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Introduction: Geographic access to novel oncology therapies, and the extent to which it may vary by potential sites of care, regions, and population characteristics, is poorly understood. We examined how expanding access to chimeric antigen receptor (CAR) T cell therapy administration sites impacts patient travel distances and time. Methods: We used geographic information system techniques to calculate shortest travel distance and time between patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) and the nearest CAR T cell therapy administration site in three scenarios: academic hospitals; academic and community multispecialty hospitals; and academic and community multispecialty hospitals plus nonacademic specialty oncology network centers. Main outcome measures were differences in travel distance and time among the scenarios and the relationship between travel time and socioeconomic status, race, rural–urban areas, and non-Hodgkin lymphoma clusters. Non-Hodgkin lymphoma incidence, socioeconomic status, and administration centers were derived from governmental/publicly available data sources. Results: Of 3922 patients eligible for CAR T cell therapy, more than 37% had to travel more than 1 h to the nearest academic hospital. Average travel time and distance were significantly reduced by 23% and 30% (P < 0.001), respectively, when access was expanded to include community hospitals plus a broader range of oncology specialty treatment centers. Compared to academic hospitals alone, increasing access to include community hospitals decreased time and distance by 7% and 8% (P < 0.01), respectively. In addition, there would be a lower proportion of sites operating as the only care provider within 25 miles if access was expanded outside of academic hospitals only. Longer travel time was associated with lower socioeconomic status. Conclusion: Many patients with DLBCL have long travel times to an academic hospital that administers CAR T cell therapy. Expanding access to care through site-of-care planning will help address regional, rural–urban, and sociodemographic equity in the geographic allocation of CAR T cell therapy. [ABSTRACT FROM AUTHOR]

In this study, we have synthesized the Zr substituted BaTi0.80Fe0.20O3 ceramics at different content of Zr from x=0.00 to 0.10 by using the solid-state route. The room temperature X-ray diffraction results confirmed the coexistence of the two tetragonal and hexagonal phases for x ≤ 0.050 of Zr content. While above 0.050 the hexagonal phase disappeared in benefit of the tetragonal phase. The Raman results confirmed the formation of these phases obtained by XRD. The scanning electron micrographs consisted of both spherical and straight grain forms for x=0.000 to 0.075, and only spherical grain form for x=0.100 attributed to the tetragonal phase. Also, the grain size increased accompanied by a decrease in density of ceramics with increasing Zr content up to 0.050 then decreased accompanied by an increase in density. Detailed studies of dielectric permittivity measurement provided a presence of two anomalies Te and TR-O at different temperatures, with a relaxation phenomenon and diffuse behavior which was very important for ceramic at x=0.075 of Zr content. The dielectric permittivity values of the two anomalies of Zr substituted BaTi0.80Fe0.20O3 ceramics increased with the increase of Zr content and the dielectric loss was minimal at x=0.100 of Zr content. The conductivity increased with increasing of Zr substitution from 0.025 to 0.075 levels while for x = 0.100 the dielectric conductivity decreased. And the Cole-Cole analysis indicated a negative thermal resistivity coefficient (NTCR) behavior of these materials and ideal Debye-type behavior. [ABSTRACT FROM AUTHOR]

The PI3K/AKT/mTOR axis promotes survival and is a frequently mutated pathway in cancer. Yet, inhibitors targeting this pathway are insufficient to induce cancer cell death as single agents in some contexts, including diffuse large B cell lymphoma (DLBCL). In these situations, combinations with inhibitors targeting BCL-2 survival proteins (ABT-199 and ABT-263) may hold potential. Indeed, studies have demonstrated marked synergy in contexts where PI3K/mTOR inhibitors suppress expression of the pro-survival protein, MCL-1. In this study, we use BH3 profiling to confirm that BCL-2 and BCL-XL support survival following PI3K pathway inhibition, and that the dual PI3K/mTOR inhibitor BEZ235 strongly synergizes with BCL-2 antagonists in DLBCL. However, we identify an alternative mechanism of synergy between PI3K/mTOR and BCL-2 inhibitors, independent of MCL-1 down-regulation. Instead, we show that suppression of AKT activation by BEZ235 can induce the mitochondrial accumulation of pro-apoptotic BAD and BIM, and that expression of a constitutively active form of AKT prevents sensitization to BCL-2 antagonism. Thus, our work identifies an additional mechanism of synergy between PI3K pathway inhibitors and BCL-2 antagonists that strengthens the rationale for testing this combination in DLBCL.

ObjectiveUnderstanding tumor microenvironment and its impact on prognosis of HIV-related lymphomas may provide insight into novel therapeutic strategies.DesignWe characterized the relationship between infiltrating immune cells with tumor characteristics, HIV disease history and survival in 80 patients with HIV-related diffuse large B-cell lymphoma (DLBCL) diagnosed in the era of combined antiretroviral therapy (1996-2007) at Kaiser Permanente California. Eighty patients with HIV-unrelated DLBCL were included for comparison.MethodsData on patients' clinical history were obtained from Kaiser Permanente's electronic health records. The density of stromal CD4, CD8 and FOXP3 T cells and CD68 macrophages, as well as tumor molecular characteristics were examined using immunohistochemistry. The associations between stromal immune infiltration and patient's clinical history or tumor characteristics were examined using Kruskal-Wallis tests or Pearson's correlation coefficient. The effect of stromal immune infiltration on 2-year mortality was evaluated in multivariable logistic regression.ResultsCompared with HIV-unrelated DLBCL, patients with HIV-related DLBCL had significantly reduced stromal CD4 and FOXP3 T cells, but increased density of macrophages. Increased density of stromal macrophages was correlated with lower circulating CD4 cell count at DLBCL diagnosis. Tumor molecular characteristics, including BCL6, p53 and cMYC expression, but not Epstein-Barr virus infection status, were significantly correlated with stromal immune infiltration, particularly FOXP3 T cells. A higher density of infiltrating CD8 T cell was significantly associated with reduced mortality in patients with HIV-related DLBCL (odds ratio = 0.30 [0.09-0.97] for ≥25 vs.

ObjectiveDyspnoea is a common, multifactorial source of functional impairment among patients with dcSSc. Our objective was to assess the reliability, construct validity and responsiveness to change of the Saint George's Respiratory Questionnaire (SGRQ) in patients with early dcSSc participating in a multicentre prospective study.MethodsAt enrolment and 1 year, patients completed the SGRQ (a multi-item instrument with four scales: symptoms, activity, impact and total), a visual analogue scale (VAS) for breathing and the HAQ Disability Index (HAQ-DI) and underwent 6 min walk distance and pulmonary function tests, physician and patient global health assessments and high-resolution CT (HRCT). We assessed internal consistency reliability using Cronbach's α. For validity we examined the ability of the SGRQ to differentiate the presence vs absence of interstitial lung disease (ILD) on HRCT or restrictive lung disease and evaluated the 1 year responsiveness to change using pulmonary function tests and patient- and physician-reported anchors. Correlation coefficients of 0.24-0.36 were considered moderate and >0.37 was considered large.ResultsA total of 177 patients were evaluated. Reliability was satisfactory for all SGRQ scales (0.70-0.93). All scales showed large correlations with the VAS for breathing and diffusing capacity of the lung for carbon monoxide in the overall cohort and in the subgroup with ILD. Three of the four scales in the overall cohort and the total scale in the ILD subgroup showed moderate to large correlation with the HAQ-DI and the predicted forced vital capacity (r = 0.33-0.44). Each scale discriminated between the presence and absence of ILD and restrictive lung disease (P ≤ 0.0001-0.03). At follow-up, all scales were responsive to change using different anchors.ConclusionThe SGRQ has acceptable reliability, construct validity and responsiveness to change for use in a dcSSc population and differentiates between patients with and without ILD.

BackgroundTrisomy 12 (+12) is detected by fluorescence in-situ hybridization (FISH) analysis in up to 20% of patients with chronic lymphocytic leukemia (CLL). Patients with +12 are known to have unique features and to carry an intermediate prognosis.Patients and methodsIn order to better define this large group, we reviewed the characteristics of 250 untreated patients with +12.ResultsWhen compared to 516 untreated patients negative for +12 by FISH, patients with +12 showed a higher incidence of thrombocytopenia, Richter transformation, and second malignant neoplasms (SMN), in addition to the expected increased rate of CD38 positivity and atypical immunophenotype. At a median follow-up of 51 months, 57% of patients needed first-line treatment; median time to first treatment was 38 months, and on multivariate analysis (MVA), it was found to be shorter in patients with advanced Rai stage, palpable splenomegaly, and deletion of 14q by conventional cytogenetic analysis. The overall response rate with first-line treatment was 94%. The median failure-free survival has not been reached, but on MVA, it was found to be shorter in patients whose disease responded in a manner other than complete remission or with FISH negativity for deletion 13q. The median overall survival for the entire group has not been reached, but MVA revealed it to be shorter in patients with an absolute lymphocyte count of > 30 × 10(9)/L or who developed SMN. Eighteen deaths have been observed so far, and Richter transformation and SMN were the leading causes of death (3 and 6, respectively).ConclusionPatients with +12 CLL show characteristic clinical and biologic features, and may benefit from increased surveillance for second cancers.

Intravascular large cell lymphoma (IVLCL) is a rare disease characterized by proliferation of malignant lymphocytes within the small blood vessel lumens. The association of IVLCL with autoimmune hemolytic anemia (AIHA) has been described in a single case report, but the true prevalence of this co-occurrence is not known because of declining autopsy rates. Here, we report a case of a 41-year-old woman who carried a diagnosis of AIHA for 2 years, with repeated hemolytic episodes that were initially well controlled with immunomodulatory treatment. At her last presentation, the patient developed rapidly progressive neurologic symptoms and leukoencephalopathy on MRI; she died 4 weeks later with a clinical impression of thrombotic microangiopathy, a known complication of AIHA. At autopsy, the brain showed widespread platelet thrombi and intraparenchymal hemorrhages characteristic of this disorder. In addition, there was evidence of a clinically unsuspected IVLCL, most likely of B-cell lineage. This case illustrates a potential association between IVLCL and AIHA, highlights the need for broad differential diagnosis in cases with atypical disease presentation or progression, and underlines the importance of autopsy in establishing the full cause of morbidity and mortality.

PurposeHIV-related diffuse large B-cell lymphoma (DLBCL) may be biologically different from DLBCL in the general population. We compared, by HIV status, the expression and prognostic significance of selected oncogenic markers in DLBCL diagnosed at Kaiser Permanente in California, between 1996 and 2007.Experimental designEighty HIV-infected DLBCL patients were 1:1 matched to 80 HIV-uninfected DLBCL patients by age, gender, and race. Twenty-three markers in the following categories were examined using IHC: (i) cell-cycle regulators, (ii) B-cell activators, (iii) antiapoptotic proteins, and (iv) others, such as IgM. Tumor marker expression was compared across HIV infection status by Fisher exact test. For markers differentially expressed in HIV-related DLBCL, logistic regression was used to evaluate the association between tumor marker expression and 2-year overall mortality, adjusting for International Prognostic Index, cell-of-origin phenotype, and DLBCL morphologic variants.ResultsExpression of cMYC (% positive in HIV-related and -unrelated DLBCL: 64% vs. 32%), BCL6 (45% vs. 10%), PKC-β2 (61% vs. 4%), MUM1 (59% vs. 14%), and CD44 (87% vs. 56%) was significantly elevated in HIV-related DLBCLs, whereas expression of p27 (39% vs. 75%) was significantly reduced. Of these, cMYC expression was independently associated with increased 2-year mortality in HIV-infected patients [relative risk = 3.09 (0.90-10.55)] in multivariable logistic regression.ConclusionsThese results suggest that HIV-related DLBCL pathogenesis more frequently involves cMYC and BCL6 among other factors. In particular, cMYC-mediated pathogenesis may partly explain the more aggressive clinical course of DLBCL in HIV-infected patients.

Pathogenesis of Richter transformation (RT) or Richter syndrome (RS) of chronic lymphocytic leukemia (CLL) is still largely unknown. Increasing evidences show that c-MYC may play a role in the development of RS. Here we report three cases of RS with overexpression of c-MYC. The first case was a 78-year-old male who initially presented with CLL and then developed diffuse lymphadenopathy and ascites shortly after. Ascites cytology showed a population of large lymphoid cells positive for MYC (8q24) rearrangement by fluorescence in situ hybridization (FISH) and overexpression of c-MYC by immunohistochemistry (IHC). The second case was a 66-year-old male presented with rapidly enlarging lymph nodes and pleural effusion after a long history of CLL. Biopsy showed large B-cells positive for c-MYC overexpression and high Ki-67 proliferation index (80-90%). The third case was a 62-year-old female with CLL who presented for lobectomy for lung adenocarcinoma. Interestingly, along with the carcinoma, large B-cell lymphoma was incidentally found which had the same immunophenotype as the CLL. FISH analysis revealed gain of c-MYC at 8q and IHC showed increased c-MYC expression. This study supports that c-MYC plays a critical role in RS.

BackgroundCurrent treatment of diffuse-large-B-cell lymphoma (DLBCL) includes rituximab, an expensive drug, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy. Economic models have predicted rituximab plus CHOP (RCHOP) to be a cost-effective alternative to CHOP alone as first-line treatment of DLBCL, but it remains unclear what its real-world costs and cost-effectiveness are in routine clinical practice.MethodsWe performed a population-based retrospective cohort study from 1997 to 2007, using linked administrative databases in Ontario, Canada, to evaluate the costs and cost-effectiveness of RCHOP compared to CHOP alone. A historical control cohort (n = 1,099) with DLBCL who received CHOP before rituximab approval was hard-matched on age and treatment intensity and then propensity-score matched on sex, comorbidity, and histology to 1,099 RCHOP patients. All costs and outcomes were adjusted for censoring using the inverse probability weighting method. The main outcome measure was incremental cost per life-year gained (LYG).ResultsRituximab was associated with a life expectancy increase of 3.2 months over 5 years at an additional cost of $16,298, corresponding to an incremental cost-effectiveness ratio of $61,984 (95% CI $34,087-$135,890) per LYG. The probability of being cost-effective was 90% if the willingness-to-pay threshold was $100,000/LYG. The cost-effectiveness ratio was most favourable for patients less than 60 years old ($31,800/LYG) but increased to $80,600/LYG for patients 60-79 years old and $110,100/LYG for patients ≥ 80 years old. We found that post-market survival benefits of rituximab are similar to or lower than those reported in clinical trials, while the costs, incremental costs and cost-effectiveness ratios are higher than in published economic models and differ by age.ConclusionsOur results showed that the addition of rituximab to standard CHOP chemotherapy was associated with improvement in survival but at a higher cost, and was potentially cost-effective by standard thresholds for patients

Intestinal lipomatosis is a rare disease. There is diffuse, unencapsulated, multifocal infiltration of mature adipose tissue into the intestinal submucosal or subserosal layers. The disease may remain asymptomatic or present with complications like intussusception, obstruction, bleeding or perforation. Here by authors report a case of a 46-year-old male patient who presented with acute abdomen to the emergency department of the hospital. An emergency preoperative workup of the patient was performed including Computed Tomography (CT) which showed a sealed caecal perforation. Following which the patient was subjected to emergency laparotomy and right hemicolectomy was performed. The histopathology specimen was intensively studied and the cause for the sealed caecal perforation was confirmed to be due to intestinal lipomatosis.

Background: Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), are associated with pulmonary hypertension (PH) and malignant lymphomas. Although the underlying mechanisms have not been completely clarified, it has been suggested that the Janus kinase 2 (JAK2) mutation, which is frequently identified in PV, can be involved in the development and/or progression of these distinct diseases in patients with MPNs. However, no reports have described the coexistence of PH and malignant lymphoma in patients with MPNs. Case Report: A 79-year-old man being treated for PV for 27 years and PH for 5 years was hospitalized due to severe dyspnea at rest. His soluble interleukin-2 receptor levels gradually increased and the chest computed tomography showed remarkable progression of the lung lesions and an enlargement of the mediastinal and axillary lymph nodes. A lymph node biopsy was performed and the patient was diagnosed with diffuse large B-cell lymphoma (DLBCL). Owing to his poor condition, chemotherapy was not initiated, and he died on the 89th day of hospitalization. The pathological autopsy revealed the destruction of alveolar structures with neoplastic space-occupying lesions of DLBCL. Multifactorial features of PH associated with MPNs, including the intimal thickening of pulmonary arteries accompanied by megakaryocytes and obstructed pulmonary arteries with organized thrombi in the lung tissue specimens, were observed. We found a JAK2 mutation based on a genetic analysis of the patient's bone marrow. Conclusions: We present the rare case of a patient who had PV with a JAK2 mutation, which coexisted with PH and DLBCL, and he developed severe refractory respiratory failure. [ABSTRACT FROM AUTHOR]

Introduction: We previously examined how expanding access to chimeric antigen receptor (CAR) T cell therapy administration sites impacted patient travel distances and time. In the current study, we estimated travel-related economic burden associated with site-of-care options among patients with relapsed/refractory diffuse large B cell lymphoma.Methods: We used geographic information system methods to quantify travel-related economic burden across three site-of-care scenarios: academic hospitals; academic and community multispecialty hospitals; and academic and community multispecialty hospitals plus nonacademic specialty oncology network centers. Socioeconomic status, administration sites, and county of residence were derived from the US Census Bureau and publicly available sources. Travel costs were based on governmental guidelines, US census wage data, and Bureau of Transportation Statistics. Travel distance and time to the nearest CAR T cell therapy administration sites were estimated from previous research.Results: Total national estimated costs associated with traveling for CAR T cell therapy were $21.1 million if CAR T cell therapy was offered exclusively in academic hospitals, and $14.7 million if expanded to include community hospitals plus nonacademic specialty oncology network centers, representing a $6.5-million reduction associated with expanding access to eligible patients. The largest cost-saving component was lodging/meals. Regional and demographic cost differences were statistically significant between academic hospitals and nonacademic hospitals/specialty oncology centers. In all scenarios, patients living below the federal poverty level (FPL) had higher weighted mean total costs versus patients living above the FPL. White and Native American patients were estimated to have the highest weighted mean total costs across race/ethnicity groups. For all subgroups, costs were reduced by expanding access beyond academic hospitals.Conclusion: CAR T cell therapy is currently restricted to academic hospitals; total travel costs could be substantially decreased if access is expanded to nonacademic hospitals and specialty oncology centers. Patients in rural areas and those living below the FPL are particularly disadvantaged by restricted access. [ABSTRACT FROM AUTHOR]

Since specular reflection often exists in the real captured images and causes deviation between the recorded color and intrinsic color, specular reflection separation can bring advantages to multiple applications that require consistent object surface appearance. However, due to the color of an object is significantly influenced by the color of the illumination, the existing researches still suffer from the near-duplicate challenge, that is, the separation becomes unstable when the illumination color is close to the surface color. In this paper, we derive a polarization guided model to incorporate the polarization information into a designed iteration optimization separation strategy to separate the specular reflection. Based on the analysis of polarization, we propose a polarization guided model to generate a polarization chromaticity image, which is able to reveal the geometrical profile of the input image in complex scenarios, e.g., diversity of illumination. The polarization chromaticity image can accurately cluster the pixels with similar diffuse color. We further use the specular separation of all these clusters as an implicit prior to ensure that the diffuse component will not be mistakenly separated as the specular component. With the polarization guided model, we reformulate the specular reflection separation into a unified optimization function which can be solved by the ADMM strategy. The specular reflection will be detected and separated jointly by RGB and polarimetric information. Both qualitative and quantitative experimental results have shown that our method can faithfully separate the specular reflection, especially in some challenging scenarios. [ABSTRACT FROM AUTHOR]

Global illuminance on an inclined plane is affected by many factors, such as geographic longitude, latitude, time, weather, plane orientation, and inclination angle. To accurately and economically predict any slope illuminance under a cloudless sky, this study proposes a calculation model for the global horizontal irradiance and illuminance under a cloudless sky. The diffuse illuminance on the tilted surface was calculated by using the Perez point source model. The relationship between the global horizontal irradiance or illuminance and the solar altitude angle under a cloudless sky was established to address the reliance of the Perez point source model on real-time test data. The measured data from the French station of the International Daylighting Measurement Program was used to verify the global horizontal irradiance and illuminance and the global vertical north, east, south, and west illuminance. The global illuminance on an arbitrary inclined plane was verified using the measured data from China. Graphical and statistical methods were used to evaluate the error of the forecast data, and the reasons for the error were analyzed. Results show that the global horizontal irradiance and illuminance under a cloudless sky are linear functions of the solar altitude angle. The relative root mean square error (RRMSE) of the predicted global horizontal irradiance and illuminance are 5.4% and 10.2%, respectively. The proposed calculation method of illuminance on a tilted surface does not rely on real-time measured data, significantly saving in test costs and predicting illuminance at any inclination angle and orientation under a cloudless sky. Except for the RRMSE of the global vertical north illuminance of 19.8%, the RRMSE of the predicted global illuminance on the inclined plane in other orientations does not exceed 10.2%. This study provides an essential reference for predicting luminance in the access zone of a road tunnel. [ABSTRACT FROM AUTHOR]

The clinico-etiological spectrum of Acute leukoencephalopathy with restricted diffusion (ALERD) is not well known in Indian population. This is likely to vary between populations and ethnicities. We retrospectively reviewed the clinicoetiological spectrum of ALERD at a tertiary care pediatric center, and described the clinical, imaging, etiological spectrum and short-term outcomes. Eleven out of 78 children with non-traumatic encephalopathy presenting to our center had a final diagnosis of ALERD. The mean age at presentation was 34.9 months (6–80 months) and 63.6% were males. The monophasic course (72.7%) and the diffuse pattern (63.6%) on neuroimaging were predominant in these children. Dengue haemorrhagic fever was the commonest underlying/triggering infection (5 of 11 children). Ten children required mechanical ventilation in view of neurogenic respiratory failure, with mean duration of ventilation of 6.4 days (Range 2–10 days). The duration of hospital stay varied from 11 to 25 days (Mean – 15.3 days). One child (9 %) died, 6 children (54.5 %) had varying degrees of cognitive impairment and 4 (36.3 %) children had a normal outcome. Children with a shorter duration of ventilation seemed to have a better outcome. Dengue haemorrhagic fever was the commonest cause, and diffuse imaging pattern with monophasic course was the commonest presentation in Indian children with ALERD. The clinical presentation and factors influencing outcome are possibly different from previously described literature. [ABSTRACT FROM AUTHOR]

Plexiform fibromyxoma (PF) of the stomach is a very rare mesenchymal tumor of the gastrointestinal tract. We report the first case of PF with 2 different growth patterns pathologically confirmed after surgical resection. The tumor was characterized microscopically as infiltrative; it demonstrated diffuse growth into the smooth muscle bundles of the muscularis propria and was also multinodular and plexiform within the myxoid stroma. Immunohistochemical analysis revealed that the tumor cells were positive or weakly positive for smooth muscle actin, vimentin, and H-caldesmon and negative for desmin, CD117, CD34, CK20, Pan-CK, Dog1, S100, ER, PR, and CD10. No mutations of C-kit and platelet-derived growth factor receptor alpha were detected. No genetic disruption of glioma-associated oncogene homolog 1 was detected by fluorescence in situ hybridization. The final diagnosis of PF was mainly based on the morphological and immunohistochemical findings. [ABSTRACT FROM AUTHOR]

Background Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in Asia and Indonesia. DLBCL could be further classified according to cell of origin as the germinal center B-cell (GCB) subtype or the non-germinal center B-cell (non- GCB) subtypes; of these, the non-GCB subtype usually has poorer prognosis. The purpose of this study is to determine the relationship between the cell-origin subtype and 3-year overall survival of patients with DLBCL at Kariadi General Hospital Semarang. Methods This research represents an observational analytical study of 36 patients with DLBCL who visited Kariadi General Hospital between January and August 2017. Data on age of diagnosis, tumor location, disease stage, and 3-year overall survival were collected. DLBCL subtype was determined via immunohistochemical examination of CD10, BCL6, and MUM1 protein expression. Data analyses, including the chi squared test and Kaplan-Meier curves, were conducted. Results The study population included 18 patients with GCB-subtype DLBCL and 18 patients with non- GCB-subtype DLBCL. No significant difference (P = 0.171) between disease stage and cell-origin subtype was noted between groups. Patients with the non- GCB subtype had a 3-year overall survival that was significantly worse than that of patients with the GCB subtype (P = 0.026). Moreover, the 3-year survival rate of patients with the non-GCB subtype of the disease was 38.9% while that of patients with the GCB subtype was 77.8%. Patients with advanced stages of DLBCL also had a 3-year overall survival that was significantly worse than those of patients with early stages of the disease (P < 0.001), with the 3-year survival rate of patients with advanced stage was 14.3%. Conclusion Patients with non-GCB-subtype DLBCL or advanced stages of the disease have a lower 3-year overall survival rate and poorer prognosis compared with those with other subtypes or earlier stages of the disease. [ABSTRACT FROM AUTHOR]

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.

ObjectiveSkin and musculoskeletal involvement are frequently present early in diffuse cutaneous systemic sclerosis (dcSSc). The current study examined the correlates for skin and musculoskeletal measures in a 1-year longitudinal observational study.MethodsPatients with dcSSc were recruited at 4 US centers and enrolled in a 1-year study. Prespecified and standardized measures included physician and patient assessments of skin involvement, modified Rodnan skin score (MRSS), durometer score, Health Assessment Questionnaire disability index, serum creatine phosphokinase, tender joint counts, and presence/absence of tendon friction rubs, small joint contractures, and large joint contractures. Additionally, physician and patient global health assessments and health-related quality of life assessments were recorded. Correlations were computed among the baseline global assessments, skin variables, and musculoskeletal variables. Using the followup physician and patient anchors, effect sizes were calculated.ResultsA total of 200 patients were studied: 75% were women, mean ± SD age was 50.0 ± 11.9 years, and mean ± SD disease duration from first non-Raynaud's phenomenon symptom was 1.6 ± 1.4 years. Physician global health assessment had large correlations with MRSS (r = 0.60) and physician-reported skin involvement visual analog scale in the last month (r = 0.74), whereas patient global assessment had large correlations with MRSS, the Short Form 36 health survey physical component scale, skin interference, and skin involvement in the last month (r = 0.37-0.72). Four of 9 skin variables had moderate to large effect sizes (0.51-1.09).ConclusionPhysician and patient global assessments have larger correlations with skin measures compared to musculoskeletal measures. From a clinical trial perspective, skin variables were more responsive to change than musculoskeletal variables over a 1-year period, although both provide complementary information.

Despite advances in treatment, including the introduction of rituximab, survival after diffuse large B-cell lymphoma (DLBCL) remains heterogeneous. However, no studies have considered the association between neighborhood socioeconomic status (SES) and race/ethnicity on DLBCL mortality before (1988-2000) and after (2001-2009) the introduction of rituximab. We studied all 33,032 DLBCL patients diagnosed between 1988-2009 in California for vital status through December 31, 2010. Patients diagnosed from 2001 to 2009 vs 1988 to 2000 had significantly decreased overall and DLBCL-specific mortality. However, those living in lower SES neighborhoods had 34% (95% confidence interval [CI], 27%-40%) and 24% (95% CI, 16%-32%) higher mortality rate from all causes and lymphoma, respectively, than patients in higher SES neighborhoods. The magnitude of mortality disparities by neighborhood SES was more marked in younger (

OBJECTIVE: To determine if changes in levels of serum microRNAs (miRNAs) were seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL). DESIGN: Serum miRNA levels were compared in 3 subject groups from the Multicenter AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62, median time before diagnosis, 8.8 months). METHODS: A total of 175 serum-enriched miRNAs were initially screened to identify differentially expressed miRNAs among these groups and the results validated by quantitative polymerase chain reaction. Receiver-operating characteristic analysis was then performed to assess biomarker utility. RESULTS: Higher levels of miR-21 and miR-122, and a lower level of miR-223, were able to discriminate HIV-infected from the HIV-uninfected groups, suggesting that these miRNAs are biomarkers for HIV infection but are not AIDS-NHL specific. Among the HIV-infected groups, a higher level of miR-222 was able to discriminate diffuse large B-cell lymphoma (DLBCL) and primary central nervous system lymphoma (PCNSL) subjects from HIV-infected subjects who did not develop NHL, with area under the receiver-operating characteristic curve of 0.777 and 0.792, respectively. At miR-222 cutoff values of 0.105 for DLBCL and 0.109 for PCNSL, the sensitivity and specificity were 75% and 77%, and 80% and 82%, respectively. CONCLUSIONS: Altered serum levels of miR-21, miR-122, and miR-223 are seen in HIV-infected individuals. Higher serum level of miR-222 has clear potential as a serum biomarker for earlier detection of DLBCL and PCNSL among HIV-infected individuals.

ObjectiveTo determine if changes in levels of serum microRNAs (miRNAs) were seen preceding the diagnosis of AIDS-related non-Hodgkin lymphoma (AIDS-NHL).DesignSerum miRNA levels were compared in 3 subject groups from the Multicenter AIDS Cohort Study: HIV-negative men (n = 43), HIV-positive men who did not develop NHL (n = 45), and HIV-positive men before AIDS-NHL diagnosis (n = 62, median time before diagnosis, 8.8 months).MethodsA total of 175 serum-enriched miRNAs were initially screened to identify differentially expressed miRNAs among these groups and the results validated by quantitative polymerase chain reaction. Receiver-operating characteristic analysis was then performed to assess biomarker utility.ResultsHigher levels of miR-21 and miR-122, and a lower level of miR-223, were able to discriminate HIV-infected from the HIV-uninfected groups, suggesting that these miRNAs are biomarkers for HIV infection but are not AIDS-NHL specific. Among the HIV-infected groups, a higher level of miR-222 was able to discriminate diffuse large B-cell lymphoma (DLBCL) and primary central nervous system lymphoma (PCNSL) subjects from HIV-infected subjects who did not develop NHL, with area under the receiver-operating characteristic curve of 0.777 and 0.792, respectively. At miR-222 cutoff values of 0.105 for DLBCL and 0.109 for PCNSL, the sensitivity and specificity were 75% and 77%, and 80% and 82%, respectively.ConclusionsAltered serum levels of miR-21, miR-122, and miR-223 are seen in HIV-infected individuals. Higher serum level of miR-222 has clear potential as a serum biomarker for earlier detection of DLBCL and PCNSL among HIV-infected individuals.

Reticulohistiocytomas are benign dermal tumors that usually present as either solitary or multiple, cutaneous nodules.  Reticulohistiocytosis can present as solitary or generalized skin tumors or cutaneous lesions with systemic involvement and are potentially associated with internal malignancy.  A woman with a solitary red nodule on her knee is described in whom the clinical differential diagnosis included dermatofibroma and amelanotic malignant melanoma.  Hematoxylin and eosin staining and immunoperoxidase studies of the biopsy specimen established the diagnosis of adult-onset reticulohistiocytoma (solitary epithelioid histiocytoma).  Reticulohistiocytoma is characterized by mononuclear, and occasionally multinuclear, histiocytes with eosinophilic “glassy” cytoplasm.  The immunohistochemical profile of a  reticulohistiocytoma demonstrates consistent positive expression for CD68 (a marker that is expressed by histiocytes but can also show positive staining in melanomas and carcinomas), CD163 (a very specific marker for histiocytes), and vimentin.  Reticulohistiocytomas show variable positive expression for MITF (microphthalmia transcription factor) and S100 protein, both of which are more commonly used as markers for melanocytes.  Recurrence of a reticulohistiocytoma is rare, even for patients with an incompletely removed lesion.  However, our patient elected to have her residual tumor completely excised.

Tarek Roshdy Elhamaky, Ahmed Mohammed Elbarky Department of Ophthalmology, Benha Faculty of Medicine, Benha University, Benha, EgyptCorrespondence: Tarek Roshdy ElhamakyDepartment of Ophthalmology, Benha Faculty of Medicine, Benha University, Qalyubiya Governorate, Benha 13511, EgyptTel +20133227819Fax +20133256457Email dr_thamakyy@yahoo.comPurpose: To evaluate the efficacy of combined limited surgical resection, amniotic membrane graft and topical mitomycin C in treatment of diffuse conjunctival squamous cell carcinoma (CSCC) diagnosed and followed up by anterior segment optical coherence tomography (AS-OCT).Subjects and methods: A prospective study was performed on 24 eyes with diffuse CSCC. Fifteen eyes underwent lesion limited resection followed by postoperative topical mitomycin C 0.04% eye drop (MMC group) while nine eyes underwent complete excision and cryotherapy (no MMC group). Amniotic membrane graft was applied in all cases. The diagnosis was based on clinical and AS-OCT specific criteria of CSCC and was confirmed by histopathological results.Results: The study population was similar between the two groups. Mean postoperative follow-up was 27.1±4.1 months. The mean extent of the limbal involvement was 7.0±0.7 and 7.25±0.6 clock hours in MMC and no MMC groups, respectively. The mean size of conjunctival defect after tumor excision in MMC group (60.8±9.2 mm2) was significantly lower than in no MMC group (92.4±17.3 mm2). Histopathological diagnosis revealed invasive SCC in all specimens. The mean preoperative conjunctival epithelial thickness decreased significantly in both groups at 2-year follow-up. It decreased from 267±24.2 and 256±19.1 μm preoperatively to 56.7±11.6 and 60.4±9.6 μm at 2-year follow-up in MMC and no MMC groups, respectively. The mean number of MMC treatment cycles was 2.1±0.85 cycles. Recurrence was recorded in zero (0%) and 1 (11%) patients at 2-year follow-up in MMC and no MMC groups, respectively. Histopathological diagnosis revealed invasive SCC in all specimens. The mean preoperative conjunctival epithelial thickness decreased significantly in both groups at 2-year follow-up. It decreased from 267±24.2 and 256±19.1 μm preoperatively to 56.7±11.6 and 60.4±9.6 μm at 2-year follow-up in MMC and no MMC groups, respectively. The mean number of MMC treatment cycles was 2.1±0.85 cycles. Recurrence was recorded in zero (0%) and 1 (11%) patients at 2-year follow-up in MMC and no MMC groups, respectively.Conclusion: The treatment of diffuse CSCC with AS-OCT guided combined therapy includes limited surgical resection, AMG, and postoperative topical MMC, achieves a complete tumor resolution and good functional and cosmetic outcomes minimizing the burden of surgery, and improves postoperative patient comfort in our study cohort.Keywords: diffuse, conjunctival squamous cell carcinoma, mitomycin C, AS-OCT, amniotic membrane graft

No abstract available. Article truncated after 150 words. Clinical History: A 56-year-old post-menopausal woman with a remote history of asthma and asymptomatic uterine fibroids presented with a macular-papular rash over the upper chest, upper medial left forearm, and medial legs, without scaling that has intermittently recurred over the previous few years. The rash is unaccompanied by fever, chills, rigors, abdominal pain, cough, conjunctivitis, urethritis, or any other mucocutaneous lesions. The patient did not note any seasonal relationships or association with food, and the rash regresses promptly with H1 or H2-blocker therapy. The patient’s past medical history was otherwise unremarkable. Her surgical history was positive only for a laparoscopic left inguinal hernia repair 7 years earlier. The patient indicated she was neither a smoker nor a drinker. Her medications included an as-needed albuterol inhaler, a steroid inhaler, a nasal steroid spray, a multivitamin, and a topical steroid. The patient’s physical examination showed normal vital signs, although her pulse rate …

Actinomycosis can mask malignant diseases. This paper reports a case of colonic diffuse large B-cell lymphoma (DLBCL), which was misdiagnosed as abdominal actinomycosis. A 76-year-old woman presented with right flank pain and weight loss. Abdominal CT and colonoscopy revealed a huge ascending colon mass. Despite the initial impression of a malignancy, a colonoscopic biopsy revealed no malignant cells, but sulfur granules and a filamentous organism suggesting actinomycosis. Intravenous penicillin G was administered under the impression of abdominal actinomycosis but her condition deteriorated rapidly. Follow up CT showed markedly increased colon mass and new multiple nodular lesions around the ascending colon. Sono-guided percutaneous biopsy of the nodular lesion was performed. The pathological result was DLBCL. The patient was scheduled to undergo chemotherapy but the patient expired due to cancer progression. The diagnosis of gastrointestinal infiltrating tumors is often difficult because a superficial biopsy usually does not provide a confirmative diagnosis. This case highlights the difficulty in making a correct diagnosis of lymphoma due to the concomitant actinomycosis. Malignant conditions must be considered in cases of actinomycosis with no response to antimicrobial therapy.

We report a case of clinically occult diffuse large B-cell lymphoma (DLBCL) of the middle turbinate (MT) identified by 18F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) in a 71-year-old man along with imaging findings. DLBCL was presented with a hypermetabolic right MT [maximum standardized uptake values (SUVmax) = 8.8 gm/dL] on 18F-FDG PET/CT, while rhinologic examination was normal. CT showed nothing but slightly more intense enhancement of the right MT compared with the opposite side. The disease progressed during next 7 months until follow-up CT demonstrated solidly enhancing mass occupying entire right nasal cavity which was intensely hypermetabolic (SUVmax = 12.8 gm/dL). Surgical biopsy confirmed the diagnosis. Follow-up CT and 18F-FDG PET/CT performed after chemotherapy demonstrated complete resolution of DLBCL of the right nasal cavity including the right MT. This is thought to be the first case report in the literature concerning clinically occult DLBCL presenting as a hypermetabolic MT on 18F-FDG PET/CT.

Abstract Background Reducing diagnostic delays in cancer has been a major interest worldwide; however, the literature on diagnostic delays in lymphoma remains scarce. Diffuse large B‐cell lymphoma (DLBCL) is the most common non‐Hodgkin's lymphoma. We aimed to determine whether certain structural factors predicted diagnostic delays in DLBCL and whether diagnostic delays impacted overall survival (OS). Methods Data were extracted via a retrospective cohort design from a single academic tertiary care referral center. A total of 104 patients were included. Time from first symptoms to diagnosis of 6 months did predict worse OS. Conclusion Our data suggest that excessive diagnostic delays of more than 6 months, ethnic minority status, and uninsured status in DLBCL may lead to worse outcomes. Efforts should be undertaken to reduce excessive diagnostic delays. More investigation needs to be done on the impacts of diagnostic delays in both DLBCL and other aggressive lymphomas.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease affecting the blood vessels, skin, and internal organs. The main pathogenic mechanisms are vascular dysregulation, tissue fibrosis due to collagen and extracellular protein deposition, and autoantibody production due to immune dysfunction. The treatment also targets these mechanisms. Various criteria including the American College of Rheumatology and the European League against Rheumatism are laid down for the clinical diagnosis of scleroderma, and treatment is tailored to the systems involved. In the initial stages of the SSc, immunosuppressants are more useful, whereas in the later stages, antifibrotic therapies are important. Vasospasm and endothelial dysfunction are seen in all stages of the disease, and hence, vascular therapies are needed throughout the course of the disease. Special care should be taken to rule out gastrointestinal, pulmonary, and renal system involvement if the primary treatment is by a dermatologist.

Objective: to describe the prevalences, characteristics, and survivals of patients with anti-topoisomerase 1 antibodies (ATA) and limited cutaneous systemic sclerosis (lSSc) and anti-centromere antibodies (ACA) and diffuse cutaneous systemic sclerosis (dSSc). Methods: patients with ATA lSSc or with ACA dSSc were included in a case-control retrospective study. Results: In our cohort of scleroderma, the prevalence of ACA dSSc and ATA lSSc was 1.1% (12/1040) and 8.9% (93/1040), respectively. ACA dSSc patients had less interstitial lung disease (ILD) (5 (41.7) vs. 74 (79.6); p < 0.01), more cardiac involvement, and more muscle involvement (3 (25) vs. 4 (4.3); p = 0.03 and 4 (33.3) vs. 4 (7.5); p = 0.02,) than ATA dSSc patients. ATA lSSc patients had a higher modified Rodnan skin score than ACA lSSc patients (4 [2–7.5] vs. 2 [0–5]; p < 0.01) and less cardiac or muscle involvement than ATA dSSc patients (6 (6.5) vs. 19 (20.4%); p < 0.01 and 15 (16.1) vs. 54 (58.1); p < 0.0001, respectively). The cumulative 5-year survival rate was 71% in ACA dSSc patients, 95% in ATA lSSc patients, 84% in ACA lSSc patients, and 66% in ATA dSSc patients (p < 0.0001). Conclusion: ATA lSSc and ACA dSSc have specific characteristics when compared to ATA dSSc or ACA lSSc. ATA lSSc patients have more ILD than ACA lSSc patients, and ATA dSSc patients have the worst prognosis. Overall, inverted phenotypes show the value of a patient assessment combining antibody and skin subset and should be considered as a separate group.

PurposeThe Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade.Patients and methodsWe conducted an international phase II study of pidilizumab, an anti-PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT.ResultsSixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E-bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab.ConclusionThis is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease.

BackgroundLymphoma is the leading cause of cancer-related death among HIV-infected patients in the antiretroviral therapy (ART) era.MethodsWe studied lymphoma patients in the Centers for AIDS Research Network of Integrated Clinical Systems from 1996 until 2010. We examined differences stratified by histology and diagnosis year. Mortality and predictors of death were analyzed using Kaplan-Meier curves and Cox proportional hazards.ResultsOf 23 050 HIV-infected individuals, 476 (2.1%) developed lymphoma (79 [16.6%] Hodgkin lymphoma [HL]; 201 [42.2%] diffuse large B-cell lymphoma [DLBCL]; 56 [11.8%] Burkitt lymphoma [BL]; 54 [11.3%] primary central nervous system lymphoma [PCNSL]; and 86 [18.1%] other non-Hodgkin lymphoma [NHL]). At diagnosis, HL patients had higher CD4 counts and lower HIV RNA than NHL patients. PCNSL patients had the lowest and BL patients had the highest CD4 counts among NHL categories. During the study period, CD4 count at lymphoma diagnosis progressively increased and HIV RNA decreased. Five-year survival was 61.6% for HL, 50.0% for BL, 44.1% for DLBCL, 43.3% for other NHL, and 22.8% for PCNSL. Mortality was associated with age (adjusted hazard ratio [AHR] = 1.28 per decade increase, 95% confidence interval [CI] = 1.06 to 1.54), lymphoma occurrence on ART (AHR = 2.21, 95% CI = 1.53 to 3.20), CD4 count (AHR = 0.81 per 100 cell/µL increase, 95% CI = 0.72 to 0.90), HIV RNA (AHR = 1.13 per log10copies/mL, 95% CI = 1.00 to 1.27), and histology but not earlier diagnosis year.ConclusionsHIV-associated lymphoma is heterogeneous and changing, with less immunosuppression and greater HIV control at diagnosis. Stable survival and increased mortality for lymphoma occurring on ART call for greater biologic insights to improve outcomes.

Background: Childhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings.Methods: In this retrospective analysis, conducted between 2010 and 2019, all pediatric patients with a diagnosis of dBSG were analyzed. The survival data were calculated in months from the date of diagnosis. Survival differences between variables were compared using the Log-rank test and the risk of death was calculated using Cox regression analysis.Results: A total of 20 patients (11 males, 55%) with a diagnosis of dBSG were included. Median age at diagnosis was 6.5 years. No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS.Conclusion: Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children. Lay summaryChildhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this 10-year retrospective study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings. A total of 20 patients with a diagnosis of dBSG were included with a median age at diagnosis of 6.5 years (5.25-8.75). No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a 3.4-fold (95% CI 1.0-12.1) higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS. Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children. [ABSTRACT FROM AUTHOR]

Most patients with diffuse large B‐cell lymphoma (DLBCL) are diagnosed at age 60 years or older. Challenges to effective therapy among older individuals include unfavorable biologic features of DLBCL, geriatric vulnerabilities, suboptimal treatment selection, and toxicities of cytotoxic chemotherapy. Wider application of geriatric assessments may help identify fit older patients who benefit from standard immunochemotherapy without unnecessary dose reductions. Conversely, attenuated regimens may provide a better balance of risk and benefit for selected unfit or frail patients. Supportive care with the use of corticosteroid‐based prephase, prophylactic growth factors, and early institution of supportive and palliative care can help maximize treatment tolerance. Several novel or emerging therapies have demonstrated favorable toxicity profiles, thus facilitating effective treatment for elderly patients. In the relapsed or refractory setting, patients who are not candidates for stem cell transplantation can benefit from newly approved options including polatuzumab vedotin‐based combinations or tafasitamab plus lenalidomide, which may have higher efficacy and/or lower toxicity than historical chemotherapy regimens. Chimeric antigen receptor T‐cell therapy has been successfully applied to older patients outside of clinical trials. In the first‐line setting, emerging immunotherapy options (bispecific antibodies) and targeted therapies (anti‐CD20 antibodies combined with lenalidomide and/or B‐cell receptor inhibitors) may provide chemotherapy‐free approaches for DLBCL. Enrolling older patients in clinical trials will be paramount to fully examine potential efficacy and toxicity of these strategies. In this review, we discuss recent advances in fitness stratification and therapy that have expanded curative options for older patients, as well as future opportunities to improve outcomes in this population. Implications for Practice: Management of diffuse large B‐cell lymphoma in older patients poses challenges due to aggressive disease biology and geriatric vulnerability. Although R‐CHOP remains standard first‐line treatment, geriatric assessment may help evaluate patients' fitness for immunochemotherapy. Corticosteroid prephase, prophylactic growth factors, and early palliative care can improve tolerance of treatment. Novel salvage options (polatuzumab vedotin‐based combinations, tafasitamab plus lenalidomide) or chimeric antigen receptor T‐cell therapy should be considered in the relapsed or refractory setting for patients ineligible for stem cell transplantation. Emerging immunotherapies (bispecific antibodies) and targeted therapies provide potential first‐line chemotherapy‐free approaches, which need to be rigorously assessed in clinical trials that involve geriatric patients. Diffuse large B‐cell lymphoma (DLBCL) is an aggressive but potentially curable cancer that mainly affects older individuals. This review presents recent advances in fitness stratification and therapy that have expanded curative options for older patients with DLBCL and future opportunities to improve outcomes in this population. [ABSTRACT FROM AUTHOR]

In the juices of sugar beet, the viscosity of the produced viscosity is determined. They contain sugars and non-sugary compounds. If they are in the form of associated or complex compounds, then when their state changes. Well under the action of external factors or at their removal from a solution it is obligatory. Its rheological properties will also change. Therefore, with the help of determining the viscosity, it is possible to conclude the complex processes that take place in juices under the action of the effects of vapor condensation cavitation, namely: the force between Leculiary bonds, the size of molecules, and the length of chemical bonds, etc. The paper presents studies of the influence of vapor-condensation cavitation effects on the change of such rheological properties of cell and diffusion juice as viscosity and surface tension. The viscosity of the steamtreated juice is affected by complex transformational changes that occur with the associated compounds under the effects of vapor-condensation cavitation, which leads to their destruction and this leads to a decrease in their molecular weight and changes in concentration. Studies have shown that with increasing steam consumption for juice processing in the range of 0 – 1.5% by weight of juice the upper tension increases. Such legitimacy is also an indirect confirmation of the processes of destruction of the association. important compounds of diffusion juice under the influence of the effects of steam condensation cavitation. [ABSTRACT FROM AUTHOR]

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Competing Interests: None disclosed.

Diffuse large B-cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and an aggressive malignancy. Galectin-3 (gal-3), the only antiapoptotic member of the galectin family, is overexpressed in DLBCL. While gal-3 can localize to intracellular sites, gal-3 is secreted by DLBCL cells and binds back to the cell surface in a carbohydrate-dependent manner. The major counterreceptor for gal-3 on DLBCL cells was identified as the transmembrane tyrosine phosphatase CD45. Removal of cell-surface gal-3 from CD45 with the polyvalent glycan inhibitor GCS-100 rendered DLBCL cells susceptible to chemotherapeutic agents. Binding of gal-3 to CD45 modulated tyrosine phosphatase activity; removal of endogenous cell-surface gal-3 from CD45 with GCS-100 increased phosphatase activity, while addition of exogenous gal-3 reduced phosphatase activity. Moreover, the increased susceptibility of DLBCL cells to chemotherapeutic agents after removal of gal-3 by GCS-100 required CD45 phosphatase activity. Gal-3 binding to a subset of highly glycosylated CD45 glycoforms was regulated by the C2GnT-1 glycosyltransferase, indicating that specific glycosylation of CD45 is important for regulation of gal-3-mediated signaling. These data identify a novel role for cell-surface gal-3 and CD45 in DLBCL survival and suggest novel therapeutic targets to sensitize DLBCL cells to death.

PurposeEpstein-Barr virus (EBV)-mediated lymphomagenesis in the setting of HIV infection has been widely accepted. However, little is known about how EBV impacts prognosis. We investigated the hypothesis that EBV infection is associated with expression of specific B-cell oncogenic markers in HIV-related diffuse large B-cell lymphoma (DLBCL) and examined the prognostic use of detecting EBV infection.Experimental designHIV-related DLBCL cases diagnosed between 1996 and 2007 within Kaiser Permanente California were identified. Immunohistochemical staining was used to analyze the expression of selected markers that are cell-cycle regulators, B-cell activators, and antiapoptotic proteins among others. EBV infection was determined by in situ hybridization of EBV RNA. Correlations between EBV and marker expression were examined using Spearman correlation coefficient. The prognostic use of EBV status was examined in multivariable Cox model adjusting for International Prognostic Index (IPI). Receiver-operating characteristics (ROC) analysis was used to evaluate improvement in model discrimination.ResultsSeventy HIV-related DLBCL cases were included (31% EBV±). EBV+ tumor was associated with increased expression of BLIMP1 and CD30 and reduced expression of BCL6 and LMO2. EBV+ tumor was independently associated with elevated 2-year overall mortality [HR, 3.3; 95% confidence interval (CI), 1.6-6.6]. Area under the ROC curve showed improved model discrimination when incorporating tumor EBV status with IPI in the prediction model [0.65 vs. 0.74 (IPI only)].ConclusionOur results suggest that EBV infection was associated with expression of several tumor markers that are involved in the NF-κB pathway and that detecting tumor EBV status may have prognostic use in HIV-related DLBCLs.

Lymphomas that develop in human immunodeficiency virus (HIV) infected patients are predominantly aggressive B-cells lymphomas. The most common HIV-associated lymphomas include Burkitt lymphoma, diffuse large B-cell lymphoma (that often involves the CNS), primary effusion lymphoma, and plasmablastic lymphoma (PBL). Of these, PBL is relatively uncommon and displays a distinct affinity for presentation in the oral cavity. In this manuscript we report a previously undescribed primary leptomeningeal form of PBL in a patient with acquired immunodeficiency syndrome. A 40-year-old HIV positive man presented with acute onset confusion, emesis, and altered mental status. Lumbar puncture showed numerous nucleated cells with atypical plasmocyte predominance. CSF flowcytometry showed kappa restriction with CD8 and CD38 positivity and negative lymphocyte markers, while the MRI showed diffuse leptomeningeal enhancement. As the extensive systemic work-up failed to reveal any disease outside the brain, an en bloc diagnostic brain and meningeal biopsy was performed. The biopsy specimen showed sheets of plasmacytoid cells with one or more large nuclei, prominent nuclear chromatin, scattered mitoses, and abundant cytoplasm, highly suggestive of plasmablastic lymphoma. HIV-associated malignancies have protean and often confusing presentations, which pose diagnostic difficulties posed to the practicing neurological-surgeons. Even in cases where an infectious cause is suspected for the meningeal enhancement, neoplastic involvement should be considered, and cytology and flow-cytometry should be routinely ordered on the CSF samples.

Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined)  = 0.64, P(combined)  = 2 × 10(-21)) located 962 bp away from rs10484561 (r(2)

Solar energy industries require an accurate estimation of global solar irradiation particularly on inclined planes. This improves the accuracy of the sizing procedures and optimizes the performance of the solar energy platforms as photovoltaic modules and flat-plate solar collectors. A variety of the transposition models have been developed and reportedly determine incidences of solar irradiance on an inclined surface. However, there is a gap in the literature regarding identifying the most promising transposition model, particularly for the Middle East and North Africa region (MENA). Therefore, this article serves two main objectives. Firstly, it compares comprehensively 24 different transposition models. Several statistical methods are used to quantify the performance of the tilted surface transposition models. Furthermore, the transposition models are compared with real, hourly measured time-series data for several Palestinian cities to identify the promising and most accurate model. The analysis was carried out on three bases: annually, monthly, and a clearness index. The transposition models prove their ability to represent the measured data during the annual and monthly analyses, but they all failed to achieve complacency in the clearness index (KtKt) for the clear sky condition (Kt > 0.78). Secondly, the article advises a reliable and accurate transposition model for the area of the MENA for clear sky conditions. The proposed model was tested for the sites under investigation, and it produces significantly better performance than the candidate transposition models.