Deciphering the Association of Epstein-Barr Virus and Its Glycoprotein M Peptide with Neuropathologies in Mice.

The reactivation of ubiquitously present Epstein-Barr virus (EBV) is known to be involved with numerous diseases, including neurological ailments. A recent in vitro study from our group unveiled the association of EBV and its 12-amino acid peptide glycoprotein M146-157 (gM146-157) with neurodegenerative diseases, viz., Alzheimer's disease (AD) and multiple sclerosis. In this study, we have further validated this association at the in vivo level. The exposure of EBV/gM146-157 to mice causes a decline in the cognitive ability with a concomitant increase in anxiety-like symptoms through behavioral assays. Disorganization of hippocampal neurons, cell shrinkage, pyknosis, and apoptotic appendages were observed in the brains of infected mice. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were found to be elevated in infected mouse brain tissue samples, whereas TNF-α exhibited a decline in the serum of these mice. Further, the altered levels of nuclear factor-kappa B (NF-kB) and neurotensin receptor 2 affirmed neuroinflammation in infected mouse brain samples. Similarly, the risk factor of AD, apolipoprotein E4 (ApoE4), was also found to be elevated at the protein level in EBV/gM146-157 challenged mice. Furthermore, we also observed an increased level of myelin basic protein in the brain cortex. Altogether, our results suggested an integral connection of EBV and its gM146-157 peptide to the neuropathologies.

Cemented bipolar hemiarthroplasty for unstable intertrochanteric fracture in elderly patients over 70 years: Boon or bane?

INTRODUCTION: The surgical management of intertrochanter femur fracture in elderly patient is still under debate. Various implants can be utilised but prosthetic replacement is gaining popularity. This study was performed to evaluate the functional and clinical outcomes of cemented bipolar arthroplasty as a primary treatment for unstable intertrochanteric fracture in elderly patients (> 70 years). MATERIALS AND METHODS: Thirty-seven patients with unstable intertrochanteric fracture in elderly patient (> 70 years) who underwent cemented bipolar hemiarthroplasty. Intra-operative and post-operative complications were noted; functional outcomes were assessed using Harris hip score (HHS). All patients were followed up for a minimum of 12 months. RESULTS: Overall 90% of patients has some minor or major intra or post-operative complication. One year mortality rate was 16% (6/37). Cardiopulmonary events were the most common life threatening incident. Mean fall in Haemoglobin was 1.6 gm/dL. The average time for full weight bearing mobilisation with the help of walker was 2.8 ± 1.2 days (1-8 days). The average duration of surgery was 58 ± 6 min (44-96 min) with an average blood loss of 126 ± 24 mL (90-380 mL). HHS at the end of 12 months was 77. CONCLUSIONS: The use of bipolar hemiarthroplasty in senile patient with unstable hemiarthroplasty gives an advantage of early weight bearing. However, it is associated with risk of significant intra or post-operative morbidity due to intra-operative trauma, surgical time and blood loss during the surgery. Although hemiarthroplasty can be a single-time solution to the complexities of intertrochanter fracture in elderly patients but should be performed in selected patients only.

Bone marrow transplant: A two-decade single centre hematology experience.

Background: Bone Marrow Transplant (BMT) is a curative form of therapy for many hematological disorders in both the adult and pediatric patients. The availability of BMT in the AFMS at AHRR for the last 02 decades has been a game changer for the patients. Methods: We reviewed our BMT data since the inception of the program till Feb 2023. Results: Over 700 patients with more than 23 different types of hematological disorders have undergone this procedure 58%% patients underwent an Autologous BMT and 42% an allogenic BMT. Autologous BMT for Multiple Myeloma and Allogenic BMT for Aplastic Anemia and Acute Leukemias have been the most common indications. 73% patients were adults, and 27% patients were of the pediatric age group. The male: female ratio was 2:1. The spectrum of allogenic Hematopoietic Stem Cell Transplant (HSCT) has expanded from Matched Sibling Donor (MSD) transplants to Matched Unrelated Donor (MUD) Transplants and Haploidentical Donor Transplants. 93% of our Allogenic BMT patients underwent a MSD BMT, 1% MUD BMT and 06% Haploidentical BMT. Today no patient with a malignant hematological disorder requiring a BMT is denied the procedure due to the lack of an HLA donor due to the availability of haploidentical BMT. Conclusion: The evolution of a BMT program has a long learning curve and the expanded pool of eligible donors has led to a situation of "transplant for all". Haploidentical HSCT for nonmalignant hematological disorders is an unmet need. CART cell therapy and Cellular therapies need to be prioritized for future inclusion.

Understanding the role of membrane cholesterol upon Epstein Barr virus infection in astroglial cells.

Background: EBV infection has long been postulated to trigger multiple sclerosis (MS) and anti-EBV antibodies showed a consistent presence in MS patients. Previous reports from our group have shown that the EBV infects different brain cells. Entry of the virus in neuronal cells is assisted by several host factors including membrane cholesterol. By using an inhibitor, methyl-ß-cyclodextrin (MßCD), we evaluated the role of membrane cholesterol in EBV infection and pathogenesis. Methodology: The membrane cholesterol depleted cells were infected with EBV and its latent genes expression were assessed. Further, EBV-mediated downstream signalling molecules namely STAT3, RIP, NF-kB and TNF-α levels was checked at protein level along with spatial (periphery and nucleus) and temporal changes in biomolecular fingerprints with Raman microspectroscopy (RS). Results: Upon treatment with MßCD, lmp1 and lmp2a suggested significant downregulation compared to EBV infection. Downstream molecules like STAT3 and RIP, exhibited a decrease in protein levels temporally upon exposure to MßCD while NF-kB levels were found to be increased. Further, the intensity of the Raman spectra exhibited an increase in triglycerides and fatty acids in the cytoplasm of EBV-infected LN-229 cells compared to MßCD+EBV. Likewise, the Raman peak width of cholesterol, lipid and fatty acids were found to be reduced in EBV-infected samples indicates elevation in the cholesterol specific moieties. In contrast, an opposite pattern was observed in the nucleus. Moreover, the ingenuity pathway analysis revealed protein molecules such as VLDLR, MBP and APP that are associated with altered profile of cholesterol, fatty acids and triglycerides with infection-related CNS disorders. Conclusion: Taken together, our results underline the important role of membrane cholesterol over EBV entry/pathogenesis in astroglia cells which further trigger/exacerbate virus-associated neuropathologies. These results likely to aid into the prognosis of neurological disease like MS.

Agroforestry systems in the mid-hills of the north-western Himalaya: A sustainable pathway to improved soil health and climate resilience.

Identifying the new tree crop combinations plays an important function in transforming the low input agriculture into land units with high economic returns, increasing carbon (C) sink and nutrients storage capacity, and acting as a panacea to achieve Sustainability Development Goals (SDGs). The present study aims to evaluate various tree-crop combinations for (i) biomass production, (ii) carbon accumulation, and (iii) soil nutrient enrichment of traditional and commercially evolved eight agroforestry systems (AFSs), including agri-silvi-horticulture system, agri-silviculture system, silvi-pasture, fruit tree, fodder tree, bamboo, melia and poplar based AFSs with sole cropping system in the mid-hill zone of the north-western Himalaya. The results demonstrated that poplar based AFS accumulated a higher amount of biomass (130.87 Mg ha-1) and carbon (65.44 Mg ha-1) closely followed by melia-based AFS. The C stored in leaf litter was higher (0.66 Mg ha-1) in poplar-based AFS, however, soil C stock was maximum (114.69 Mg ha-1) under bamboo-based AFS. Overall, the Melia based AFS exhibited a higher rate of carbon dioxide mitigation (19.30 Mg ha-1 yr-1) and C-sequestration (5.26 Mg ha-1 yr-1) than other studied AFSs. Moreover, soil macro-nutrients (available N, P, K, S and Ca) were maximum under bamboo-based AFS, on the other hand, the fruit-based AFS had the higher concentrations of micro-nutrients i.e., Cu (3.05), Fe (31.10 mg g-1) and Mn (17.31 mg g-1). The soil microbial counts were higher in poplar-based AFS, whereas, the soil quality index improved significantly under bamboo based and fruit tree based AFSs. Hence, it can be concluded that the experimentally evolved AFSs represent an effective approach for boosting C-sequestration, soil fertility, regenerating the soil and sustainability of hill agriculture in the north-western Himalayas over traditional AFSs and sole cropping.

Medicinal and therapeutic properties of garlic, garlic essential oil, and garlic-based snack food: An updated review.

Garlic (Allium sativum) is an edible tuber belonging to the family Liliaceae. It has been used since ancient times as a spice to enhance the sensory characteristics of food and as a household remedy for the treatment of a variety of ailments. Garlic has been studied for its medicinal and therapeutic effects in the treatment of various human diseases for a long time. Health benefits associated with the consumption of garlic are attributed to the various sulfur compounds present in it such as allicin, ajoene, vinyl-dithiin, and other volatile organosulfur compounds which are all metabolized from alliin. Several researches in the literature have shown evidence that garlic exhibits antioxidant, antiviral, anti-microbial, anti-fungal, antihypertensive, anti-anemic, anti-hyperlipidemic, anticarcinogenic, antiaggregant, and immunomodulatory properties. The present review identifies and discusses the various health benefits associated with the consumption of garlic, its essential oil, and bioactive constituents, along with exploring the various snack-food products developed by incorporating garlic.

Data on differential pathogenic ability of Helicobacter pylori isolated from distinct gastric niches.

Helicobacter pylori infection is associated with various gastrointestinal diseases and gastric cancer. Our data shows the H. pylori isolates and their associated pathology, isolated from two different stomach niches: gastric epithelium and gastric juice. Gastric adenocarcinoma (AGS) cells were infected with H. pylori juice (HJ1, HJ10 and HJ14) and biopsy (HB1, HB10 and HB14) isolates for 6, 12 and 24 hrs. To determine the cell migration ability of the infected cells, scratch wound assay was performed. The decrease in the wound area was measured by Image J software. Status of cell proliferation accessed by counting the cell number through trypan blue exclusion method. Further assessment of pathogenic potential and carcinogenic ability of the isolates was done by determining the genomic instability in the cell post infection. Cells were stained with DAPI and number of micro and macro nuclei was counted in the acquired images. The data will be helpful in understanding the difference in the carcinogenic ability of H. pylori with respect to their physiological niche.

Virtual planning on contralateral hemipelvis for posteriorly fixed acetabular fractures.

BACKGROUND: Open reduction and internal fixation is a standard treatment for displaced acetabular fractures using 3.5 mm reconstruction plates contoured intra-operatively. This process is difficult and time consuming hence resulting in increased surgical morbidity. Virtual surgical planning is now being commonly used worldwide to aid in management of such complex problems. Patient-specific reconstruction plate pre contoured using virtual surgical planning on contralateral intact hemipelvis will be helpful in achieving better surgical outcomes. Also, it has an added advantage of considerably reducing the time and effort spent in virtual pre-operative planning process. METHODOLOGY: This study was performed in 30 patients with acetabulum fracture who were fixed posteriorly via Kocher-Langenbeck approach. Virtual planning was done on contralateral hemipelvis to prepare patient-specific pre-contoured plates and mirrored to the fractured side. The time required for virtual planning on fractured and normal side was recorded and compared. The efficiency of plates so prepared were accessed in terms of outcome variables like duration of surgery, blood loss, reduction obtained on X-ray as well as CT Scan. RESULT: Time required for virtual planning was more on fractured side and lesser when it was done using normal hemipelvis with mean values of 81.83 (sd = 28.02) min and 15.67 (sd = 6.12) min, respectively. Values of blood loss, duration of surgery and reduction as accessed on X-ray and CT scan were comparable or even better than compared to other studies. CONCLUSION: Contralateral normal pelvis can be used for virtual preoperative planning making the whole process easier and less time consuming.

Monitoring the Progress of Treatment in Fracture Non-Union: The Role of Alkaline Phosphatase and Ultrasonography.

Objective To evaluate the role of serum alkaline phosphatase (ALP) and ultrasonography (USG) in monitoring the progress of treatment in diaphyseal non-unions. Methods This prospective observational cohort study included adult patients with diaphyseal fractures of major long bones previously treated with internal fixation and eventually resulting in non-union. Following the definitive treatment for non-union, the patients were followed-up periodically for six months, and serial monitoring of the levels of ALP and USG were performed along with radiographs (X-rays) to ascertain the status of the union. Results After an initial rise at seven weeks, ALP levels declined to normal values in fractures which united, whereas they remained high in cases of persistent non-union. Similarly, after an elevation of the vascular resistive index (RI) at around 12 weeks in all the patients, it decreased in cases progressing to union, while it remained persistently high even at 24 weeks in fractures failing to unite. Cases of persistent non-union continued to show hypoechogenic callus at 24 weeks instead of converting into hyperechogenic callus, as observed in cases which progressed to union. Conclusion Significant changes suggestive of union appeared simultaneously on the X-rays, USG and ALP levels during the follow-up. However, a serial examination of the ALP levels and USG during the follow-up gave a hint of the direction of progress in the healing process of fracture non-union. Their role in monitoring the outcome of non-union is more complimentary than supplementary to the X-rays.

Monitoring the Progress of Treatment in Fracture Non-Union: The Role of Alkaline Phosphatase and Ultrasonography / Monitoramento da evolução do tratamento da ausência de consolidação da fratura: Papel da fosfatase alcalina e da ultrassonografia

Abstract Objective To evaluate the role of serum alkaline phosphatase (ALP) and ultrasonography (USG) in monitoring the progress of treatment in diaphyseal non-unions. Methods This prospective observational cohort study included adult patients with diaphyseal fractures of major long bones previously treated with internal fixation and eventually resulting in non-union. Following the definitive treatment for non-union, the patients were followed-up periodically for six months, and serial monitoring of the levels of ALP and USG were performed along with radiographs (X-rays) to ascertain the status of the union. Results After an initial rise at seven weeks, ALP levels declined to normal values in fractures which united, whereas they remained high in cases of persistent non-union. Similarly, after an elevation of the vascular resistive index (RI) at around 12 weeks in all the patients, it decreased in cases progressing to union, while it remained persistently high even at 24 weeks in fractures failing to unite. Cases of persistent non-union continued to show hypoechogenic callus at 24 weeks instead of converting into hyperechogenic callus, as observed in cases which progressed to union. Conclusion Significant changes suggestive of union appeared simultaneously on the X-rays, USG and ALP levels during the follow-up. However, a serial examination of the ALP levels and USG during the follow-up gave a hint of the direction of progress in the healing process of fracture non-union. Their role in monitoring the outcome of nonunion is more complimentary than supplementary to the X-rays.

Resumo Objetivo Avaliar o papel da concentração sérica de fosfatase alcalina (FA) e da ultrassonografia no monitoramento do progresso do tratamento da ausência de consolidação em fraturas diafisárias. Métodos Este estudo de coorte observacional prospectivo incluiu pacientes adultos com fraturas diafisárias dos principais ossos longos previamente submetidas a fixação interna sem consolidação. Após o tratamento definitivo, os pacientes foram avaliados periodicamente por seis meses, com realização seriada de ultrassonografia, determinação da concentração de FA e radiografias para verificar a presença de consolidação. Resultados Após um aumento inicial em sete semanas, os níveis de FA voltaram ao valor normal em pacientes com fraturas consolidadas, mas continuaram elevados nos casos de ausência de consolidação. Da mesma forma, após uma elevação do índice de resistência (IR) vascular em cerca de 12 semanas em todos os pacientes, o IR diminuiu nos casos que progrediram para consolidação, mas continuou alto até as 24 semanas em fraturas não consolidadas. Os casos com ausência de consolidação ainda apresentavam calo hipoecogênico às 24 semanas, que não se converteu no calo hiperecogênico observado nos casos que progrediram para consolidação. Conclusão Alterações significativas sugestivas de consolidação foram simultaneamente observadas nas radiografias, na ultrassonografia e na concentração de FA durante o período de acompanhamento. No entanto, a realização seriada de exames da concentração de FA e de ultrassonografia durante o acompanhamento indicou o progresso da consolidação da fratura. Seu papel no monitoramento da ausência de consolidação é mais complementar do que suplementar à radiografia.

Safety and efficacy of azathioprine in immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is a benign hematological disorder characterized by low platelet counts in peripheral blood and spectrum of various bleeding manifestations. Azathioprine is one of the effective, readily available, and affordable immunosupressants available for ITP management in developing countries. We aimed to study the efficacy and long-term safety profile of our patients with ITP who were treated with azathioprine. METHOD: This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India. The patients who had received at least one line of therapy before receiving azathioprine were included in this study. All patients received oral azathioprine at a dose of 1 mg/kg/day (50 mg or 100 mg tablet formulations were used), which was increased up to 2 mg/kg/day depending upon the response and adverse effects. RESULT: Sixty-three patients were analyzed. Their median age was 28 years (range 15-68); 29/63 patients (46.03%) were females. The median duration from diagnosis to azathioprine initiation was 539 days (323 days-980.5 days). The patients included in the study had received a median of 3 (range 1-6) prior lines of therapies; 38/63 patients (60.32%) had received ≥3 prior therapies. Six patients (9.5%) had relapsed after splenectomy, and 16 patients (25.4%) had relapsed after receiving rituximab. The mean baseline platelet count was 10000/µL. The median time to response was 95 days (90 days-not reached) and the cumulative overall response rate (complete and partial response) at day 90 was 38.1%. Only one patient achieved complete response with azathioprine in our study. The cumulative rate of relapse at five years was 21.2%. Twenty-six patients stopped azathioprine after achieving some response (CR/PR) with Azathioprine for a median duration of 1067.5 days (range: 236 days-2465 days). They were followed up for a median of 870 days (range: 392 days-1928 days), and twelve of them relapsed. Twenty-six patients (26/63, 41.27%) reported one or more adverse events while on azathioprine. Leucopenia was the most frequent adverse event, followed by anemia and hepatobiliary laboratory abnormalities. Serious adverse events (grade ≥3 CTCAEv4) were noted in three patients (4.7%). One patient succumbed to severe sepsis multiorgan dysfunction while being on treatment. CONCLUSION: We conclude that azathioprine has a good response rate in chronic ITP patients. It is well-tolerated with minimal and manageable side effects.

Real-world Experience of Rituximab in Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is a relapsing-remitting disease often requiring more than one line of therapy. Rituximab is a recommended second-line therapy, but the real-world data on its efficacy and safety from resource constraint settings is limited. We aimed to analyze the safety and efficacy of rituximab in ITP. This is a single-center, retrospective study. This study was conducted at a tertiary care hospital in Northern India from 2005 to 2019. On audit of medical records, all patients of ITP (n-513) who had received rituximab (n-81) were screened for inclusion. Patients whose response assessment was not possible were excluded. Finally, 66 patients were analyzed using statistical packages of Python v3.7. The cumulative incidence of overall response on day 20 was 30.61%, and day 30 was 51.72%. The median time to response was 28 day (range 21-51 day). Cumulative incidence of complete response was 16.67%, and partial response 37.88%. After a median follow-up of 789 day (range 181-5260 day), the cumulative incidence of relapse was 30.32%, 36.12%, and 56.57% at 1, 2, and 5 years respectively. There was no effect of age, sex, duration of disease, lines of therapy received, and platelet count on either cumulative incidence of overall response or relapse. ANA positivity was significantly related to the better cumulative incidence of overall response (p = 0.012), but not with relapse. Infusion-related reactions were the commonest adverse event noted (n-4, grade ≥ 3 CTCAEv4). Rituximab and its generic version are safe and effective second line agent in ITP with a good overall response and sustained response.

Survival Outcomes of Newly Diagnosed Multiple Myeloma at a Tertiary Care Center in North India (IMAGe: 001A Study).

PURPOSE: The outcomes of patients with myeloma from developing countries are often lacking because of poor record maintenance. Publications from such settings are also limited because of the retrospective nature of the data collection. Information technology can bridge these gaps in developing countries with real-time data maintenance. We present the real-time survival data of the patients with myeloma from a tertiary care center in North India using one such indigenously built software. PATIENTS AND METHODS: These are real-time data of all patients with myeloma presenting to a tertiary care center from North India. The patient characteristics (demographics, baseline disease characteristics, risk stratification, and outcomes) were recorded contemporaneously. The survival of the study population was analyzed and grouped based on various disease characteristics at diagnosis. RESULTS: The median age of the study population (N = 696) was 65.9 (34.9-94.9) years with male predominance (65%). The median follow-up was 3.7 years (0-18.6 years) with the median overall survival (OS) not achieved. The OS of the study population at 1, 3, and 5 years was 94% (n = 558), 87.5% (n = 394), and 83.1% (n = 267), respectively. Most of the patients presented in advanced stages based on International Staging System (III:70%). On Kaplan-Meier analysis, the presence of weight loss (P = .01), renal dysfunction (P = .047), and anemia at diagnosis (P = .004) had a significant impact on survival. On Cox proportional model univariate analysis, the presence of renal dysfunction, anemia, and weight loss had the significant hazard ratio of 1.68 (1-2.82, P = .049), 3.18 (1.39-7.29, P = .0063), and 2.81 (1.22-6.42, P = .014), respectively, whereas on multivariate analysis of hypercalcemia, renal disease, anemia, and bone disease (CRAB) features, only anemia was found to have a significant hazard ratio of 2.56 (1.01-6.47, P = .046). CONCLUSION: The real-world data show OS comparable with the published western literature. Only anemia was found to have significant impact on survival. The use of such software can aid in better data-keeping in resource-constrained settings.

Assessment of union in fractures: Role of Serum Alkaline Phosphatase and Ultrasonography.

INTRODUCTION: Fracture union is a fundamental goal in orthopaedics. There is variability in assessment and lack of consensus on reliability of various methods to evaluate progress of union. The purpose of this study was to study the temporal association of non-conventional methods i.e. Serum Alkaline Phosphatase (ALP) and Ultrasound (USG) in assessment of fracture healing with reference to plain radiographs (X-ray). METHODOLOGY: This was a prospective observational cohort study of 161 adult patients with surgically treated long bone diaphyseal fractures. Plain radiographs, ALP and USG evaluation was done every 6 weekly for 6 months. USG evaluation included assessment of echogenicity and Doppler measurement of Vascular Resistance Index (RI) of callus. Fractures were considered united when X-ray showed bridging callus. ALP and USG changes over the follow-up period were analysed based on the final outcome of fractures. RESULTS AND CONCLUSION: 151 patients showed signs of fracture union at final follow-up. ALP which peaked at 6 weeks in all cases always remained within the laboratory reference range in cases progressing to union; whereas in cases of non-union the levels recorded higher. ALP value was the earliest positive predictor showing progress towards union. Beyond 12 weeks, Hyperechogenicity on Gray scale USG and serial measurement of RI on Doppler USG were found to better confirm progress in fracture union than X-rays. Combined evaluations of ALP and USG appear as promising investigations in assessment of the progress in fracture union.

Labrador Sea freshening linked to Beaufort Gyre freshwater release.

The Beaufort Gyre (BG), the largest Arctic Ocean freshwater reservoir, has drastically increased its liquid freshwater content by 40% in the past two decades. If released within a short period, the excess freshwater could potentially impact the large-scale ocean circulation by freshening the upper subpolar North Atlantic. Here, we track BG-sourced freshwater using passive tracers in a global ocean sea-ice model and show that this freshwater exited the Arctic mostly through the Canadian Arctic Archipelago, rather than Fram Strait, during an historical release event in 1983-1995. The Labrador Sea is the most affected region in the subpolar North Atlantic, with a freshening of 0.2 psu on the western shelves and 0.4 psu in the Labrador Current. Given that the present BG freshwater content anomaly is twice the historical analog studied here, the impact of a future rapid release on Labrador Sea salinity could be significant, easily exceeding similar fluxes from Greenland meltwater.

Real-world experience of eltrombopag in immune thrombocytopenia.

Immune thrombocytopenia (ITP) is characterized by decreased platelet count in the peripheral circulation. The first-line therapy is corticosteroids with 53-80% overall response rate. Eltrombopag has been used as second-line therapy in ITP for over a decade now. The long-term efficacy and safety profile have been widely reported in the western world. However, the data from the resource-constraint settings of the developing world is scarce. We aim to present the real-life experience of efficacy and safety of eltrombopag from the resource-constraint settings. This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India from 2012-2019. On audit of medical records, patients of ITP receiving eltrombopag were screened for inclusion. Patients whose treatment outcomes were not available were excluded. Finally, 53 patients were analyzed using statistical packages of Python v3.7. The patients' median age was 35 years (range 17-78), with 23 (43.4%) being female. The median time to response was 35 days (range 28-50 days) and the cumulative overall response rates (ORR) at day 30, day 60 and day 90 were 41.5%, 69.8%, and 81.1% respectively. A total of 10 patients on eltrombopag relapsed during follow up. The cumulative rate of relapse at one year, three years, and five years were 6.6%, 25.3%, and 47.7%, respectively. There was no significant difference in outcome (response rate or relapse) in any subgroups depending on age, sex, duration of disease, number of prior lines of treatment, splenectomy, or baseline platelet count. Six patients stopped eltrombopag after having a median sustained response for 796 days (range 658-1185), and after a median follow up of 624 days (range 92-1339), they continued to be in remission. Seventeen patients (17/53, 32%) reported one or more adverse events while on eltrombopag therapy. A total of 49 adverse events (n=4, grade ≥3 CTCAEv4) were noted. Anemia was the most frequent adverse event followed by hepatobiliary dysfunction as reflected by deranged AST/ALT or raised bilirubin. The use of eltrombopag among adult ITP patients in resource-constraint settings was well-tolerated and yielded excellent overall response. The benefit was found to be sustained on long-term follow up. However, events like anemia, hepatobiliary, and thrombotic complications merit closer follow up.

Status of kinases in Epstein-Barr virus and Helicobacter pylori Coinfection in gastric Cancer cells.

BACKGROUND: Helicobacter pylori (H. pylori) and Epstein - Barr virus (EBV) plays a significant role in aggressive gastric cancer (GC). The investigation of genes associated with these pathogens and host kinases may be essential to understand the early and dynamic progression of GC. AIM: The study aimed to demonstrate the coinfection of EBV and H. pylori in the AGS cells through morphological changes, expression of the kinase and the probable apoptotic pathways. METHODS: Genomic DNA isolation of H. pylori and its characterization from clinical samples were performed. RT-qPCR of kinases was applied to scrutinize the gene expression of kinases in co-infected GC in a direct and indirect (separated through insert size 0.45 µm) H. pylori infection set up. Morphological changes in co-infected GC were quantified by measuring the tapering ends of gastric epithelial cells. Gene expression profiling of apoptotic genes was assessed through RT-qPCR. RESULTS: An interleukin-2-inducible T-cell kinase (ITK) showed significant upregulation with indirect H. pylori infection. Moreover, Ephrin type-B receptor six precursors (EPHB6) and Tyrosine-protein kinase Fyn (FYN) showed significant upregulation with direct coinfection. The tapering ends in AGS cells were found to be extended after 12 h. A total of 24 kinase genes were selected, out of which EPHB6, ITK, FYN, and TYK2 showed high expression as early as 12 h. These kinases may lead to rapid morphological changes in co-infected gastric cells. Likewise, apoptotic gene expression such as APAF-1 and Bcl2 family genes such as BAD, BID, BIK, BIM, BAX, AND BAK were significantly down-regulated in co-infected AGS cells. CONCLUSION: All the experiments were performed with novel isolates of H. pylori isolated from central India, for the functional assessment of GC. The effect of coinfection with EBV was more profoundly observed on morphological changes in AGS cells at 12 h as quantified by measuring the tapering of ends. This study also identifies the kinase and apoptotic genes modulated in co-infected cells, through direct and indirect approaches. We report that ITK, EPHB6, TYK2, FYN kinase are enhanced, whereas apoptotic genes such as APAF-1, BIK, FASL, BAX are significantly down-regulated in AGS cells coinfected with EBV and H. pylori.

Pectoralis Minor Index: Does Ethnicity Hold Relevance? Estimation of Pectoralis Minor Length in the Indian Population and Its Correlation with Hand Length.

OBJECTIVE: Pectoralis Minor Index (PMI) is a proposed parameter to evaluate the pectoralis minor length (PML), eliminating the effect of subject's variability of height. Neither a PMI standard value nor any cutoff value to label a shortened pectoralis minor (PM) has been accepted yet, which can be applied to every individual. Moreover, the length of the PM has never been correlated to any fixed reference in the body. Hence, we estimated the PML in the Indian population and investigated its correlation to the individual's hand length. METHODOLOGY: A cross-sectional study was conducted including 100 adult subjects without any shoulder pathology. Subjects with history of fracture/treatment involving upper limb/spine were excluded. Two assessors evaluated the height, PM length and hand length of subjects. PMI and hand correlation was evaluated using their mean values. RESULTS: Mean PML and PMI for dominant and non-dominant shoulder were calculated to be 18.11/18.21 cm and 10.53/10.59, respectively. Mean hand length of dominant and non-dominant hand was found to be 18.27 cm and 18.31 cm, respectively. Pearson correlation coefficient between right/left PML with right/left hand length was 0.67 and 0.63, respectively, suggesting a good correlation (p < 0.01). CONCLUSIONS: PMI varies in different ethnic groups, which makes PMI a less reliable indicator for managing shoulder pain in ethnic groups where reference values are yet not available. Contralateral PMI can be used as a reference value in unilateral shoulder pathologies with short PML. Hand length can become an important parameter in evaluating painful shoulders even in bilateral pathologies. Hand length can be used as an easy and quick technique to compare the PML and effect of physiotherapy in patients with diagnosis of short PML, attending follow-up OPD. Though, a study comparing PML of normal subjects and patients with shoulder pain will be further required in different ethnic groups for further validation of this study.

3D Printed Patient-Specific Acetabular Jig for Cup Placement in Total Hip Arthroplasty.

INTRODUCTION: Acetabular cup placement is an important modifiable factor determining complication rates like aseptic loosening and hip dislocation related to faulty cup placement, which by standard method is largely dependent upon eyeballing and surgeon's judgment. We evaluated a self-designed, low-cost, patient-specific acetabular jig to guide cup placement in total hip arthroplasty in comparison to conventional technique. METHODS: It was a prospective randomized control study. Thirty-six patients were categorized into group-A & group-B. In group-A, virtually designed acetabular jig was 3 Dimensional (3D) printed and used intra-operatively to guide cup placement. In group-B, the standard method of cup placement was used. Acetabular cup placement was evaluated on post-operative x-rays and compared between two groups. RESULTS: In group-A, angle of anteversion were significantly in centre of range of safe zone as compared to group B in which hip is maximally stable with more precision in creating hip centre as compared to group-B without any significant(p = 0.325) increase in surgical time or blood loss. CONCLUSION: Computed tomography (CT) scan based virtual pre-operative templating and cup placement guided by virtually designed, patient-specific acetabular jig is a low-cost tool with a short learning curve which can be designed and made available easily. It is a useful tool in decreasing chances of malpositioning of cup and recreates hip centre close to anatomical one especially in cases where anatomy has been distorted such as bony ankylosis and developmental dysplasia of hip.