Using a quality improvement tool, Plan-Do-Study-Act cycle, to boost TB notification in India post-Covid-19 pandemic.

Quality improvement tools such as the Plan-Do-Study-Act (PDSA) cycle hold tremendous potential to improve the quality of healthcare in India. The electronic-PDSA tool was previously developed by CETI (Collaboration to Eliminate TB among Indians) and successfully piloted in small groups. In this study the e-PDSA was scaled up across the nation over a brief 10 week period to boost TB notification by training District Tuberculosis Officers (DTOs) virtually post-Covid-19 pandemic. Quality improvement counselors, who were interns from Masters in Public Health Institutions, were liaisons to "hand-hold" and assist the DTOs through the PDSA cycle. The course was voluntary and offered to all DTOs through Central TB Division and State TB Officers from May 2022 to July 2022. Of the 779 Districts in India and nearly equal number of DTOs, 546 (70%) DTOs enrolled in the course and of these 437 (80%) conducted a PDSA while 342 (43%) districts/DTOs did not enroll or did not complete a PDSA. With a baseline notification in February-March-April 2022 and intervention in May-June-July 2022; 55% of the districts in the PDSA group showed improvement in TB Notification compared to 45% in the non-PDSA group. When data was analyzed by population (not district) there was a trend in increase in notification post-pandemic in both PDSA and non-PDSA groups, and the PDSA group had a slightly higher 5.6 per 100,000 population improvement compared to 5.0 per 100,000 in the non-PDSA group. The cost of intervention was $40,000 or $92 per DTO for three months. The course was highly acceptable with DTOs rating 4.3 out of 5 in recommending the course to other DTOs. Our data shows that a large scale-up of the PDSA cycle is feasible, economical and effective with little additional resources. The focus was on increasing the efficiency of the existing processes well within the authority of the DTO. Repeat cycle of PDSA with notification and other measures such as presumptive sputum examination could significantly impact the program and help to achieve TB Free India.

Hodgkin Lymphoma in Children Under 5 Years: Do They Behave Differently?

The median age of presentation for Hodgkin lymphoma (HL) is lower in developing countries with a higher proportion under 5 years of age possibly attributable to the high prevalence of Epstein-Barr virus-driven disease. It is unclear whether the clinical presentation and outcomes of this cohort are different with concern regarding late effects being most pronounced in this age group. We report the outcome of children under 5 years of age enrolled in the InPOG-HL-15-01, the first multicentric collaborative study for newly diagnosed children and adolescents with HL from India. Thirty-five (9%) of the study population was younger than 5 years with a striking male preponderance of 34:1. They were less likely to have bulky disease, mediastinal or splenic involvement. The outcomes appear to be at least as favorable as in the older patient group. Efforts need to be made to evolve treatment strategies that spare this very young cohort from potential late effects.

Validation of Accuracy of Non-Invasive Imaging Methods (Magnetic Resonance Imaging (MRI) Fat Fraction Calculation and Computed Tomography (CT) Liver Attenuation Index) for Hepatic Graft Fat Quantification in Living Liver Transplant Donors.

BACKGROUND Diagnosis of significant hepatic graft steatosis remains vital for success of any transplant program as it has an impact on donor morbidity and recipient survival. Even histopathological quantification faces limitations. The present study compared the diagnostic accuracy of CT-LAI and MRI fat fraction imaging with histopathological analysis for donor graft parenchymal fat quantification. MATERIAL AND METHODS CT-LAI and MR-FF values and histopathological fat quantification results of 273 patients were identified from electronic records of the author's institutes from September 2015 to April 2020. Data analysis was done using SPSS version 21.0. RESULTS Most participants were young with nearly equal sex distribution and significant number of overweight and obese patients. Moderate agreement and significant positive correlation were found between MR fat fraction (%) and biopsy-macrosteatosis (%). Diagnostic accuracy and negative predictive value of MRI for fat fraction calculation was high (95.24% and 98.07% for fat fraction of 10% threshold, respectively), and it further improved for fat fraction threshold of 15%. CONCLUSIONS MRI-based fat quantification calculation displayed near-perfect negative predictive values and very high diagnostic accuracy, suggesting that it can obviate the need for biopsy in patients with graft fat percentage <10% on MRI.

Enter the Matrix: Factorization Uncovers Knowledge from Omics.

Omics data contain signals from the molecular, physical, and kinetic inter- and intracellular interactions that control biological systems. Matrix factorization (MF) techniques can reveal low-dimensional structure from high-dimensional data that reflect these interactions. These techniques can uncover new biological knowledge from diverse high-throughput omics data in applications ranging from pathway discovery to timecourse analysis. We review exemplary applications of MF for systems-level analyses. We discuss appropriate applications of these methods, their limitations, and focus on the analysis of results to facilitate optimal biological interpretation. The inference of biologically relevant features with MF enables discovery from high-throughput data beyond the limits of current biological knowledge - answering questions from high-dimensional data that we have not yet thought to ask.

Giant fibroadenoma with massive infarction masquerading as malignancy: a case report.

Fibroadenoma is a common benign breast lesion that usually affects women in their second and third decade of life and usually present as small mobile painless lump. However, it is important to recognize that a small percentage have been shown to progress to giant fibroadenomas. Giant fibroadenomas can undergo infarction leading to significant morbidity and difficulty to distinguish from the more aggressive phyllodes tumors or carcinoma. We report an interesting case of giant fibroadenoma (17 × 11 × 7 cm) with massive infarction during lactation, further complicated by lactational mastitis with close resemblance to cystosarcoma phyllodes. Detailed clinical evaluation and proper investigation in the form of USG breast and PET-CT scan helped us to delineate the nature of pathology. Simple excision of lesion with curvilinear incision was done with excellent cosmetic outcome. Histopathologic features were consistent with fibroadenoma (giant) with large areas of infarction. Fibroadenoma breast has varied clinical presentations. The course of disease may be complicated by pregnancy, lactation and inflammatory processes. Massive infarction may make the picture more dubious and masquerade with malignant transformation altering our treatment decision. The presence of necrosis on core biopsy or intra-operative finding should be cautiously interpreted and is not itself a sign of malignancy. Detailed clinical evaluation and comprehensive workup should be done before embarking on radical treatment.

A case of Philadelphia chromosome positive acute lymphoblastic leukemia with partial trisomy of chromosome 1q involving chromosome 13 as the acceptor-A novel cytogenetic finding.

The Philadelphia (Ph) chromosome is infrequently found in acute lymphoblastic leukemia and is associated with poor prognosis. We present a case of Ph chromosome positive B cell-acute lymphoblastic leukemia with the partial trisomy of chromosome 1q involving chromosome 13 as the acceptor which has never been reported in the English literature. Jumping translocation (JT) of chromosome 1 is rare and is associated with disease progression and poor prognosis. Herein, we report the first case of Ph chromosome positive B cell-acute lymphoblastic leukemia with coexisting jumping translocation of chromosome 1 leading to trisomy of chromosome 1q. Dismal prognosis associated with synchronous presence of a Ph chromosome and JT leading to a partial trisomy of chromosome 1q may carry significant prognostic and therapeutic implications. This may be an incidental finding and further studies with large patient cohorts and clinical outcomes are needed to definitively determine the predictive value of this cytogenetic finding.

Accelerated Mini-batch Randomized Block Coordinate Descent Method.

We consider regularized empirical risk minimization problems. In particular, we minimize the sum of a smooth empirical risk function and a nonsmooth regularization function. When the regularization function is block separable, we can solve the minimization problems in a randomized block coordinate descent (RBCD) manner. Existing RBCD methods usually decrease the objective value by exploiting the partial gradient of a randomly selected block of coordinates in each iteration. Thus they need all data to be accessible so that the partial gradient of the block gradient can be exactly obtained. However, such a "batch" setting may be computationally expensive in practice. In this paper, we propose a mini-batch randomized block coordinate descent (MRBCD) method, which estimates the partial gradient of the selected block based on a mini-batch of randomly sampled data in each iteration. We further accelerate the MRBCD method by exploiting the semi-stochastic optimization scheme, which effectively reduces the variance of the partial gradient estimators. Theoretically, we show that for strongly convex functions, the MRBCD method attains lower overall iteration complexity than existing RBCD methods. As an application, we further trim the MRBCD method to solve the regularized sparse learning problems. Our numerical experiments shows that the MRBCD method naturally exploits the sparsity structure and achieves better computational performance than existing methods.

Blastic plasmacytoid dendritic cell neoplasm: a report of 2 cases.

Blastic plasmacytoid dendritic cell neoplasm is a recently classified aggressive hematodermic neoplasm derived from plasmacytoid dendritic cells. We describe two cases of this neoplasm, one a 15 year old child and other a 65 year male. The diagnosis was made by evaluating the detailed clinical history, morphology and flow cytometric findings. The diagnosis is rendered difficult owing to common morphological and flow cytometric overlaps. The neoplasms were characterized by skin and soft tissue involvement and strong CD4/CD56 positivity. These neoplasms are highly aggressive and have many diagnostic overlaps. Strong suspicion and detection will help in early therapeutic interventions.

Optimized regression for efficient function evaluation.

In many applications of regression, one is concerned with the efficiency of the estimated function in addition to the accuracy of the regression. For efficiency, it is common to represent the estimated function as a rectangular lattice of values-a lookup table (LUT)-that can be linearly interpolated for any needed value. Typically, a LUT is constructed from data with a two-step process that first fits a function to the data, then evaluates that fitted function at the nodes of the lattice. We present an approach, termed lattice regression, that directly optimizes the values of the lattice nodes to minimize the post-interpolation training error. Additionally, we propose a second-order difference regularizer to promote smoothness. We demonstrate the effectiveness of this approach on two image processing tasks that require both accurate regression and efficient function evaluations: inverse device characterization for color management and omnidirectional super-resolution for visual homing.

Utility of a limited panel of calretinin and Ber-EP4 immunocytochemistry on cytospin preparation of serous effusions: A cost-effective measure in resource-limited settings.

BACKGROUND: Differentiation between reactive, but morphologically atypical, mesothelial cells and adenocarcinoma in effusions can be problematic. Elaborate immunohistochemical panels have been devised. Techniques like DNA analysis, flow/image cytometry, and K-ras mutation analysis are research oriented and difficult to perform in routine, especially in resource-poor centers. We evaluated the efficacy of a limited two-antibody panel comprising calretinin and Ber-EP4 on cytospin and cell block preparations, in 100 effusion samples. MATERIALS AND METHODS: Fifty cases of reactive mesothelial hyperplasia and 50 cases of adenocarcinoma diagnosed by cytomorphology in ascitic/pleural fluid specimens over a 2-year period were assessed. The diagnoses were confirmed by clinical/histopathologic correlation. Cytospin smears were made in all. Cell blocks were prepared, wherever adequate fluid was available. Immunocytochemistry (ICC) for calretinin and Ber-EP4 was performed. RESULTS: Forty-five of the reactive effusion cases (90%) were calretinin reactive and Ber-EP4 negative. Among the adenocarcinoma cases, 49 (98%) were calretinin negative but Ber-EP4 positive. Thus, both calretinin and Ber-EP4 had a high sensitivity (90% and 98%, respectively), as well as a high specificity (100% and 86%, respectively). In the 21 reactive mesothelial cases, whose cell blocks were made, results were comparable to those on cytospin. However, of the 19 adenocarcinoma cases in which cell blocks were prepared, all were Ber-EP4 immunopositive except for three, which were positive on cytospin, implying false-negative results on cell blocks. CONCLUSIONS: A limited panel of two monoclonal antibodies, calretinin and Ber-EP4, may be useful in cytology, as a "primary antibody panel", for accurate diagnosis and patient management. Additionally, ICC can be performed easily on cytospin preparations, which gave results comparable to cell blocks in our study.

A rare case of low-grade myofibroblastic sarcoma of the femur in a 38-year-old woman: a case report.

INTRODUCTION: Primary myofibroblastic sarcoma of the bone is a rare spindle cell tumour with, to the best of our knowledge, only eight cases reported in the available English language literature. The disease's rarity and its low-grade features make an accurate diagnosis difficult in most cases. The differential diagnoses of this unusual tumour include various benign entities as well as other sarcomas. Due to the difference in prognosis, a precise pathologic diagnosis is essential, which requires a combination of thorough morphologic examination, immunohistochemistry and electron microscopy wherever available. CASE PRESENTATION: We report the case of a 38-year-old Indian woman with a lytic lesion in her left femur. The tumour was associated with cortical destruction and soft tissue extension. A biopsy from the soft tissue component showed features suggestive of a low-grade malignant mesenchymal tumour. Excision of the tumour was performed and histopathological examination showed a low-grade spindle cell sarcoma with collagenous stroma. Expressions of vimentin and smooth muscle actin were also noted. Ultrastructural examination confirmed its myofibroblastic nature. A final diagnosis of low-grade myofibroblastic sarcoma of the left femur was thus rendered. CONCLUSION: Low-grade myofibroblastic sarcoma is one of the rarer osseous spindle cell sarcomas depicting a favourable prognosis in the cases reported so far. Its diagnosis requires ancillary techniques like immunohistochemistry and electron microscopy. To the best of our knowledge, we report the ninth case in the literature and the first case from our subcontinent.

Well-differentiated mesenteric liposarcoma with osseous metaplasia: a potential diagnostic dilemma for the pathologist.

BACKGROUND: Mesenteric liposarcoma is a rare intra-abdominal sarcoma with very few cases reported in the available English literature. Incomplete resection of the tumor leads to recurrence, and recurrent tumors carry a risk of dedifferentiation. Dedifferentiation in liposarcoma manifests as a nonlipogenic sarcoma, which is usually high-grade and may show osteosarcomatous differentiation rarely. To the best of our knowledge, osteoid metaplasia in a well-differentiated liposarcoma without evidence of dedifferentiation has not been documented in the available literature. CASE: We describe the case of a middle-aged adult man with a well-differentiated liposarcoma of the mesentery. The patient presented with a recurrent tumor 5 years after the initial surgery. At recurrence, the histological features were those of a well-differentiated liposarcoma with focal osseous metaplasia without any evidence of dedifferentiation in the extensive sections examined. CONCLUSION: Osseous metaplasia is a rare phenomenon in lipomas and dedifferentiated liposarcomas. Such an occurrence in a recurrent well-differentiated liposarcoma is a perplexing problem due to the potential confusion with dedifferentiation. This needs to be recognized to avoid overzealous chemotherapy and/or radiotherapy, which is required for dedifferentiated tumors.

Invasive papillary carcinoma of male breast.

Breast carcinoma is uncommon in males and constitutes less than one per cent of all cancers in men. Invasive papillary carcinoma is a rare morphological type of breast cancer. Since papillary carcinoma has a favorable prognosis as compared to other histopathological subtypes, an accurate diagnosis is essential. We report two cases of this rare histological type of male breast cancer. A 62-year-old man presented with a lump in the central quadrant of right breast and underwent simple mastectomy. Histological examination showed features of invasive papillary carcinoma. The other case was of an 81-year-old male patient with a subareolar mass in the right breast. Wide local excision of the lump showed features of an intracystic invasive papillary carcinoma. The patient subsequently underwent simple mastectomy, however, no residual tumor was found in the resection specimen. Both the patients were free of disease at one year of follow-up. Invasive papillary carcinoma is an uncommon morphological type of breast cancer in males. The intracystic variant of papillary carcinoma is extremely unusual and may be missed on cytological examination. A thorough sampling is essential for an accurate diagnosis of invasion in these cases.

Primary neuroendocrine carcinoma of thymus: a rare cause of Cushing's syndrome.

Thymomas constitute majority of the thymic neoplasms. In contrast, neuroendocrine tumors (carcinoid and neuroendocrine carcinoma) of thymus are extremely rare. Thymic carcinoids may present rarely with Cushing's syndrome due to the ectopic production of adrenocorticotropic hormone (ACTH). Recognition of this association is imperative for appropriate management of patients. We describe three cases of rare atypical carcinoid tumor (neuroendocrine carcinoma) of the thymus. Case 1, of a 26-year-old man presenting with Cushing's syndrome, case 2--a 23-year-old female with Cushingoid features, and Case 3--a 39-year-old man complaining of progressively worsening dyspnea. Computed tomography (CT) scans of chest in all three patients revealed anterior mediastinal mass. Excision of tumors and histological examination of the three tumors showed a carcinoid tumor with nuclear pleomorphism, increased mitotic activity and focal necrosis. The features suggested a diagnosis of atypical carcinoid tumor in all the three cases. The tumor cells in Cases 1 and 2 showed focal immunohistochemical staining for ACTH. Atypical carcinoid (neuroendocrine carcinoma, well-differentiated and moderately-differentiated) of the thymus is a rare thymic tumor which carries a worse prognosis compared to thymoma and requires aggressive therapy. Hence, an accurate diagnosis is essential.

Suprasellar ganglioglioma presenting with diabetes insipidus in a young boy: a rare clinical presentation.

OBJECTIVE: Gangliogliomas are rare tumors composed of an admixture of glial and neuronal components. These usually occur in young patients, who present with therapy-resistant seizures. Clinical presentation of ganglioglioma with diabetes insipidus is extremely rare with only one case reported earlier in the available literature. Due to this rarity, ganglioglioma is not considered in the differential diagnosis in a patient with diabetes insipidus. CASE: A 7-year boy presented with polyuria, polydipsia, and progressive visual loss for 18 months. Investigations revealed diabetes insipidus. Radiographic studies of the brain showed a solid and cystic mass in the suprasellar region effacing the third ventricle. Intraoperatively, diffuse thickening of bilateral optic nerves and optic chiasma was noted and a diagnosis of optic glioma was considered. A biopsy of the mass was taken, which on histopathological examination showed features of ganglioglioma. The patient was referred for further radiotherapy but was lost to follow-up. CONCLUSION: Diabetes insipidus as a presenting symptom of ganglioglioma is extremely rare. This benign tumor should be kept in mind in patients with central diabetes insipidus and a suprasellar mass lesion. This report describes the second such case in the literature.