renal masses (CRMs) discovered during ultrasound examination. All patients underwent CT and MRI scans and histopathology. Three radiologists independently assessed CRMs using BCv2019 and assigned Bosniak class to each CRM using CT and MRI. The final analysis included 60 histopathologically confirmed CRMs (41 were malignant and 19 were benign). RESULTS: Discordance between CT and MRI findings was noticed in 50% (30/60) CRMs when data were analyzed in terms of the Bosniak classes. Of these, 16 (53.3%) were malignant. Based on consensus reviewing, there was no difference in the sensitivity, specificity, and accuracy of the BCv2019 with MRI and BCv2019 with CT (87.8%; 95% CI = 73.8-95.9% versus 75.6%; 95% CI = 59.7-87.6%; p = 0.09, 84.2%; 95% CI = 60.4-96.6% versus 78.9%; 95% CI = 54.4-93.9%; p = 0.5, and 86.7%; 95% CI = 64.0-86.6% versus 76.7%; 95% CI = 75.4-94.1%; p = 0.1, respectively). The number and thickness of septa and the presence of enhanced nodules accounted for the majority of variations in Bosniak classes between CT and MRI. The inter-reader agreement (IRA) was substantial for determining the Bosniak class in CT and MRI (k = 0.66; 95% CI = 0.54-0.76, k = 0.62; 95% CI = 0.50-0.73, respectively). The inter-modality agreement of the BCv219 between CT and MRI was moderate (κ = 0.58). CONCLUSION: In terms of BCv2019, CT and MRI are comparable in the classification of CRMs with no significant difference in diagnostic accuracy and reliability. KEY POINTS: • There is no significant difference in the sensitivity, specificity, and accuracy of the BCv2019 with MRI and BCv2019 with CT. • The number of septa and their thickness and the presence of enhanced nodules accounted for the majority of variations in Bosniak classes between CT and MRI. • The inter-reader agreement was substantial for determining the Bosniak class in CT and MRI and the inter-modality agreement of the BCv219 between CT and MRI was moderate.

A Pattern Reconfigurable Antenna Using Eight-Dipole Configuration for Energy Harvesting Applications.

A pattern reconfigurable antenna, composed of eight elements, is proposed for energy harvesting applications. Pattern reconfigurable antennas are a promising technique for harvesting from different wireless sources. The radiation pattern of the proposed antenna can be steered electronically using an RF switch matrix, covering an angle range from 0 to 360 degrees with a step size of 45 degrees. The proposed antenna primarily consists of an eight-dipole configuration that shares the same excitation. Each dipole is excited using a balun comprising a quarter-wavelength grounded stub and a quarter-wavelength open-circuit stub. The proposed antenna operates in the frequency range of 4.17 to 4.5 GHz, with an impedance bandwidth of 7.6%. By switching between the different switches, the antenna can be steered with a narrower rotational angle. In addition, the antenna can work in an omnidirectional mode when all switches are in the ON state simultaneously. The results demonstrate a good agreement between the numerical and experimental findings for the reflection coefficient and radiation characteristics of the proposed reconfigurable antenna.

Inhaled corticosteroids' effect on COVID-19 patients: A systematic review and meta-analysis of randomized controlled trials.

Background: More than six million people died due to COVID-19, and 10-15% of infected individuals suffer from post-covid syndrome. Corticosteroids are widely used in the management of severe COVID-19 and post-acute COVID-19 symptoms. This study synthesizes current evidence of the effectiveness of inhaled corticosteroids (ICS) on mortality, hospital length-of-stay (LOS), and improvement of smell scores in patients with COVID-19. Methods: We searched Embase, Web of Science, PubMed, Cochrane Library, and Scopus until Aug 2022. The Cochrane risk of bias tool was used to assess the quality of studies. We evaluated the effectiveness of ICS in COVID-19 patients through measures of mortality, LOS, alleviation of post-acute COVID-19 symptoms, time to sustained self-reported cure, and sense of smell (visual analog scale (VAS)). Results: Ten studies were included in the meta-analysis. Our study showed a significant decrease in the LOS in ICS patients over placebo (MD = -1.52, 95% CI [-2.77 to -0.28], p-value = 0.02). Patients treated with intranasal corticosteroids (INC) showed a significant improvement in VAS smell scores from week three to week four (MD =1.52, 95% CI [0.27 to 2.78], p-value = 0.02), and alleviation of COVID-related symptoms after 14 days (RR = 1.17, 95% CI [1.09 to 1.26], p-value < 0.0001). No significant differences were detected in mortality (RR= 0.69, 95% CI [0.36 to 1.35], p-value = 0.28) and time to sustained self-reported cure (MD = -1.28, 95% CI [-6.77 to 4.20], p-value = 0.65). Conclusion: We concluded that the use of ICS decreased patient LOS and improved COVID-19-related symptoms. INC may have a role in improving the smell score. Therefore, using INC and ICS for two weeks or more may prove beneficial. Current data do not demonstrate an effect on mortality or time to sustained self-reported cure. However, the evidence is inconclusive, and more studies are needed for more precise data.

COVID-19 in a lung transplant recipient: Exploring the diagnostic role of circulating exosomes and the clinical impact of advanced immunosuppression.

Exosomes isolated from plasma of lung transplant recipients with allograft injury contain donor-derived lung self-antigens (collagen V and Kα1 tubulin) and human leukocyte antigen (HLA) molecules. We present a case of a 76-year-old, female lung transplant recipient treated for acute cellular rejection with methylprednisolone and anti-thymocyte globulin, who subsequently contracted SARS-CoV-2 and developed a sharp increase in the mean fluorescent intensity of anti-HLA antibodies. Analysis of circulating exosomes during rejection, but before SARS-CoV-2 infection, revealed the presence of lung self-antigens and HLA class II molecules. After the patient contracted SARS-CoV-2, exosomes with the SARS-CoV-2 spike protein were also found. After resolution of infectious symptoms, exosomes with SARS-CoV-2 spike protein were no longer detected; however, exosomes with lung self-antigens and HLA class II molecules persisted, which coincided with a progressive decline in spirometric flows, suggesting chronic lung allograft dysfunction. We propose that the analysis of circulating exosomes may be used to detect allograft injury mediated by both rejection and infection. Furthermore, the detection of exosomes containing viral proteins may be helpful in identifying allograft injury driven by viral pathogens.

A Guideline-Based Policy to Decrease Intensive Care Unit Admission Rates for Accidental Hypothermia.

RATIONALE: Despite guidelines advising passive rewarming for mild accidental hypothermia (AH), patients are frequently admitted to intensive care unit (ICU) for active rewarming using a forced-air warming device. We implemented a new policy at our institution aimed at safely reducing ICU admissions for AH. We analyzed our practice pre- and post-policy intervention and compared our experiences with acute care hospitals in Connecticut. METHODS: A retrospective chart review was performed on 203 participants with AH identified by primary and secondary discharge codes. Our new policy recommended passive rewarming on the medical floors for mild hypothermia (>32°C) and ICU admission for moderate hypothermia (<32°C). Practices of other Connecticut hospitals were obtained by surveying ICU nurse managers and medical directors. RESULTS: Over a 3-year period, prior to rewarming policy change, 64% (n = 92) of patients with AH were admitted to ICU, with a mean ICU length of stay (LOS [SD]) of 2.75 (2.2) days. After the policy change, over a 3-year period, 15% (n = 9) were admitted to ICU (P < .001), with an ICU LOS of 2.11 (0.9) days (P = 0.005). In both groups with AH, altered mental status, infection, and acute alcohol intoxication were the most common diagnoses at presentation. Alcohol intoxication was more prevalent in the post-policy intervention group, pre 17% versus post 46% (P < .001). No complications such as dermal burns or cardiac arrhythmias were noted with forced-air warming device use during either time period. Among the 29 hospitals surveyed, 20 used active rewarming in ICU or intermediate care units and 9 cared for patients on telemetry units. Most hospitals used active external rewarming for core body temperature of <35°C; however, 37% of hospitals performed active rewarming at temperatures >35°Cor lacked a policy. CONCLUSIONS: Reserving forced-air warming devices for the treatment of moderate-to-severe hypothermia (<32°C) significantly reduced ICU admissions for AH.

High levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) in the serum are associated with poor prognosis in HPV-negative squamous cell oropharyngeal cancer.

BACKGROUND: An emerging subset of oropharyngeal squamous cell carcinomas (OPSCC) is caused by HPV. HPV-positive OPSCC has a better prognosis than HPV-negative OPSCC, but other prognostic markers for these two different diseases are scarce. Our aim was to evaluate serum levels and tumor expression of matrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and to assess their prognostic role in HPV-positive and HPV-negative OPSCC. MATERIALS AND METHODS: A total of 90 consecutive OPSCC patients diagnosed and treated with curative intent at the Helsinki University Hospital between 2012 and 2016 were included. Serum samples were prospectively collected. An immunofluorometric assay and an enzyme-linked immunosorbent assay were used to determine MMP-8 and TIMP-1 serum concentrations, respectively. HPV status of the tumors was determined using a combination of HPV-DNA genotyping and p16-INK4a immunohistochemistry. The endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: High TIMP-1 serum levels were strongly and independently associated with poorer OS (adjusted HR 14.7, 95% CI 1.8-117.4, p = 0.011) and DFS (adjusted HR 8.7, 95% CI 1.3-57.1, p = 0.024) among HPV-negative patients; this association was not observed in HPV-positive OPSCC. Although TIMP-1 was immunoexpressed in the majority of the tumor tissue samples, the level of immunoexpression was not associated with prognosis, nor did MMP-8 serum levels. CONCLUSION: Our results indicate that serum TIMP-1 levels may serve as an independent prognostic marker for HPV-negative OPSCC patients.

The expression and prognostic value of stem cell markers Bmi-1, HESC5:3, and HES77 in human papillomavirus-positive and -negative oropharyngeal squamous cell carcinoma.

Human papillomavirus is detected in over 50% of oropharyngeal squamous cell carcinomas. Human papillomavirus-positive oropharyngeal squamous cell carcinomas differ from human papillomavirus-negative tumors, and both expression patterns are classified as distinct entities. The Bmi-1 oncogene is a well-known member of the mammalian polycomb-group family. HESC5:3 and HES77 are newly developed monoclonal antibodies produced against undifferentiated embryonic stem cells. Our aim was to explore their roles in both human papillomavirus-positive and -negative oropharyngeal squamous cell carcinomas. Our cohort comprised 202 consecutive oropharyngeal squamous cell carcinoma patients diagnosed and treated with curative intent. We used tissue microarray tumor blocks to study the immunohistochemical expression of Bmi-1, HESC5:3, and HES77. We compared the expressions of these stem cell markers with p16 immunoexpression and human papillomavirus status, as well as with other characteristics of the tumor, and with patients' clinical data and follow-up data. Human papillomavirus- and p16-positive tumors expressed less Bmi-1 and more HESC5:3 than the negative tumors. HES77 expression was high in human papillomavirus-positive oropharyngeal squamous cell carcinoma, but it did not correlate with p16 positivity. In our multivariable model, Bmi-1 and HESC5:3 were still associated with human papillomavirus, but the association between human papillomavirus and HES77 remained absent. In conclusion, Bmi-1, HESC5:3, and HES77 may have a different role in human papillomavirus-positive and human papillomavirus-negative tumors. There was no correlation between Bmi-1, HESC5:3, and HES77 expression and survival.

Treponema denticola chymotrypsin-like protease as associated with HPV-negative oropharyngeal squamous cell carcinoma.

BACKGROUND: An opportunistic oral pathogen, Treponema denticola (Td), has been linked to orodigestive carcinogenesis, but its role in oropharyngeal squamous cell carcinoma (OPSCC) has remained open. We evaluated the presence of Td chymotrypsin-like protease (Td-CTLP) in a series of 201 unselected consecutive OPSCC patients, and the relation of the Td-CTLP to human papillomavirus (HPV) status, to expression of toll-like receptors (TLR) 5, 7, and 9, and to clinical parameters and patient outcome. METHODS: Clinicopathological data came from hospital registries. The expression of cell surface-bound Td-CTLP was evaluated by immunohistochemistry. Immunoexpression of TLRs 5, 7, and 9, and HPV status we studied earlier in this patient series. RESULTS: We detected Td-CTLP in 81% of the OPSCC, and especially in HPV-negative tumours (48% of all OPSCCs). Among the HPV-positive tumours (52% of all OPSCCs), low Td-CTLP expression associated with low TLR 5 and high TLR 7 expression. Among those HPV-negative, higher TLR 5 and lower TLR 7 expression associated with high Td-CTLP expression. Strong Td-CTLP expression associated with poor disease-specific survival, but no similar association among HPV-positive and HPV-negative subgroups emerged. CONCLUSIONS: Td-CTLP was highly expressed in OPSCC and was associated with the HPV status of tumour tissue.

Outcomes of switching to dasatinib after imatinib-related low-grade adverse events in patients with chronic myeloid leukemia in chronic phase: the DASPERSE study.

Chronic, low-grade adverse events are common in patients with chronic myeloid leukemia who are treated with imatinib. These events may decrease patient quality of life and adherence, and may ultimately contribute to a suboptimal response. Alternative, second-generation tyrosine kinase inhibitors, such as dasatinib, are available with the potential to reduce adverse events, improve tolerability, and support long-term treatment goals. We present the final, primary analysis of DASPERSE/CA180-400 (NCT01660906), an open-label, multicenter, phase IV study designed to determine whether chronic, low-grade nonhematologic adverse events in imatinib-treated patients improve after switching to dasatinib, without affecting efficacy. Of the 121 chronic, grade 1/2, imatinib-related adverse events identified at baseline in 39 patients, 77% resolved or improved within 3 months after switching to dasatinib. Dasatinib maintained a consistent safety profile; headache (33%), pleural effusion (26%), fatigue (23%), and rash (23%) were the most common treatment-related adverse events after the switch. Patients either maintained (56%) or improved (44%) their molecular response on dasatinib. Patients who switched to dasatinib also experienced improved patient-reported symptom burden from baseline as assessed by the MD Anderson Symptom Inventory for chronic myeloid leukemia (on a 1-10 scale, mean change in disease-specific score was - 2.24 and core symptom severity score was - 1.06). Overall, the efficacy and quality of life/symptom burden improved in many patients, despite the onset of dasatinib-related adverse events in most patients. This suggests that imatinib-treated patients with chronic, low-grade adverse events could benefit from switching to treatment with dasatinib.

Efficacy of contrast-enhanced FDG PET/CT in patients awaiting liver transplantation with rising alpha-fetoprotein after bridge therapy of hepatocellular carcinoma.

OBJECTIVE: To assess the diagnostic accuracy and illustrate positive findings of contrast-enhanced fluorine-18 fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) image in patients awaiting liver transplantation (LT) with rising alpha-fetoprotein (AFP) after bridge therapy of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This prospective study included 100 patients who were waiting for LT and who previously underwent locoregional therapy (LRT) of HCC. These patients had rising AFP levels on a routine follow-up examination awaiting LT. All patients underwent a contrast-enhanced 18F-FDG PET/CT examination. We calculated for each patient the maximum standardised uptake value (SUVmax) of the tumour and the ratio of the tumoral SUVmax to the normal-liver SUVmax. The diagnostic accuracy and positive contrast-enhanced findings of 18F-FDG PET/CT were established by histopathology and clinical and imaging follow-up as the reference standards. RESULTS: Contrast-enhanced 18F-FDG PET/CT detected tumour relapse in 78 patients (13 patients had intrahepatic lesions, 10 patients had extrahepatic metastases and 55 patients with combined lesions). The sensitivity, specificity and accuracy values of contrast-enhanced 18F-FDG PET/CT examination in the detection of HCC recurrence were 92.8%, 94.1% and 93%, respectively. A significant correlation was found between the AFP level and SUVmax ratio (r = 0.2283; p = 0.0224). The best threshold for 18F-FDG PET positivity was >1.21. CONCLUSION: Contrast-enhanced 18F-FDG PET/CT is a valuable tool for the detection of intrahepatic HCC recurrence or extrahepatic metastasis following rising AFP levels after LRT of HCC, and should be incorporated during routine workup awaiting LT. KEY POINTS: • 18F-FDG PET/CT is a valuable tool for the detection of HCC recurrence • 18 F-FDG PET/CT should be incorporated during routine workup awaiting liver transplantation • Significant correlation was found between AFP level and SUVmax ratio • The best threshold for 18 F-FDG PET positivity was >1.21 • The ideal cut-off value for AFP was >202.

Expression of hormone receptors in oropharyngeal squamous cell carcinoma.

OBJECTIVES: Hormone receptors play an important role in many types of cancers. Alongside factors associated with human papillomavirus (HPV) infection, hormonal receptors may impact the tumorigenesis of oropharyngeal cancer. MATERIALS AND METHODS: This study consists of 199 consecutive oropharyngeal squamous cell carcinoma (OPSCC) patients diagnosed and treated with a curative intent. We examined androgen (AR), estrogen (ER; both alpha and beta), and progesterone receptor (PR) expressions using immunohistochemistry comparing tumor and patient characteristics. RESULTS: AR was expressed in 16%, PR in 27% and ER-beta in 63% of the tumors. HPV- and p16-positive tumors expressed more AR and less PR than their negative counterparts. High PR expression was associated with poor disease-specific and locoregional recurrence-free survival. CONCLUSION: AR, PR, and ER-beta are expressed in OPSCC, and AR and PR expressions are associated with HPV and p16 status. Furthermore, PR appears to have prognostic significance. This may allow us to investigate the role of anti-hormone receptors in the treatment of OPSCC.

Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients.

A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated with tumor recurrence. After adjustment, among HPV-positive OPSCC patients, high TLR 5 and low TLR 7 expression were associated with poor disease-specific survival. Our results indicate that TLR 5 and 7 may have a role in the prognostication of HPV-positive OPSCC, however, further studies are needed to clarify the comprehensive role of these TLRs in OPSCC.

A phase 2 safety study of accelerated elotuzumab infusion, over less than 1 h, in combination with lenalidomide and dexamethasone, in patients with multiple myeloma.

Elotuzumab, an immunostimulatory SLAMF7-targeting monoclonal antibody, induces myeloma cell death with minimal effects on normal tissue. In a previous phase 3 study in patients with relapsed/refractory multiple myeloma (RRMM), elotuzumab (10 mg/kg, ∼3-h infusion), combined with lenalidomide and dexamethasone, demonstrated durable efficacy and acceptable safety; 10% (33/321) of patients had infusion reactions (IRs; Grade 1/2: 29; Grade 3: 4). This phase 2 study (NCT02159365) investigated an accelerated infusion schedule in 70 patients with newly diagnosed multiple myeloma or RRMM. The primary endpoint was cumulative incidence of Grade 3/4 IRs by completion of treatment Cycle 2. Dosing comprised elotuzumab 10 mg/kg intravenously (weekly, Cycles 1-2; biweekly, Cycles 3+), lenalidomide 25 mg (daily, Days 1-21), and dexamethasone (28 mg orally and 8 mg intravenously, weekly, Cycles 1-2; 40 mg orally, weekly, Cycles 3+), in 28-day cycles. Premedication with diphenhydramine, acetaminophen, and ranitidine (or their equivalents) was given as in previous studies. If no IRs occurred, infusion rate was increased in Cycle 1 from 0.5 to 2 mL/min during dose 1 (∼2 h 50 min duration) to 5 mL/min for the entire infusion by dose 3 and also during all subsequent infusions (∼1-h duration). Median number of treatment cycles was six. No Grade 3/4 IRs occurred; only one Grade 1 and one Grade 2 IR occurred, both during the first infusion. These data support the safety of a faster infusion of elotuzumab administered over ∼1 h by the third dose, providing a more convenient alternative dosing option for patients.

Lymphocytosis after treatment with dasatinib in chronic myeloid leukemia: Effects on response and toxicity.

BACKGROUND: The proliferation of clonal cytotoxic T-cells or natural killer cells has been observed after dasatinib treatment in small studies of patients with chronic myeloid leukemia (CML). METHODS: The incidence of lymphocytosis and its association with response, survival, and side effects were assessed in patients from 3 large clinical trials. Overall, 1402 dasatinib-treated patients with newly diagnosed CML in chronic phase (CML-CP), CML-CP refractory/intolerant to imatinib, or with CML in accelerated or myeloid-blast phase were analyzed. RESULTS: Lymphocytosis developed in 32% to 35% of patients and persisted for >12 months. This was not observed in the patients who received treatment with imatinib. Dasatinib-treated patients in all stages of CML who developed lymphocytosis were more likely to achieve a complete cytogenetic response, and patients who had CML-CP with lymphocytosis were more likely to achieve major and deep molecular responses. Progression-free and overall survival rates were significantly longer in patients with CML-CP who were refractory to or intolerant of imatinib and had lymphocytosis. Pleural effusions developed more commonly in patients with lymphocytosis. CONCLUSIONS: Overall, lymphocytosis occurred and persisted in many dasatinib-treated patients in all phases of CML. Its presence was associated with higher response rates, significantly longer response durations, and increased overall survival, suggesting an immunomodulatory effect. Prospective studies are warranted to characterize the functional activity of these cells and to assess whether an immunologic effect against CML is detectable. Cancer 2016;122:1398-1407. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.