The Diagnostic Accuracy of Bone Marrow Biopsy Versus PET/CT Scan in Identifying Bone Marrow Involvement in Diffuse Large B Cell Lymphoma Patients at a Cancer Hospital.

Background It is of great importance to assess bone marrow involvement (BMI) in diffuse large B cell lymphoma (DLBCL) for staging, prognostic, and therapeutic purposes. The gold standard method used for the identification of bone marrow involvement is bone marrow biopsy (BMB), but it has certain drawbacks. In recent years, positron emission tomography/computed tomography (PET/CT) has become a highly effective method in the diagnosis and staging of lymphoma. Objective The objective of this study is to estimate the diagnostic accuracy of PET/CT in identifying bone marrow involvement in DLBCL patients in a cancer care hospital in Lahore, using BMB as a reference standard. Methods This descriptive cross-sectional study was conducted at the Department of Pathology of Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC) from January 1, 2013, to December 31, 2018. A retrospective data of 146 patients fulfilling the inclusion and exclusion criteria was retrieved from the hospital information system (HIS). The inclusion criteria include patients aged 18-80 years, of either gender, and with a confirmed diagnosis of DLBCL on tissue biopsy. The exclusion criteria include patients who had started chemotherapy or radiotherapy for DLBCL or were using granulocyte colony-stimulating factor (G-CSF) prior to their PET/CT scan. All patients underwent PET/CT and BMB, and the diagnostic accuracy of PET/CT was calculated, with BMB taken as the reference standard. Results The mean age of cases was 52.73 ± 16.27 years. There were 95 (65.1%) male and 51 (34.9%) female cases, with a high male-to-female ratio. In the present study, 32.19% of cases had bone marrow involvement on BMB, and 34.2% of cases had bone marrow involvement on PET/CT. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall diagnostic accuracy of PET/CT were found to be 93.61%, 93.93%, 88%, 96.88%, and 93.84%, respectively. Conclusion It is concluded that PET/CT scan has good sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. So, it is suggested to choose this non-invasive technique because the presence of a disease in extra-medullary space can also be detected and the evaluation of bone marrow in the whole body can be performed. PET/CT scan is an effective imaging modality in the detection of bone marrow involvement in DLBCL patients, and its relative advantages over bone marrow biopsy might conclude this to be a preferred technique.

The Frequency of Immunofluorescence Antinuclear Antibody Patterns and Extractable Nuclear Antigen: Experience From a Large Laboratory in Pakistan.

Background Autoimmune disorders have shown an increasing incidence in the last few years. The systemic response to the disorder is characterized by the expression of antinuclear antibody (ANA), which serves as the serological hallmark of autoimmunity. Its presence may indicate either a systemic autoimmune disease such as systemic lupus erythematosus (SLE), scleroderma, and polymyositis/dermatomyositis or an organ-specific condition such as autoimmune thyroiditis and hepatitis. The systemic response may vary from one individual to another in each population. Several specific autoantibodies are also found to be associated with specific rheumatic diseases. Aim We aim to report the frequency of ANA positivity, ANA immunofluorescence patterns, and the presence of extractable nuclear antigen (ENA) among the general Pakistani population from one of the largest laboratories in Pakistan. Material and methods A total of 1,966 blood samples from a random Pakistani population were included, who were referred by their physicians with suspicion of autoimmune disease. These blood samples were subjected to ANA testing by indirect immunofluorescence method, and subsequently, positive samples were further analyzed for ENA detection in the Section of Chemical Pathology, Department of Pathology at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. An ANA titer of ≥1:80 was taken as positive. ANA was divided into subgroups based on titer: negative, weakly positive (titer of 1:80 or 1:160), moderately positive (titer of 1:320 or 1:640), and strongly positive (titer of ≥1:1280). Further, the frequency of ANA in male and female participants was studied in different age groups (2 to <10, 10 to <20, 20 to <30, 30 to <40, 40 to <50, 50 to <60, 60 to <70, 70 to <80, and 80+ years). Results This study included 1,966 participants, out of which 1,100 (55%) were ANA-positive at a titer of ≥1:80. Out of these ANA positives, the proportion of weakly positive (titer of 1:80 or 1:160), moderately positive (titer of 1:320 or 1:640), and strongly positive (titer of ≥1:1280) were 48.7%, 2.6%, and 4.2%, respectively. The ages ranged from two to 91 years, with a mean age of 43.64 ± 17.4 years. Females (75.5%) showed predominance over males (24.5%) in all age groups, with a ratio of 3:1. The age group in which most ANA positivity was found was 30 to <40 years. Among 1,100 ANA-positive sera, 383 (34.8%) participants tested positive for at least one out of 15 ENA. The most frequent autoantibodies noticed were anti-recombinant Ro52 (Ro52) (19.8%), anti-Sjogren's syndrome type A (SSA) (17.2%), and anti-ribonucleoprotein (RNP) (13.3%). The most prevalent ANA patterns were nuclear homogeneous (27.7%), followed by nuclear speckled (26.5%). Conclusion The frequency of ANA positivity is high in the Pakistani population and differs in different sex and age groups.

Feasibility of using CT radiomic signatures for predicting CD8-T cell infiltration and PD-L1 expression in renal cell carcinoma.

Objectives: To identify computed tomography (CT)-based radiomic signatures of cluster of differentiation 8 (CD8)-T cell infiltration and programmed cell death ligand 1 (PD-L1) expression levels in patients with clear-cell renal cell carcinoma (ccRCC). Methods: Seventy-eight patients with pathologically confirmed localized ccRCC, preoperative multiphase CT and tumor resection specimens were enrolled in this retrospective study. Regions of interest (ROI) of the ccRCC volume were manually segmented from the CT images and processed using a radiomics panel comprising of 1708 metrics. The extracted metrics were used as inputs to three machine learning classifiers: Random Forest, AdaBoost, and ElasticNet to create radiomic signatures for CD8-T cell infiltration and PD-L1 expression, respectively. Results: Using a cut-off of 80 lymphocytes per high power field, 59 % were classified to CD8 highly infiltrated tumors and 41 % were CD8 non highly infiltrated tumors, respectively. An ElasticNet classifier discriminated between these two groups of CD8-T cells with an AUC of 0.68 (95 % CI, 0.55-0.80). In addition, based on tumor proportion score with a cut-off of > 1 % tumor cells expressing PD-L1, 76 % were PD-L1 positive and 24 % were PD-L1 negative. An Adaboost classifier discriminated between PD-L1 positive and PD-L1 negative tumors with an AUC of 0.8 95 % CI: (0.66, 0.95). 3D radiomics metrics of graylevel co-occurrence matrix (GLCM) and graylevel run-length matrix (GLRLM) metrics drove the performance for CD8-Tcell and PD-L1 classification, respectively. Conclusions: CT-radiomic signatures can differentiate tumors with high CD8-T cell infiltration with moderate accuracy and positive PD-L1 expression with good accuracy in ccRCC.

ACTH-secreting parotid acinic cell carcinoma unusually reported as a paraneoplastic syndrome.

Paraneoplastic syndromes, induced by an immunological cross-reaction or hormone/peptide secretion, are an atypical presentation of tumors. Some tumors, such as small cell lung cancer and bronchial carcinoid, can be adrenocorticotropic hormone (ACTH) secreting tumors. Less commonly, parotid acinic cell carcinoma can be ACTH-secreting tumor leading to Cushing's syndrome. Few literature cases have described ACTH related paraneoplastic syndrome of parotid adenocarcinoma. Because of the rarity of the condition, little is known about the management and prognosis of this phenomenon. In this report, we highlighted the case of a 59-year-old male with a past medical history of parotid adenocarcinoma treated with surgery, chemotherapy, and radiation therapy presented with clinical and biochemical signs of hyperaldosteronism. Abdominal ultra-sound, computed tomography, and magnetic resonance imaging showed hepatic mass. Liver biopsy with immunohistochemistry confirmed the presence of parotid adenocarcinoma secreting ACTH. He is on paclitaxel and carboplatin medication with good clinical response.

Oncogenic KRAS-Induced Protein Signature in the Tumor Secretome Identifies Laminin-C2 and Pentraxin-3 as Useful Biomarkers for the Early Diagnosis of Pancreatic Cancer.

KRAS mutations characterize pancreatic cell transformation from the earliest stages of carcinogenesis, and are present in >95% of pancreatic ductal adenocarcinoma (PDAC) cases. In search of novel biomarkers for the early diagnosis of PDAC, we identified the proteins secreted by the normal human pancreatic cell line (HPDE) recently transformed by inducing the overexpression of the KRASG12V oncogene. We report a proteomic signature of KRAS-induced secreted proteins, which was confirmed in surgical tumor samples from resected PDAC patients. The putative diagnostic performance of three candidates, Laminin-C2 (LAMC2), Tenascin-C (TNC) and Pentraxin-3 (PTX3), was investigated by ELISA quantification in two cohorts of PDAC patients (n = 200) eligible for surgery. Circulating levels of LAMC2, TNC and PTX3 were significantly higher in PDAC patients compared to the healthy individuals (p < 0.0001). The Receiver Operating Characteristics (ROC) curve showed good sensitivity (1) and specificity (0.63 and 0.85) for LAMC2 and PTX3, respectively, but not for TNC, and patients with high levels of LAMC2 had significantly shorter overall survival (p = 0.0007). High levels of LAMC2 and PTX3 were detected at early stages (I−IIB) and in CA19-9-low PDAC patients. In conclusion, pancreatic tumors release LAMC2 and PTX3, which can be quantified in the systemic circulation, and may be useful in selecting patients for further diagnostic imaging.

An Uncommon Presentation of Carcinosarcoma of the Stomach and a Minimally Invasive Approach for Treatment.

Carcinosarcoma is a rare malignant neoplasm that is composed of both epithelial and mesenchymal tumor components. Gastric carcinosarcoma is even more rare and is often diagnosed at a late stage. In this report, we investigate a case of early gastric carcinosarcoma with regional lymph node metastasis in a 78-year-old woman. The patient underwent partial gastrectomy, lymphadenectomy, and splenectomy. The tumor was confined to the gastric submucosa, and a biopsy specimen led to a histological diagnosis of carcinosarcoma with adenocarcinoma, squamous-cell carcinoma, and undifferentiated pleomorphic sarcoma components. Metastasis was present in one lymph node and displayed osteosarcomatous differentiation. Vigilant monitoring for recurrence and metastatic disease will be required for this patient.

Practices of vitamin D supplementation leading to vitamin D toxicity: Experience from a Low-Middle Income Country.

INTRODUCTION: The trend of prescribing VD preparations for nonspecific body aches and self-medication has increased significantly. The importance of vitamin D toxicity (VDT) has been underestimated and under recognized. This study was done to determine the frequency toxicity (>150 ng/ml) in subjects for 25-hydroxyvitamin D (25OHD) and evaluate the vitamin D (VD) supplements used by these subjects. METHODOLOGY: This descriptive cross-sectional study was conducted at the Section of Chemical Pathology, Aga Khan University Hospital Karachi from April 2020 to March 2021. Subjects with 25OHD toxicity were contacted and information related to history of calcium and VD supplementation were collected. The statistical analysis was performed using the Microsoft Excel 2016. RESULTS: Over a year period 105398 subjects were tested for serum 25OHD, of which 0.34% (n = 364) subjects had 25OHD level of >150 ng/ml. After satisfying exclusion criteria 186 subjects (78 were <18 years of age and 108 were adults) were included in final analysis. All of these were using VD supplements and the main indications were delayed growth/short height (43.7%, n = 34) and aches or pains in (54.6%, n = 59) in pediatric and adult subjects respectively.Most of the subjects were taking supplements orally (74.1%, n = 138). Commonly prescribed preparation in adults and pediatric was 200,000 IU (70.4%, n = 76) and 400 IU (35.9%, n = 28) respectively. Most subjects took supplements for 1-3 months (68.3%, n = 127). Stated total supplementation ranged from 20,000 IU to 3600,000 IU in pediatric subjects and 200,000 IU to 96,00,000 IU in adults. CONCLUSIONS: Supplementation is a leading cause of potential toxic levels of 25OHD. The condition can be prevented by careful use of VD supplements and consistent monitoring.

Hematological Parameters and Demographic Distribution of Hemoglobinopathies and Various Hemoglobin Variants.

Background The study was conducted to find the prevalence of hemoglobinopathies along with their geographical/ethnic distribution to highlight the region of high prevalence that can be used to guide screening. Method Results of blood samples received for hemoglobin variants determination by high-performance liquid chromatography (HPLC) were retrospectively analyzed at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore. Blood samples were assayed for CBC (complete blood count), red blood cell morphology, and hemoglobin analysis by HPLC. CBC was performed on Sysmex XN 9000 analyzer (Sysmex, Kobe Japan), peripheral smears to review RBC morphology were stained with Wright-Giemsa stain, and HPLC was performed on BIO-RAD variant II (Bio-Rad Laboratories, Hercules, USA). Results Hemoglobinopathies were identified in 9.7% (n=997) out of 10,297 samples. Beta thalassemia trait was the most common hemoglobinopathy recognized with a prevalence of 5% (n=516), with the maximum number of cases in the Lahore district of Punjab province. The next most common hemoglobinopathy identified was sickle cell disease with a frequency of 1.43% (n=148) and the maximum cases from the Dera Ismail Khan district of the Khyber Pakhtunkhwa province. The additional important hemoglobinopathies found were sickle cell trait, hemoglobin-D Punjab trait, and compound heterozygote for sickle and beta thalassemia. Conclusion Hemoglobinopathies are the most common inherited disorders in Pakistan and worldwide. Screening for hemoglobinopathies is recommended in high-prevalence districts of Pakistan. Sickle cell screening is also recommended in newborns in the high prevalence area of Pakistan, such as the northwest regions.

CT-based radiomics stratification of tumor grade and TNM stage of clear cell renal cell carcinoma.

OBJECTIVES: To evaluate the utility of CT-based radiomics signatures in discriminating low-grade (grades 1-2) clear cell renal cell carcinomas (ccRCC) from high-grade (grades 3-4) and low TNM stage (stages I-II) ccRCC from high TNM stage (stages III-IV). METHODS: A total of 587 subjects (mean age 60.2 years ± 12.2; range 22-88.7 years) with ccRCC were included. A total of 255 tumors were high grade and 153 were high stage. For each subject, one dominant tumor was delineated as the region of interest (ROI). Our institutional radiomics pipeline was then used to extract 2824 radiomics features across 12 texture families from the manually segmented volumes of interest. Separate iterations of the machine learning models using all extracted features (full model) as well as only a subset of previously identified robust metrics (robust model) were developed. Variable of importance (VOI) analysis was performed using the out-of-bag Gini index to identify the top 10 radiomics metrics driving each classifier. Model performance was reported using area under the receiver operating curve (AUC). RESULTS: The highest AUC to distinguish between low- and high-grade ccRCC was 0.70 (95% CI 0.62-0.78) and the highest AUC to distinguish between low- and high-stage ccRCC was 0.80 (95% CI 0.74-0.86). Comparable AUCs of 0.73 (95% CI 0.65-0.8) and 0.77 (95% CI 0.7-0.84) were reported using the robust model for grade and stage classification, respectively. VOI analysis revealed the importance of neighborhood operation-based methods, including GLCM, GLDM, and GLRLM, in driving the performance of the robust models for both grade and stage classification. CONCLUSION: Post-validation, CT-based radiomics signatures may prove to be useful tools to assess ccRCC grade and stage and could potentially add to current prognostic models. Multiphase CT-based radiomics signatures have potential to serve as a non-invasive stratification schema for distinguishing between low- and high-grade as well as low- and high-stage ccRCC. KEY POINTS: • Radiomics signatures derived from clinical multiphase CT images were able to stratify low- from high-grade ccRCC, with an AUC of 0.70 (95% CI 0.62-0.78). • Radiomics signatures derived from multiphase CT images yielded discriminative power to stratify low from high TNM stage in ccRCC, with an AUC of 0.80 (95% CI 0.74-0.86). • Models created using only robust radiomics features achieved comparable AUCs of 0.73 (95% CI 0.65-0.80) and 0.77 (95% CI 0.70-0.84) to the model with all radiomics features in classifying ccRCC grade and stage, respectively.

Establishing reference interval for thyroid-stimulating hormone in children below two-year ages in Pakistani population.

INTRODUCTION: Reference intervals (RIs) of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) are age, assay and population specific. Currently, the age and assay-specific RIs for TSH are not available for children under two years of age. This study aimed to establish reference intervals for serum concentrations of TSH and FT4 in healthy children aged 1-24 months as per CLSI C28-A3 guidelines. METHODS: This prospective cross-sectional study was conducted in children from 1 to 24 months visiting the clinical laboratory for serum vitamin D testing but without any recent illness, hospitalization, medication and history of maternal thyroid diseases from August 2018 to March 2019 were invited to participate in the study.Serum TSH and FT4 were measured on ADVIA Centaur (Siemens Diagnostics, US), using chemiluminescence immunoassay. Kolmogorov-Smirnov test assessed normality of the data and RIs based on central 95% of the population were established using the non-parametric approach. RESULTS: After excluding one subject with confirmed congenital hypothyroidism, a total of 131 children were included in the study. The median (IQR) age of the study subjects was 12 months (11), and majority 78 (59.5%) were boys. The RIs were established using non-parametric approach as the data was not normally distributed. Reference interval for TSH was 0.73-4.94 µIU/mL and for FT4 was 0.81-1.51 ng/dl. CONCLUSION: We established assay-specific RIs for serum TSH and FT4 in children aged 1-24 months in our population. The RIs were slightly lower from RIs developed on other platforms in different population.

A cross sectional evaluation of the corona-score for swift identification of SARS-CoV-2 infection at a tertiary care hospital in Pakistan.

BACKGROUND: The Corona-Score is one of the first and most widely used predictive model for coronavirus 2 (SARS-CoV-2) infection. The purpose of this study was to validate the performance of Corona-Score in a cohort of Pakistani patients pursuing care for suspected infection. METHODS: After seeking institution's ethical committee exemption, results of serum lactate dehydrogenase (LDH), C-reactive protein (CRP), ferritin, absolute lymphocyte and neutrophil counts, chest x-ray findings and demographics of suspected COVID-19 cases with respiratory symptoms were recouped from electronic medical record. The pre-validated score as proposed by Kurstjens S et al., was calculated. The subjects were divided into SARS-CoV-2 positive and negative on the basis of reverse transcription-polymerase chain reaction (RT-PCR) findings. Median and interquartile range (IQR) was calculated for the score in the two groups and the difference was assessed using the independent sample median test. Receiver operating characteristics (ROC) curve analysis was plotted. Statistical analyses were carried out using SPSS 26, with statistical significance set at p value < 0.05. RESULTS: A total of sixty cases, 30 (50%) RT-PCR positive and 30 (50%) negative with a median Corona-Score of 3.5 (IQR: 0-6) and 1.5 (IQR: 0-4) respectively, were evaluated. A p-value of 0.61 showing no statistically significant between group differences was observed. The area under the curve of Corona-Score in our population of patients was 0.59 (95% CI: 0.45-0.74). Using the cut-off values of four originally identified by Kurstjens et al. the model displayed 43.3% sensitivity and 70% specificity with an overall accuracy of 56.67%. CONCLUSION: Corona-Score displayed a lower diagnostic accuracy which may be attributable to the different genetic framework, viral strain and severity of the disease in Pakistanis compared to the population where this score was originally validated. However, large multi-center studies across the country are dire need of time to evaluate the score in overly exhausted health care setup and limited availability of PCR testing.

Pentraxin 3 is a stromally-derived biomarker for detection of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC), characterized by dense desmoplastic stroma laid down by pancreatic stellate cells (PSC), has no reliable diagnostic biomarkers for timely detection. A multi-center cohort of PDAC patients and controls (chronic pancreatitis, intra-ductal papillary neoplasms, gallstones and otherwise healthy) donated serum in an ethically approved manner. Serum PTX3 above 4.34 ng/mL has a higher sensitivity (86%, 95% confidence interval (CI): 65-97%) and specificity (86%, 95% CI: 79-91%), positive predictive value (97%) and likelihood ratio (6.05), and is superior when compared to serum CA19-9 and CEA for detection of PDAC. In vitro and ex vivo analyses of PTX3, in human PDAC samples, PSCs, cell lines and transgenic mouse model for PDAC, suggest that PTX3 originates from stromal cells, mainly PSC. In activated PSC, PTX3 secretion could be downregulated by rendering PSC quiescent using all-trans-retinoic acid (ATRA). PTX3 organizes hyaluronan in conjunction with tumor necrosis factor-stimulated gene 6 (TSG-6) and facilitates stellate and cancer cell invasion. In SCALOP clinical trial (ISRCTN96169987) testing chemo-radiotherapy without stromal targeting, PTX3 had no prognostic or predictive role. However, in STARPAC clinical trial (NCT03307148), stromal modulation by ATRA even at first dose is accompanied with serum PTX3 response in patients who later go on to demonstrate disease control but not those in whom the disease progresses. PTX3 is a putative stromally-derived biomarker for PDAC which warrants further testing in prospective, larger, multi-center cohorts and within clinical trials targeting stroma.

Diagnostic Accuracy of the Forns Score for Liver Cirrhosis in Patients With Chronic Viral Hepatitis.

Introduction Liver cirrhosis is an irreversible and end-stage disease. It results from chronic liver damage characterized by the replacement of normal liver tissue by fibrosis, leading to the progressive loss of liver function. Making an early diagnosis of cirrhosis is important for patients with chronic hepatitis because early antiviral therapy can prevent the progression of cirrhosis and even induce regression. There have been efforts to develop surrogate markers for liver cirrhosis as the biopsy is invasive, costly, and difficult to standardize. Methods This was a cross-sectional study conducted at the Section of Chemical Pathology, the Department of Pathology and Laboratory Medicine in Collaboration with the Section of Gastroenterology, Department of Medicine, the Aga Khan University, from January to December 2018. A total of 90 patients (>18 years of age) with a history of chronic viral hepatitis, who were attending the FibroScan® (Echosens, Paris, France) clinic were included. Patients with a history of autoimmune liver diseases and hepatocellular carcinoma were excluded from the study. Blood samples withdrawn were analyzed on ADVIA Centaur® (Siemens Healthineers, Erlangen, Germany), and Forns scores were calculated based on the following four parameters: patient age, total cholesterol, gamma-glutamyl transferase (GGT), and platelet count. Results The median age of the patients was 38.5 years [interquartile range (IQR): 21]. Among the study population, 59 (65.6%) were males and 31 (34.4%) were females; 26 patients showed reactivity for hepatitis B surface antigen (HBsAg), and 63 patients were found chronic with hepatitis C virus (HCV). The proportion of HCV was observed to be higher as compared with that of Hepatitis B virus (HBV). Nineteen patients were found to have jaundice and only one patient had ascites. An Area Under the Receiver Operating Curve (AUROC) was generated to determine the diagnostic accuracy of the Forns score. It was observed that the Forn score value of >7.110 had an AUROC of 0.9928 (95% CI: 0.9821-1.003, p-value: <0.001) with a sensitivity of 100% (95% CI: 91.19-100.0%) and specificity of 94% (95% CI: 83.45-98.75%), with a higher positive likelihood ratio of 16.67. Conclusion This study found the Forns score to be sensitive and specific in diagnosing liver cirrhosis in patients with chronic hepatitis. The Forns score at a cutoff of 7.11 is highly sensitive as well as a specific noninvasive method that can be used to ascertain the status of fibrosis in chronic hepatitis patients.

Metabolic reprogramming of terminally exhausted CD8+ T cells by IL-10 enhances anti-tumor immunity.

T cell exhaustion presents one of the major hurdles to cancer immunotherapy. Among exhausted CD8+ tumor-infiltrating lymphocytes, the terminally exhausted subset contributes directly to tumor cell killing owing to its cytotoxic effector function. However, this subset does not respond to immune checkpoint blockades and is difficult to be reinvigorated with restored proliferative capacity. Here, we show that a half-life-extended interleukin-10-Fc fusion protein directly and potently enhanced expansion and effector function of terminally exhausted CD8+ tumor-infiltrating lymphocytes by promoting oxidative phosphorylation, a process that was independent of the progenitor exhausted T cells. Interleukin-10-Fc was a safe and highly efficient metabolic intervention that synergized with adoptive T cell transfer immunotherapy, leading to eradication of established solid tumors and durable cures in the majority of treated mice. These findings show that metabolic reprogramming by upregulating mitochondrial pyruvate carrier-dependent oxidative phosphorylation can revitalize terminally exhausted T cells and enhance the response to cancer immunotherapy.

An audit of transfusion reaction monitoring and reporting at a cancer hospital in Pakistan - a step towards haemovigilance.

OBJECTIVE: To monitor the frequencies of different adverse transfusion reactions and to assess the compliance of clinical staff with the process of sending proper transfusion reaction workup within the specified time. METHODS: The retrospective audit was conducted at the blood bank of Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised all transfusion reaction forms received from July 1, 2017, to June 30, 2018. The forms were analysed for type of blood component, time in which it was received by the blood bank, whether or not the form was completely filled, whether or not all required samples were provided, and the type of reaction. RESULTS: Of the 12,787 units dispensed and transfused, 50(0.39%) transfusion reactions were noted. Allergic was the most frequent type 24(48%). Red cells accounted for 38(76%) of the reactions. In 58(95%) cases, reaction forms were completely filled. Blood bags in 36(59%) and post-transfusion ethylenediaminetetra acetic acid samples in 35(57.3%) cases were received at blood bank within 2 hours of reaction. CONCLUSIONS: Incidence of transfusion reactions was found to be low as there was good compliance with procedures on the part of the clinical staff.

Debilitating Manifestation of a Disease with Multiple Names: A Severe Case of Sclerosing Mesenteritis.

Sclerosing mesenteritis (SM) is a rare inflammatory condition with unknown etiology that affects the mesenteric adipose tissue. We present a case of a 49-year-old male with severe abdominal pain who underwent abdominal biopsy confirming the presence of adipose inflammation and necrosis. The diagnosis of SM was made, and the patient was treated with prednisone and tamoxifen. As this condition is rare, there are no standard guidelines for management. This case aims to outline a possible treatment plan.

Evaluation of serum ferritin for prediction of severity and mortality in COVID-19- A cross sectional study.

BACKGROUND: Ferritin even though widely recognized as a representative of total body iron stores, its prognostic utility is linked with COVID-19. This study was aimed at evaluation of the association of ferritin with severity in Coronavirus disease 2019 (COVID-19), hospitalized patients and to test the hypothesis that it is an independent predictor of mortality. MATERIAL AND METHODS: This study was conducted at Chemical Pathology, Department of Pathology and Laboratory Medicine, Aga Khan University (AKU), Karachi. Medical records of all in-patients including both genders, and all age groups with documented COVID-19 from 1st March to 10th August 2020 were reviewed. The subjects were divided into two categories severe and non-severe COVID-19; and survivors and non-survivors. The details were recorded on a pre-structured performa. Between-group differences were tested using the Mann-Whitney's U-test. The receiver operating characteristic curve was plotted for ferritin with severity and mortality. A binary logistic regression was used to identify variables independently associated with mortality. The data was analyzed using Statistical Package for the Social Sciences (SPSS). RESULTS: A total of 336 in patients were reviewed as declared COVID-19 positive during the study duration, and 157 were included in the final analysis including 108 males and 49 females. Statistically significant difference in ferritin was found in the two categories based on severity and mortality. Binary logistic regression showed ferritin to be an independent predictor of all-cause mortality supplemented with an AUC of 0.69 on ROC analysis. CONCLUSIONS: Serum ferritin concentration is a promising predictor of mortality in COVID-19 cases.

An objective approach to evaluate novice robotic surgeons using a combination of kinematics and stepwise cumulative sum (CUSUM) analyses.

BACKGROUND: Current evaluation methods for robotic-assisted surgery (ARCS or GEARS) are limited to 5-point Likert scales which are inherently time-consuming and require a degree of subjective scoring. In this study, we demonstrate a method to break down complex robotic surgical procedures using a combination of an objective cumulative sum (CUSUM) analysis and kinematics data obtained from the da Vinci® Surgical System to evaluate the performance of novice robotic surgeons. METHODS: Two HPB fellows performed 40 robotic-assisted hepaticojejunostomy reconstructions to model a portion of a Whipple procedure. Kinematics data from the da Vinci® system was recorded using the dV Logger® while CUSUM analyses were performed for each procedural step. Each kinematic variable was modeled using machine learning to reflect the fellows' learning curves for each task. Statistically significant kinematics variables were then combined into a single formula to create the operative robotic index (ORI). RESULTS: The inflection points of our overall CUSUM analysis showed improvement in technical performance beginning at trial 16. The derived ORI model showed a strong fit to our observed kinematics data (R2 = 0.796) with an ability to distinguish between novice and intermediate robotic performance with 89.3% overall accuracy. CONCLUSIONS: In this study, we demonstrate a novel approach to objectively break down novice performance on the da Vinci® Surgical System. We identified kinematics variables associated with improved overall technical performance to create an objective ORI. This approach to robotic operative evaluation demonstrates a valuable method to break down complex surgical procedures in an objective, stepwise fashion. Continued research into objective methods of evaluation for robotic surgery will be invaluable for future training and clinical implementation of the robotic platform.

Central memory CD8+ T cells derive from stem-like Tcf7hi effector cells in the absence of cytotoxic differentiation.

Central memory CD8+ T cells (Tcm) control systemic secondary infections and can protect from chronic infection and cancer as a result of their stem-cell-like capacity to expand, differentiate, and self-renew. Central memory is generally thought to emerge following pathogen clearance and to form based on the de-differentiation of cytolytic effector cells. Here, we uncovered rare effector-phase CD8+ T cells expressing high amounts of the transcription factor Tcf7 (Tcf1) that showed no evidence of prior cytolytic differentiation and that displayed key hallmarks of Tcm cells. These effector-phase Tcf7hi cells quantitatively yielded Tcm cells based on lineage tracing. Mechanistically, Tcf1 counteracted the differentiation of Tcf7hi cells and sustained the expression of conserved adult stem-cell genes that were critical for CD8+ T cell stemness. The discovery of stem-cell-like CD8+ T cells during the effector response to acute infection provides an opportunity to optimize Tcm cell formation by vaccination.

Impact of COVID-19 on laboratory professionals-A descriptive cross sectional survey at a clinical chemistry laboratory in a developing country.

BACKGROUND: The lab professionals at one end are at increased risk of contracting the infection while on the other end have to deal with the various challenges during the Coronavirus Disease 2019 (COVID-19) outbreak. This survey was undertaken to analyze the lab professionals' perspectives, in terms of the challenges, financial implications, fears, motivation and satisfaction from organizational processes and policies adopted, amid the COVID-19 crisis. MATERIAL & METHODS: The study utilized a cross-sectional survey design. The survey was administered online via the google docs survey tool from medical laboratory professionals (n = 64) serving at the section of Clinical Chemistry, department of Pathology and Laboratory Medicine, the Aga Khan University (AKU), Pakistan from June 4th to 14th 2020. A team consisting of three Clinical Chemistry consultants serving as faculty at the section, designed the survey questionnaire. The responses were recorded on a five-point Likert Scale (1 = strongly disagree, 2 = disagree, 3 = neutral, 4 = agree and 5 = strongly agree). The statistical analysis was performed using the Microsoft Excel 2013. Frequency and percentages were calculated for gender, experience and designation while descriptive results based on the responses were also recorded. RESULTS: The response rate was 78% (n = 50). 60% responded that the current lifestyle adopted during the pandemic was not better than the traditional one. The fear of employment termination and financial challenges were being faced by 42% and 78% respondents respectively. The quality of family life was improved in 54% cases while 96% were of the view that their social activities at work have suffered. Whereas, 22% were not satisfied by the measures taking by the management during the outbreak. CONCLUSION: The findings of this survey provide laboratorians' perspective, in times of such crisis and provides us certain lessons to prepare for such unpredicted situations in future.