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Hesperidin has gained major interest recently due to the outbreak of COVID-19. The traction has led to more research being conducted on the compound hesperidin. Recent studies have shown its anti-inflammatory and anti-viral attributes, which have beneficial effects on severe acute respiratory syndrome (SARS-CoV-2). Hesperidin has also shown unique effects on the protein of SARS-CoV-2, which lead to a good preventative measure for SARS-CoV-2. Hesperidin also causes a suppression of appetite, which helps to combat obesity through the release of cholecystokinin. Furthermore, hesperidin has shown cardioprotective properties, which cause an increase in plasma high-density lipoprotein levels and a decrease in plasma low-density lipoprotein levels. Hesperidin is also used in combination with the Japanese herb Rikkunshito, which has shown potential in a discovery of a new drug for gastrointestinal motility as hesperidin can depolarize pacemaker potential in interstitial cells of Cajal (ICC). The chemo-preventive effects of hesperidin are caused by its antioxidant effect, which may prevent tissue necrosis due to oxidative stress. The photo-protective effect of hesperidin can reduce the damage to the skin caused by UV rays. Hesperidin also possesses wound-healing properties.Copyright © 2023 Bentham Science Publishers.
ABSTRACT
BACKGROUND: Hyperviscosity syndrome (HVS) is an infrequent but life-threatening complication of multiple myeloma (MM) and classically presents with the triad of mucosal bleed neurological and visual disturbances. HVS is typically associated with Immunoglobulin M (IgM) MM and very rarely may complicate IgG MM. Even suspicion of HVS necessitates therapy based on clinical severity rather than the calculated degree of viscosity. While plasmapheresis promptly decreases serum viscosity by 30-50% early initiation of antimyeloma therapy is crucial to prevent rebound phenomena. AIM OF THE STUDY: In this context, we report a case of IgG MM which despite being complicated by HVS had gratifying outcome attributable to early clinical suspicion and consequent prompt therapeutic intervention. METHOD(S): Case report - A 60-year-old lady presented with headache altered sensorium blurring of vision and bleeding from both nostrils of two days duration. She also had breathlessness on exertion and generalized fatigue for one month. Clinical evaluation was remarkable for pallor hypertension (blood pressure - 160/96 mm Hg) tachypnea (respiratory rate - 26/minute) with blood clots in nostrils bleeding from gums dry tongue and skin bruising on the arms. Besides altered mentation neurological evaluation revealed bilateral venous congestion and perivenular flame-shaped hemorrhages on direct ophthalmoscopy. There were no features of heart failure peripheral lymphadenopathy or organomegaly. Her initial blood sampling was difficult as blood was rapidly clogging during sampling itself. After rapid saline infusion, samples could be drawn and processed. Hemogram showed normocytic normochromic anemia (hemoglobin-6.3%g/ dL) thrombocytopenia (platelets -71 000/mm3) and rouleaux formation without hemolysis or blast cells on peripheral blood smear. SARS-CoV-2 PCR was negative. She had reversal of albumin-globulin ratio (total protein -10.6 g/dL;albumin -2.1 g/dL) hypercalcemia (corrected calcium - 14 mg/dL) and raised creatinine of 2.5 mg/dL. Her coagulation profile was essentially normal. Computed tomography images of head chest and abdomen were essentially normal. Further evaluation revealed M-spike (5.3%gm/dL) on serum protein electrophoresis raised IgG (4.69 g/dL) increased kappa light chain (kappa 171 mg/L lambda 24.3 mg/L;ratio -7) on serum-free light chain assay monoclonal band of IgG Kappa on serum immune-fixation electrophoresis. Bone marrow aspiration revealed 60% plasma cells (Figure-1) with sheets of plasma cell on bone marrow biopsy having kappa-restriction on immunohistochemistry thereby confirming multiple myeloma and ruled out remote possibility of lymphoplasmacytic lymphoma-related HVS. In view of presumptive HVS complicating multiple myeloma patient was managed with urgent plasmapheresis and consequently initiated on bortezomib-based anti-myeloma triplet therapy including lenalidomide and dexamethasone (VRd) besides supportive therapy for hypercalcemia and acute kidney injury. After three sessions of plasmapheresis patient showed complete resolution of symptoms of HVS with remarkable change in plasma color (Figure-2). Her acute kidney injury also recovered by day-7, and she went home walking on day-10 of her hospitalization. Two months later she was tolerating her chemotherapy well with complete resolution of hypergammaglobulinemia. Six months later she is in complete remission and is being planned for autologous hematopoietic stem cell transplant. RESULT(S): Discussion - Classical triad of HVS include mucosal bleed, neurological disorders, and visual disturbances.5 Presence of oro-nasal bleed mandates thorough retinal evaluation since hemorrhages may occur without visual symptomatology. Furthermore, clinical signs include hypertension, congestive heart failure5, priapism6, and decreased hearing merit consideration. Structure of protein is an important determinant of viscosity, whereby spherical proteins rotate through plasma and contribute very little and large linear proteins spin end over end and raise viscosity disproportionatel . Likewise, IgM (molecular weight of 950 Kd) has a high axial length-to-width ratio and, therefore, raises plasma viscosity at levels above 5 g/ dL. IgA circulates as a dimer, and results in HVS at levels above 7 g/dL7. HVS complicating IgG MM with IgG circulating as a monomer (molecular weight of 180 Kd) is rare and accounts for less than 5% of cases and requires IgG level usually above 10 g/dL7. Even presumptive suspicion of HVS necessitates therapy based on clinical severity rather than the calculated degree of viscosity as correlation between serum viscosity and clinical manifestation is not precise;nevertheless, symptoms attributable to HVS are rare if serum viscosity is less than 4 centipoise (CP) [normal value -1.5 CP]. With rapid symptomatic relief following plasmapheresis, absence of further therapeutic and prognostic implications and logistic constraints, serum viscosity and Ig G subtyping8 couldn't be estimated in the index case. As IgM is predominantly limited to intravascular space (over 80%), only a single session of plasma exchange (removal of 1-1.5 plasma volume) typically, decrease plasma viscosity by 30% to 50%, and reduce IgM level by 60%9 and is generally sufficient to abate acute symptoms in patients with IgM-related HVS. In contrast, maximum of three sessions of plasmapheresis10 may be needed in IgG-related HVS (due to late and less efficient removal of IgG as it is near equally distributed between the intravascular space and extravascular space) or if the viscosity remains over six CP11. Although International Myeloma Working Group does not specifically identify HVS as myeloma-defining event, clearly its presence warrants Bortezomib-based chemotherapy for rapid decline of Ig levels.5 However, pharmacological treatment should never be considered as an alternative to plasma exchange for immediate hyperviscosity reduction.5 Moreover, patients with HVS tend to have plasma volume expansion;hence, actual anemia may be partially dilutional. Consequential red blood cell transfusion can have negative rheological impact of adding red cells to the circulation and further increase in blood viscosity and worsen HVS.5 Therefore, red blood cell transfusion is recommended only after blood viscosity reduction. Symptomatic HVS consequent to IgG MM with IgG levels below 5 g/dL7 is infrequent and hence reported for its novelty. Moreover, early clinical suspicion of HVS and consequent pre-emptive plasmapheresis (even before completion of work-up of MM) may improve clinical outcome as evident in the index case. CONCLUSION(S): To conclude, neurological dysfunction at presentation of MM with / without mucosal bleed and visual disturbance should caution us toward an albeit infrequent, yet devastating complication of HVS, which is otherwise potentially reversible subject to early clinical suspicion and prompt initiation of appropriate therapy.
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Background: Cardiac calcification is a broad entity encompassing calcific deposits in the valves, coronary arteries, aortic root, myocardium, endocardium, or pericardium. It is reported in approximately 19 percent of post myocardial infarction (MI) patients. (1) Coronary artery disease is by far the commonest cause of endo-myocardial calcification, other causes include endomyocardial fibrosis, myocarditis, metastatic calcification in chronic kidney disease patients. Post - acute coronavirus (COVID) syndrome is defined as the persistence of symptoms even beyond 4 weeks of onset of acute symptoms. (2) A recent study has shown that, beyond the first 30 days after infection, individuals with COVID are at increased risk of incident cardiovascular disease including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure and thromboembolic disease. (3) This study cited the risk and additional burden of ischemic heart disease outcome as an hazard ratio of 1.66 (95% confidence interval of 1.52 - 1.80) and 7.28 (95% confidence interval 5.8 - 8.88) per 1000 population respectively. (3) We present an interesting case of a forty-three-year-old man with endo-myocardial calcification with ischemic cardiomyopathy (ICMP) and severely reduced left ventricular (LV) global longitudinal strain (GLS) in post COVID syndrome. Case report: A forty - three-year-old man presented to us with gradually worsening dyspnea on exertion - New York Heart Association (NYHA) grade II at present - and pedal edema since the past 6 months. He had a history of COVID infection prior to that for which he received institutional care and was discharged uneventfully - not requiring any intensive care stay during the hospitalization. On presentation now a 12-lead electrocardiogram was done which revealed left bundle branch pattern. He underwent - an echocardiogram which showed a reduced ejection fraction of 38 % along with regional wall motion abnormality in anterior, apical and lateral wall;a computed tomogram of thorax which did not reveal any lung disease but endo - myocardial calcification. (Fig 3) He further underwent myocardial strain imaging using echocardiography, which revealed a severely reduced LV GLS. (Fig 4) Routine blood investigations including inflammatory markers and Troponin levels were within normal limit, brain natriuretic peptide (BNP) levels were found to be very high. The patient underwent coronary angiogram which revealed significant disease in distal left main coronary artery and ostio-proximal left anterior descending and left circumflex artery. After detailed heart team discussion along with patient relatives the patient was advised coronary artery bypass grafting. The patient took discharge and went to a different hospital to undergo the same. Conclusion(s): Acute Coronavirus infection has already been wreaking havoc all around the globe since the past 3 years. We have now showcased a unique and devastating consequence of the post COVID state in a relatively young man. [Formula presented] [Formula presented] Copyright © 2022
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Introduction: Autologous stem cell transplant (ASCT) remains the backbone therapeutic modality with the highest progression-free survival (PFS) and overall survival (OS) benefit even in the era of the novel agents in newly diagnosed multiple myeloma (NDMM). The survival post-transplant can be prolonged using maintenance therapies. The regimen with maximum benefit is still debated, with bortezomib showing PFS benefit even in the high-risk myeloma. Aims & Objectives: This randomized phase II trial is aimed at studying the efficacy (as measured by overall survival (OS), progression- free survival (PFS)), and safety of post-ASCT different maintenance regimens in patients with NDMM. Material(s) and Method(s): Multicentric open-label interventional study with randomized allocation, parallel assignment, with intention-totreat analysis. Recruitment was prospective starting 01 Jan 2017, including all NDMM patients eligible for the study. Remission status was evaluated at D100 and every 6 months for 2y post-ASCT, including MRD analysis by multicolor flow cytometry (MFC) and PET/CT. The four arms included (Arm-A) bortezomib alone (V), (Arm-B) bortezomib in combination with cyclophosphamide and dexamethasone (VCD), (Arm-C) bortezomib in combination with lenalidomide (VR), and (Arm-D) Lenalidomide starting D100 till 2y post-ASCT. Adverse events with CTACE grade<2 were defined as non-serious and the rest as serious. JMP ver. 13 was used for statistical analysis and p<0.05 was considered significant. Kaplan Meier statistics was used for survival analysis. Result(s): A total of 123 patients have enrolled of which 92 patients completed the study protocol and the rest 31 patients were excluded because of protocol deviation due to the COVID pandemic. The median age of the study population was 54.5y (35-76y) with a male preponderance (67%). There was no statistically significant difference between the four arms on the log-rank test in the OS (p-0.99), clinical PFS (p-0.65), biochemical PFS (p-0.6), or MFC-based PFS (p-0.83). There was a statistically significant difference between the four arms on the log-rank test (p-0.0185) on PET/CT-based PFS (PFS being in a descending order VCD>V>VR>R regimen). The all-cause mortality of the study participants was 19.57% (n-18) and the difference in deaths among the various groups was not statistically significant (p-0.85). The tolerability, serious and non-serious adverse were significantly higher amongst Arm D patients. Conclusion(s): We conclude that there was no difference in OS between the different regimens. Patients on Lenalidomide-only therapy had significantly inferior Imaging-PFS.
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Background: Patients with inadequate amounts of copper often present with cytopenias and exhibit dysplasia on bone marrow, mimicking myelodysplastic syndrome (MDS) and pose diagnostic difficulties. Method(s): This cross-sectional observational study was performed from January 2020 to June 2021. Patients diagnosed with MDS were included in the study and serum copper levels were measured by the Inductively Coupled Plasma Mass Spectrometry (ICPMS) method. Copper supplementation with intravenous copper chloride 2.5mg daily for the first two weeks, followed by oral 3mg copper sulfate thrice daily for the next three months, was given for copper-deficient patients. Response assessment was performed with repeat hemogram and serum copper levels. Result(s): A total of 57 patients were diagnosed with MDS, of these, 33 (57.89%) were males and 24 (42.10%) were females. The mean age was 54.3+/-14.6 years (13-81). The distribution of patients in different types of MDS was MDS-SLD in 15, MDS-MLD in 18, MDS-EB1 in 7, MDS-EB2 in 8, and MDS-U in 9 patients. Anemia was seen in (87.71%) of patients, with mean hemoglobin 7.6+/-2.1g/dL (4.6-14.5g/dL). Neutropenia was seen in 31 (54.38%) with a mean absolute neutrophil count(ANC) of 2073+/-2139/muL (211-10,952/muL). Thirty seven (64.91%) patients had thrombocytopenia with a mean platelet count of 1,05,298+/-1,21,769/muL (9,000-6,74,000/muL). The mean serum copper levels were 146.69+/-42.36mug/dL (54.2-254.0mug/dL). Only three (5.26%) patients out of 57 were found to have copper deficiency. All three patients with low copper levels were found to have anemia, thrombocytopenia, and mildly raised serum erythropoietin levels. All three patients had dyserythropoiesis on bone marrow examination, and only one patient each had cytoplasmic vacuolations in erythroid precursors and dysmegakaryopoiesis. Among the three patients with copper deficiency, two patients had significant improvement in cytopenias after copper supplementation, and one had lost follow-up due to COVID-19. Conclusion(s): This study is the first from India to evaluate the role of copper in patients presenting with predominantly hematological manifestations. For patients presenting with cytopenias or marrow dysplasia resembling MDS, copper deficiency should be considered in the differential diagnosis. Legal entity responsible for the study: The authors. Funding(s): Has not received any funding. Disclosure: All authors have declared no conflicts of interest. Copyright © 2022
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Background: Caregivers not being allowed into the COVID wards prevented them from being involved in caring for their relatives in respect of day-to-day activities such as eating, drinking, and walking to the washroom. The aim of this study was to observe the challenges faced by patients admitted to intensive care unit (ICU) with COVID-19 pneumonia. We also observed the impact of two simple nursing interventions related to feeding and defecation and noted their impact in terms of patient's satisfaction. Materials and Methods: A semi-structured feedback questionnaire was prepared to cover common challenges faced by patients after interview with 10 patients admitted at a COVID ICU. Two simple nursing interventions were performed related to feeding and defecation. Results: Breathlessness was the most common issue as all the patients admitted were hypoxic. Inability to perform routine day-to-day functions such as feeding, drinking, sitting, and walking were other common issues. Emotional issues like anxiety, fear homesickness, and loneliness were also very high. Most (69.44%) patients were satisfied with a blended diet which was easy to take for patients with breathlessness. Most (77.28%) of patients were satisfied with intervention of helping them sit on a commode chair while on oxygen. Conclusion: During this pandemic, where all our efforts seemed insufficient in face of this unprecedented crisis yet these small seemingly insignificant steps helped both the patients as well as nurses in making the atmosphere more positive.
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The world as we know it has changed over a short period of time, with the rise and spread of the deadly novel Corona virus known as COVID-19, the world will never be the same again. This study explores the devastating effects of the novel virus pandemic, the resulting lockdown, thus the need to transform the offline classroom into an online classroom. It explores and describes the numerous online teaching platforms, study materials, techniques, and technologies’ being used to ensure that educating the students does not stop. Furthermore, it identifies the platforms, technologies which can be used to conduct online examination in a safe environment devoid of cheating. Additionally, it explores the challenges facing the deployment of online teaching methods. On the basis of literature review, a framework was proposed to deliver superior online class room experience for the students, so that online classroom is as effective as or even better than offline classrooms. The identified variables were empirically tested with the aid of a structured questionnaire;there were 487(according to Craitier and Morgan)150 number of respondents who were purposefully sampled. The results indicate that students prefer the multimedia means of studies. As a result of binary logistic regression, poor internet connection, awareness on COVID-19, enough sources of materials, recommends massive open online course, favourite online methods, and satisfaction with online study are significant in the model or attitudes towards delivering of online classes during lockdown COVID-19 pandemic at 5% level of significance. The study recommends online teaching methods, but finally, the study concludes that satisfaction with online study is significant in the model or attitudes towards delivering of online classes during lockdown COVID-19 pandemic at 5% level of significance. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.