Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment.

Cancer stem cells (CSCs), or tumor-initiating cells (TICs), are small subpopulations (0.0001-0.1%) of cancer cells that are crucial for cancer relapse and therapy resistance. The elimination of each CSC is essential for achieving long-term remission. Metabolic reprogramming, particularly lipids, has a significant impact on drug efficacy by influencing drug diffusion, altering membrane permeability, modifying mitochondrial function, and adjusting the lipid composition within CSCs. These changes contribute to the development of chemoresistance in various cancers. The intricate relationship between lipid metabolism and drug resistance in CSCs is an emerging area of research, as different lipid species play essential roles in multiple stages of autophagy. However, the link between autophagy and lipid metabolism in the context of CSC regulation remains unclear. Understanding the interplay between autophagy and lipid reprogramming in CSCs could lead to the development of new approaches for enhancing therapies and reducing tumorigenicity in these cells. In this review, we explore the latest findings on lipid metabolism in CSCs, including the role of key regulatory enzymes, inhibitors, and the contribution of autophagy in maintaining lipid homeostasis. These recent findings may provide critical insights for identifying novel pharmacological targets for effective anticancer treatment.

Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.

Cancer stem cells represent a resilient subset within the tumor microenvironment capable of differentiation, regeneration, and resistance to chemotherapeutic agents, often using dormancy as a shield. Their unique properties, including drug resistance and metastatic potential, pose challenges for effective targeting. These cells exploit certain metabolic processes for their maintenance and survival. One of these processes is autophagy, which generally helps in energy homeostasis but when hijacked by CSCs can help maintain their stemness. Thus, it is often referred as an Achilles heel in CSCs, as certain cancers tend to depend on autophagy for survival. Autophagy, while crucial for maintaining stemness in cancer stem cells (CSCs), can also serve as a vulnerability in certain contexts, making it a complex target for therapy. Regulators of autophagy like AMPK (5' adenosine monophosphate-activated protein kinase) also play a crucial role in maintaining CSCs stemness by helping CSCs in metabolic reprogramming in harsh environments. The purpose of this review is to elucidate the interplay between autophagy and AMPK in CSCs, highlighting the challenges in targeting autophagy and discussing therapeutic strategies to overcome these limitations. This review focuses on previous research on autophagy and its regulators in cancer biology, particularly in CSCs, addresses the remaining unanswered questions, and potential targets for therapy are also brought to attention.

Molecular Chaperonin HSP60: Current Understanding and Future Prospects.

Molecular chaperones are highly conserved across evolution and play a crucial role in preserving protein homeostasis. The 60 kDa heat shock protein (HSP60), also referred to as chaperonin 60 (Cpn60), resides within mitochondria and is involved in maintaining the organelle's proteome integrity and homeostasis. The HSP60 family, encompassing Cpn60, plays diverse roles in cellular processes, including protein folding, cell signaling, and managing high-temperature stress. In prokaryotes, HSP60 is well understood as a GroEL/GroES complex, which forms a double-ring cavity and aids in protein folding. In eukaryotes, HSP60 is implicated in numerous biological functions, like facilitating the folding of native proteins and influencing disease and development processes. Notably, research highlights its critical involvement in sustaining oxidative stress and preserving mitochondrial integrity. HSP60 perturbation results in the loss of the mitochondria integrity and activates apoptosis. Currently, numerous clinical investigations are in progress to explore targeting HSP60 both in vivo and in vitro across various disease models. These studies aim to enhance our comprehension of disease mechanisms and potentially harness HSP60 as a therapeutic target for various conditions, including cancer, inflammatory disorders, and neurodegenerative diseases. This review delves into the diverse functions of HSP60 in regulating proteo-homeostasis, oxidative stress, ROS, apoptosis, and its implications in diseases like cancer and neurodegeneration.

Patient Advocates for Clinical Research (PACER): A Step Toward Ethical, Relevant, and Truly Participatory Clinical Research in India.

Background Clinical research presents a promising path for improving healthcare in contemporary India. Yet, researchers identify gaps in trust, awareness, as well as misconceptions about being a '"guinea pig." We proposed building the capacity of training patient advocacy groups (PAGs) in patient-centered clinical research and through them creating aware patients as research partners. Methodology Patient Advocates for Clinical Research (PACER) is a tiered program to share information and education about clinical research with PAGs. Tier one is a self-paced online learning course, followed by workshops on clinical research, Good Clinical Practice, research consent, case studies, and group discussions. Results A total of 20 PAGs represented by 48 participants, active in areas of pediatric cancer, breast cancer, multiple myeloma, type I diabetes, spinal muscular atrophy, sickle cell disease, and inflammatory bowel diseases, participated. Among 48 participants 30 successfully completed the online course (multiple-choice question evaluation score cut-off >70%), attaining an average score of 23.9 ± 2.1 out of 30. Overall, 48 participants attended workshop 1 and 45 workshop 2, with 140 participants joining the focus group discussion (FGD). An overall improvement of 9.4% (𝜒2 = 46.173; p < 0.001) for workshop 1 and 8.2% (𝜒2 = 25.412; p < 0.001) for workshop 2 was seen in knowledge gain about clinical research. The FGD raised issues such as misleading information from research teams, unethical recruitment, incomprehensible information sheets, and limited trial-related knowledge fostering fear of participation in clinical research. Conclusions Multimodal and tiered learning of clinical research such as that used by PACER has a good participatory and learning response from PAGs and may be further explored.

Clinical Outcomes of Autologous Hematopoietic Stem Cell Transplant in Multiple Myeloma Patients: A 5-year Experience from a Single Centre in North India.

Swati PabbiIntroduction Multiple myeloma (MM) forms a significant proportion of hematological malignancies. Autologous transplantation continues to be an effective consolidation strategy in resource-restricted settings such as India. Objectives The main objective of the study was to analyze the clinical outcomes of autologous hematopoietic stem cell transplant (HSCT) in MM patients in a single tertiary care center in north India over a period of 5 years. Materials and Methods This retrospective observational study was conducted in a tertiary care center in north India. Data of all MM patients who underwent HSCT between January 2014, and December 2018, were analyzed. The outcome of HSCT was investigated in terms of transplant-related mortality (TRM), progression-free survival (PFS), overall survival (OS), and relapse. PFS and OS were calculated by Kaplan-Meier method and differences between the groups were tested for statistical significance using the two-tailed log-rank test. Life-table method was used for the estimation of survival rate at 1, 3, 5, and 6 years. Results Patient characteristics and survival post-transplant was similar to other published Indian studies. In total, 378 patients were diagnosed with MM in our hospital between 2014 and 2018. One hundred ninety-three patients were found to be eligible for autologous HSCT, out of which 52 ended up having a transplant giving us a high percentage (26.9%) of patients receiving a transplant in our setting. Transplant-related mortality (TRM) was nil in the present study. The mean PFS and OS were 62.8 and 70.1 months, respectively. The mean PFS and OS rates at 5 years were 75.3% and 84.2%, respectively. The average cost estimate of HSCT in our setting was 7.2 lakh Indian national rupees. Conclusion Autologous HSCT is a safe procedure with nil 100-day mortality in present series. Moreover, considering the cost of novel agents, autologous transplant remains a cost-effective way for prolonging remission and time-to-next treatment in India.

Cost-effectiveness of population-based screening for oral cancer in India: an economic modelling study.

Background: Oral cancer screening reduces mortality associated with oral cancer. The current study evaluated the cost-effectiveness of commonly used screening techniques, namely conventional oral examination (COE), toluidine blue staining (TBS), oral cytology (OC), and light-based detection (LBD) in the Indian scenario. Methods: The study used a Markov modelling approach to estimate the cost and health outcomes of four different approaches (COE, TBS, OC, and LBD) for screening oral cancer over time from a societal perspective. The discount rate was assumed as 3%. The outcomes estimated were oral cancer incident cases, deaths averted, and quality-adjusted life years (QALYs). To address the high burden of risk factors (tobacco and/or alcohol) in India, two Markov models were developed: Model A adopted a mass-screening strategy, whereas Model B adopted a high-risk screening strategy versus no screening. Probabilistic sensitivity analysis (PSA) was undertaken to address any parameter uncertainty. Findings: Mass-screening using LBD at three years had the least incident cases (3271.68) and averted the maximum number of oral cancer deaths (459.76). High-risk screening using COE at ten years interval incurred the least lifetime cost of 2,292,816.21 US$ (182,794,468.26 INR). The high-risk strategies (US$/QALY), namely COE 5 years (-29.21), COE 10 years (-90.68), TBS 10 years (-60.54), and LBD 10 years (-13.51), were dominant over no-screening. Interpretation: The most cost-saving approach was the conventional oral examination at an interval of 10 years for oral screening in high-risk populations above 30 years of age. Funding: Department of Health Research, Ministry of Health & Family Welfare, Government of India.

PCL retention demonstrates better functional scores and gait patterns in total knee arthroplasty using a medial congruent insert-a prospective study.

PURPOSE: Despite Total Knee Arthroplasty (TKA) being one of the most successful procedures for end stage arthritis, nearly 20% of patients undergoing this procedure remain dissatisfied. Various design options have been introduced to reduce this cohort of patients. One such option has been the introduction of the medial congruent (MC) polyethylene design. This study was undertaken to evaluate outcome measures and gait analysis in patients undergoing bilateral single stage TKA where the posterior cruciate ligament (PCL) was retained or excised in contralateral knees. METHODS: 60 bilateral TKA's were performed by a single surgeon using a MC design option from July to Sep 2021. The study lots included patients between the ages of 55 and 70 years with fixed varus deformity of degenerative aetiology, and Kellgren Lawrence Grade 3 and 4 radiological changes. Exclusion criteria were previous surgery to the lower extremities, sero positive arthropathies, post traumatic arthritis, valgus deformity, flexion contractures > 20°, and any pre-existing pathology impacting gait, e.g., poliomyelitis, or neuromuscular disorders. The PCL was retained or sacrificed on contralateral sides for the purpose of this study. Functional scores, outcomes and gait analysis on level and gradient walking were evaluated at a follow-up of 18 months. RESULTS: At 18, months the Range of Motion (ROM) improved from a preoperative value of 97.3 ± 11.5 to 110.3 ± 6.1 on the PCL retained side (MC-PCL) and from 96.5 ± 10.8 to 113 ± 5.8 on the PCL excised side (MC-PCLX). Knee Society Score (KSS-2011) improved from a preoperative value of 21.2 ± 4.5 to 89.8 ± 3.4 at 18 months postoperatively on the MC-PCL side and from 21.5 ± 4 to 88.2 ± 3.7 on the MC-PCLX side. Forgotten Joint Score (FJS-12) was 8.8 ± 0.7 on the MC-PCL side and 8.1 ± 0.9 on the MC-PCLX side 18 months after surgery. Our gait analysis evaluation demonstrated a lower forefoot pressure in the MC-PCL group in comparison to the MC-PCLX group when subjects were made to walk on a 30° upward incline. This difference was found to be statistically significant. CONCLUSION: In this study, while ROM was greater in the MC-PCLX study lot, patient satisfaction was higher in the MC-PCL study lot. Gait assessment demonstrated lower forefoot pressure while ascending an incline of 30° in the MC-PCL study lot as compared to the MC-PCLX study lot approximating normal gait patterns. LEVEL OF EVIDENCE: II.

Simplified Zygomatic Implant Perforated (Zip) Flap for Rehabilitation in Low Level Maxillary Defects.

Rehabilitation in Low level maxillectomy cases has plethora of options right from local flaps to microvascular flaps. Subsequent to flap surgery, a maxillary dental rehabilitation can be demanding and a fixed or removable prosthesis is obligatory to provide them with near-normal function and aesthetics. Unlike the original ZIP flaps which were dedicated to microvascular flaps, we present here our unique experience with ZIP-Temporalis flap specifically for rehabilitation for patients of CAM (covid associated mucormycosis), its methods, advantages and limitations.

Dapagliflozin for inpatient hyperglycemia in cardiac surgery patients with type 2 diabetes: randomised controlled trial (Dapa-Hospital trial).

AIMS: To examine the efficacy and safety of dapagliflozin in the treatment of hyperglycemia in cardiac surgery patients with type 2 diabetes (T2D). METHODS: Cardiac surgery patients with T2D (n = 250) were randomly assigned (1:1) to receive dapagliflozin plus basal-bolus insulin (DAPA group) or basal-bolus insulin alone (INSULIN group) in the early postoperative period. The primary outcome was mean difference in daily blood glucose (BG) concentrations between groups. The major safety outcomes were the occurrence of severe ketonemia/diabetic ketoacidosis (DKA) and hypoglycemia. All analyses were performed according to the intention-to-treat principle. RESULTS: The median age of the patients was 61 years (range, 55-61), and 219 (87.6%) were men. Overall, the randomization blood glucose was 165 mg/dL (SD, 37) and glycated hemoglobin was 7.7% (SD, 1.4). There were no differences in mean daily BG concentrations (149 vs. 150 mg/dL), mean percentage of readings within target BG of 70-180 mg/dL (82.7% vs. 82.5%), total daily insulin dose (mean, 39 vs. 40 units/day), number of daily insulin injections (median, 3.9 vs. 4), length of hospital stay (median, 10 vs. 10 days), or hospital complications (21.6% vs. 24.8%) between the DAPA and INSULIN groups. The mean plasma ketone levels were significantly higher in the DAPA group than in the INSULIN group at day 3 (0.71 vs. 0.30 mmol/L) and day 5 (0.42 vs. 0.19 mmol/L) of randomization. Six patients in the DAPA group developed severe ketonemia, but no patient developed DKA. There were no differences in the proportion of patients with BG < 70 mg/dL (9.6% vs. 7.2%) between the two groups. CONCLUSION: Dapagliflozin complementary to basal-bolus insulin does not improve glycemia further over and above the basal-bolus insulin alone in hospitalized cardiac surgery patients. Dapagliflozin significantly increases plasma ketones levels. Safety of dapagliflozin in hospitalized patients needs further investigation. Trial registration ClinicalTrials.gov NCT05457933.

Recovery and post-operative analgesic efficacy from fentanyl- versus dexmedetomidine-based anesthesia in head and neck cancer surgery: A prospective comparative trial.

Background: Opioids such as fentanyl are being used frequently in the management of postoperative period, whereas non-opioid drugs such as dexmedetomidine are now commonly being used as adjuvants during the perioperative period to hasten the fast recovery and better outcome in the post-operative period because of their anesthetic and analgesic property. The recovery profile was measured by the emergence of anesthesia and pain characteristics. We aimed to evaluate and compare the efficacy of dexmedetomidine and fentanyl in the surgery of head and neck cancer patients. Methods: Prospective double-blind study on 60 patients with the American Society Anesthesiologists (ASA) grade I and II were randomly divided into two groups. Group DM received a loading dose of dexmedetomidine 1 µg/kg over 10 min followed by a maintenance dose of 0.5 µg/kg/h and Group FM received a loading dose of fentanyl 2 µg/kg/h for over 10 min followed by 1 µg/kg/h maintenance dose. Data were analyzed using a Chi-square test or Student's 't' test. Results: The group DM was hemodynamic stable as compared to group FM. The perturbation during extubation emergence was significantly lower in group DM as compared to that in group FM. A total of four patients were severely agitated in group FM, whereas it was absent in group DM. Severe agitation was significantly different between Group FM and Group DM. The visual analog scale (VAS) was lower among patients of Group DM as compared to Group FM at all times except at 4 h. Conclusions: The infusion of dexmedetomidine was better in controlling emergence agitation, postoperative pain, and achieving peri-operative hemodynamic stability as compared to fentanyl.

Efficacy and safety of degludec U100 versus glargine U300 for the early postoperative management of patients with type 2 diabetes mellitus undergoing coronary artery bypass graft surgery: A non-inferiority randomized trial.

AIMS: To compare the efficacy and safety of degludec U100 versus glargine U300 for the early postoperative management of patients with type 2 diabetes mellitus (T2D) undergoing coronary artery bypass graft (CABG) surgery. METHODS: A total of 239 patients were randomly assigned (1:1) to receive a basal-bolus regimen in the early postoperative period using degludec U100 (n = 122) or glargine U300 (n = 117) as basal and glulisine before meals. The primary outcome was mean differences between groups in their daily BG concentrations. The major safety outcome was the occurrence of hypoglycemia. RESULTS: There were no differences in mean daily BG concentrations (157 vs. 162 mg/dl), mean percentage of readings within target BG of 70-180 mg/dl (74% vs. 73%), daily basal insulin dose (19 vs. 21 units/day), length of stay (median [IQR]: 9 vs. 9 days), or hospital complications (21.3% vs. 21.4%) between treatment groups. There were no differences in the proportion of patients with BG <70 mg/dl (15.6% vs. 23.1%) or <54 mg/dl (1.6% vs. 4.3%) between degludec-100 and glargine-300 groups. CONCLUSIONS: Treatment with degludec U100 is as effective and safe as glargine U300 for the early postoperative hospital management of patients with T2D undergoing CABG.

Cholangioscopic classification of post-living donor liver transplantation biliary strictures can predict their natural history and response to therapy.

BACKGROUND: The study aimed to assess the morphology of post-living donor liver transplant (LDLT) anastomotic biliary strictures using cholangioscopy and assess the impact of morphology on its prognosis. METHODS: A single centre, prospective, observational study was conducted at a tertiary care teaching hospital from August 2014 to July 2016. Single operator cholangioscopy (SOC) was used to assess post-LDLT anastomotic biliary strictures at presentation in 24 patients. Analysis included demographic and biochemical characteristics, time to stricture development, endoscopic procedural details, time to remodelling and development of recurrence on follow-up. RESULTS: Two distinct patterns of strictures were identified, type I with minimal inflammatory changes and type II with severe inflammatory changes. Guidewire cannulation was successful in 23 out of 24 (95.8%) patients. There was no significant difference between the two types of strictures based on aetiology of liver disease, CTP and MELD scores, time taken for the development or laboratory parameters at presentation. However, type II strictures required more sessions of dilatation (4 vs. 2; P = 0.002), longer duration for resolution (282.5 vs. 201.5 days, P = 0.095) and more number of stents. CONCLUSIONS: Addition of cholangioscopy tends to improve stricture cannulation rates at ERCP. It offers a useful classification of post-LDLT strictures with prognostic and therapeutic significance. Type II strictures tend to require more sessions of endotherapy than type I strictures over a longer duration for remodelling.

Effect of Spiritual Music on Old-Age Patients Undergoing Lower Limb Surgery Under Spinal Anesthesia.

Context: Music is ubiquitous and found in all cultures; it elicits both physiological and psychological responses in its listener. It has been proven that music reduces perception of pain and dosages of anesthetics and sedatives used during surgery. Aims: To study the effect spiritual music on perioperative anxiety and hemodynamic parameters in elderly patients undergoing procedures under spinal anesthesia. Settings and Design: A prospective, randomized controlled study. Subjects and Methods: Eighty patients fulfilling inclusion criteria were enrolled and randomly divided in two equal groups. Patients were transferred to the operation theater with the spiritual music still being played in Group I, while no music was played in Group C. Under aseptic precautions, neuraxial blockade was performed at L3/L4 interspace. Music was played throughout the surgery in Group I. Intraoperative visual analog scale for anxiety (VASA) was recorded. At the end of the surgery, spiritual music was stopped. The study parameters were recorded. Statistical Analysis Used: A significant difference in the proportions of male and female candidates between the two groups was calculated using Chi-squared test. Significant differences in the mean VASA scores and blood pressures (systolic blood pressure [SBP] and diastolic blood pressure [DBP]) between the two groups were calculated using Student's t-test. Results: No significant difference was observed between preoperative VASA score (P = 0.29) of both the groups, whereas a significant difference was present in intraoperative (P < 0.01) and postoperative VASA score (P < 0.01) of both the groups. In Group I, requirement for sedative was significantly lower (P < 0.01). Heart rate in Group I was on lower side, suggesting decrease in anxiety. No significant difference was observed in SBP or DBP of the patients of both the groups. Conclusions: Spiritual music can act as a noninvasive, simple, and inexpensive intervention for elderly patients to alleviate perioperative anxiety. It can also reduce the need for sedatives intraoperatively, thereby lowering the risk of side effects.

Hepatosplenic T-cell lymphoma diagnosed using flow cytometry. A single-center study of 12 cases from North India.

Background: Hepatosplenic T-cell lymphoma (HSTCL) is a rare fatal T-cell neoplasm with unique clinical and laboratory features. There is, however, significant morphological and immunophenotypic heterogeneity which may lead to diagnostic dilemma. Aims and Objectives: The study was aimed to study the prevalence and clinic-pathological spectrum of this rare variant of T cell lymphoma in the Indian subcontinent. Material and Methods: A retrospective analysis of all consecutive cases of HSTCL diagnosed over a period of 6 years was carried out. The clinical and laboratory parameters of all these patient were reviewed and analysed. Results: A total of 12 cases of HSTCL were diagnosed during this period which accounted for 1.76% of all non-Hodgkin's lymphomas (NHLs) and 9.1% of all T-cell NHLs. The median (range) age of presentation was 23 (16-30) years.Leukocytosis, peripheral blood (PB) involvement, and a blastic morphology were noted in 41%, 67%, and 58% of the cases, respectively. FCI proved these cells to have a mature, dual-negative (CD4-/CD8-) T-cell phenotype with a gamma-delta T-cell receptor restriction. Frequent loss of CD5 expression (84%) was also noted. These patients invariably had a fatal outcome and majority died within a year of diagnosis. Conclusion: The incidence of leukocytosis and a blastoid morphology is quite frequent in HSTCL. Hence, a differential diagnosis of HSTCL should always be considered in young patients presenting with splenomegaly and exhibiting atypical lymphoid/blastoid cells in the PB or a marrow. An FCI can readily diagnose and differentiate them from an acute lymphoblastic leukemia/lymphoma.

Real-world challenges in the management of acute myeloid leukemia: a single-center experience from North India.

BACKGROUND: The outcome of acute myeloid leukemia (AML) in low-middle-income countries (LMIC) is dismal due to delayed clinical presentation and infection-related complications. We aimed to analyze the outcome of patients with AML and the factors associated with its prognosis. METHODS: A retrospective observational study was conducted at a tertiary care university hospital in North India from January 2015 to December 2019. RESULTS: A total of 137 AML patients (median age 32 year (3-66 years) received intensive chemotherapy during study period. The median delay from diagnosis to treatment was 45 days (6-177 days). Among the 352 febrile neutropenia (FN) episodes analyzed, 175 (49.7%) were culture positive; Gram-negative multi-drug resistant organism (MDRO) sepsis during induction being 57.4% with 34.5% infections due to carbapenem-resistant Enterobacteriaceae (CRE) leading to a mortality rate of 14.6%. The median EFS and OS were 12.0 ± 1.57 (95% CI 8.91-15.08) and 15.0 ± 2.44 (95% CI 10.21-19.78) months respectively. Multivariable analysis revealed significant difference in median OS between favorable vs high risk AML groups (20.0 (95% CI: 12.50-27.49) vs 9.0 (95% CI: 2.99-15.01) months; p = 0.002); time from diagnosis to treatment (< 30 days vs ≥ 30 days; not reached vs 9.0 (95% CI: 6.81-11.18) months; p = 0.001), performance status (1 vs 2 vs 3; not reached vs 12.0 (95% CI: 10.32-13.67) vs 4.0 (95% CI:2.77-5.22); p = 0.001), and attainment of complete remission vs induction failure (not reached vs 6.0 (95% CI: 3.78-8.21); p = 0.002). CONCLUSION: Patient-related factors like delayed treatment initiation and high incidence of MDRO-associated sepsis are critical determinants of AML outcome in LMIC.

CD26 expression on circulating CD34+/CD38- progenitor population is a specific and reliable tool for the rapid flow cytometric diagnosis of chronic myeloid leukemia-A single-center validation study.

BACKGROUND: Recently, CD26 have been identified as one of the promising and specific marker for the identification of leukemic stem cells (LSCs) in chronic myeloid leukemia (CML). METHODS: This was a prospective, observational validation study. Peripheral blood (PB) samples from suspected cases of CML and other hematolymphoid neoplasm were evaluated for the expression of CD26 on stem cells (SC) (CD45 dim/CD34+/CD38-) fraction by flow cytometry (FCM) using a single tube four-color antibodies cocktail: CD45-V500 /CD26-PE/CD34-PerCPcy5.5/CD38-APC-H7. The diagnosis of CML was confirmed using cytogenetics and/or molecular studies. Additionally, 12 paired PB and bone marrow (BM) samples of CML cases were compared for the proportion of CD26+ LSCs. RESULTS: Expression of CD26 on the SC fraction was invariably noted in all cases (116/116) of CML, irrespective of the disease phase and transcript type. None of other neoplasm (0/26), including the Ph + ALLs expressed CD26. Proportion of SCs expressing CD26 was variable with a median (range) proportion being 61.3% (7.6%-98.6%). Evaluation of paired PB and BM samples showed similar proportion of CD26 + LSCs (R2 : 0.969). CONCLUSION: We confirmed that FCM evaluation of CD26 expression in the PB LSCs is a rapid and specific tool for CML diagnosis. Its utility as a marker for residual disease evaluation can also be explored in the future.

Autophagy Is Polarized toward Cell Front during Migration and Spatially Perturbed by Oncogenic Ras.

Autophagy is a physiological degradation process that removes unnecessary or dysfunctional components of cells. It is important for normal cellular homeostasis and as a response to a variety of stresses, such as nutrient deprivation. Defects in autophagy have been linked to numerous human diseases, including cancers. Cancer cells require autophagy to migrate and to invade. Here, we study the intracellular topology of this interplay between autophagy and cell migration by an interdisciplinary live imaging approach which combines micro-patterning techniques and an autophagy reporter (RFP-GFP-LC3) to monitor over time, during directed migration, the back-front spatial distribution of LC3-positive compartments (autophagosomes and autolysosomes). Moreover, by exploiting a genetically controlled cell model, we assessed the impact of transformation by the Ras oncogene, one of the most frequently mutated genes in human cancers, which is known to increase both cell motility and basal autophagy. Static cells displayed an isotropic distribution of autophagy LC3-positive compartments. Directed migration globally increased autophagy and polarized both autophagosomes and autolysosomes at the front of the nucleus of migrating cells. In Ras-transformed cells, the front polarization of LC3 compartments was much less organized, spatially and temporally, as compared to normal cells. This might be a consequence of altered lysosome positioning. In conclusion, this work reveals that autophagy organelles are polarized toward the cell front during migration and that their spatial-temporal dynamics are altered in motile cancer cells that express an oncogenic Ras protein.

Waldenström Macroglobulinemia: Clinico-pathological Profile and Treatment Outcomes of Patients from a Tertiary Care Centre of North India.

Waldenstorms Macroglobulinemia (WM) is a rare mature B cell neoplasm characterized by a lymphoplasmacytic lymphoma and an IgM monoclonal protein. It is managed by Rituximab based chemotherapy. A single-centre retrospective study was carried out to analyse the clinical presentation, laboratory features, and treatment outcomes of all consecutive patients of WM, diagnosed over a period of 86 months. First-line treatment regimens included RCD (Rituximab/Cyclophosphamide/Dexamethasone), BDR (Bortezomib /Dexamethasone/ Rituximab) and (Lenalidomide/Dexamethasone). A total of 26 patients of WM were diagnosed during this period, with a median age of 65 years. Majority (89%) of these patients were of intermediate (47%) to high risk (42%). An overall response rate of 76.4% was achieved. RCD was found superior to BDR in terms of treatment response. For those who required 2nd line chemotherapy, the median time to next treatment was 22 months. To conclude, a late presentation and higher risk categories were common in our cohort of patients. Treatment outcome was comparable to those reported in western literature. RCD regimen was found to be a better treatment option in terms of overall survival.

Deviations from a clinical pathway post pancreatoduodenectomy predict 90-day unplanned re-admission.

Aim: To determine the frequency and relevance of deviations from a post pancreatoduodenectomy (PD) clinical care pathway. Materials & methods: A retrospective analysis using a prospectively maintained database of a post-PD clinical care pathway was carried out between May 2016 and March 2018. Patients were divided based on the number of factors deviating from the clinical care pathway (Group I: no deviation; Group II: deviation in 1-4 factors; Group III: deviation in 5-8 factors). The analysis included profiling of patients on different demographic and clinical as well as medical and surgical outcome parameters (discharge by postoperative day 8 and 90-day unplanned re-admission rate). Results: Post-PD clinical care pathways are feasible but deviations from the pathway are frequent (91%). An increase in frequency of deviations from the pathway was significantly associated with increased risk of POPF and delayed gastric emptying, delayed discharge, risk of mortality and 90-day unplanned re-admission rate. Conclusion: Deviations from a post-PD clinical care pathway are common. Poor nutrition and cardiac co-morbidities are associated with an increased likelihood of deviation. As the number of deviations increase, so does the risk of significant complications and interventions, delayed discharge and 90-day re-admission rate.