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.
ABSTRACT
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
ABSTRACT
What can the hospitality industry do to reduce the risk of transmission of COVID-19? Part is recognizing that HVAC systems play a role in mitigating the risk of airborne transmission of COVID-19.1 At the beginning of the pandemic, hospitality facilities, including hotels and restaurants, quickly aligned with guidance from the CDC,2,3 WHO4 and other credible organizations such as ASHRAE5,6 by adjusting operating guidelines to increase outdoor air dilution and improve filtration, where possible, while maintaining guest and associate comfort. This article discusses a comprehensive study recently conducted by the authors to investigate the efficacy of portable air purifiers to improve air quality in public spaces. © 2021 Amer. Soc. Heating, Ref. Air-Conditoning Eng. Inc.. All rights reserved.
ABSTRACT
What can the hospitality industry do to reduce the risk of transmission of COVID-19? Part is recognizing that HVAC systems play a role in mitigating the risk of airborne transmission of COVID-19.(1) At the beginning of the pandemic, hospitality facilities, including hotels and restaurants, quickly aligned with guidance from the CDC,(2,3) WHO4 and other credible organizations such as ASHRAE(5,6) by adjusting operating guidelines to increase outdoor air dilution and improve filtration, where possible, while maintaining guest and associate comfort. This article discusses a comprehensive study recently conducted by the authors to investigate the efficacy of portable air purifiers to improve air quality in public spaces.