Type-B lactic acidosis associated with progressive multiple myeloma

Abdullah, Sameer; Ali, Muhamad; Sabha, Marwa

doi:10.15537/smj.2015.2.10205

Cited by 10 publications

(10 citation statements)

References 9 publications

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“…First, pH of MM cell conditioned media was tested at different time points. We found that 72 h of MM cell culture generate acidic tumor microenvironment close to the pH tumor environment cited in the literature around 6.5-7.1 [27-29]. The pH of the conditioned media was measured after 72 h of culture and found a significant decreased in pH in MM-conditioned media (6.94 ± 0.23) compared to normal PB MNCS-conditioned media (8.38 ± 0.01) and non-conditioned media (8.6 ± 0.05) (Fig.…”

Section: Resultsmentioning

confidence: 63%

“…We have previously shown that chitosan swelling (as a first step for drug release) is pH dependent, in which chitosan swelling is increased in acidic pH and enhance release for its encapsulated materials [41], due to hydration of the protonated amine groups under acidic conditions [42]. Tumor microenvironment is reported to be more acidic than normal healthy tissue [27-29], and our model demonstrated similar pH in the MM cultures to these reported in the literature. We further confirm that anti-CD38 NPs swelling was pH dependent, and that acidic tumor microenvironment induced increase swelling compared to normal microenvironment.…”

Section: Discussionmentioning

confidence: 99%

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Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma

Puente

Luderer

Federico

et al. 2018

Journal of Controlled Release

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The establishment of more effective treatments that can circumvent chemoresistance in Multiple Myeloma (MM) is a priority. Although bortezomib (BTZ) is one of the most potent proteasome inhibitors available, still possesses limitations related to dose limiting side effects. Several strategies have been developed to improve the delivery of chemotherapies to MM by targeting different moieties expressed on MM cells to nanoparticle delivery systems (NPs), which have failed mainly due to their heterogeneous expression on these cells. Our goal was to test CD38 targeted chitosan NPs as novel targeting moiety for MM to improve the potency and efficacy of BTZ in MM cells and reduce the side effects in healthy tissue. We have showed preferential BTZ release in tumor-microenvironment, specific binding to MM cells, and an improved drug cellular uptake through BTZ diffusion from the surface and endocytosed NPs, which translated in enhanced proteasome inhibition and robust cytotoxic effect on MM cells when BTZ was administered through anti-CD38 chitosan NPs. Furthermore, the anti-CD38 chitosan NPs specifically delivered therapeutic agents to MM cells improving therapeutic efficacy and reducing side effects in vivo. The anti-CD38 chitosan NPs showed low toxicity profile allowing enhancement of proteasome-inhibitory activity and specificity of BTZ by endocytosis-mediated uptake of CD38 representing a promising therapy in MM.

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Section: Resultsmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma

Puente

Luderer

Federico

et al. 2018

Journal of Controlled Release

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“…Despite persistent elevation of lactate, he remained stable and was extubated. He was discharged to ward after 5 days, in much improved condition but with lactate still in range of 5–10 mM, a phenomenon that has been described in patients with multiple myeloma [28–30]. He was diagnosed by a posteriori consensus of clinicians as having type B lactic acidosis due to multiple myeloma.…”

Section: Resultsmentioning

confidence: 95%

Using pCO₂ Gap in the Differential Diagnosis of Hyperlactatemia Outside the Context of Sepsis: A Physiological Review and Case Series

Waldauf

Jiroutková

Duška

2019

Critical Care Research and Practice

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Introduction There is an inverse relationship between cardiac output and the central venous-arterial difference of partial pressures of carbon dioxide (pCO2 gap), and pCO2 gap has been used to guide early resuscitation of septic shock. It can be hypothesized that pCO2 gap can be used outside the context of sepsis to distinguish type A and type B lactic acidosis and thereby avoid unnecessary fluid resuscitation in patients with high lactate, but without organ hypoperfusion. Methods We performed a structured review of the literature enlightening the physiological background. Next, we retrospectively selected a series of case reports of nonseptic critically ill patients with elevated lactate, in whom both arterial and central venous blood gases were simultaneously measured and the diagnosis of either type A or type B hyperlactataemia was conclusively known. In these cases, we calculated venous-arterial CO2 and O2 content differences and pCO2 gap. Results Based on available physiological data, pCO2 can be considered as an acceptable surrogate of venous-arterial CO2 content difference, and it should better reflect cardiac output than central venous saturation or indices based on venous-arterial O2 content difference. In our case report of nonseptic patients, we observed that if global hypoperfusion was present (i.e., in type A lactic acidosis), pCO2 gap was elevated (>1 kPa), whilst in the absence of it (i.e., in type B lactic acidosis), pCO2 gap was low (<0.5 kPa). Conclusion Physiological rationale and a small case series are consistent with the hypothesis that low pCO2 gap in nonseptic critically ill is suggestive of the absence of tissue hypoperfusion, mandating the search for the cause of type B lactic acidosis rather than administration of fluids or other drugs aimed at increasing cardiac output.

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“…Most reported cases of type B lactic acidosis are associated with hematological malignancies. Multiple case reports have been reported with patients of multiple myeloma, 21 lymphoma, and leukemia 22 complicated by type B lactic acidosis. The data on solid tumors are limited, and we performed literature search using PubMed with the search terms “type B lactic acidosis” and “lactic acidosis and colon cancer.” Our case represents the second case in the literature in the last 20 years, associating colorectal cancer with severe type B lactic acidosis.…”

Section: Discussionmentioning

confidence: 99%

Fatal Type B Lactic Acidosis Associated With Metastatic Colorectal Cancer: A Case Report With Review of Literature, Pathogenesis, and Treatment

Gharia

Seegobin

Mahida

et al. 2018

Journal of Investigative Medicine High Impact Case Reports

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Type B lactic acidosis associated with malignancy is a life-threatening complication and mostly seen in hematological malignancies but can also be seen in solid tumors. We report a rare case of a 64-year-old female diagnosed with metastatic adenocarcinoma of the colon with liver metastasis associated with severe type B lactic acidosis. We discuss pathophysiology, previously reported cases, and their outcomes. The most widely used therapies are bicarbonate infusion, thiamine supplementation, chemotherapy, and supportive care but is associated with poor outcomes, and no standard treatment recommendations are available. Early chemotherapy administration remains the only intervention that has shown some survival benefit. Physicians should be aware and proactive for early diagnosis and management of this condition with further research needed to guide optimal therapy.

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Type-B lactic acidosis associated with progressive multiple myeloma

Cited by 10 publications

References 9 publications

Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma

Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma

Using pCO₂ Gap in the Differential Diagnosis of Hyperlactatemia Outside the Context of Sepsis: A Physiological Review and Case Series

Fatal Type B Lactic Acidosis Associated With Metastatic Colorectal Cancer: A Case Report With Review of Literature, Pathogenesis, and Treatment

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Type-B lactic acidosis associated with progressive multiple myeloma

Cited by 10 publications

References 9 publications

Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma

Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma

Using pCO2 Gap in the Differential Diagnosis of Hyperlactatemia Outside the Context of Sepsis: A Physiological Review and Case Series

Fatal Type B Lactic Acidosis Associated With Metastatic Colorectal Cancer: A Case Report With Review of Literature, Pathogenesis, and Treatment

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Using pCO₂ Gap in the Differential Diagnosis of Hyperlactatemia Outside the Context of Sepsis: A Physiological Review and Case Series