Correlation of light and electron microscopic morphometric parameters of glomerular capillaries with serum creatinine and proteinuria.

Waste products in the bloodstream are filtered by the glomerular capillaries in the kidneys and excreted into the urine. When making a differential diagnosis of kidney diseases, structural assessment of glomeruli using histological, ultrastructural, and immunological studies is crucial. This study assessed the microscopic and ultrastructural morphometric parameters of glomerular capillaries and examined their correlation with serum creatinine and proteinuria. A total of 60 kidney biopsy cases received by the transmission electron microscope (TEM) laboratory for diagnosis were included in the study. Toluidine blue stained 300 nm thick sections of TEM tissue blocks were scanned for glomerular morphometry by a whole slide imaging system, and the estimation of Bowman's capsule (BC) area, glomerular capillary lumen diameter (GCLD), glomerular capillary density (GCD), glomerular capillary surface area density (GCSA), and percentage of glomerular capillary lumen space (%GCLS) was performed with QuPath software. TEM images of 70 nm thick sections were used for the evaluation of endothelial fenestration diameter (EFD), glomerular basement membrane (GBM) thickness, and podocyte foot process (PFP) effacement. Proteinuria and serum creatinine showed positive correlations with GBM thickness and PFP effacement. Negative correlations of serum creatinine were observed with EFD, %GCLS, and GCSA. Hence, glomerular filtration is greatly affected by the total area of the glomerular capillary surface and structural changes of GBM. Reduction of glomerulus filtration due to foot process effacement and thickening of GBM results in damage to the filtration barrier leading to the leakage of plasma protein into urine.

Comparison of HbA2 Using High Performance Liquid Chromatography Versus Haemoglobin Capillary Zone Electrophoresis.

Thalassemia is among the most common hereditary disorders in the world. Approximately 5% of the world's population are carriers of hemoglobinopathies, and 2.9% are carriers of beta thalassemia. Haemoglobin A2 (HbA2) constitutes less than 3% of the total hemoglobin (Hb) in adults, and the determination of Hb A2 levels is important to diagnose the beta thalassemia trait (BTT). In some cases, the level of HbA2 is not typically elevated, and some difficulties may arise in making the diagnosis. Cation exchange high-performance liquid chromatography (HPLC) and HbCZE (haemoglobin capillary zone electrophoresis) are considered acceptable methods to diagnose BTT, but these vary in their accuracy and cut-offs. In this study, we attempted to compare HbA2 values using two methods, HPLC and HbCZE, in 536 whole blood samples sent by physician-ordered hemoglobinopathy screening over two years. This included antenatal women, patients with anemia not responding to iron, and cases of familial screening where either a child or a sibling had been diagnosed with hemoglobinopathy or thalassemia. The performance characteristics of both machines were compared for the detection of the 5 most common hemoglobin variants: Hb A, HbF, HbS, Hb C, and HbE. On comparing the HbA2 values, the HPLC showed higher values for HbA2 as compared to HbCZE, while the HbF and HbS measurement agreement was good between both methods. Normal ranges and mean normal values of HbA2 differ between different methods and different manufacturers; hence, each institute using these machines should validate its cutoffs.

An extremely rare case of Rogers syndrome or thiamine responsive megaloblastic anemia.

ABSTRACT: Rogers syndrome is an extremely rare autosomal recessive syndrome of which only 100 cases are known worldwide. It is characterized by thiamine-responsive megaloblastic anaemia, diabetes mellitus and sensorineural deafness. It results from the deficiency of a thiamine transporter protein. We herein report a 16-year-old Indian male referred to our centre with complaints of refractory anaemia, deafness, diabetes pulmonary arterial hypertension and tricuspid regurgitation. Based on the clinical features and haematologic picture and dramatic response of anaemia to thiamine therapy the possibility of a TRMA was considered. Sequencing analysis for TRMA revealed a homozygous c.242dup (p.Tyr81Ter) mutation of the SLC19A2 gene.

Bisphosphonate Osteonecrosis in a Case of Langerhans Cell Histiocytosis: Report of a Case and Review of Literature.

Langerhans Cell histiocytosis is a rare multisystem disease originating from dendritic cell lines primarily characterized by osteolytic lesion of the skeleton. Chemotherapy along with bisphosphonates have been used to control the progression of the disease and prevent the osteolysis associated with the disease. Bisphosphonate osteonecrosis of the jaws is a common finding following treatment with bisphosphonates for osteoporosis, metastatic tumors to the bone or the osteolytic lesions of multiple myeloma. The article highlights a rare case of bisphosphonate osteonecrosis of the mandible in a case of long-standing Langerhans cell histiocytosis.

Post-graduate training in Laboratory Medicine: Potential to fill a crucial gap in Indian healthcare system.

Quality Laboratory services with a widespread reach is the core of a healthcare system of the country. Diagnostic services at all levels requires technical expertise of different laboratory specialists. However the presence of all specialist together in one setup is always not possible due to limited number of trained manpower. Even today, diagnostic laboratory services remain unsupervised. To void this gap, All India Institute of Medical Sciences (AIIMS) New Delhi, in 1988, opened up the patient-centric department of Laboratory Medicine with a centralised specimen collection centre and a core laboratory performing the majority of the routine laboratory investigations, offering a one-window solution to both patients and clinicians. In 1997, a three-year postgraduate Masters degree (MD) in Laboratory Medicine was started. This medical specialty encompasses the art of test selection, test operation, and test interpretation to manage patients. It aligns with the recent technological advancement of automation and advanced instrumentation that are breaking boundaries of the traditional medical laboratories of pathology, biochemistry, and microbiology. This postgraduate model ensures that the laboratory services are accessible, affordable, and available to both patients and clinicians without compromising quality care. Laboratory Medicine is emerging as an answer to one of the several inadequacies and pitfalls of the Indian health system.

Myeloid sarcoma: an uncommon presentation of myeloid neoplasms; a case series of 4 rare cases reported in a tertiary care institute.

Myeloid sarcoma (MS) is a rare extramedullary neoplasm of myeloid cells, which can arise before, concurrently with, or following hematolymphoid malignancies. We report 04 such cases of MS, diagnosed in this institute over a period of 6 years, during various phases of their respective myeloid neoplasms/leukemias. These cases include MS occurring as a relapse of AML (Case 1), MS occurring as an initial presentation of CML (Case 2), MS occurring during ongoing chemotherapy in APML (Case 3), and MS presenting as a progression of MDS to AML (Case 4). In the absence of relevant clinical history and unemployment of appropriate immunohistochemical (IHC) studies, these cases have a high risk of being frequently misdiagnosed either as Non-Hodgkin's Lymphoma (NHL) or small round cell tumors or undifferentiated carcinomas, which may further delay their management, making an already bad prognosis worse. This case series has been designed to throw light on the varied presentation of MS and the lineage differentiation of its neoplastic cells through the application of relevant IHC markers along with their clinical correlation.

Comparative performance analysis of 2D and 3D gamma metrics for patient specific QA in VMAT using Octavius 4D with 2D-Array 1500.

INTRODUCTION: Gamma pass percentage (GPP) is the predominant metric used for Patient Specific Quality Assurance (PSQA) in radiation therapy. The dimensionality of the measurement geometry in PSQA has evolved from 2D planar to 3D planar, and presently to state-of-the-art 3D volumetric geometry. We aim to critically examine the performance of the three-dimensional gammas vis-à-vis the older gamma metrics of lower dimensionality to determine their mutual fungibility in PSQA, using clinically approved Volumetric Arc Therapy (VMAT) plans. METHODS AND MATERIALS: Gamma pass percentages derived from PSQA for VMAT plans using Octavius 4D phantom with 2D-Array 1500 and its proprietary software were recorded. 2D planar, 3D planar, and 3D volumetric gamma pass percentages were retrospectively extracted for multiple treatment plans at three sites, using three acceptance limits, and for two modes of normalization. The differences in mean pass percentages, and the pairwise correlation between geometries were calculated within limits of statistical significance. RESULTS: A significant increase in mean pass rates was observed from 2D planar to 3D planar geometries. The difference was less pronounced from 3D planar to 3D volumetric. 2D planar v/s 3D planar showed a significant degree of correlation among themselves, which was not seen against most of the 3D volumetric pass rates. CONCLUSION: The mean gamma pass rates show conclusive evidence of the benefits of shifting from 2D planar to higher dimensions measurement geometries, but the benefits of using 3D volumetric compared to 3D planar is not always unequivocal. The correlations show mixed results regarding the interdependence of pass percentages at different geometries.

Clinical audit of dose-escalated radical radiotherapy for advanced cervical carcinoma using a pragmatic protocol (3 fractions of 8 Gy HDR brachytherapy).

INTRODUCTION: Recent image-guided brachytherapy data suggests, dose-escalation to a cumulative EQD2 (equivalent dose delivered at 2 Gy/#) of ≥87 Gy is associated with significantly better disease control. We present a clinical audit of a pragmatic radical radiotherapy protocol for advanced cervical cancer, using fewer fractions of brachytherapy than in the presently most popular protocol. MATERIAL & METHODS: Between July 2015 and December 2018, 96 consecutive advanced cervical carcinoma patients were treated by pelvic external beam radiotherapy (EBRT) (50 Gy/25fractions/5 weeks) ± weekly intravenous chemotherapy followed by image guided high dose rate (HDR) brachytherapy, using intracavitary/interstitial/hybrid techniques (intended point A dose: 8 Gy/fractions) × 3 fractions (cumulative target EQD2 ≥ 86 Gy). Insertion was done individually for each fraction of treatment. RESULTS: All patients completed their intended radiation protocol. 93.8% patients achieved complete response, while 6.2% patients achieved only partial response; no patients had stable/progressive disease. Out of the patients with partial response, 4.2% (4 out of 5 cases) cases of central/nodal residual disease underwent salvage surgery. At a median follow up of 21 months, 8.3% (8) patients had local failure, 1.1% (1) had nodal failure and 3.1% (3) had distant failures. Median Failure Free Survival was 29 months (26.5-31.5 months). On follow up, 6.3% and 3.2% patients had grade 2 or worse rectal and bladder morbidities respectively. CONCLUSION: The protocol under study has been safe and effective in achieving dose-escalated radical chemoradiation in advanced cervical carcinoma. The use of fewer insertions of brachytherapy is logistically easier & can also be expected to improve compliance.

Dosimetric analysis of Deep Inspiratory Breath-hold technique (DIBH) in left-sided breast cancer radiotherapy and evaluation of pre-treatment predictors of cardiac doses for guiding patient selection for DIBH.

INTRODUCTION: The risk of radiotherapy-associated cardiovascular disease has been a concern for decades in breast cancer survivors. The objective of our study is to evaluate the dosimetric benefit of Deep Inspiratory Breath-hold technique (DIBH) on organs-at-risk (OAR) sparing in left-sided breast cancer radiotherapy and to find out pre-treatment predictors of cardiac doses for guiding patient selection for DIBH. MATERIAL AND METHODS: Pre-radiotherapy planning CT scans were done in Free Breathing (FB) and in DIBH [using Active Breathing Coordinator system (ABC™)] in 31 left sided breast cancer patients. 3DCRT plans were generated for both scans. Comparison of anatomical and dosimetric variables were done using paired t test and correlation was evaluated using Pearson correlation. Linear regression was used to get independent predictors of cardiac sparing and Receiver Operating Characteristic (ROC) curve analysis was done to find out the specific threshold of the predictors. RESULTS: There was a 39.15% reduction in mean heart dose in DIBH compared to FB (2.4 Gy vs 4.01 Gy) (p < 0.001), 19% reduction in maximum Left Anterior Descending (LAD) dose and a 9.9% reduction in ipsilateral lung mean dose (p = 0.036) with DIBH. A significant correlation was observed between reduction in Heart Volume in Field (HVIF) and Maximum Heart Depth (MHD) with reduction in mean heart dose. Reduction in HVIF (ΔHVIF) independently predicted cardiac sparing. CONCLUSION: DIBH leads to significant reduction in OAR doses and is suggested for all patients of left-sided breast cancer undergoing radiotherapy. However, HVIF and MHD predicted for cardiac sparing and threshold criteria of ΔHVIF and ΔMHD may be used by centres with high workload to select patients for DIBH.

A plant-by-plant strategy for high-ambition coal power phaseout in China.

More than half of current coal power capacity is in China. A key strategy for meeting China's 2060 carbon neutrality goal and the global 1.5 °C climate goal is to rapidly shift away from unabated coal use. Here we detail how to structure a high-ambition coal phaseout in China while balancing multiple national needs. We evaluate the 1037 currently operating coal plants based on comprehensive technical, economic and environmental criteria and develop a metric for prioritizing plants for early retirement. We find that 18% of plants consistently score poorly across all three criteria and are thus low-hanging fruits for rapid retirement. We develop plant-by-plant phaseout strategies for each province by combining our retirement algorithm with an integrated assessment model. With rapid retirement of the low-hanging fruits, other existing plants can operate with a 20- or 30-year minimum lifetime and gradually reduced utilization to achieve the 1.5 °C or well-below 2 °C climate goals, respectively, with complete phaseout by 2045 and 2055.

Sigma Metrics: A Valuable Tool for Evaluating the Performance of Internal Quality Control in Laboratory.

Background Six Sigma is a widely accepted quality management system that provides an objective assessment of analytical methods and instrumentation. Six Sigma scale typically runs from 0 to 6, with sigma value above 6 being considered adequate and 3 sigma being considered the minimal acceptable performance for a process. Methodology Sigma metrics of 10 biochemistry parameters, namely glucose, triglycerides, high-density lipoprotein (HDL), albumin, direct bilirubin, alanine transaminase, aspartate transaminase, urea nitrogen, creatinine and uric acid, and hematology parameters such as hemoglobin (Hb), total leucocyte count (TLC), packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and platelet were calculated by analyzing internal quality control (IQC) data of 3 months (June-August 2019). Results Sigma value was found to be > 6 for triglyceride, HDL, Hb, TLC, and MCH, signifying excellent results and no further modification with respect to IQC. Sigma value was between 3 and 6 for glucose, albumin, creatinine, uric acid, PCV, and MCHC, implying the requirement of improvement in quality control (QC) processes. Sigma value of < 3 was seen in AST, ALT, direct bilirubin, urea nitrogen, platelet, and MCV, signifying suboptimal performance. Discussion Six Sigma provides a more quantitative framework for evaluating process performance with evidence for process improvement and describes how many sigmas fit within the tolerance limits. Thus, for parameters with sigma value < 3, duplicate testing of the sample along with three QCs three times a day may be used along with stringent Westgard rules for rejecting a run. Conclusion Sigma metrics help assess analytical methodologies and augment laboratory performance.

Circumnavigation on Multiple Circles Around a Nonstationary Target With Desired Angular Spacing.

In this article, the objective for a group of nonholonomic agents is to achieve multicircular circumnavigation with any desired angular spacing around a nonstationary target. A cooperative protocol is proposed to achieve this objective and, additionally, generalizes the circumnavigation problem of unicycle vehicles around a target (moving and stationary). Due to the nonholonomic constraints, existing protocols cannot be extended directly to achieve this objective. Thus, the proposed algorithm is worked out from the desired geometry to achieve the objective. A fixed-time consensus estimator is designed under a cyclic digraph to arrive at the desired interagent angular separation in the target-centric frame. The target information and desired formation parameters are assumed to be known to only one agent partially. Due to uncertainty in the target's motion, it is assumed that the target's acceleration and angular velocity are unknown. Fixed-time estimators under a digraph address the lack of information. The tracking controller drives the agents to the desired position around the target, thus making the errors go to zero instead of any finite bounds. The controller guarantees the bounded control effort irrespective of the error magnitude. The numerical examples are presented to show the effectiveness of the algorithm.

Myeloid sarcoma: an uncommon presentation of myeloid neoplasms; a case series of 4 rare cases reported in a tertiary care institute

Myeloid sarcoma (MS) is a rare extramedullary neoplasm of myeloid cells, which can arise before, concurrently with, or following hematolymphoid malignancies. We report 04 such cases of MS, diagnosed in this institute over a period of 6 years, during various phases of their respective myeloid neoplasms/leukemias. These cases include MS occurring as a relapse of AML (Case 1), MS occurring as an initial presentation of CML (Case 2), MS occurring during ongoing chemotherapy in APML (Case 3), and MS presenting as a progression of MDS to AML (Case 4). In the absence of relevant clinical history and unemployment of appropriate immunohistochemical (IHC) studies, these cases have a high risk of being frequently misdiagnosed either as Non-Hodgkin's Lymphoma (NHL) or small round cell tumors or undifferentiated carcinomas, which may further delay their management, making an already bad prognosis worse. This case series has been designed to throw light on the varied presentation of MS and the lineage differentiation of its neoplastic cells through the application of relevant IHC markers along with their clinical correlation.

Fusing subnational with national climate action is central to decarbonization: the case of the United States.

Approaches that root national climate strategies in local actions will be essential for all countries as they develop new nationally determined contributions under the Paris Agreement. The potential impact of climate action from non-national actors in delivering higher global ambition is significant. Sub-national action in the United States provides a test for how such actions can accelerate emissions reductions. We aggregated U.S. state, city, and business commitments within an integrated assessment model to assess how a national climate strategy can be built upon non-state actions. We find that existing commitments alone could reduce emissions 25% below 2005 levels by 2030, and that enhancing actions by these actors could reduce emissions up to 37%. We show how these actions can provide a stepped-up basis for additional federal action to reduce emissions by 49%-consistent with 1.5 °C. Our analysis demonstrates sub-national actions can lead to substantial reductions and support increased national action.

Containing a pandemic with public actions and public trust: the Kerala story.

We study the Covid pandemic in the Indian state of Kerala, and document the state's remarkable success in containing the pandemic's first wave. By identifying Kerala's initial conditions when it was hit by the pandemic, and different components of the state's Covid policy, we conclude: While being subject to resource constraints faced by an Indian state located in a federal structure, Kerala contained its first Covid wave by preemptively formulating a comprehensive set of public actions-government actions that were supported and complemented by the state's citizens. This was achieved by leveraging and reinforcing the citizen's public trust in the state. Specifically, the state's pandemic response contained supportive measures to ensure that poor lives were not pitted against rich lives; rather, the aim was to protect all lives and livelihoods.

Retrospective study on performance of constancy check device in Linac beam monitoring using Statistical Process Control.

AIM: To examine the application of Statistical Process Control (SPC) and Ishikawa diagrams for retrospective evaluation of machine Quality Assurance (QA) performance in radiotherapy. BACKGROUND: SPC is a popular method for supplementing the performance of QA techniques in healthcare. This work investigates the applicability of SPC techniques and Ishikawa charts in machine QA. MATERIALS AND METHODS: SPC has been applied to recommend QA limits on the particular beam parameters using the QUICKCHECK webline QA portable constancy check device for 6 MV and 10 MV flattened photon beams from the Elekta Versa HD linear accelerator (Linac). Four machine QA parameters - beam flatness, beam symmetry along gun target direction and left-right direction, and beam quality factor (BQF) - were selected for retrospective analysis. Shewhart charts, Exponentially Weighted Moving Average (EWMA) charts and Cumulative Sum (CUSUM) charts were obtained for each parameter. The root causes for a failure in machine QA were broken down into an Ishikawa diagram enabling the user to identify the root cause of error and rectify the problem subsequently. RESULTS: Shewhart charts and EWMA charts applied could detect loss in control in one variable in the 6 MV beams and in all four variables in 10 MV beams. CUSUM charts detected offsets in the readings. The Ishikawa chart exhaustively included the possible errors that lead to loss of control. CONCLUSION: SPC is proven to be effective for detection of loss in control in machine QA. The Ishikawa chart provides the set of probable root causes of machine error useful while troubleshooting.