Search

Abstract Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. The present review consolidates current understanding of marrow fibrosis. We searched PubMed without time restriction using key words: bone marrow and fibrosis as the main stem against the terms: growth factors, cytokines and chemokines, morphology, megakaryocytes and platelets, myeloproliferative disorders, myelodysplastic syndrome, collagen biosynthesis, mesenchymal stem cells, vitamins and minerals and hormones, and mechanism of tissue fibrosis. Tissue marrow fibrosis-related papers were short listed and analysed for the review. It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. Megakaryocytes and platelets are either directly involved or are important intermediaries in stimulating mesenchymal stem cells. MMPs, TIMPs, TGF-β, PDGRF, and basic FGF and CRCXL4 chemokines are involved in these processes. Genetic and epigenetic changes underlie many of these conditions.

Abstract Circulating tumor plasma cells (CTPCs) provide a noninvasive alternative for measuring tumor burden in newly diagnosed multiple myeloma (NDMM). Moreover, measurable residual disease (MRD) assessment in peripheral blood (PBMRD) can provide an ideal alternative to bone marrow MRD, which is limited by its painful nature and technical challenges. However, the clinical significance of PBMRD in NDMM still remains uncertain. Additionally, data on CTPC in NDMM patients not treated with transplant are scarce. We prospectively studied CTPC and PBMRD in 141 NDMM patients using highly sensitive multicolor flow cytometry (HS‐MFC). PBMRD was monitored at the end of three cycles (PBMRD1) and six cycles (PBMRD2) of chemotherapy in patients with detectable baseline CTPC. Patients received bortezomib‐based triplet therapy and were not planned for an upfront transplant. Among baseline risk factors, CTPC ≥ 0.01% was independently associated with poor progression‐free survival (PFS) (hazard ratio [HR] = 2.77; p = 0.0047) and overall survival (OS) (HR = 2.9; p = 0.023) on multivariate analysis. In patients with detectable baseline CTPC, undetectable PBMRD at both subsequent time points was associated with longer PFS (HR = 0.46; p = 0.0037), whereas detectable PBMRD at any time point was associated with short OS (HR = 3.25; p = 0.004). Undetectable combined PBMRD (PBMRD1 and PBMRD2) outperformed the serum‐immunofixation‐based response. On multivariate analysis, detectable PBMRD at any time point was independently associated with poor PFS (HR = 2.0; p = 0.025) and OS (HR = 3.97; p = 0.013). Thus, our findings showed that CTPC and PBMRD assessment using HS‐MFC provides a robust, noninvasive biomarker for NDMM patients not planned for an upfront transplant. Sequential PBMRD monitoring has great potential to improve the impact of the existing risk stratification and response assessment models.

Background: Research conducted in medical colleges in India is often considered to be of poor quality. The study was done to assess the cause for such occurrence. Materials and Methods: Papers published in indexed journals between 1985 to 2017 were reviewed and the data was synthesized. Results: Poor infrastructure, heavy patient load, restricted number of faculties who had limited exposure to research methodologies, private practice, lack of incentive to do good quality research, poor mentoring, lack of research tradition, research fund, ancillary infrastructures, and copy cat research were found to be some of the reasons. Discussions and Solutions: Teachers education, provision of better infrastructure and funding, short term fellowships at both undergraduate and postgraduate levels, proper assessment for promotion of teachers, training in research methodology, multicentric research, R & D research bases in medical colleges, looking for solutions for day-to-day challenges through operational and translational mode are some of the solutions. Training from undergraduate levels on elements of research needed to be encouraged.

NA

Background : We evaluated albumin cobalt binding (ACB) assay as a prognostic marker for severe malaria in a medical college setting . Methods :Consecutive adult patients admitted with both vivax and falciparum malaria were evaluated with ACB assay at the time of admission. Detailed work up and individual patient directed management were instituted in addition to immediate artemisin based antimalarial therapy. Results :100 consecutive patient ( 50 with vivax and 50 with falciparum malaria ) were evaluated . Reference range for ACB assay was established using 50 adult healthy ( 25 male and 25 female ) individuals . 16 out of 50 p. falciparum infected developed complicated malaria. All malaria infected patients had high ACB levels ( P

Abstract  Antineutrophil cytoplasmic antibody (ANCA) is often used in the laboratory to confirm paucicellular vasculitis like Wegener’s granulomatosis, Churg Strauss syndrome or polyarteritis nodosa in the presence of suggestive clinical features. In tropical countries, tuberculosis, leprosy and, occasionally, malaria can produce clinical features similar to a vasculitic illness and all the three infections are known to be associated with auto antibodies. We tested 318 patients suffering from malaria, tuberculosis or leprosy for ANCA positivity. ANCA positivity was found in 19%, 32% and 30% of malaria, tuberculosis and leprosy patients (Pradhan V, Badakere S, Shankarkumar V, Iyer Y, Ghosh K, Karnad D, Indian J Malariol, 39:51–59, 2002; Pradhan V, Badakere S, Ghosh K, Pawar A, Indian J Med Sci, 58:283–288, 2004a; Pradhan V, Badakere S, Shankarkumar V, Lepr Rev, 75:50–56, 2004b), respectively, raising the possibility that ANCA positivity with clinical features suggestive of vasculitis in tropical countries may even be related to the background noise of this seropositivity caused by one of these three infections rather than confirming the diagnosis of paucicellular vasculitis. Hence, one should be careful about the background noise of ANCA positivity caused by these infections while diagnosing a vasculitic illness. [ABSTRACT FROM AUTHOR]

Surgical resection stands as the preeminent therapeutic approach for both primary hepatocellular carcinoma and metastatic liver malignancies. Its efficacy is contingent upon the attainment of a comprehensive excision while ensuring a sufficient future liver remnant (FLR). However, post-hepatectomy liver failure (PHLF) remains a significant challenge, particularly in patients with preexisting liver disease. The present study aims to investigate the predictive value of the preoperative indocyanine green retention test at 15 min (ICG-R15) in identifying patients at risk of PHLF following major liver resection. This retrospective review focused on patients who underwent the ICG-R15 test before major liver resection between August 2021 and January 2023. All patients underwent standard preoperative evaluation and staging. Patients with primary or metastatic liver cancer planned for major resection and undergoing ICG-R15 were included in the study. Patients with elevated serum bilirubin (> 3 mg/dl) and those not undergoing liver resection or minor liver resection (< 3 segments) were excluded from the study. PHLF was defined by the International Study Group of Liver Surgery (ISGLS) criteria. Follow-up was performed to identify 90-day morbidity. Using univariate and multivariate logistic regression analyses, we confirmed independent risk parameters that predicted postoperative major complications and severe PHLF. The study included 72 patients who underwent preoperative ICG-R15 testing prior to major liver resection. PHLF occurred in 28 patients (38.9%), with 24 patients (33.3%) classified as severity score B and 3 patients (4.16%) had severity score C. Univariate analysis revealed future liver remnant (FLR), ICG-R15, and blood transfusion as predictors of PHLF. Multivariate analysis confirmed FLR (p = 0.019) and ICG-R15 (p = 0.032) as significant predictors. Receiver operating characteristic curve analysis yielded an area under the curve of 0.642 for ICG-R15 in predicting PHLF. An optimal cut-point of 7.5 was determined. Our study highlights the importance of preoperative risk assessment of liver function evaluation using the ICG-R15 test, to predict the risk of PHLF following liver resection. Implementing appropriate interventions, especially in patients with borderline FLR, can improve surgical outcomes and enhance patient safety. Further research and prospective studies are essential to refine risk prediction models and improve rates of PHLF after liver resections. [ABSTRACT FROM AUTHOR]

Introduction: As a result of centralisation of haemophilia care to a limited number of intramural settings, many persons with haemophilia have to travel long distances to attend their haemophilia specialised treatment centre. However, regular physiotherapy treatment can be provided by primary care physiotherapists in the person's own region. Due to the rarity of the disease most primary care physiotherapists have limited experience with this population. This study aims to provide a clinical practice guideline for primary care physiotherapists working with persons with bleeding disorders., Method: A list of the most urgent key-questions was derived from a previous study. Literature was summarised using the grading of recommendations assessment, development, and evaluation (GRADE) evidence-to-decision framework. Recommendations were drafted based on four 90 min consensus meetings with expert physiotherapists. Recommendations were finalised after feedback and >80% consensus of all stakeholders (including PWH, physiotherapists, haematologists and the corresponding societies)., Results: A list of 82 recommendations was formulated to support primary care physiotherapists when treating a person with a bleeding disorder. These recommendations could be divided into 13 categories: two including recommendations on organisation of care, six on therapy for adult patients with bleeding disorders and five on therapy adaptations for paediatric care. Therapy recommendations included treatment after a joint- or muscle bleed, haemophilic arthropathy, chronic synovitis, non-haemophilia related conditions and orthopaedic surgery., Conclusion: An evidence-based practice guideline, based on current evidence from literature and clinical expertise, has been developed for primary care physiotherapists treating a person with haemophilia. To improve care, the recommendations should be implemented in daily practice., (© 2024 The Author(s). Haemophilia published by John Wiley & Sons Ltd.)

Bone marrow fibrosis represents an important structural change in the marrow that interferes with some of its normal functions. The aetiopathogenesis of fibrosis is not well established except in its primary form. The present review consolidates current understanding of marrow fibrosis. We searched PubMed without time restriction using key words: bone marrow and fibrosis as the main stem against the terms: growth factors, cytokines and chemokines, morphology, megakaryocytes and platelets, myeloproliferative disorders, myelodysplastic syndrome, collagen biosynthesis, mesenchymal stem cells, vitamins and minerals and hormones, and mechanism of tissue fibrosis. Tissue marrow fibrosis-related papers were short listed and analysed for the review. It emerged that bone marrow fibrosis is the outcome of complex interactions between growth factors, cytokines, chemokines and hormones together with their facilitators and inhibitors. Fibrogenesis is initiated by mobilisation of special immunophenotypic subsets of mesenchymal stem cells in the marrow that transform into fibroblasts. Fibrogenic stimuli may arise from neoplastic haemopoietic or non-hematopoietic cells, as well as immune cells involved in infections and inflammatory conditions. Autoimmunity is involved in a small subset of patients with marrow fibrosis. Megakaryocytes and platelets are either directly involved or are important intermediaries in stimulating mesenchymal stem cells. MMPs, TIMPs, TGF-β, PDGRF, and basic FGF and CRCXL4 chemokines are involved in these processes. Genetic and epigenetic changes underlie many of these conditions. Highlights: Fibrosis of the marrow is always secondary to a primary event which may be clonal or non clonal. Megakaryocytes and platelets form the central arm in myelofibrosis. Haemopoietic stem cells, clonal or activated in various inflammatory processes, immune cells and megakaryocytes (clonal or activated) interact with mesenchymal stem cells of GLI+ and Lep+ subsets that differentiate into myofibroblasts, -fibroblasts and fibrocytes. At each of these steps different cytokines, vitamins, hormones and minerals interact to produce the fibrocollagenous matrix. TGF-β and CXCL4 are important growth factors and chemokines assist this process. PDGFα, VEGF, angiopoietin, bFGF-, BMP pathway and inflammatory/oxidative cytokine pathways and tissue oxygen sensing mechanism via HID1α are also involved in the process in specific cases. Vitamins, hormones, minerals, and protease/anti-protease balance finally determine the extent of fibrosis. Many signals converge to produce TGF-β that stimulates marrow fibrosis. There may be a healthy noradrenergic input to the marrow vasculature that prevents fibrosis. Epigenetic regulation of fibrosis is getting increasing attention for understanding the process and directing targeted therapy. Addressing these signals with various targeted therapies alone or in combination are being developed (e.g ruxolotinib in PMF) [ABSTRACT FROM AUTHOR]

There are significant challenges in managing haemophilia patients in developing countries. These challenges are (i) Lack of proper health care infrastructure and human resources suitable for haemophilia care (ii) Competing health care priorities of the government. (iii) Lack of penetrance of medical insurance in the population. (iv) Lesser visibility of the haemophilia patients in health care system (v) Low awareness across the medical profession, population and the policy makers about the condition (vi) Non availability of factor concentrates (vii) Inadequate utilization of knowledge for reducing factor concentrate use. (viii) Inadequate pain relief (ix) Challenges due to inhibitor developing (x) Viral hepatitis & (xi) Lack of research publications relevant to the country are some of the challenges faced by PWH for their management in developing country. The solutions are not easy but development of a strong patient organization with linkages with World Federation of Haemophilia is an important initial step. Following that internal and international twinning, use of internal sources, strong advocacy programme targeting government, doctors, opinion makers will solve many of the challenges in the time to come. [ABSTRACT FROM AUTHOR]

Hemostasis research in India has a long history considering the fact that it is one of the youngest specialities in the world. If we take creation of prothrombin time (PT) test as one of the beginning of modern hemostsis research, then the specialty is no older than 60 years. School of Tropical Medicine Kolkata, Banaras Hindu University, All India Institute of Medical Sciences at Delhi, Christian Medical College at Vellore, Post Graduate Institute of Medical Education and Research at Chandigarh, and KEM Hospital at Mumbai contributed substantially in defining various bleeding disorders in our country. Unfortunately, some of these institutes are no longer as active in the field as they used to be. Currently, the Institute of Immunohaematology at Mumbai, Chrstian medical College at Vellore, and All India Institute of Medical Sciences at Delhi are actively engaged in hemostsis research in India. Developing prenatal diagnostic technologies, mutation detection of various hemostatic disorders, developing low-cost management technologies for hemophilia, and other bleeding disorders are becoming important present day research activity in the area of hemostasis in addition to age old areas of prevalence and unusual case description studies. Entry of many new corporate hospitals, development of structured postgraduate training program in hematology, and easy availability of instruments and reagents are likely to foster further growth in this area of medical research in India in future. [ABSTRACT FROM PUBLISHER]

Last quarter of twentieth century and the first 10 years of 21st century has seen phenomenal development in haematological pharmacotherapy. Tailor made chemotherapeutic agents, vast array of monoclonal antibodies, epigenetic modifiers, growth factors for red cells white cells and platelets, peptidomimetics as growth factors, newer thrombin inhibitors, safer plasma derived protein molecules, recombinant molecules, newer immunomodulators, enzyme replacement therapy and above all a plethora of targetted molecules targeting innumerable pathways involved in cell division, growth, proliferation and apoptosis has given immense number of clinically usable molecules in the hand of modern haematologists to treat diverse hitherto untreatable haematological disorders effectively. In addition many old molecules are finding newer uses in diverse fields, thalidomide as an antiangiogenic molecule is a prime example of this genre. Present overview has tried to capture this rapidly evolving area in a broad canvas without going into details of indications and contraindications of the use of various drugs. [ABSTRACT FROM AUTHOR]

Chronic synovitis in severe hemophilia is a painful debilitating condition eventually affecting greater than 20% severe hemophilia patients in developing countries. Though this complication is all but eliminated in the countries with advanced hemophilia care and having access to generous factor concentrate replacement, the same can not be said for 80% of the hemophilia patients in the world who live in developing countries. In developing countries chronic synovitis can be treated conservatively with short course of steroid, factor replacement, physiotherapy and splintage. Failing this, chemical or radioactive synoviorthesis give worthwhile remission and relief in 70–80% of the severely affected patients who fail to respond to conservative therapy. We found a short course of Cox-2 (etoricoxib) inhibitor to be an extremely useful adjunct. The role of d-Pencillamine, Thalidomide and inhibitors of matrix metalloproteinases needs to be explored. HLA-B27 was found to be strongly associated with chronic synovitis in hemophilia in one of the studies and this marker in a hemophilia patient may suggest need for more intensive replacement and other therapy in these patients to prevent chronic synovitis. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 61-year-old man admitted for permanent pacemaker implantation due to complete heart block. Topics include family history being unremarkable except for heart block, essential hypertension, and type 2 diabetes in first-degree relatives; and showing routine haematological and biochemical tests, chest X-ray, and CT scan of the brain showing no abnormality.