Response assessment by positron emission tomography-computed tomography as compared with contrast-enhanced computed tomography in childhood Hodgkin lymphoma can reduce the need for radiotherapy in low- and middle-income countries.

INTRODUCTION: The InPOG-HL-15-01, a multicentric prospective study, used a risk-stratified and response-based approach with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) backbone to treat children and adolescents with newly diagnosed Hodgkin lymphoma (HL) and reduce the use of radiation therapy (RT). Children/adolescents with bulky disease or inadequate response at early response assessment (ERA) after two cycles of chemotherapy were assigned to receive RT. For ERA, positron emission tomography computed tomography (PET-CT) was recommended but not mandatory in view of limited access. This study aimed to compare the impact of using contrast-enhanced computed tomography (CECT) and PET-CT on treatment decisions and outcomes. METHODOLOGY: 396 patients were enrolled and 382 had an ERA at the assigned time point. Satisfactory response was defined as Deauville score 3 or less for patients undergoing PET-CT and complete response (CR)/very good partial response (VGPR) for patients undergoing CECT. Outcomes of interest incorporate 5 year event-free survival (EFS), EFS including abandonment (EFSa), and overall survival (OS). RESULTS: At ERA, satisfactory response was documented in 277 out of 382 (72.5%) participants and this was significantly higher in PET-CT (151 out of 186, 81.2%) as compared with CECT-based assessments (126 out of 196, 64.3%) respectively (p value < .001). Amongst the 203 patients with nonbulky disease (wherein the indication for RT was entirely dependent on ERA), 96 out of 114 (84.2%) and 61 out of 89 (68.5%) patients achieved a satisfactory response according to the PET-CT and CECT (p value = .008) respectively and hence a lesser proportion of patients in the PET-CT arm received RT. Despite a lower usage of RT the 5 year OS of both groups, ERA based on CECT (91.8%) versus PET-CT (94.1%) was comparable (p value = .391) and so was the 5 year EFS (86.7 vs. 85.5%, p value = .724). CONCLUSION: Use of PET-CT as the modality for ERA is more likely to indicate a satisfactory response as compared with CECT and thereby decreases the need for RT in response-based treatment algorithm for HL-afflicted children. The reduction in the application of RT did not impact the overall outcome and plausibly would lower the risk of delayed toxic effects.

Phase II study of interim PET-CT-guided response-adapted therapy in advanced Hodgkin's lymphoma.

BACKGROUND: Combination chemotherapy ABVD (doxorubicin, bleomycin, vinblastine and dacarabazine) cures ∼70% of patients with advanced Hodgkin's lymphoma (aHL, stages IIB, III and IV) while more toxic escalated BEACOPP (EB, combination of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone) increases cure rates to 85%. Patients with a positive interim positron emission tomography-computerized tomography (PET-CT) scan after two cycles (PET-2) of ABVD have very poor outcomes with continued ABVD. Intensifying therapy with EB in PET-2-positive patients ('response-adapted therapy') may improve cure rates, whereas the negative patients can continue ABVD alone. PATIENTS AND METHODS: Eligible patients with newly diagnosed aHL received two cycles of ABVD and underwent PET-2 (scored with semi-quantitative 5-point visual criteria, 'Deauville score'). PET-2-negative patients continued four additional cycles of ABVD, whereas PET-2-positive patients received four cycles of EB. A phase II sample size of 50 was estimated keeping the lower and higher proportion of rejection of the event-free survival (EFS) as 70% and 85%, respectively. RESULTS: Fifty patients [median age 28 (12-60) years; male : female: 39 : 11; stages: IIB-3 (6%), III-29 (58%) and IV-18 (36%); International Prognostic Score (IPS): 0-3: 34 (68%); 4-7: 16 (32%)] were enrolled; 49 underwent PET-2. Eight (16%) were PET-2-positive, whereas 41 (84%) were negative. Forty-seven were evaluable for EFS and all 50 for overall survival (OS). The 2-year EFS was 76% (95% CI: 68-83) and OS was 88% (95% CI: 82-94). PET-2 was strongly prognostic-2-year EFS, negative versus positive: 82% versus 50%; P = 0.013. CONCLUSION: PET-2 response-adapted strategy could not achieve EFS of 85% in aHL. However, escalated therapy improved outcomes in PET-2-positive patients compared with historical data. TRIAL REGISTRATION: CTRI/2012/06/002741 (http://www.ctri.nic.in) and NCT01304849 (http://www.clinicaltrials.gov).

Sensory quality of broiler breast meat influenced by low atmospheric pressure stunning, deboning time and cooking methods.

Stunning method (low atmospheric pressure stunning, LAPS and electrical stunning, ES), deboning time (0.75 h and 4 h), and cooking method (baking, frying, and sous vide) were evaluated for their impact on the descriptive sensory characteristics and consumer acceptability of breast meat (n=576, 144 birds per stunning × deboning time combination). Sensory evaluation was conducted by trained descriptive (n=8) and consumer (n=185) panels. On average, no differences (P>0.05) existed in the sensory acceptability of fried and sous vide cooked broiler breast treatment combinations. However, for oven-baking, the LAPS treatment that was deboned at 4 h was more acceptable (P<0.05) than other treatments and the ES and LAPS 4 h samples had greater (P<0.05) acceptability for texture than their ES and LAPS 0.75 h counterparts. Since consumers were highly variable in their liking of chicken breast treatments, consumers were grouped into clusters for each cooking method based on liking and preference. Cluster analysis data revealed that the largest groups of consumers liked (score≥6.0) all chicken breast treatments, but a larger proportion of consumers liked the 4 h LAPS and ES treatments when compared to the 0.75 h LAPS and ES treatments for all cooking methods. In addition, the consumers who indicated that baked chicken breast was highly acceptable preferred (P<0.05) 4 h LAPS over the 4 h ES samples. Based on sensory results, chicken breast meat from all stunning and deboning method combinations was highly acceptable to the majority of consumers, but the LAPS 4 h treatment had enhanced sensory characteristics when baked.

Gut Colonization With Antibiotic-Resistant Escherichia coli Pathobionts Leads to Disease Severity in Ulcerative Colitis.

BACKGROUND: Escherichia coli is a Gram-negative commensal of human gut. Surprisingly, the role of E. coli in the pathogenesis of ulcerative colitis (UC) has not been explored until now. METHODS: Human gut microbiota composition and meta-gut resistome were evaluated using metagenomics. Antibiotic susceptibility of E. coli isolates against different class of antibiotics was investigated. Further, the genome sequence analysis of E. coli isolates was performed to gain insight into the antimicrobial resistance (AMR) mechanism and virulence factors. Gut proteome of UC and non-UC was examined to understand the effect of resistant bacteria on host physiology. RESULTS: In UC patients, meta-gut resistome was found to be dominated by AMR genes (829) compared to healthy controls (HC) [518]. The metagenome study revealed a higher prevalence of AMR genes in the rural population (378 in HC; 607 in UC) compared to the urban (340 in HC; 578 in UC). Approximately, 40% of all E. coli isolates were multi-drug resistant (MDR), with higher prevalence in UC (43.75%) compared to HC (33.33%). Up-regulated expression of antimicrobial human proteins (lactotransferrin, azurocidin, cathepsin G, neutrophil elastase, and neutrophil defensin 3) and inflammatory mediator (Protein S100-A9 and Protein S100-A8) suggest microbial infection in UC gut. CONCLUSIONS: In addition to the conventional culturomics method, a multi-omics strategy provides deeper insights into the disease etiology, emergence of MDR pathobionts, and their roles in the disruption of the healthy gut environment in UC patients.

Experiences of mental health services by people with intellectual disabilities from different ethnic groups: a Delphi consultation.

BACKGROUND: Patient experience of those accessing mental health services has been found to be different between ethnic groups. Although the needs of people with intellectual disabilities (ID) from different ethnic communities are being increasingly recognised, little has been published about their experiences of mental health services. The aim of this study was to establish whether there are any differences in the experiences of people with ID and mental health problems from two ethnic communities in South London. METHOD: A two-round Delphi process was utilised. White British and Black or Black British service users from a specialist community-based mental health service for adults with ID completed a specially compiled questionnaire. Statements on participants' experiences, including satisfaction with care, staff members' attitudes, cultural awareness and level of support, were rated using a Likert scale. RESULTS: Twenty-four out of 32 participants (75%) completed both rounds of the Delphi consultation. Consensus (≥80% agreement with the group median) was reached for 20 items in the White group and five items in the Black group. All responses that reached consensus were positive about the services that were being received. The Black group were less positive about a range of their experiences, including the use of medication. CONCLUSIONS: People with ID from two ethnic groups were able to successfully complete a Delphi consultation regarding their experiences of mental health services. Broad consensus on positive experiences of services was reached in the White group but not for the Black participants.

The effects of low atmosphere stunning and deboning time on broiler breast meat quality.

Research was conducted to determine the effect of stunning method (low atmosphere pressure, LAPS, and electrical stunning, ES) and deboning time (0.75 and 4 h) on breast meat quality (n = 576, 144 birds per treatment) in a commercial processing plant. Breast meat quality was evaluated through determining pH, Commission Internationale d'Eclairage L*a*b*, cooking yield, shear force, and consumer acceptability. The onset of rigor mortis was more rapid (P < 0.05) in breast meat from LAPS-stunned birds compared with ES-stunned birds, but no differences existed (P > 0.05) among stunning methods with respect to final pH at 24 h. As expected, breast meat that was deboned at 4 h required less shear force (P < 0.05) to cut through the breast than samples that were deboned at 0.75 h postmortem, but no differences existed between breast meat from LAPS or ES broilers that were deboned at the same time postmortem. However, when samples were marinated with 2% NaCl and 0.5% phosphate, there was no difference in Allo-Kramer shear force between ES 4 h and LAPS 4-h samples, but the ES 0.75-h samples had lower shear force values (P < 0.05) than the LAPS 0.75-h samples. On average, the LAPS 4-h treatment had greater overall acceptability ratings (P < 0.05) than other treatments, and the ES and LAPS 4-h treatments had more acceptable (P < 0.05) texture than the ES and LAPS 0.75-h treatments. Cluster analysis revealed that the 2 largest consumer groups liked all chicken breast fillet treatments, but a larger proportion of consumers liked the 4-h LAPS and ES treatments compared with the 0.75-h LAPS and ES treatments. In addition, consumers who rated baked chicken breast as at least moderately acceptable preferred (P < 0.05) the 4-h LAPS samples over the 4-h ES samples. The present study revealed that both the LAPS and ES systems can be successfully used in commercial poultry plants without detrimental breast fillet quality problems with respect to color, texture, and consumer acceptance.

Embryonal tumor with multilayered rosettes: Two case reports with a review of the literature.

Embryonal tumor with multilayered rosettes (ETMR) is a well-recognized histopathological variant of primitive neurectodermal tumors of the central nervous system. This tumor depicts histopathological features that are common to both ependymoblastoma (EBL) and neuroblastoma. Here we report two pediatric cases of ETMR, one exhibiting dominant neuronal differentiation and the other with dominant glial differentiation, thereby expanding the previously known pathologic spectrum. The varying histological features, common morphologic diagnostic difficulties as well as variable postsurgical survival of this entity compared to similar embryonal tumors are highlighted.

Salvage Using Polatuzumab Vedotin Based Therapy in Relapsed Refractory Large B-Cell Lymphomas: Early Experience from a Real-World Middle-Income Setting Using Named-Patient Compassionate Access Program.

Polatuzumab vedotin is a novel immunotherapy antibody-drug conjugate targeting CD79b. It has been used in relapsed/refractory (R/R) large B-cell lymphomas since its FDA approval in 2019. Presently, this drug is unaffordable or unavailable for patients in Lower-Middle Income Countries (LMIC) like India. This is a retrospective study of adult (> 18 years) patients with R/R large B-cell lymphoma failing two prior lines of therapy, who received Polatuzumab based salvage therapy on a compassionate or named-patient access program. Between May 2019 and April 2022, 10 patients received Polatuzumab vedotin, and 9 were evaluable. The most common regimen used was Polatuzumab-Bendamustine-Rituximab. Out of 43 infusions administered, the adverse event profile was manageable [One grade-2 infusion reaction, 4 patients developed grade 3-4 hematological toxicity and none had grade 3-4 non-hematological toxicities]. Ten infusions were administered in the day care service. After a median of 4.5 cycles (range 1-8), 4 patients achieved CR, 2 had partial response (PR), and 3 had progressive disease (PD). With a median follow up of 491 days (range 8-1048 days), four patients are alive (three in CR and one in PR), three patients have died and three patients were lost to follow up. Early real-world experience from a LMIC setting demonstrates feasibility and a favourable safety profile of Polatuzumab vedotin based approach, along with encouraging response rates in a subset of patients.

Advanced MRI in Rosai-Dorfman disease: correlation with histopathology.

Rosai-Dorfman disease is an idiopathic benign lymphoproliferative disorder that can, on rare occasions, cause intracranial or intraspinal lesions with non-specific features on conventional imaging. For this reason, its diagnosis is based on the classical pathological findings of histiocyte proliferation and emperipolesis. In this case report, we describe the imaging features of Rosai-Dorfman disease as visualized by newer types of MRI sequences, such as diffusion tensor imaging (DTI), susceptibility-weighted imaging (SWI) and perfusion-weighted imaging (PWI). In fact, combining the findings of conventional cross-sectional imaging with high fractional anisotropy (FA), a low apparent diffusion coefficient (ADC), mild blooming on SWI and decreased perfusion can help to make the diagnosis of Rosai-Dorfman disease. These newer tools can also be used to clarify the pathology of Rosai-Dorfman disease.

Mean intensity curve on dynamic contrast-enhanced susceptibility-weighted perfusion MR imaging--review of a new parameter to differentiate intracranial tumors.

Dynamic susceptibility contrast (DSC) perfusion imaging has been in clinical use for various indications, including characterization and grading of intracranial neoplasms. However, several technical factors can lead to pitfalls in image interpretation. This review discusses the extraction of T1 and T2* information from mean curve analysis of DSC perfusion imaging of various brain tumors, which provides further insights into tumor biology and, thus, may be useful in the differential diagnosis of such tumors. Indeed, by looking at the mean time-signal intensity curve from the tumor bed in addition to the rCBV maps, it is possible to obtain further inferences of capillary density and lesion leakiness. When dynamic contrast enhanced (DCE) T1 perfusion is not available, DSC perfusion with mean curve analysis appears to be a valid alternative for characterizing various brain neoplasms in a routine clinical setting.

Diagnostic significance of humoral immune responses to recombinant antigens of Mycobacterium tuberculosis in patients with pleural tuberculosis.

Mycobacterium tuberculosis bacilli are seldom demonstrated in tuberculous pleural effusion (TPE) by conventional bacteriological methods. In this study, an indirect enzyme-linked immunosorbent assay (ELISA) was developed to detect IgG against four mycobacterial recombinant antigens (ESAT-6, PlcA, HspX and Tb8.4) in 69 pleural fluids of patients with TPE and 71 patients with malignant pleural effusion. To increase the sensitivity of the assay, a multi-antigen cocktail containing all the above antigens were also used. IgG positivity in ELISA for PlcA, HspX, Tb8.4, ESAT-6 antigens and multi-antigen complex were 49.3, 60.8, 49.3, 53.6 and 75.4% respectively. Each one of the above four antigens and their multi-antigen cocktail were highly specific in distinguishing tuberculous and malignant pleural effusion. This new generation immunoassay will serve as a useful marker for the diagnosis of pleural tuberculosis patients in whom M. tuberculosis bacilli were not demonstrated by bacteriological methods.

Germinoma of medulla.

Germinoma occurring in the medulla oblongata is extremely rare. We report a case of primary intracranial germinoma arising in the medulla oblongata of a 24-year-old postpartum female who presented with progressive weakness of upper and lower limbs, seventh nerve palsy, and decreased palatal movements. Her MR imaging showed a heterointense mass lesion in the posterior portion of upper medulla, the histology of which was reported as germinoma. Germ cell tumors should be considered in the differential diagnosis of tumors occurring in the brain stem.

Advanced magnetic resonance imaging with histopathological correlation in papillary tumor of pineal region: report of a case and review of literature.

Papillary tumors of the pineal region are recently described as rare mass lesions with limited literature available on their natural history and imaging features. Magnetic resonance imaging (MRI) including perfusion, diffusion, and spectroscopic features were described in an 18-year-old girl with papillary tumor of pineal region. A well-defined, T1 hyperintense and contrast-enhancing mass lesion was noted in pineal region with few cystic spaces within. Solid portion of lesion showed minimal diffusion restriction with average apparent diffusion coefficient of 0.812 Χ 10 -3 mm 2 /s; on MR spectroscopy elevated myo-inositol peak with reduced N-acetylaspartate and elevated choline in the tumor. On perfusion study there was significantly high relative cerebral blood volume (rCBV) (6-9 times) and relative cerebral blood flow (rCBF). Our findings agree with previous descriptions of cystic areas with T1 hyperintense appearance of this tumor but very high level of tumor perfusion, diffusion restriction, and presence of myo-inositol peak are important imaging findings and may correlate with the recent reports of high tumor recurrence in these cases.

Role of diffusion tensor imaging in differentiating subtypes of meningiomas.

PURPOSE: Meningiomas are the most common extraaxial intracranial type of tumor, and their management and prognosis depend on their grade and histology. Diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are two new imaging techniques that have proved helpful in elucidating the microarchitecture of brain tumors. The aim of the present study was to assess the role of diffusion and diffusion tensor metrics in the identification and classification of meningioma grades and subtypes. METHODS AND MATERIALS: A total of 21 consecutive patients with meningioma were included in this retrospective study, of whom 16 had benign meningiomas (three fibroblastic, 11 transitional/mixed, two meningothelial) and five had atypical meningiomas. Tumor mean diffusivity (Dav), fractional anisotropy (FA), linear anisotropy (CL), planar anisotropy (CP), spherical anisotropy (CS) and eigenvalues (e1, e2, e3) were measured in all cases, and differences in diffusion tensor metrics between atypical, fibroblastic and other benign (transitional, meningothelial) meningiomas were statistically analyzed using the Mann-Whitney test. RESULTS: No statistically significant differences were found among the mean Dav values for atypical, fibroblastic and other benign meningiomas. Both atypical and fibroblastic meningiomas showed significantly higher mean FA values and lower mean CS values compared with other meningiomas (P<0.01), but no statistically significant difference in these values between each other. Atypical meningiomas showed higher CL values compared with fibroblastic and other benign meningiomas but, again, the difference was not statistically significant. Both atypical and fibroblastic meningiomas showed statistically significantly higher CP values and lower e3 values compared with transitional meningiomas (P<0.01). CONCLUSION: These results suggest that diffusion tensor metrics may be helpful in the differentiation of atypical, fibroblastic and other benign meningiomas.

Glioma grading: sensitivity, specificity, positive and negative predictive values of diffusion and perfusion imaging.

PURPOSE: The purpose of our study was to determine the statistical significance of thresholds of relative cerebral blood volume (rCBV), apparent diffusion coefficient (ADC) and ADC ratios in grading cerebral gliomas. MATERIALS AND METHODS: In this retrospective study, 51 patients with histopathologically confirmed primary cerebral gliomas who had undergone conventional MR imaging, dynamic contrast-enhanced T2*-weighted perfusion MR imaging and diffusion MR imaging were included. A retrospective blinded analysis of the imaging findings including the perfusion and diffusion parameters was done. The rCBV measurements were obtained from regions of maximum perfusion. Minimum ADC values were obtained from the region of maximum hypointensity within the tumor and from the corresponding opposite white matter. Tumor grade determined with the two methods were then compared with the histopathologic grade. Mann-Whitney tests were performed to compare the DWI and PWI between tumor types. Receiver operating characteristic analyses were performed to determine optimum thresholds for tumor grading and also to calculate the sensitivity, specificity, PPV, and NPV for identifying high-grade gliomas. RESULTS: Statistical analysis demonstrated a threshold value of 2.91 for rCBV to provide sensitivity, specificity, PPV, and NPV of 94.7, 93.75, 90.0, and 96.8%, respectively, in determining high-grade gliomas. An ADC value of 98.50 mm(2)/s was defined as a threshold below which tumors were classified as high-grade gliomas and a sensitivity, specificity, PPV, and NPV of 90, 87.1, 81.81 and 93.10% respectively, were obtained. Significant differences were noted in the rCBV ratios, ADC and ADC ratios between low- and high-grade gliomas (P < 0.0001). CONCLUSION: Combining PWI and DWI with conventional MR imaging increases the accuracy of pre-operative imaging grading of glial neoplasms. The rCBV measurements had the most superior diagnostic performance in predicting glioma grade. Absolute ADC values or ADC ratios were also helpful in preoperative grading of gliomas. Threshold values can be used in a clinical setting to evaluate tumors preoperatively for histologic grade and provide a means for guiding treatment and predicting postoperative patient outcome.

Dot-immunobinding assay.

Dot-immunobinding assay (Dot-Iba) is a simple and highly reproducible immunodiagnostic method. Antibody or antigen is dotted directly onto nitrocellulose membrane (NCM) discs. The diagnostic material to be checked can be incubated on this disc. Presence of antigen-antibody complex in NCM discs can be directly demonstrated with enzyme-conjugated antiglobulins and substrate. Development of a purple-pink colored, insoluble substrate product in the NCM will be considered a positive result in the assay. This assay allows the processing of multiple specimens at a time and the entire operational procedures require only 4-6 h. Dot-Iba is rapid, and the technical steps involved in the assay are much simpler than in the other immunoassays such as enzyme-linked immunosorbant assay in detecting circulating antigen and antibody in clinical samples. The Dot-Iba showed an overall sensitivity of 60% for tuberculous meningitis diagnosis and no false positive results were encountered. Hence, this assay is highly specific for the diagnosis of paucibacillary diseases such as extrapulmonary tuberculosis. Dot-Iba is best suited to laboratories in developing world where there are constraints in laboratory resources.