Impaired pharyngeal reflex responses to negative pressure: a novel cause of sleep apnea in multiple sclerosis.

Obstructive sleep apnea (OSA) is common in people with multiple sclerosis (MS). However, people with MS often do not have "typical" anatomical risk factors (i.e., nonobese and female predominance). Accordingly, nonanatomical factors such as impaired upper-airway muscle function may be particularly important for OSA pathogenesis in MS. Therefore, this study aimed to investigate genioglossus (largest upper-airway dilator muscle) reflex responses to brief pulses of upper-airway negative pressure in people with OSA and MS. Eleven people with MS and OSA and 10 OSA controls without MS matched for age, sex, and OSA severity were fitted with a nasal mask, pneumotachograph, choanal and epiglottic pressure sensors, and intramuscular electrodes into genioglossus. Approximately 60 brief (250 ms) negative pressure pulses (approximately -12 cmH2O mask pressure) were delivered every 2-6 breaths at random during quiet nasal breathing during wakefulness to determine genioglossus electromyogram (EMGgg) reflex responses (timing, amplitude, and morphology). Where available, recent clinical MRI brain scans were evaluated for the number, size, and location of brainstem lesions in the group with MS. When present, genioglossus reflex excitation responses were similar between MS participants and controls (e.g., peak excitation amplitude = 229 ± 85% vs. 282 ± 98% baseline, P = 0.17). However, ∼30% of people with MS had either an abnormal (predominantly inhibition) or no protective excitation reflex. Participants with MS without a reflex had multiple brainstem lesions including in the hypoglossal motor nucleus which may impair sensory processing and/or efferent output. Impaired pharyngeal reflex function may be an important contributor to OSA pathogenesis for a proportion of people with MS.NEW & NOTEWORTHY This study investigated the function of an important reflex that helps protect the upper airway from closing during negative (suction) pressure in people with and without multiple sclerosis (MS) and obstructive sleep apnea (OSA). We found that ∼30% of people with MS had either no protective reflex or an abnormal reflex response. These findings indicate that impaired upper-airway reflex function may be an important contributor to OSA for a substantial proportion of people with MS.

Haemorrhage and Calcification on Susceptibility-Weighted Imaging : A Quick and Reliable Qualitative Technique for Differentiating Lesions with Ambiguous Phase.

PURPOSE: Haemorrhage and calcification can be qualitatively distinguished on susceptibility-weighted imaging (SWI) using phase information, but it is unclear how to make this distinction in a subset of lesions with ambiguous phase, containing a mixture of positive and negative values. This work investigates the validity of qualitative phase assessment at the cranial or caudal margins in classifying such lesions as haemorrhagic or calcific, when quantitative susceptibility mapping is not available to the neuroradiologist. METHODS: In a retrospective review of magnetic resonance imaging examinations acquired between July 2015 and November 2019, 87 lesions with ambiguous phase which could be confidently determined to be haemorrhagic or calcific were identified. Two blinded neuroradiologists independently classified these lesions as haemorrhagic or calcific using 3 approaches: qualitative phase assessment at the lesions' cranial or caudal margins, dominant phase, and in-plane margins. Combined sensitivities and specificities of these analyses were calculated using a generalised linear mixed model with random effects for reader. RESULTS: Assessment at the cranial or caudal margins achieved a sensitivity of 100% for haemorrhage and calcification, which was significantly superior (p < 0.05) to dominant phase assessment with sensitivities of 52% for haemorrhage (95% confidence interval, CI 43-61%) and 54% for calcification (95% CI 42-66%), as well as in-plane margin assessment with 28% (95% CI 18-38%) and 46% (95% CI 36-56%). CONCLUSION: Haemorrhage and calcification can be reliably distinguished in lesions with ambiguous phase on SWI by qualitative review of the phase signal at the cranial or caudal margins.

Comparative sound detection abilities of four decapod crustaceans.

Sound perception and detection in decapod crustaceans is surprisingly poorly understood, even though there is mounting evidence for sound playing a critical role in many life history strategies. The suspected primary organ of sound perception is the paired statocysts at the base of the first antennal segment. To better understand the comparative sound detection of decapods, auditory evoked potentials were recorded from the statocyst nerve region of four species (Leptograpsus variegate, Plagusia chabrus, Ovalipes catharus, Austrohelice crassa) in response to two different auditory stimuli presentation methods, shaker table (particle acceleration) and underwater speaker (particle acceleration and pressure). The results showed that there was significant variation in the sound detection abilities between all four species. However, exposure to the speaker stimuli increased all four species sound detection abilities, in terms of both frequency bandwidth and sensitivity, compared with shaker table-derived sound detection abilities. This indicates that there is another sensory mechanism in play as well as the statocyst system. Overall, the present research provides comparative evidence of sound detection in decapods and indicates underwater sound detection in this animal group was even more complex than previously thought.

Comprehensive analysis of peripheral T-cell and natural killer/T-cell lymphoma in Asian patients: A multinational, multicenter, prospective registry study in Asia.

BACKGROUND: Peripheral T-cell lymphomas (PTCLs) are uncommon and their frequency is regionally heterogeneous. Several studies have been conducted to evaluate the clinical features and treatment outcomes of this disease entity, but the majority of these were conducted in limited areas, making it difficult to comprehensively analyze their relative frequency and clinical features. Furthermore, no consensus treatment for PTCLs has been established. Therefore, we conducted an Asia-specific study to understand the relative frequency of PTCLs and assess treatments and their outcomes in Asian patients. METHODS: We performed a multinational, multicenter, prospective registry of adult patients with PTCLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated. FINDINGS: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57%) had stage III or IV. Extranodal natural killer (NK)/T- cell lymphoma was the most common subtype (n = 139,28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL, n = 120,24.7%), PTCL-not otherwise specified (PTCL-NOS, n = 101,20.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n = 34,6.9%), and ALK-negative ALCL (n = 30,6.2%). The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6-31.6) and 83.6 months (95% CI, 56.7-110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to one another. INTERPRETATION: This multinational, multicenter study identified the relative frequency of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently used. FUNDING: Samsung Biomedical Research Institute.

Thrombectomy in stroke of unknown onset, wake up stroke and late presentations: Australian experience from 2 comprehensive stroke centres.

Two recent randomized controlled trials (RCTs) showed selected patients treated with endovascular thrombectomy (EVT) more than 6 h from acute ischemic stroke (AIS) onset had significant improvement in functional outcome at 90 days compared with standard care alone. Our aim is to determine the outcome and predictors of good outcome in AIS patients undergoing EVT with unknown-onset, or late presentation, stroke after 6 h from time last seen well, or witnessed stroke onset, at two Australian comprehensive stroke centres. A retrospective analysis of functional outcome and mortality at 90-days from a prospective cohort of 56 consecutive patients with unknown-onset, or late presentation, stroke with large vessel occlusion (LVO) in the anterior cerebral circulation undergoing EVT over a 15-month period (2016-2017). We evaluated factors which correlated with good functional outcome defined as a 90-day modified Rankin scale (mRS) 0-2. Recanalization times and symptomatic intracranial haemorrhage (sICH) rates were also examined. A good functional outcome was achieved in 35 patients (62%). Eight patients died (14%). Median time-to-recanalization was 7.6 h. SICH occurred in four patients (7%). Factors which predicted good 90-day functional outcome included baseline National Institutes of Health Stroke Scale (NIHSS) < 16, 24 h NIHSS < 10, baseline Alberta Stroke Program Early CT Score (ASPECTS) ≥ 8, pre-procedural CT perfusion imaging and LVO lesion location. This study shows good 'real world' outcomes, comparable to published RCTs, in patients with unknown-onset, or late presentation, stroke treated with EVT more than 6 h from stroke onset.

Can eye-tracking metrics be used to better pair radiologists in a mammogram reading task?

PURPOSE: To propose a framework for optimal pairing of radiologists when reading mammograms based on their search patterns. MATERIALS AND METHODS: Four experienced and four less-experienced radiologists were asked to assess 120 cases (59 with cancers) while their eye positions were tracked. Fourteen eye-tracking metrics were extracted to quantify the differences among radiologists' visual search pattern. For each radiologist and metric, less-experienced radiologists and expert readers were ranked based on the level of similarities in gaze patterns (from the most different to the most similar). Less-experienced readers and experts were also ranked based on the values of area under the receiver operating characteristic curve (AUC) after pairing (the best possible way of ranking). Using the Kendall's tau distance, rankings based on different metrics were compared with the best possible ranking. Using paired Wilcoxon signed-rank test, the AUC values when pairing in the best way were compared with pairing based on different metrics. Finally, we investigated the robustness of pairing strategies against the small sample size. RESULTS: For ranking the experienced radiologists, results from eight metrics were as good as the best possible ranking. For the less-experienced ones, only one metric resulted in a ranking comparable to the best possible way of ranking. The AUC values of pairings based on these metrics did not differ significantly from the best pairing scenario. Compared to the pairings based on the cognitive metrics, the ranking based on AUC values varied more greatly with the sample size, suggesting that it is less robust against the small sample size compared to the cognitive metrics. CONCLUSION: Different pairings may have different effects on performance; some are detrimental while some improve the performance of the pair. Using the suggested cognitive metrics, we can optimize the pairings even with a small dataset.

Recurrence quantification analysis of radiologists' scanpaths when interpreting mammograms.

PURPOSE: The purpose of this study was to Propose a classifier based on recurrence quantification analysis (RQA) metrics for distinguishing experts' scanpaths from those of less-experienced readers and to explore the association of spatiotemporal dynamics of the mammographic scanpaths with the characteristics of cases and radiologists using RQA metrics. MATERIALS AND METHODS: Eye movements were recorded from eight radiologists (two cohorts: four experienced and four less-experienced) while reading 120 mammograms (59 cancer, 61 normal). Ten RQA measures were extracted for each recorded scanpath. The measures described the temporal distribution of recurrent fixations as well as laminar and deterministic eye movements. Recurrent fixations are fixations that are located close to a previously fixated point in a scanpath. Deterministic eye movements represent looking back and forth between two locations, while laminar eye movements indicate detailed scanning of an area with consecutive fixations. The RQA metrics along with six conventional eye-tracking parameters were used to construct a classifier for distinguishing experts' scanpaths from those of less-experienced readers. Leave-one-out cross validation was used for evaluating the classifier. For each reader cohort, the ANOVA analysis was done to study the relationship of RQA measures with breast density, case pathology, readers' expertise, and readers' decisions on the case. The proportions of laminar and deterministic movements involved fixations in the location of lesions were also compared for two reader cohorts using two proportion z-tests. RESULTS: All RQA measures differed significantly between scanpaths of experienced readers and those of less-experienced readers. The classifier achieved an area under the receiver operating characteristic curve of 0.89 (0.87-0.91) for detecting experts' scanpaths. Proportionately more refixations and laminar and deterministic sequences were in the location of the lesion for the experienced cohort compared to the less-experienced cohort (all P-values < 0.001). Eight and four RQA measures differed between normal and cancer cases for the experienced and less experienced readers, respectively. None of metrics differed between fatty and dense breasts for the less experienced readers, while two measures resulted into a significant difference for the experienced readers. For experts, six measures differed significantly between true negatives and false positives and nine were significantly different between true positives and false negatives. For the less-experienced cohort, the corresponding figures were seven and one measures, respectively. CONCLUSION: The RQA measures can quantify the differences among experienced and less experienced radiologists. They also capture differences among experts' scanpaths related to case pathology and radiologists' decisions on the case.

iCAP: An Individualized Model Combining Gaze Parameters and Image-Based Features to Predict Radiologists' Decisions While Reading Mammograms.

This study introduces an individualized tool for identifying mammogram interpretation errors, called eye-Computer Assisted Perception (iCAP). iCAP consists of two modules, one which processes areas marked by radiologists as suspicious for cancer and classifies these as False Positive (FP) or True Positive (TP) decisions, while the second module classifies fixated but not marked locations as False Negative (FN) or True-Negative (TN) decisions. iCAP relies on both radiologists' gaze-related parameters, extracted from eye tracking data, and image-based features. In order to evaluate iCAP, eye tracking data from eight breast radiologists reading 120 two-view digital mammograms were collected. Fifty-nine cases had biopsy proven cancer. For each radiologist, a user-specific support vector machine model was built to classify the radiologist' s reported areas as TPs or FPs and fixated locations as TNs or FNs. The performances of the classifiers were evaluated by utilizing leave-one-out cross validation. iCAP was tested retrospectively in a simulated scenario in which it was assumed that the radiologists would accept all iCAP decisions. Using iCAP led to an average increase of 12%±6% in the number of correctly localized cancer and an average decrease of 44.5%±22.7% in the number of FPs per image.

Brain metastasis in sarcoma: Does metastasectomy or aggressive multi-disciplinary treatment improve survival outcomes.

AIM: Brain metastasis is rare in sarcoma. Prognostic factors, optimal management strategies and therapeutic outcomes of such patients are not well studied. We aimed to evaluate the incidence, clinical characteristics and treatment outcomes of parenchymal brain metastasis in sarcoma patients. METHODS: This is a single center retrospective analysis. Overall survival (OS) was calculated from the time of diagnosis of brain metastasis to time of death. RESULTS: Sixteen patients (2.1%) with complete electronic medical records treated at our institution from 2002 to 2010 were identified. Median age was 52 years; 88% had additional sites of metastases. Eight different subtypes of soft tissue and bone sarcoma were identified. Eighty-one percent of the patients developed metachronous brain metastasis at a median of 14 months after initial sarcoma diagnosis. Thirty-eight percent of patients had solitary brain metastasis and 44% underwent aggressive therapy for brain metastasis, defined as either surgical resection or multimodality treatment. The remaining 56% received conservative treatment (either whole brain radiation alone, chemotherapy alone or best supportive care). Median OS for the entire cohort was 3.5 months (95% CI 1.1-6.3 months). A trend toward improved OS was observed with an aggressive treatment approach, 3.7 months versus 1.2 months (P = 0.077) and the usage of chemotherapy (P = 0.071). CONCLUSION: Brain metastasis in sarcoma is rare, usually coexists with significant systemic disease and is associated with a grave prognosis. Use of chemotherapy and an aggressive treatment approach in well-selected patients may be associated with improved survival. Prospective studies are needed to confirm these findings.

Panobinostat in combination with bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma: an open-label, multicentre phase 2 trial.

BACKGROUND: Patients with relapsed or refractory peripheral T-cell lymphoma have a poor prognosis after conventional chemotherapy. Approved novel agents have only modest single-agent activity in most subtypes of peripheral T-cell lymphoma. Panobinostat is a potent oral pan-deacetylase inhibitor. Findings of many preclinical studies have shown synergistic antilymphoma activity when panobinostat is combined with the proteasome inhibitor bortezomib. We aimed to study the effect of panobinostat and bortezomib in patients with relapsed or refractory peripheral T-cell lymphoma. METHODS: In this open-label, multicentre phase 2 trial, we recruited patients aged 21 years or older with relapsed or refractory peripheral T-cell lymphoma who had received at least one previous line of systemic therapy from five tertiary hospitals in Singapore, Malaysia, and South Korea. Patients received 20 mg oral panobinostat three times a week and 1·3 mg/m(2) intravenous bortezomib two times a week, both for 2 of 3 weeks for up to eight cycles. The primary endpoint was the proportion of patients who achieved an objective response in accordance with the International Working Group revised response criteria; analyses were by intention to treat. The study is completed and is registered with ClinicalTrials.gov, number NCT00901147. FINDINGS: Between Nov 9, 2009, and Nov 26, 2013, we enrolled 25 patients with various histological subtypes of peripheral T-cell lymphoma. Of 23 patients assessable for responses, ten (43%, 95% CI 23-63) patients had an objective response, of which five were complete responses. Serious adverse events were reported in ten (40%) of 25 patients. Common treatment-related grade 3-4 adverse events included thrombocytopenia (17 [68%]), neutropenia (ten [40%]), diarrhoea (five [20%]), and asthenia or fatigue (two [8%]). We recorded peripheral neuropathy of any grade in ten (40%) patients. INTERPRETATION: Combined proteasome and histone deacetylase inhibition is safe and feasible and shows encouraging activity for patients with peripheral T-cell lymphoma. Our findings validate those of preclinical studies showing synergism in the combination and represent a rational way forward in harnessing the full potential of novel agents in peripheral T-cell lymphoma. FUNDING: Novartis Pharmaceuticals, Janssen Pharmaceuticals, and Singhealth Foundation.

Carotid artery inflammation associated with gemcitabine-based therapy: a special report.

Vasculitis is an inflammation that can present as acute or chronic in nature, which causes changes in the walls of blood vessels, including thickening, weakening, narrowing and scarring. Gemcitabine, an antimetabolite chemotherapeutic agent, is generally well tolerated with a favorable side effect profile. However, there is increasing evidence that it is associated with vasculitis, which can affect small and large vessels. In this case report, we report a patient who has experienced fever with severe tenderness over right carotid artery, which occurred on the fifth day after the administration of gemcitabine. The exact mechanism of gemcitabine-induced vasculitis is unknown but cessation of gemcitabine and initiation of anti-inflammatory treatment appears to aid in the resolution of the clinical syndrome.

One Patient, Two Uncommon B-Cell Neoplasms: Solitary Plasmacytoma following Complete Remission from Intravascular Large B-Cell Lymphoma Involving Central Nervous System.

Second lymphoid neoplasms are an uncommon but recognized feature of non-Hodgkin's lymphomas, putatively arising secondary to common genetic or environmental risk factors. Previous limited evaluations of clonal relatedness between successive mature B-cell malignancies have yielded mixed results. We describe the case of a man with intravascular large B-cell lymphoma involving the central nervous system who went into clinical remission following immunochemotherapy and brain radiation, only to relapse 2 years later with a plasmacytoma of bone causing cauda equina syndrome. The plasmacytoma stained strongly for the cell cycle regulator cyclin D1 on immunohistochemistry, while the original intravascular large cell lymphoma was negative, a disparity providing no support for clonal identity between the 2 neoplasms. Continued efforts atcataloging and evaluating unique associations of B-cell malignancies are critical to improving understanding of overarching disease biology in B-cell malignancies.

Cytomegalovirus infection and end-organ disease in Asian patients with lymphoma receiving chemotherapy.

This study aimed to describe the epidemiology and risk factors for cytomegalovirus (CMV) infection and end-organ disease in patients with lymphoma undergoing potentially curative or salvage therapy. We retrospectively reviewed 534 patients with lymphoma treated at an Asian tertiary cancer center between January 2007 and December 2010. Overall, 48 patients (9.0%) experienced CMV infection, with 12 patients (25.0%) being further diagnosed with CMV end-organ disease. Many patients with CMV infection were male, with poor performance status, non-Hodgkin lymphoma and advanced disease, and received rituximab use. Moreover, patients receiving rituximab and HyperCVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone) regimens had a high rate of CMV end-organ disease. In Asian patients with lymphoma receiving curative or salvage therapy, CMV infection was relatively common (9.0%). Most of these were likely to be reactivation in nature. A small group, especially those on rituximab or HyperCVAD, developed CMV end-organ disease (12/534). Such patients should be monitored closely for CMV end-organ disease. Alternatively, prophylaxis should be studied.

Extranodal natural killer/T-cell lymphoma involving the gastrointestinal tract: analysis of clinical features and outcomes from the Asia Lymphoma Study Group.

BACKGROUND: The gastrointestinal (GI) tract is one of the most common extranasal sites in extranodal NK/T-cell lymphoma (ENKTL). However, data regarding ENKTL involving the GI tract are relatively scarce. Thus, we performed a multicenter, multinational retrospective study to analyze clinical features and treatment outcomes of ENKTL involving the GI tract. PATIENTS AND METHODS: Patients with ENKTL involving the GI tract diagnosed in twelve participating centers between 1991 and 2012 were retrospectively analyzed from five Asian countries. RESULTS: The analysis of 81 patients with ENKTL involving the GI tract revealed that more than 60% of patients presented as advanced disease with B symptoms. 55 patients (68%) had GI manifestations including abdominal pain (n = 26, 32%), GI tract bleeding (n = 17, 21%) and bowel perforation (n = 12, 15%). The most common GI site was the small intestine, including the jejunum and ileum (n = 57, 70.3%). There were 34 patients (42%) who received systemic chemotherapy while 33 patients (41%) underwent surgery plus chemotherapy. However, 35 patients (43%) died due to disease progression, and treatment-related mortality including sepsis occurred in 17 patients (21%). Thus, the median overall survival was 7.8 months (95% Confidence interval: 3.9 - 11.7 months). Patients who could undergo surgery plus chemotherapy showed a trend of better survival than those treated with chemotherapy alone. CONCLUSION: Overall, the data indicated that ENKTL involving the GI tract has a dismal prognosis despite active treatment including chemotherapy and surgery. Thus, more effective treatment strategies are required for this disease entity.

Hepatitis B virus reactivation in B-cell lymphoma patients treated with rituximab: analysis from the Asia Lymphoma Study Group.

BACKGROUND: Hepatitis B virus (HBV) reactivation is increasing, as rituximab has become widely used for B-cell lymphoma. Thus, prevention and management of HBV reactivation are important in HBV-endemic areas. METHODS: Hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)-positive patients and HBsAg-negative/HBV core antibody (HBcAb)-positive patients who received rituximab-containing chemotherapy was investigated by the Asia Lymphoma Study Group via retrospective (n=340), and the results were compared to cross-sectional analysis with patients who were prospectively monitored in a single institute (n=127). The goal of the study was to define the frequency of HBV reactivation and the efficacy of antiviral prophylaxis. RESULTS: HBV reactivation was found in 27.8% of HBsAg-positive patients (45/162) in the retrospective analysis, being significantly less frequent in patients receiving antiviral prophylaxis than those not (22.9%, 32/140 versus 59.1%, 13/22; p<0.001). Lamivudine was most commonly used (96/162, 59.3%), but more than 20% of HBsAg-positive patients showed breakthrough HBV reactivation. In the cross-sectional analysis, a reduced rate of HBV reactivation occurred for entecavir as compared with lamivudine prophylaxis (6.3% versus 39.3%; p<0.05). HBV DNA monitoring of HBsAg-negative/HBcAb-positive patients in the cross-sectional analysis showed HBV reactivation in only 2.4% of cases. CONCLUSIONS: This is the largest study of HBV reactivation in patients receiving rituximab-containing chemotherapy to date, and we defined the probability of HBV reactivation in an HBV-endemic region.

The effect of JPEG2000 compression on detection of skull fractures.

RATIONAL AND OBJECTIVES: To investigate the effect of the Joint Photographic Experts Group (JPEG2000) 30:1 and 60:1 lossy compression on the detection of cranial vault fractures when compared to JPEG2000 lossless compression. MATERIALS AND METHODS: Fifty cranial computed tomography (CT) images were processed with three different level of JPEG2000 compression (lossless, 30:1 lossy, and 60:1 lossy) creating three sets of images. These were presented to five musculoskeletal specialists and five neuroradiologists. Each reader read at two of the three compression levels. Twenty-two cases contained a single fracture; the remaining 28 cases contained no fractures. Observers were asked to identify the presence or absence of a fracture, to locate its site, and rate their degree of confidence. Receiver operating characteristic (ROC), jackknife free-response receiver operating characteristic (JAFROC) and the Dorfman-Berbaum-Metz multiple reader multiple case (DBM-MRMC) analyses were used to explore differences between the lossless and lossy compressed images. RESULTS: JPEG2000 lossless and 30:1 lossy compression demonstrated no significant difference in their performance with JAFROC and DBM-MRMC analysis (P < .416); however, JPEG2000 30:1 lossy compression demonstrated significantly better performance than 60:1 lossy compression (P < .016). A significant increase in misplaced confidence ratings was also seen with 60:1 (P < .037) over 30:1 lossy and lossless compression. CONCLUSION: JPEG2000 60:1 compression degrades the detection of skull fractures significantly while increasing the confidence with which readers rate fractures compared with 30:1 lossy and lossless compression. JPEG2000 30:1 lossy compression does not significantly change performance when compared to JPEG2000 lossless for the detection of skull fractures on CT.

Clinical pharmacy services and research for lymphoma patients at a cancer center.

At the National Cancer Centre Singapore, which is currently the largest ambulatory cancer centre in Singapore, clinical pharmacists have taken upon responsibilities to provide direct pharmaceutical care in the center's lymphoma team since 2006. Given the complexity and intricacies of lymphoma treatments, clinical pharmacists are often positioned to ensure supportive care is optimized among these patients. Besides management of chemotherapy-related and supportive care issues, clinical pharmacists play a pivotal role in guiding cost-effective and safe prescribing. In collaboration with the medical team, they are also involved in conducting practice research in order to optimize the delivery of pharmaceutical care. In this report, the dedicated services and research activities conducted by clinical pharmacists of a lymphoma team will be discussed.

Does the proliferation fraction help identify mature B cell lymphomas with double- and triple-hit translocations?

AIMS: The entity 'B cell lymphoma, unclassifiable, with features intermediate between diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL)' refers to B cell neoplasms that share overlapping characteristics of BL and DLBCL. A subset of these 'grey-zone lymphomas' possesses C-MYC and IGH translocations but, in addition, contains additional rearrangements of BCL2 and/or BCL6 genes. The aim of this study was to investigate if the proliferation fraction by Ki67 immunostaining can be used to identify such double-/triple-hit lymphomas. METHODS AND RESULTS: We studied 492 cases of mature aggressive B cell neoplasms by histology, immunohistochemistry and interphase fluorescence in-situ hybridization (FISH) using break-apart probes against C-MYC, BCL2, BCL6, IGH, MALT1, PAX5 and CCND1. Forty Burkitt lymphomas and 28 cases of MYC(+) double-/triple-hit lymphomas were identified. Of the latter, 77% and 54% displayed proliferation fractions exceeding 75% and 90%, respectively. With a cut-off of >75% by Ki67 immunostaining, the sensitivity and specificity for detection of MYC(+) double/triple translocations was 0.77 and 0.36. Raising the proliferation fraction criterion to >90% improved the specificity to 0.62 at the expense of a low sensitivity of 0.54. CONCLUSIONS: Immunostaining for Ki67 is not a useful approach to prescreen B cell lymphomas for MYC(+) double/triple translocations.

Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma.

UNLABELLED: The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identified Janus kinase 3 (JAK3) somatic-activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. Further validation of the prevalence of JAK3 mutations was determined by Sanger sequencing and high-resolution melt (HRM) analysis in an additional 61 cases. In total, 23 of 65 (35.4%) cases harbored JAK3 mutations. Functional characterization of the JAK3 mutations support its involvement in cytokine-independent JAK/STAT constitutive activation leading to increased cell growth. Moreover, treatment of both JAK3-mutant and wild-type NKTCL cell lines with a novel pan-JAK inhibitor, CP-690550, resulted in dose-dependent reduction of phosphorylated STAT5, reduced cell viability, and increased apoptosis. Hence, targeting the deregulated JAK/STAT pathway could be a promising therapy for patients with NKTCLs. SIGNIFICANCE: Gene mutations causing NKTCL have not been fully identified. Through exome sequencing, we identified activating mutations of JAK3 that may play a significant role in the pathogenesis of NKTCLs. Our findings have important implications for the management of patients with NKTCLs.