Awj Farooqi*
DOI: DOI: 10.37421/ 2165-7831.2022.12.294
DOI: 10.37421/ 2165-7831.2022.12.293
DOI: 10.37421/2165-7831.2022.12.291
DOI: 10.37421/ 2165-7831.2022.12.295
Dengue is one of the most commonly encountered infectious diseases in tropical countries. The features overlap with other causes of Acute Febrile Illness, and a rapid diagnosis is required in most centers. The usual modalities of diagnosis are serological based, where NS1 antigen, IgM, or IgG antibodies are assayed. Fast card-based kits are available but are less reliable than their (enzyme-linked immunosorbent assay) ELISA-based counterparts. There has been a recent automation boom in all healthcare facilities sectors. Automated hematological analyzers are an integral part of it, providing much additional information other than blood counts. Among these research parameters are HFLC (High Fluorescence Lymphocyte Count) and CPD (Cell Population Data) provided by the Sysmex XN series. These have taken the interest of pathologists, and some research articles are available that analyze these parameters' utility in the expeditious diagnosis of dengue. Studies show that HFLC is increased in AFI and correlates with dengue. Some studies have drawn Receiver Operating Curves (ROC) for determining cut-off values to differentiate dengue from other AFI. Jayaram et al. calculated a cut-off of 1.35% with 82.8% sensitivity and 87% specificity. Chabbra et al. computed a cut-off of 1.75% with 52% sensitivity and 90% specificity, a positive predictive value (PPV) of 72%, and a negative predictive value (NPV) of 80%. They also did a regression analysis on CPD and found that LY-X, LY-Z, LY-WX, LY-WZ, and MO-X were independent predictors of dengue fever. Ningombam et al. had different cut-off values for NS-1 antigen-positive only, IgM antibody-positive and dual-positive dengue patients, of 5.2%, 3.2%, and 2.6%, respectively. These studies show promising results and can help manage dengue patients, especially in resource-constrained settings in endemic zones, leading to better managing of dengue patients.
DOI: 10.37421/2165-7831.2024.14.331
DOI: 10.37421/2165-7831.2024.14.334
Proliferative retinopathy is a significant ocular complication associated with Chronic Myeloid Leukemia (CML) and other forms of leukemia. Understanding the various ophthalmological manifestations and their management is important for improving patient outcomes. This review aims to provide a comprehensive overview of the ocular alterations seen in leukemia patients, with a particular focus on proliferative retinopathy in CML, its delayed manifestation and management strategies.
A thorough literature review was conducted, emphasizing key studies and case reports that highlight the ocular complications of leukemia, particularly those related to proliferative retinopathy in CML. Leukemia can cause a range of ophthalmic manifestations, including retinal hemorrhages, microaneurysms and neovascularization. Proliferative retinopathy, characterized by abnormal neovascularization is more common in chronic leukemias like CML. This condition often presents in the advanced stages of CML and can significantly impair vision if not managed promptly. The pathogenesis involves chronic hypoxia, leukostasis and inflammatory mediators, leading to the formation of fragile new blood vessels. Delayed manifestation of proliferative retinopathy in CML underscores the importance of regular ophthalmological surveillance, even in patients with well-controlled systemic disease.
Early detection and timely intervention are essential in managing proliferative retinopathy in CML. A multidisciplinary approach involving both hematologists and ophthalmologists is essential for optimal patient care. Regular follow-up and vigilant screening for ocular changes can significantly improve the prognosis and quality of life for leukemia patients. This review highlights the need for ongoing research and education to better understand and manage the ocular complications of leukemia.
Xiaoxian Zhao, Feng Lin and Eric D. Hsi*
DOI: 10.37421/2165-7831.2024.14.333
CD6 is one of the first discovered lymphocyte receptors. It is expressed on all T cells, a NK cell subset, and B-lymphocyte B1a subsets. CD6 is involved in cell-to-cell interaction and modulation of adaptive immune responses. It is also implicated in the pathogenesis of a variety of immune-mediated conditions. CD6 and its two major known ligands (CD166 and CD318) have emerged as new therapeutic targets for autoimmune diseases. Recent studies explored the distribution of CD6 in both T-cell lymphomas and aggressive NK/T cell neoplasms, and evaluated the activities of CD6-antibody drug conjugate in both in vitro and in vivo mouse models for these malignancies. In this mini-review, we highlight the current understanding of CD6 as a therapeutic target in autoimmune disease, T cell lymphoma and aggressive NK/T cell neoplasms.
DOI: 10.37421/2165-7831.2024.14.335
DOI: 10.37421/2165-7831.2024.14.332
DOI: 10.37421/ 2165-7831.2024.14.321
Rao Prabhala*, Hannah Seah, Vaishnavi Bade and Srikanth Talluri
DOI: 10.37421/ 2165-7831.2024.14.323
Kazuta Yasui, Akihiro Fuchizaki, Yoshihiro Takihara and Takafumi Kimura*
DOI: 10.37421/2165-7831.2024.14.322
Since regenerative therapy with stem cells is believed to exert an effect based on their proliferation and differentiation potential, anything that would cause the loss of these capacities, such as irradiation, may negate the anticipated effect. In this study, X-irradiated (XR) mononuclear cells were prepared from umbilical cord blood. Even though hematopoietic stem/progenitor cell activity was diminished in the XR cells, the regenerative activity was surprisingly conserved and aided recovery from experimental stroke in mice. Here, we provide evidence indicating the possible therapeutic mechanisms by which damaged cerebrovascular endothelial cells may be rescued by low-molecular-weight metabolites supplied by injected XR cells via gap junctions as energy sources to improve blood flow in the infarcted area. Thus, XR cells may exhibit tissue repair capabilities through the activation of endothelial cells, rather than via cell-autonomous effects.
DOI: 10.37421/ 2165-7831.2024.14.325
Niccolò Caselli* and Francisco Monroy
DOI: 10.37421/2165-7831.2024.14.324
Rashmi Srivastava* and Swati Mishra
DOI: 10.37421/2165-7831.2024.14.317
The blood flow through w-shaped tapered artery in the presence of catheter is discussed. The equations governing the fluid flow have been solved analytically under the assumption of the mild stenosis. The blood flow behavior through the w-shaped stenosed artery is considered using the Prandlt fluid model and the flow of blood is considered as suspension of nano-particles. The analysis with respect to various parameters arising out of fluid and geometry considered, on temperature distribution of the w-shaped stenosis as well as across the entire length of the stenosis has been reported. Heat transfer phenomena have been examined for the physical features of the flow of blood through a stenosed artery, which is tapered in shape and with the presence of a clot. The temperature profile has been discussed with graphs for several different parameters of clot size, stenosis height, heat source, and sink parameter. It is observed that in converging tapering the temperature provides greater values as estimated together with the non-tapered arteries and diverging tapering arteries
Giuseppe Bertuglia, Sara Bringhen, Benedetto Bruno and Giulia Benevolo*
DOI: 10.37421/ 2165-7831.2024.14.316
Nyein Wint Yee Theik, Vedant Shah, Abhi Shah*, Viraj Panchal, Bhavya Vyas and Sanket Bharadwaj
DOI: 10.37421/ 2165-7831.2024.14.318
Background: Thrombotic Thrombocytopenic Purpura (TTP) is a rare, potentially fatal disease with multisystem involvement. ADAMTS13 assays are often used for supporting the diagnosis, here we present a rare case of TTP with normal ADAMTS13 levels.
Case presentation: A 39-year-old female presents with syncopal episodes, blurred vision in both eyes during a patch test, headaches, and tenderness over the abdomen, all against a backdrop of hypertensive emergency. She had a history of chronic hypertension managed on medications, iron deficiency secondary to fibroid and an episode of provoked deep vein thrombosis and pulmonary embolism with negative work-up of thrombophilia. Labs revealed low hemoglobin of 9.8 mg/dl, platelet in the range of 52,000/ ml, 3 mEq/L potassium, with high levels of Creatinine (Cr) 6.7 mg/dl and Blood Urea Nitrogen (BUN) levels of 59 mg/ dl. Due to the clinical triad of thrombocytopenia, hemolysis pattern and neurological manifestation, ADAMTS13 essay was ordered. Thrombophilia work-up showed haptoglobin was less than 20 mg/dl, LDH of 752 U/L, and a normal ADAMTS13 level. PLASMIC score was 5, suggestive of moderate risk. With high levels of abnormal creatinine levels and BUN, renal biopsy was done to look for the cause of acute kidney injury in the setting of suspected TTP which revealed diffuse thrombotic microangiopathy, along with moderate to chronic changes with greater than 50% tubular atrophy and interstitial fibrosis. CT scan of the brain was negative for detecting any cause of syncope; MRI showed lacunar infarcts secondary to thromboembolism. A provisional diagnosis of TTP with normal ADAMTS13 level was made and she was started on plasma exchange. Drastic symptom improvement was noted with FFP and 8 units of plasma exchange.
Sonu Kalyan, Om Thakur, Behnam Rafiee and Mark T. Friedman*
DOI: 10.37421/ 2165-7831.2024.14.320
Patient Blood Management (PBM) programs are a growing need in healthcare to stem overutilization of blood products. Aside from the fact that blood transfusions are associated with infectious and noninfectious risks, there are further pressures driving key reasons to control overutilization, including a narrowing gap between blood donor collections and transfusions, an association of reduced transfusions with improved patient outcomes, and the need to reduce healthcare costs associated with blood product transfusions. Implementation of a PBM program involves different stages of development that can lead to a successful program, eligible for certification. Maintenance of the program requires active oversight and surveillance to ensure peak performance.
DOI: 10.37421/2165-7831.2024.14.315
Acute Promyelocytic Leukemia (APL) has become the most curable subtype of acute myeloid leukemia in adults with the advent of the differentiating agents, all-trans retinoic acid and arsenic trioxide. However, Early Death (ED) remains a challenge and represents the last major obstacle to the cure of almost every patient. An overwhelming majority of ED in APL is attributable to life-threatening bleeding, a phenomenon driven by complex alterations in the coagulation system. Therefore, prompt recognition of APL and immediate initiation of All-Trans Retinoic Acid (ATRA) in emergency departments–prior to confirmation of the diagnosis–is essential. All-trans retinoic acid must be immediately available, which is often problematic since most institutions will see very few APL patients in a year and will not find it cost-effective to maintain a supply. Aggressive management of the coagulopathy and less common causes of ED, such as the differentiation syndrome and infections, is required. Since emergency departments and immediate care healthcare professionals are often the first to encounter a patient with APL, their training should include comprehensive diagnostic and initial management details. Recent data suggest that early consultation with a colleague with expertise in APL for initial hour-by-hour management is very helpful in reducing the ED rate. Tackling this last major obstacle in the cure of all patients requires providers to astutely recognize the disease and manage patients according to recommended guidelines.
DOI: 10.37421/ 2165-7831.2023.13.309
Maureen Via M Comia*, Charles Eryll S Sy and Jomell C Julian
DOI: 10.37421/2165-7831.2023.13.305
Reasoning: Movement of Persistent Myelogenous Leukemia (CML) to further developed stages can include hypermethylation, which is connected to opposition or prejudice to imatinib. This hypermethylation has likewise been viewed as a negative prognostic component free of imatinib reaction and from CML stage, consequently decitabine, a hypomethylating specialist, can be an appealing treatment choice for cutting edge stage CML.
Objective: This foundational survey and meta-examination expects to research the job of low-portion decitabine among patients with cutting edge stage CML. Technique: This was performed by the articulation of Favored Announcing Things for Orderly Surveys and Meta-Examinations (PRISMA).
Results: Four (4) studies from 86 articles screened were qualified to be evaluated in this fundamental audit and meta-investigation. These were stage I/II preliminaries including 81 high level stage CML patients and utilized low-portion decitabine (5 to 20 mg/m2), with two examinations utilizing tyrosine kinase inhibitors.
Results of hematologic and cytogenetic reaction, and endurance were evaluated in the meta-examination; with hematologic reaction being leaned toward among cutting edge stage CML patients upon openness with low-portion decitabine (p=0.05). Endurance was likewise preferred among responders to low-portion decitabine, but this was not huge.
Conversation and end: Low-portion decitabine can be a compelling and safe therapy choice in cutting edge stage CML, particularly in additional fragile patients that couldn't endure more escalated chemotherapy regimens.
Notwithstanding, this study is restricted by couple of studies accessible on this point, subsequently further randomized controlled preliminaries can be explored to characterize the job of decitabine and its ideal portion among this subset of patients
DOI: 10.37421/2165-7831.2023.13.306
Ahmet Sencer Ergin*, Rıza Deryol, Ezgi Altinsoy and Salim Demirci
DOI: 10.37421/ 2165-7831.2023.13.307
Background: The Prognostic Nutritional Index (PNI), a valuable parameter for predicting short-term and long-term postoperative outcomes in patients undergoing cancer surgery, is calculated based on serum albumin concentration and peripheral blood lymphocyte count. However, few studies have investigated the clinical significance of PNI in the surgical treatment of colorectal cancer. Therefore, we aimed to examine the relationship between PNI and short-term outcomes in patients with colorectal cancer.
Methods: This retrospective study included 328 patients who underwent surgery for colorectal cancer. The prognostic nutritional status was calculated based on admission data as follows: 10* serum albumin (g/dl)+0.005* total lymphocyte count (per mm3). Then we evaluated the relationship between PNI value and postoperative complications in colorectal cancer patients.
Results: Patients with low PNI (<35.3) had a significantly higher rate of postoperative complications (p<0.05) than those with a high PNI (≥35.3). In Univariate analysis low PNI (p=0.015), open surgical approach (p=0.010), tumor location (p=0.008), N stage ≥ 2 (p=0.037), serum albumin concentration (p=0.015) and CEA level ≥ 5 (p=0.017) were significantly associated with high complications rate. However, in multivariate analyses, low preoperative PNI was not identified as an independent factor for postoperative complications.
Conclusion: Preoperative PNI is a valuable marker for postoperative complications in patients with colorectal cancer.
Tahsin Ahmed Rupok*, Sunandan Dey, Shahnaz Parvin Sweety and Bayezid Bostami
DOI: 10.37421/2165-7831.2023.13.308
Background: Personality trait is a complex trait of an individual, which has been hypothesized to have link with diseases. It is believed that understanding personality traits of an individual can assist to prevent the diseases. Therefore, scientists are trying to explore potential factors that can predict the personality traits of an individual. Blood groups could be a potential predictor because some researchers have found a linkage between ABO genes and genes related to the development of personality traits in someone. Few studies have already found a significant relationship between blood groups and personality traits. However, there is still a paucity of researches to reach out a conclusion on this topic. Our study is another attempt to find out the possible relationship between blood groups and personality traits.
Method: The present study was a cross-sectional study which used a 50 items big-five factor personality inventory developed by Goldberg for data collection. A total of 148 participants responded to the study among them 85 participants were males and 65 were females. A two way multivariate analysis (MANOVA) was performed using IBM SPSS Statistics version 26.
Result: MANOVA results revealed neither the significant main effect of blood groups [F (15,414)=1.102, p>0.05] nor had the significant interaction effect of blood groups and gender [F (15,414)=1.111, p>0.05] on the combined dependent variables. However, this study found a significant main effect of gender on the combined dependent variables [F (5,136)=4.520, p=0.001, (1-β)=0.967, η2=0.143].
Conclusion: The present study did not support the idea that there is significant relationship between blood groups and personality traits. But, the idea that male personality significantly differs from female personality was well-supported by this study.
DOI: 10.37421/ 2165-7831.2023.13.312
Ephrem Haile*, Adugna Tasew, Amha Gebremedhin, Abdulaziz Sherif and Fissehatsion Tadesse
DOI: 10.37421/2165-7831.2023.13.311
Background: Patients with multiple myeloma are being seen at an increasing frequency in different indigenous African population. However, local data regarding the demographic profile, clinical characteristics, risk stratification, and treatment outcome of these patients is lacking. This study was designed to fill this existing gap in our setup. Hence, it will aid in the revision of treatment guidelines based on local data on the efficacy of existing treatment regimens and risk stratification of patients with a newly diagnosed multiple myeloma.
Methods: A single centered Hospital-based retrospective Cohort study was conducted from January 2015 to December 2019. Eighty patients with newly diagnosed MM who received non-proteasome inhibitor-based therapy at TASH, Addis Ababa, Ethiopia were analyzed in the study.
Results: Out of the 80 patients in this cohort, 51(63.8%) of the patients were males (M: F ratio 1.76:1) and the median age at diagnosis was 52 years. The commonest complications identified were anemia (56.3%) and pathologic fracture (55%). The commonest comorbid conditions were; systemic hypertension (24%), CKD (6.3%), and diabetes (5%). The median Progression-Free Survival (PFS) and Overall Survival (OS) of patients were found to be 17.5 and 20 months respectively. This study also identified factors like advanced DS stage, presence of plasmacytoma, renal dysfunction, elevated serum LDH, high levels of serum protein, and monoclonal M-protein to have adverse implication on the OS and PFS of patients.
Conclusion: Multiple Myeloma is more common in the male population group and our patients are younger than the western population. Myeloma treatment regimens like CP and CPT are found to be less effective in our patients than in patients elsewhere. This is likely to be due to the advanced stage at presentation. In resource-limited setups, where determination of cytogenetic features of myeloma is difficult, different clinical and laboratory parameters can still serve as prognostic markers of treatment outcome and patient survival.
DOI: 10.37421/ 2165-7831.2023.13.313
Majid Naderi, Maryam Emami*, Mohammad Shojaei, Tahmine Davoodi and Dor Mohammad Kordi Tamandani*
DOI: 10.37421/2165-7831.2023.13.314
Acute Lymphoblastic Leukemia (ALL) is the most prevalent malignancy among children. The primary therapeutic modality involves the administration of induction chemotherapy alone or in combination with diverse curative strategies. Existing evidence suggests that epigenetic mechanisms may serve as mediators of the influence of inherited genetic variations on phenotypic characteristics. Consequently, our investigation aimed to ascertain the potential role of DNA methylation in mediating the impact of genetic risk loci on childhood ALL. In mammals, the JAK/STAT pathway represents the principal signaling mechanism for a wide array of cytokines and growth factors. Activation of JAK induces cell proliferation, migration, differentiation, and apoptosis. A multitude of therapeutic interventions have been devised to modulate this signaling pathway, exhibiting varying degrees of efficacy and shortcomings. Pioneeringly, this study sheds light on the methylation status of JAK2 and STAT3, as well as the mRNA expression profiles, in ALL patients both prior to and following administration of the drug. We examined to determine whether there were any alterations in methylation and gene expression between the two genes during chemotherapy treatment.
This study, which took place from 2015 to 2017, utilized a case-control design. It included 50 blood samples from individuals recently diagnosed with Acute Lymphoblastic Leukemia (ALL) who had not yet received any chemotherapy drugs. After a two-month period of receiving the drug, these samples were retested. The study population consisted of 23 males and 27 females with a mean age of 7.52 ± 4.13. Additionally, 50 blood samples from healthy volunteers without any significant medical conditions were included in the study. This control group also consisted of 23 males and 27 females, with a mean age of 12.36 ± 5.63. All samples were stored at a temperature of -80°C until molecular analysis could be conducted. The methylation frequency of the JAK2 gene was found to be 35 (70%) in the blood sample taken from the newly diagnosed patient (referred to as sample1), 18 (36%) in the blood sample taken after the patient received chemotherapy (referred to as sample 2), and 3 (6%) in the blood samples from the healthy controls. The STAT3 gene exhibited a methylation rate of 54% (N=27) in sample1, 32% (N=16) in sample 2, and 4% (N=2) in the control group. A comparison between methylated and unmethylated samples indicated a significant disparity between the cases and controls in terms of JAK2 (OR1=36.55; 95%CI: 9.81 to 136.10, P < 0.0001) and STAT3 (OR1=28.17; 95% CI: 6.16 to 128.80, P<0.0001). Additionally, a notable distinction was observed between patients who underwent chemotherapy and the healthy individuals in relation to JAK2 (OR2=8.81; 95%CI: 2.39 to 32.40, P=0.0011) and STAT3 (OR2=11.29; 95%CI: 2.43 to 52.38, P=0.0020). In alternative terms, when we assessed the methylation status in patients subsequent to the administration of a chemotherapy drug in relation to their pre-treatment condition, a statistically significant finding was observed in JAK2 (OR3=4.14; 95%CI: 1.79 to 9.57, P=0.0009). However, no disparities were identified in STAT3 (OR3=2.49; 95%CI: 1.10 to 5). Within the framework of this investigation, we examined the disparity between the methylation of promoter DNA and the expression of genes within this pathway among patients who received the drug on the initial day, as well as the disparities with the control group. Chemotherapy drugs impeded the cell cycle and mitigated the adverse effects, particularly in the context of bone marrow metastasis, which was reliant on patient relapse in subsequent years.
Justin Marley* and Nisha Marley
DOI: 10.37421/ 2165-7831.2023.13.300
The COVID-19 pandemic has claimed over 1 million lives globally and results from the SARS-CoV-2 virus. COVID-19 is associated with a coagulopathy. In this mixed-methods PRISMA-compliant scoping review, we set out to determine if ARDS, sepsis and DIC could account for the coagulopathy and if there were any other features of the coagulopathy we could determine so as to inform future research. Methods: We used a search strategy to identify papers with clinically relevant thromboembolic events in COVID-19. We then developed a technique referred to as an Abridged Thematic Analysis (ATA) to quickly identify themes in the papers so as to increase the yield of clinically relevant information. We further developed Validated Abridged Thematic Analysis (VATA) to validate the resulting taxonomy of themes. Finally we developed a number of methods that can be used by other researchers to take forwards this work. Results: We identified 56 studies with 10,523 patients, 456 patients with COVID-19 and Thromboembolic Events (TBE’s) and 586 thrombembolic events. There was an average of 1.3 TBE’s per patient. There were five main arterial territories with corresponding clinical sequelae: Acute limb ischaemia, myocardial infarcts, strokes, mesenteric ischaemia and pulmonary embolism. We also identified DVT’s. There were two further groups: medical-device-related coagulopathy and dermal lesions. In a subgroup of 119 patients we found mortality ranged from 26% in DVT to 79% in acute limb ischaemia although there was evidence of selection bias in the latter group. All patients were hospitalised and the average age of survivors was 63 versus 73 for those who died. 91/150 patients with TE’s had fever. From the ATA, we identified 16 characteristics of the clotting pathology in COVID-19. From the VATA, we identified 34 mechanisms leading to coagulopathy and grouped them according to Virchow’s triad of vascular damage, stasis and hypercoagulability. Coagulopathy occurred with and without each of ARDS, Sepsis and DIC. We conclude that COVID-19 leads to the syndrome of a viral clotting fever in a subgroup of patients and that the presentation of coagulopathy and fever should raise the possibility of COVID-19 as a differential. We make recommendations for future research studies.
Lai Weng Soon*, Stefanie Hung Kar Yan, Ahmad Muhsin Mohammad Nor and Tee Sow Kuan
DOI: 10.37421/2165-7831.2023.13.301
COVID-19 pneumonia had been a global pandemic with major mortality and morbidity globally. It is associated with venous thromboembolism, especially in the population that requires admission, oxygen support, or ventilator support. Arterial thrombosis remains rare complication for this disease, more-so with multi-organ arterial thrombosis. We report a case of spinal cord and small bowel infarction in a COVID-19 patient.
DOI: 10.37421/ 2165-7831.2023.13.302
DOI: 10.37421/ 2165-7831.2023.13.304
Regular exercise helps to combat multifarious diseases by improving overall health of the individual. A recent study has proven that regular exercise can reduce the serious illness associated with COVID-19. Circulating miRNAs released from the muscles during strenuous exercise has also been found to have antiinflammatory effects. So, it was hypothesized that regular exercise might be releasing therapeutic miRNAs in the blood that might be reducing the immunological chaos in COVID-19 patients. Using network and systems biology approach, mRNA targets of 3 upregulated exomiRs (hsa-miR-486-5 p, hsa-miR-215-5 p, hsa- miR-941) in the blood of regularly exercising adults were mapped in the blood of COVID-19 patients. hsa-miR-215-5 p, hsa-miR-486-5 p and hsa-miR-941 were found to target 8, 93 and 99 upregulated mRNAs respectively. Functional enrichment analysis showed that hsa-miR-486-5 p might be preventing thrombosis and aggravated inflammation in regularly exercising COVID-19 patients. Thus, hsa-miR-486-5 p can be considered to have therapeutic roles against immunological damage caused by COVID-19.
Srimanta Chandra Misra*, Gaetano Lucania, Valentina Guarino and Alberto Santagostino
DOI: 10.37421/ 2165-7831.2023.13.303
Peripheral T-Cell Lymphomas (PTCL) are an uncommon and heterogeneous group of disorders arising from the innate and adaptive immune system. This review deals with the basis and major revisions to the current PTCL classification. Each entity in the 2016 classification has been reviewed on the basis of cell origin, genetic landscape and recent therapeutic options. The objective of this study was to conduct a review of the normal immune system, signalling pathways and tumor microenvironment in order to understand the heterogeneity of certain entities as well as to uncover the potential therapeutics. A brief evaluation of a normal immune system, implication of the JAK-STAT pathway and tumor microenvironment was performed to explain the heterogeneity of PTCL. Attempts were also made to optimize current standard and personalized management approaches. Fulfilling the current unmet needs in PTCL require optimization of the intensity and number of courses of chemotherapy in first-line treatment, choosing the right strategy of intensification such as ASCT versus improved HSCT and lastly, tailoring the salvage treatment within the currently available options including HSCT, chemo-immunotherapy and targeted therapy. Further knowledge would pave a better future to better manage PTCL.
Tatsuya Masuda, Tomoo Daifu, Masamitsu Mikami, Hiroshi Sugiyama* and Yasuhiko Kamikubo*
DOI: 10.37421/2165-7831.2023.13.296
Malignant Rhabdoid Tumor (MRT) is a quite rare malignant pediatric disease that occurs primarily in infants and young children. Although most patients with MRT are treated with the intensive multimodal treatment, the results are unsatisfied and there is no established standard of care for MRT. Therefore, there is a great need for more effective treatment(s) for MRT. Recently, we have demonstrated that RUNX1 silencing and “CROX (Cluster Regulation of RUNX)” strategy using our novel RUNX inhibitor (Chb-M') strongly reduce MRT cell proliferation rate via the augmentation of p53-mediated apoptotic pathway in vitro and in vivo. In this mini-review, we describe the molecular characteristics of our RUNX inhibitor, DNA-alkylating Pyrrole-Imidazole (PI) polyamides, and its anti-tumor effects on a variety of cancers including MRT. Finally, we discuss the precise molecular mechanisms behind p53-mediated apoptosis induced by RUNX inhibition in MRT cells.
Seema Gupta* and Arunima Ghosh
DOI: 10.37421/ 2165-7831.2023.13.297
DOI: 10.37421/ 2165-7831.2023.13.298
Despite having a basic grasp of laser wavelengths and dose ranges, there was no consensus on whether continuous mode or pulsing mode should be used, which is more dependable, and what determinants should be used to support the parameters of a pulsating laser. The molecular and cellular mechanisms of cold laser treatment have been investigated. The many types of pulsed lasers available have been described as the factors that influence the creation of their pulses. Investigations that were dissolved by continuous and/or pulsed laser modes were evaluated in vivo and in vitro. The laser therapy pulse repetition rates were matched. Several notable confirmations have shown that pulse mode has different effects on wound healing and damaged tissue than continuous mode. To completely assess the performance of cold laser treatment in cutaneous wounds healing, measurable clinical research that associates cellular effects in addition to biological processes is required. More research is needed to confirm these findings for a variety of wound types and treatments in a variety of settings, including pulsating mode structures. Future research should concentrate on well-controlled studies that rationally determine laser types and therapy parameters.
DOI: 10.37421/ 2165-7831.2023.13.295
DOI: 10.37421/2165-7831.2023.13.299
Background: Age-related differences in Multiple Myeloma (MM) are studied in clinical and genomic context, however, transcriptome changes have not yet been determined. The aim of this study is to identify the genes that are expressed differently in young and old patient groups and to examine the relationship of these genes with biological pathways and the drugs that can be used.
Methods: The MMRF CoMMpass cohort RNA-Seq data (n=634) was used to analyze differentially expressed genes between young and old patients. GO term and KEGG gene-set enrichment analysis were conducted using R packages. Drug-gene interactions were detected using DGIdb.
Results: Globally, 523 genes (366 upregulated, 157 downregulated) were differentially expressed (p<0.05) in young patients. Totally 220 GO terms, mostly related to immune regulation pathways were enriched. “Cytokine-cytokine receptor interaction” gene-set was enriched in KEGG GSEA. Among the highest expression difference, genes involved in immune regulation (FCGR1A, FCER1G, TLR2), known proto-oncogenic genes (BCL2, FGR) and genes under investigation for association with various cancers (RGL4, MT-RNR1, ETS2, ENPP3, FUT7, NTNG2, PRAM1) were identified. Drugs associated with the pathways affected by these genes were identified.
Conclusion: Further investigation of differentially expressed genes in young patients may shed light on new treatment options.
Musluh Hakseven*, Özhan Çetindağ, Gökhan Avşar, Rıza Deryol, Cem Azılı, Gözde Sırgancı, Serdar Culcu, Serkan Akbulut and Ali Ekrem Ünal
DOI: 10.37421/2165-7831.2022.12.012
Introduction: Gastric Cancer (GC) is one of the most common cancers that can result in death. Markers are needed to detect gastric cancer early and manage treatment. We aimed to reveal the relationship between Carcinoembryonic Antigen (CEA) level and Fibrinogen-Albumin Ratio (FAR) and prognosis in gastric cancer, as well as to examine the relationship of these values with the number of metastatic lymph nodes and TNM stage.
Materials and methods: The data of 805 consecutive gastrectomy patients were analyzed retrospectively. A total of 461 patients were included. The optimal cut- off values of CEA and FAR were 2.43 ng/mL and 1.26, respectively. Patients were stratified into three groups based on this cutoff value: CEA-FAR=0 (CEA<2.43 ng/mL and FAR<1.26), CEA-FAR=1 (CEA ≥ 2.43 ng/mL or FAR ≥ 1.26), and CEA-FAR=2 (CEA ≥ 2.43 ng/mL and FAR ≥ 00201.26).
Results: There was a significant relationship between high CEA and stage (p=0.040), N status (p=0.017), and lymph node metastasis (p=0.004), and also there was a significant correlation between high FAR value and grade (p=0.003), stage (p<0.001), T status (p<0.001), N status (p<0.001) and metastatic lymph node count (p<0.001). Overall and disease-free survival were significantly different between the three CEA-FAR groups.
Conclusion: We believe that pre-operative FAR and CEA values are independent predictors of survival. FAR and CEA are potential prognostic indicators for resectable gastric cancer due to their easy access and low cost. Considering survival and prognosis in patients with very high preoperative CEA and FAR values, neoadjuvant chemotherapy should also be considered.
DOI: 10.37421/2165-7831.2022.12.013
DOI: 10.37421/2165-7831.2022.12.014
DOI: 10.37421/ 2165-7831.2022.12.015
Najmeh Parhizgari, Farhad Rezaei, Mohammad-Reza Khatami, Sayed Mahdi Marashi, Mohammad Farahmand, Farzane Behnezhad, Monireh Derakhshani, Fatemeh Ajami-Nezhad and Talat Mokhtari-Azad*
DOI: 10.37421/2165-7831.2022.12.016
Background: In spite of antiviral prophylaxis regimens, Cytomegalovirus (CMV) remains a major reason for morbidity and allograft failure in kidney transplant recipients. This study aimed to investigate the incidence of early or late onset of CMV viremia in kidney transplant recipients and evaluate the correlation of laboratory findings and graft origin with CMV viremia.
Methods: In this prospective case-control study, 192 kidney recipients were evaluated for the timing and potential risk factors based on detectable CMV viremia (≥200 copies/ml) and all-correlates were assessed using multivariate logistic regression models.
Results: 153 participants from examined patients were eligible to enter the study. The risk of CMV viremia with viral loads ≥200 copies/ml was receiving a graft from a deceased donor. Importantly, CMV viremia mostly occurred 4 months after transplantation, while the patients were expected to be on CMV prophylaxis.
Conclusions: Receiving a renal graft from a deceased donor significantly raises the incidence of viremia in renal transplant patients. The median month of CMV viremia occurrence was month 4th after transplantation. Serum testing showed a significant increase in creatinine and a decrease in platelets in the CMV positive group compared to the control group. Our results indicated that the viremia has not affected the survival of the allograft or patient.
DOI: 10.37421/2165-7831.2021.11.e134
DOI: 10.37421/2165-7831.2021.11.e135
DOI: 10.37421/2165-7831.2021.11.257
DOI: 10.37421/2165-7831.2021.11.258
DOI: 10.37421/2165-7831.2021.11.259
DOI: 10.37421/ 2165-7831.2022.12.286
Qiang Pu, Lin Wang, Guojun Kang, Changbao Liu, Changfeng Yang, Jia Luo* and Yongfu Huang*
DOI: 10.37421/ 2165-7831.2022.12.287
Circulating exosomal miRNAs released into all body fluids have incredible functionality and stability. Their expression is associated with multiple pathological conditions, can be used as informative biomarkers when assessing and monitoring the body’s physiopathological status. However, there is no consensus on reference miRNAs for circulating exosomal reference and abundance normalization. The present study aimed to quantify 16 potential reference miRNAs in ten porcine body fluids using qRT-PCR. Further, their stability was quantified by combining multiple gold-standard statistical tools, including BestKeeper, GeNorm, and NormFinder. The identified miRNAs were comprehensively ranked. The top-ranked miRNA was recommended as the optimal reference miRNAs for data normalization. To identify more stable genes, the body fluids were assigned into three groups based on the collection point, they are in vivo (bile, bladder fluid, and gastric juice), in vitro (colostrum, ordinary milk, semen, and urine) and in the blood (UVBP, UABP and PBS). The most stable optimal circulating exosomal reference miRNAs in the body fluids were let-7b-5p (miR-93) in bile, miR-92a in bladder fluid, miR-93 in gastric juice, let-7b-5p in colostrum, miR-92a in ordinary milk and urine, miR-25 in semen, let-7b-5p in UVBP, miR-25 in UABP and U6 in PBS. Overall, miR-93, miR-451 (miR-92a), and miR-25 are the bona fide reference miRNA for qRT-PCR data normalization of body fluids in vivo, in vitro, and blood, respectively. Across all body fluids, miR-451 was the most stable when determining the miRNA abundance in the circulating exosomes
Srimanta Chandra Misra*, Eric W. Nacoulma, Alberto Santagostino and Valentina Guarino
DOI: 10.37421/ 2165-7831.2022.12.289
Flordeluna Z Mesina*, Jomell C Julian, Jesus Relos, Rosalio Torres, Maureen Via M Comia, June Marie P Ongkingco and Jimmy R. Lafavilla
DOI: 10.37421/2165-7831.2022.12.288
Introduction: The Novel Coronavirus (COVID-19) has gripped our country with strain as well as effecting our health system. Currently, there are no standard guidelines in its treatment but the possible benefits of convalescent plasma in limiting complications and treating COVID-19 disease is being looked upon.
Objective: This study aims to determine the effectiveness and safety of using convalescent plasma in improving clinical course of hospitalized patients diagnosed with COVID-19.
Methods: This is a quasi-experimental (prospective analytical) multi-center study of 65 patients who received convalescent plasma therapy (CPT).
Results: Median age of patients who were given CPT was 60 years, were predominantly male (68%), and presented with severe COVID-19 pneumonia. Median hemoglobin presented was 138 g/dl, median WBC count was 7.54 × 10 9 /L and median platelet count was 239,500 × 109/L. All inflammatory markers were increased, and both PaO2 and PFR were deranged. Statistically significant decrease in hemoglobin and LDH, and increase in platelet were seen after intervention of CPT. There was statistically significant longer length of stay among CPT recipients, and there was also noted less mortality in BAT group although this is insignificant.
Conclusion: Convalescent plasma may have shown no significant impact in the recovery rate and outcome compared to patients who have not received convalescent plasma therapy, but its administration was proven to be safe among all patients regardless of the level of severity and clinical profile.
Kenjiro Nagai*, Syo Nagai, Yuji Okubo and Keisuke Teshigawara
DOI: 10.37421/2165-7831.2022.12.290
Amplified Natural Killer Cell (ANK) therapy has been modified to enhance the safety and efficacy of original (LAK) immunotherapy. This is a method of removing Natural Killer (NK) cells from the patient's own blood, culturing and amplifying the NK cells, increasing their ability to specifically attack cancer, and returning them for treatment. It is generally effective against all cancers. Experienced a case in which ANK therapy was remarkably effective against ATL, prostate cancer, and breast cancer. Treatment of ATL is basically chemotherapy, but it is not effective and has many side effects. Chemotherapy is also the main treatment for solid cancer patients whose condition has progressed in the same way, and the elderly, renal failure, and heart failure patients cannot be treated. ANK therapy is highly effective in ATL cases and is also very effective in certain solid tumor cases. Considering the mechanism of action of ANK therapy from the accumulation of cases so far and research reports so far, it is effective for ATL with many PD positive tumor cells because it effectively kills PD-L1 positive tumor cells. Some types of solid tumors, such as lymphoma, gastric cancer, lung cancer, breast cancer, and prostate cancer, have many PD-L1-positive tumor cells. By measuring PD-L1-positive tumor cells and treating those with high levels, it may be possible to provide treatments that are more effective, have fewer side effects, and are safer than existing treatments.
DOI: 10.37421/ 2165-7831.2022.12.279
DOI: 10.37421/ 2165-7831.2022.12. 276
DOI: 10.37421/ 2165-7831.2022.12.277
DOI: 10.37421/ 2165-7831.2022.12.e148
DOI: 10.37421/ 2165-7831.2022.12. 275
DOI: 10.37421/ 2165-7831.2022.12.011
DOI: 0.37421/ 2165-7831.2022.12. e002
DOI: DOI: 10.37421/ 2165-7831.2022.12.008
DOI: DOI: 10.37421/ 2165-7831.2022.12.009
DOI: DOI: 10.37421/ 2165-7831.2022.12.010
Satoshi Miwa, Ryota Chijimatsu*, Hideshi Ishii and Taku Saito
DOI: 10.37421/2165-7831.2021.11.266
Mesenchymal stem/stromal cells (MSCs) have been widely studied for regeneration therapy in various organs/diseases and are currently being developed for clinical practice. Despite the hope brought by MSC therapy, the characteristics of MSCs remain ambiguous, where cells have distinct features depending on their sources and species. With regard to cartilage therapy, MSCs from the bone marrow and synovium have been clinically examined based on their differentiation into chondrocytes in animal studies. However, recent studies have outlined other reparative mechanisms of MSCs, such as paracrine effects. Thus, the regeneration mechanisms are still elusive, and the key features of MSCs that determine their reparative activity have not been established. In this review, we summarize the current literature and discuss the importance of the assays to evaluate “human” MSCs considering the in vivo environment and reparative mechanisms.
DOI: 10.37421/2165-7831.2021.11.e141
DOI: 10.37421/2165-7831.2021.11.267
DOI: 10.37421/2165-7831.2021.11.e140
DOI: 10.37421/2165-7831.2021.11.268
Yusuke Murakami and Naomi Yamashita*
DOI: 10.37421/2165-7831.2021.11.263
DOI: 10.37421/2165-7831.2021.11.264
DOI: 10.37421/2165-7831.2021.11.e138
DOI: 10.37421/2165-7831.2021.11.e139
Rainer Seitz*, Lutz Gürtler and Wolfgang Schramm
DOI: 10.37421/2165-7831.2021.11.265
The COVID-19 pandemic so far caused millions of deaths, and the therapeutic options for high-risk patients are far from being satisfactory. Active immunization by vaccines against SARS-CoV-2 spike protein provides good protection from a severe course of COVID-19. It has been explored in numerous clinical trials, whether also passive immunization by transfusion of convalescent plasma could positively influence the course of COVID-19. Large randomized clinical trials failed to demonstrate a benefit for patients with advanced disease. However, the antibody dose and timing of transfusion might have contributed to this negative result. Randomized clinical trials are necessary to make evidence-based progress in the development of therapeutic options, and this holds true also for “natural” concepts. However, even highquality trials are just a tool to test predefined hypotheses. Arguments are presented that convalescent plasma should be further evaluated in clinical trials as proactive, quasi “prophylactic” treatment by giving a sufficient amount of CCP early enough (before massive virus replication). A solid scientific foundation for the principle of target specific and temporarily adapted passive immunization would be very important even beyond COVID-19 as fast and flexible instrument also in future outbreaks of novel pathogens.
DOI: 10.37421/2165-7831.2021.11.e137
DOI: 10.37421/2165-7831.2021.11.e136
DOI: 10.37421/2165-7831.2021.11.262
Zeeshan Ansar Ahmed, Muhammad Shariq Shaikh, Muhmmad Hasan Hayat, Hamayail Ansari, Huzaifa Bin Rashid, Tariq Moatter and Zeeshan Ansar Ahmed*
DOI: 10.37421/2165-7831.2021.11.261
In Pakistan the disease burden of Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) is quite high, yet there is a lack of scientific evidence regarding the spectrum of BCR-ABL rearrangement variants in CML and ALL. Knowing about BCR-ABL rearrangement is important in determining the prognosis and treatment strategy of disease at the time of diagnosis. This study included a total of 685 patients, out of which there were 644 CML patients and 41 ALL patients, from October 2016-July 2019. From the CML group, 270 patients were reported to have the BCR-ABL1 transcript, from which 50% were males. Whereas in the ALL group, 35 patients were reported to have the BCR-ABL1 transcript out of which 65.7% were males. Proportions of BCR-ABL transcript type differed between the two groups, with b3a2 (63.3%) and b2a2 (34.8%) transcript types having the highest frequency in CML patients, whereas e1a2 (77.1%) and b3a2 (11.3%) transcript types were found to have the highest frequency in ALL patients. Our data shows transcript genotypes in CML and ALL patients in an Asian population, which may be useful to guide the clinical management and assess prognosis. Since the majority of our CML population had the b3a2 transcript, they have a better prognosis and treatment response.
Alphonsus Ogbonna Ogbuabor*, Peter Uwadiegwu Achukwu, Silas Anayo Ufelle and Daniel Chukwuemeka Ogbuabor
DOI: 10.37421/2165-7831.2021.11.260
The JAK-STAT pathway mediates signals that are involved in hematopoiesis. Aberrant JAK-STAT signaling has been identified in myeloproliferative neoplasm making the pathway a novel therapeutic target for myeloproliferative neoplasms through the application of JAK inhibitors. A major limitation to therapy with the current JAK inhibitors is a lack of selectivity which results in toxicity to patients. It is thought that increasing the selectivity of inhibitors will reduce toxicity observed with JAK inhibition therapy. System biology is a novel technology that holds great potentials for increasing the selectivity of JAK inhibitors. Its Application to drug designing can broaden the spectrum as well as repurpose the available JAK inhibitors for improved clinical outcome and possible cure for myeloproliferative neoplasms. This review presents an overview on the role of system biology in JAK inhibition therapy for myeloproliferative neoplasms.
DOI: 10.37421/2165-7831.2024.14.326
Pin Yao*, Lu Zhang, Jia Lin, Ruo-Wen Sun, Ru-Nan Wang, Hang-Fei Qu, Bo-Xuan Fang and Shuo Feng*
DOI: 10.37421/2165-7831.2024.14.330
Angelos Giannakoulas, Marios Nikolaidis, Grigorios D. Amoutzias and Nikolaos Giannakoulas*
DOI: 10.37421/2165-7831.2024.14.329
Puja M. Jagasia, Iulianna C. Taritsa, Kazimir Bagdady and Megan Fracol*
DOI: 10.37421/ 2165-7831.2024.14.327
Silicone breast implants have been linked to the development of cancers such as Breast Implant Associated-Anaplastic Large Cell Lymphoma (BIA-ALCL) and lesser understood conditions Breast Implant Illness (BII). The pathogenesis of BIA-ALCL has been linked to T-cell activation and proliferation in the capsule of textured breast implants. The effect of silicone breast implants on B cell-mediated immune reactions is not broadly understood. To cultivate a better understanding of how breast implants, affect B-cell mediated immune responses, both local in the capsule and potentially systemically, the authors performed a systematic review. After screening 1096 articles, 39 studies met inclusion criteria. Of the 39 studies meeting inclusion criteria, 23 studied human subjects, 14 studied animal models and 2 studied in vitro models. These studies focused on B cell-mediated immune responses on either a systemic level by examining antibody formation or on a local level by examining the breast implant capsule. Common results included the presence of anti-silicone antibodies and autoantibodies frequently implicated in autoimmune diseases. B lymphocytes found in the breast implant capsule were shown to form germinal centers and plasma cells, which secrete antibodies. Importantly, ten studies showed no indication that B cell-mediated immunity was significantly different in breast implant exposed subjects compared to those without implants. Exposure to silicone breast implants can result in B-cell mediated immune responses such as antibody formation. More research is needed to link these findings to the clinical manifestations of breast implant associated pathology.
Sara Herrera-De La Mata, Syed Hasan Arshad, Ramesh J Kurukulaaratchy and Grégory Seumois*
DOI: 10.37421/ 2165-7831.2024.14.328
Patients with severe uncontrolled asthma represent a distinct endotype with persistent airway inflammation and remodeling that is refractory to corticosteroid treatment. CD4+ TH2 cells play a central role in regulating asthma pathogenesis, and biologic therapies targeting their cytokine pathways have had promising outcomes. However, not all patients respond well to such treatment, and their effects are not always durable nor reverse airway remodeling. This observation raises the possibility that other CD4+ T cell subsets and their effector molecules may drive airway inflammation and remodeling. We performed single-cell transcriptome analysis of >50,000 airway CD4+ T cells isolated from Bronchoalveolar Lavage (BAL) samples from 30 patients with mild and severe asthma. We observed striking heterogeneity in the nature of CD4+ T cells present in asthmatics' airways with Tissue-Resident Memory (TRM ) cells making a dominant contribution. Notably, in severe asthmatics, a subset of CD4+ TRM cells (CD103-expressing) was significantly increased, comprising nearly 65% of all CD4+ T cells in the airways of male patients with severe asthma when compared to mild asthma (13%). This subset was enriched for transcripts linked to T Cell Receptor (TCR) activation (HLA-DRB1, HLA-DPA1) and cytotoxicity (GZMB, GZMA) and, following stimulation, expressed high levels of transcripts encoding for pro-inflammatory non-TH2 cytokines (CCL3, CCL4, CCL5, TNF, LIGHT) that could fuel persistent airway inflammation and remodeling. Our findings indicate the need to look beyond the traditional T2 model of severe asthma to better understand the heterogeneity of this disease.
Journal of Blood & Lymph received 443 citations as per Google Scholar report
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