Doxorubicin and zoledronate treatment in a dog with hemophagocytic histiocytic sarcoma.

A 6-year-old castrated male greyhound dog was referred for hemophagocytic histiocytic sarcoma (HHS) diagnosed following splenectomy. Severe thrombocytopenia, mild hypoalbuminemia, mild hypocholesterolemia, and mild hyperbilirubinemia were present. Abdominal ultrasound findings were concerning for hepatic metastasis. Doxorubicin and zoledronate combination therapy was initiated. The dog improved clinically and its thrombocytopenia, hypoalbuminemia, and hyperbilirubinemia resolved. The dog appeared well for 147 d before tumor progression was noted. The dog was treated with lomustine as a final measure, with no response. The dog survived for 6 mo with chemotherapy. To the authors' knowledge, this is the first report of clinical benefit of chemotherapy for HHS. Key clinical message: Doxorubicin should be considered for treating canine HHS since this variant of the disease is historically refractory to lomustine. Further research regarding efficacy of doxorubicin and zoledronate should be pursued.

Traitement à la doxorubicine et au zolédronate chez un chien atteint de sarcome histiocytaire hémophagocytaire. Un lévrier mâle castré de 6 ans a été vu pour un sarcome histiocytaire hémophagocytaire (HHS) diagnostiqué à la suite d'une splénectomie. Une thrombopénie sévère, une hypoalbuminémie légère, une hypocholestérolémie légère et une hyperbilirubinémie légère étaient présentes. Les résultats de l'échographie abdominale étaient préoccupants quant aux métastases hépatiques. Un traitement associant doxorubicine et zolédronate a été instauré. Le chien s'est amélioré cliniquement et sa thrombocytopénie, son hypoalbuminémie et son hyperbilirubinémie ont disparu. Le chien semblait en bonne santé pendant 147 jours avant de constater une progression tumorale. Le chien a été traité avec de la lomustine comme mesure finale, sans réponse. Le chien a survécu 6 mois grâce à la chimiothérapie. À la connaissance des auteurs, il s'agit du premier rapport faisant état d'un bénéfice clinique de la chimiothérapie pour le HHS.Message clinique clé :La doxorubicine doit être envisagée pour traiter le HHS canin puisque cette variante de la maladie est historiquement réfractaire à la lomustine. Des recherches plus approfondies concernant l'efficacité de la doxorubicine et du zolédronate devraient être poursuivies.(Traduit par Dr Serge Messier).

The correlation between paclitaxel chemotoxicity and the plasma albumin level in cancer patients.

WHAT IS KNOWN AND OBJECTIVE: The aim of this study was to evaluate the pharmacokinetics of paclitaxel in cancer patients with hypoalbuminemia following paclitaxel-containing chemotherapy and to provide a reference for the prevention of adverse events (AEs) after paclitaxel administration. METHODS: Peripheral blood was collected from cancer patients treated with paclitaxel. The plasma concentration of paclitaxel was determined by ultra-high performance liquid chromatography after 24 ± 8 h of chemotherapy, and individual paclitaxel time above a threshold concentration of 0.05 µmol/L (Tc>0.05 ) was calculated using the population pharmacokinetic model. Haematological and non-haematological toxicities were monitored after chemotherapy, and the correlation between different chemotherapy toxicities and Tc>0.05 was evaluated using the Prism software. RESULTS AND DISCUSSION: The enrolled patients were divided into the hypoalbuminemia group and normal albumin level group. The mean Tc>0.05 values in the normal albumin level and hypoalbuminemia groups were 36.89 and 24.93 h, respectively (P < 0.001). The risk of myelosuppression was positively correlated with Tc>0.05 . Due to the lower Tc>0.05 , the incidences of immediate AEs such as gastrointestinal reactions and rashes were higher in the hypoalbuminemia group than in the normal albumin level group, and the incidences of delayed AEs such as myelosuppression and neurotoxicity were lower in the hypoalbuminemia group. WHAT IS NEW AND CONCLUSIONS: Plasma albumin level has a conclusive effect on Tc>0.05 , which can predict the potential clinical toxicity of paclitaxel. The study provides a theoretical basis for administration of paclitaxel.

[Risk of infection in cancer patients colonized by extended expectrum p-lactamases and carbapenem producing Enterobacteriaceae]. / Riesgo de infección en pacientes oncológicos colonizados por bacterias productoras de p-lactamasas de espectro extendido y enterobacterias productoras de carbapenemasas.

BACKGROUND: The prevalence of multi-resistant microorganisms is a public health problem that continues to grow globally. There is a population that is mainly susceptible to being colonized and subsequently infected, and these are cancer patients. AIM: To identify the clinical and pathological characteristics of cancer patients and their relationship with infection with ESBL and CPE producing microorganisms. METHODS: A retrospective and analytical study was conducted between January 1, 2019 and June 30, 2020 in three hematooncological units. RESULTS: We included 3315 patients of which 217 (6.5%) were colonized by microorganisms producing ESBL and CPE. Of these, 106/217 (48.8%) had at least one episode of infection. The most frequently isolated microorganism was Klebsiella pneumoniae 29/106 (27.4%). Of those infected, 18/106 (17%) presented infection by the same colonizing microorganism. Mucositis (p = 0.002), age over 65 years (p = 0.041), hypoalbuminemia (p < 0.01), neutropenia (p < 0.01) and the presence of invasive devices (p < 0.01) demonstrated a relationship with development of infection. The presence of hypoalbuminemia (OR 3.3, CI 1.5-7.1, P < 0.01), invasive devices (OR 5.8, CI 3.0-11.4, p < 0.01) and neutropenia (OR 4.1, CI 1.5-11.4, p < 0.01) predict the development of infections.

Baseline Factors Predictive of the Receipt of Second-Line Chemotherapy After Nab-Paclitaxel Plus Gemcitabine for Patients With Advanced Pancreatic Cancer.

OBJECTIVE: Second-line (2L) chemotherapy is important for improved survival in patients with advanced pancreatic cancer (APC). However, approximately half of patients with APC do not receive 2L chemotherapy because of disease progression or adverse events. Baseline factors predictive of the receipt of 2L chemotherapy remain unknown. Therefore, we investigated predictive factors for the receipt of 2L chemotherapy in patients with APC. METHODS: Between January 2015 and March 2020, 53 patients with APC received nab-paclitaxel plus gemcitabine (AG) as first-line chemotherapy at our institute. Of these 53 patients, 29 patients received 2L chemotherapy, and 23 patients received best supportive care. Patients' characteristics were compared retrospectively, and predictive factors for the receipt of 2L chemotherapy were evaluated. RESULTS: Sarcopenia and hypoalbuminemia at baseline were independent negative predictive factors for the receipt of 2L chemotherapy in multivariate analysis. Although the presence of sarcopenia did not affect the relative dose intensity through 8 weeks of AG therapy, patients with hypoalbuminemia had a significantly lower relative dose intensity. CONCLUSIONS: Sarcopenia and hypoalbuminemia at baseline might be negative predictive factors for the receipt of 2L chemotherapy after AG treatment in patients with APC.

Crotalid Polyvalent F(ab)2 Antivenom Treatment in a Red-Tailed Hawk (Buteo jamaicensis).

Envenomation in avian species can result in death, with few cases of successful treatment described. A juvenile, wild-caught, intact female red-tailed hawk (Buteo jamaicensis) used in falconry was presented for emergency evaluation after being bitten by a Northern Pacific rattlesnake (Crotalus oreganus) approximately 2 hours before presentation. On presentation, the bird was quiet, alert, and responsive, with moderate swelling and discomfort of the digits on the right foot. Complete blood count (CBC) and plasma biochemistry abnormalities included a regenerative left shift, severe lymphopenia, and a moderate hypoproteinemia characterized by moderate hypoalbuminemia. Analgesic and antibiotic medications were administered during hospitalization. In addition, 5 mL of VenomVet was administered intravenously with crystalloid fluids over 60 minutes; no adverse effects were noted secondary to infusion. Improvement in the swelling was observed immediately after antivenom administration and nearly resolved within 12 hours. Complete resolution of digital swelling with no discomfort on palpation of that foot was observed 1 week after initial presentation. Blood collected at the 1 week reexamination was submitted for a CBC and plasma biochemistry panel. The results of the CBC revealed a reduced regenerative left shift, increased heterophil count, and a moderate monocytosis; the lymphopenia was resolved. A mild hypoalbuminemia still persisted. Ten months after presentation, the bird was reported to be doing well with no changes in function of the right foot and subsequently released from captivity.

Safety of Tepotinib in Patients With MET Exon 14 Skipping NSCLC and Recommendations for Management.

INTRODUCTION: The MET inhibitor tepotinib demonstrated durable clinical activity in patients with advanced MET exon 14 (METex14) skipping NSCLC. We report detailed analyses of adverse events of clinical interest (AECIs) in VISION, including edema, a class effect of MET inhibitors. PATIENTS AND METHODS: Incidence, management, and time to first onset/resolution were analyzed for all-cause AECIs, according to composite categories (edema, hypoalbuminemia, creatinine increase, and ALT/AST increase) or individual preferred terms (pleural effusion, nausea, diarrhea, and vomiting), for patients with METex14 skipping NSCLC in the phase II VISION trial. RESULTS: Of 255 patients analyzed (median age: 72 years), edema, the most common AECI, was reported in 69.8% (grade 3, 9.4%; grade 4, 0%). Median time to first edema onset was 7.9 weeks (range: 0.1-58.3). Edema was manageable with supportive measures, dose reduction (18.8%), and/or treatment interruption (23.1%), and rarely prompted discontinuation (4.3%). Other AECIs were also manageable and predominantly mild/moderate: hypoalbuminemia, 23.9% (grade 3, 5.5%); pleural effusion, 13.3% (grade ≥ 3, 5.1%); creatinine increase, 25.9% (grade 3, 0.4%); nausea, 26.7% (grade 3, 0.8%), diarrhea, 26.3% (grade 3, 0.4%), vomiting 12.9% (grade 3, 1.2%), and ALT/AST increase, 12.2% (grade ≥ 3, 3.1%). GI AEs typically occurred early and resolved in the first weeks. CONCLUSION: Tepotinib was well tolerated in the largest trial of a MET inhibitor in METex14 skipping NSCLC. The most frequent AEs were largely mild/moderate and manageable with supportive measures and/or dose reduction/interruption, and caused few withdrawals in this elderly population.

Prognostic model in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitors after platinum failure.

Immune checkpoint inhibitors (ICIs) have become a standard treatment for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy. However, the prognostic factors for patients with mUC receiving ICIs are not well established. We retrospectively collected clinical and laboratory data and reviewed the survival outcomes of patients with mUC who were treated with ICIs after platinum-based chemotherapy. We used univariate and multivariable Cox proportional hazard models to identify independent prognostic factors, and the concordance index (C-index) to evaluate the performance of the new prognostic model. In addition, bootstrap analysis was employed for internal validation of the prognostic model. A total of 224 patients were included in the study. With a median follow-up of 10.5 months (interquartile range, 5.1-17.4 months), median overall survival (OS) was 13.6 months (95% confidence interval [CI], 9.7-17.3 months). In multivariable analysis, independent prognostic factors predicting adverse OS were the presence of liver metastasis (LM), hypoalbuminemia, and neutrophil-lymphocyte ratio (NLR) >5. When patients were categorized into 3 risk groups, median OS was not reached (NR) (95% CI, 17.3-NR), 9.5 months (6.8-NR), and 2.9 months (2.3-4.4) for patients with a score of 0, 1, and 2+, respectively. The C-index for the new model was 0.763 (95% CI, 0.739-0.787). A novel prognostic model, including LM, hypoalbuminemia, and NLR, was developed and validated to estimate OS in patients with platinum-refractory disease on second- or subsequent-line ICI therapy. Further investigations, including prospective validation, are needed.

Circulating Serum MiRNA-8074 as a Novel Prognostic Biomarker for Multiple Myeloma.

MiRNA-8074 is a molecule with the potential to regulate the expression of key genes related to the pathogenesis of multiple myeloma (MM), i.e., TP53, MYC, MAPK1, and KIAA. We analyzed the predictive and prognostic value of miRNA-8074 expression in MM patients. In total, 105 newly diagnosed MM patients treated with thalidomide (n = 27), bortezomib (n = 41) and bortezomib with thalidomide (n = 37) were studied. For miRNA analysis, the column method and the Real-Time PCR technique with specific TaqMan Fast Advanced Master Mix and TaqMan probes were used. Factors that were associated with a significant reduction in progression-free survival (PFS) included: ECOG > 1, ISS stage III, low hemoglobin, thrombocytopenia, hypoalbuminemia, abnormal renal function, elevated creatinine, GFR < 60 mL/min/1.73 m2, elevated LDH, del(17p), t(11;14), the use of a single drug regimen (thalidomide or bortezomib) and high miRNA-8074 expression (HR = 2.01, 95% CI: 1.16-3.49; p = 0.0233). In addition to the known prognostic factors, such as ECOG > 1, Durie-Salmon stage III, diagnosis of light chain disease or non-secreting MM, renal failure, hypoalbuminemia, hypercalcemia, high ß2-microglobulin, elevated LDH, and t(14;16), a high expression of miRNA-8074 was significantly associated with a higher risk of death (HR = 4.12, 95% CI: 2.20-7.70; p = 0.0009). In summary, miRNA-8074 may be a useful diagnostic tool to assess the prognosis in MM patients.

Riesgo de infección en pacientes oncológicos colonizados por bacterias productoras de p-lactamasas de espectro extendido y enterobacterias productoras de carbapenemasas / Risk of infection in cancer patients colonized by extended expectrum p-lactamases and carbapenem producing Enterobacteriaceae

INTRODUCCIÓN: La prevalencia de microorganismos multirresistentes es un problema de salud pública que continúa creciendo a lo largo del mundo. Existe una población principalmente susceptible de ser colonizada y posteriormente infectarse, son los pacientes oncológicos. OBJETIVO: Identificar las características clínicas y patológicas de los pacientes oncológicos y su relación con la infección con microorganismos productores de BLEE y EPC. PACIENTES Y MÉTODOS: Se condujo un estudio retrospectivo y de carácter analítico entre el primero de enero de 2019 y el 30 de junio de 2020 en tres unidades hemato-oncológicas. RESULTADOS: Incluyó a 3.315 pacientes, de los cuales 217 (6,5%) se encontraban colonizados por microorganismos productores de BLEE y EPC; de éstos, 106/217 (48,8%) presentaron al menos un episodio de infección. El microorganismo más frecuentemente aislado fue Klebsiella pneumoniae, en 29/106 (27,4%). De los infectados, 18/106 (17%) presentaron infección por el mismo microorganismo colonizador. La mucositis (p = 0,002), edad mayor a 65 años (p = 0,041), hipoalbuminemia (p < 0,01), neutropenia (p < 0,01) y la presencia dispositivos invasivos (p < 0,01) demostraron una relación con el desarrollo de infección. CONCLUSIÓN: La presencia de hipoalbuminemia (OR 3,3, IC 1,5-7,1, p < 0,01), dispositivos invasivos (OR 5,8, IC 3.0-11,4, p < 0,01) y neutropenia (OR 4,1, IC 1,5-11,4, p < 0,01) predicen el desarrollo de infecciones.

BACKGROUND: The prevalence of multi-resistant microorganisms is a public health problem that continues to grow globally. There is a population that is mainly susceptible to being colonized and subsequently infected, and these are cancer patients. AIM: To identify the clinical and pathological characteristics of cancer patients and their relationship with infection with ESBL and CPE producing microorganisms. METHODS: A retrospective and analytical study was conducted between January 1, 2019 and June 30, 2020 in three hematooncological units. RESULTS: We included 3315 patients of which 217 (6.5%) were colonized by microorganisms producing ESBL and CPE. Of these, 106/217 (48.8%) had at least one episode of infection. The most frequently isolated microorganism was Klebsiella pneumoniae 29/106 (27.4%). Of those infected, 18/106 (17%) presented infection by the same colonizing microorganism. Mucositis (p = 0.002), age over 65 years (p = 0.041), hypoalbuminemia (p < 0.01), neutropenia (p < 0.01) and the presence of invasive devices (p < 0.01) demonstrated a relationship with development of infection. The presence of hypoalbuminemia (OR 3.3, CI 1.5-7.1, P < 0.01), invasive devices (OR 5.8, CI 3.0-11.4, p < 0.01) and neutropenia (OR 4.1, CI 1.5-11.4, p < 0.01) predict the development of infections.

Hypothesis of using albumin to improve drug efficacy in cancers accompanied by hypoalbuminemia.

A common problem in many cancers is the resistance of some patients to common drugs or relapse. Hypoalbuminemia has been reported in some of resistant cancer patients.This article evaluates the usefulness of albumin in the treatment of drug-resistant cancers with hypoalbuminemia based on available evidences.Rapid metabolism and drug excretion from the body is one of the causes of drug resistance. Albumin is the major plasma protein to which almost all drugs are bound. There is some evidence that increasing drug binding to albumin has beneficial effects on drug efficacy in some cancers and cancer cells. On the other hand, some reports have shown that cancer cells can use albumin as the energy and amino acid source.We have hypothesized that in this particular group of cancers, adding albumin to a treatment regimen could have a beneficial effect on drug efficacy and dosage. In fact, excess albumin can prevent rapid metabolism of drug by increasing the fraction of albumin-bound drug, and can increase drug delivery to cancer cells due to the absorption of drug-albumin complex by cancer cells.

Population Pharmacokinetic Analysis and Dosing Optimization Based on Unbound Daptomycin Concentration and Cystatin C in Nonobese Elderly Patients with Hypoalbuminemia and Chronic Kidney Disease.

PURPOSE: This study evaluated the population pharmacokinetics of daptomycin in nonobese elderly patients with hypoalbuminemia and chronic kidney disease (CKD) using the glomerular filtration rate estimated from cystatin C (eGFRcys) and estimated its optimal dose. METHODS: We performed population pharmacokinetic analysis of the unbound concentrations of daptomycin. The probability of target attainment of 90% for achieving an area under the concentration-time curve of unbound daptomycin at steady state/ minimum inhibitory concentration ratio of ≥66.6 was stochastically simulated. RESULTS: In the population pharmacokinetic analysis of 25 patients aged ≥65 years, the two-compartment model using eGFRcys and age as covariates of clearance in central compartment of unbound daptomycin were optimal. The unbound fraction rate (fu) was 0.05-0.14. According to the Monte Carlo simulation, the optimal doses for patients with eGFRcys of 20-60 mL/min and aged 65-95 years were calculated as 200-500 mg q24h. CONCLUSION: These results suggest that establishing the dose using total concentrations may result in under- or overestimation caused by alterations in fu. The optimal dose for nonobese elderly patients with hypoalbuminemia and CKD depends on eGFRcys and age, and a standard dose may be insufficient for some patients.

Impact of hypoalbuminemia on the prognosis of relapsed/refractory B-cell lymphoma treated with axicabtagene ciloleucel.

INTRODUCTION: Hypoalbuminemia is a known adverse prognostic factor in lymphomas. Yet, it is unknown if axicabtagene ciloleucel (axi-cel) overcomes the adverse prognostic impact of hypoalbuminemia in relapsed/refractory large B-cell lymphoma. METHODS: We conducted a retrospective analysis across three Mayo Clinic centers to assess the relationship of hypoalbuminemia (defined as a serum albumin (SA) levels ≤ 3.5 g/dL) on outcomes of patients treated with axi-cel. RESULTS: This analysis included 81 patients. Two patients had no available SA levels preceding axi-cel infusion. Eighteen patients (22.8%) had hypoalbuminemia with a median SA of 3.3 g/dL. Patients with normal SA had a statistically higher ORR than those without hypoalbuminemia (P = .018). There was no difference in 1-year PFS and OS between the group with hypoalbuminemia and the group with normal SA levels (48% vs 49%, P = .81) and (74% vs 73%, P = .97), respectively. There was no difference in the severity or median duration of cytokine release syndrome or neurotoxicity between the two groups. CONCLUSION: Notwithstanding the limitations related to the relatively small sample size, axi-cel therapy appears to overcome the adverse effect of hypoalbuminemia on OS and PFS. Large multicenter clinical studies are certainly needed to validate these findings.

A randomized trial of albumin infusion to prevent intradialytic hypotension in hospitalized hypoalbuminemic patients.

BACKGROUND: Intradialytic hypotension (IDH) is a frequent complication of intermittent hemodialysis (IHD), occurring from 15 to 50% of ambulatory sessions, and is more frequent among hospitalized patients with hypoalbuminemia. IDH limits adequate fluid removal and increases the risk for vascular access thrombosis, early hemodialysis (HD) termination, and mortality. Albumin infusion before and during therapy has been used for treating IDH with the varying results. We evaluated the efficacy of albumin infusion in preventing IDH during IHD in hypoalbuminemic inpatients. METHODS: A randomized, crossover trial was performed in 65 AKI or ESKD patients with hypoalbuminemia (albumin < 3 g/dl) who required HD during hospitalization. Patients were randomized to receive 100 ml of either 0.9%sodium chloride or 25% albumin intravenously at the initiation of each dialysis. These two solutions were alternated for up to six sessions. Patients' vital signs and ultrafiltration removal rate were recorded every 15 to 30 min during dialysis. IDH was assessed by different definitions reported in the literature. All symptoms associated with a noted hypotensive event as well as interventions during the dialysis were recorded. RESULTS: Sixty-five patients were submitted to 249 sessions; the mean age was 58 ([Formula: see text] 12), and 46 (70%) were male with a mean weight of 76 ([Formula: see text] 18) kg. The presence of IDH was lower during albumin sessions based on all definitions. The hypotension risk was significantly decreased based on the Kidney Disease Outcomes Quality Initiative definition; (15% with NS vs. 7% with albumin, p = 0.002). The lowest intradialytic SBP was significantly worse in patients who received 0.9% sodium chloride than albumin (NS 83 vs. albumin 90 mmHg, p = 0.035). Overall ultrafiltration rate was significantly higher in the albumin therapies [NS - 8.25 ml/kg/h (- 11.18 5.80) vs. 8.27 ml/kg/h (- 12.22 to 5.53) with albumin, p = 0.011]. CONCLUSION: In hypoalbuminemic patients who need HD, albumin administration before the dialysis results in fewer episodes of hypotension and improves fluid removal. Albumin infusion may be of benefit to improve the safety of HD and achievement of fluid balance in these high-risk patients. ClinicalTrials.gov Identifier: NCT04522635.

Janus Kinase Inhibitors Ameliorated Gastrointestinal Amyloidosis and Hypoalbuminemia in Persistent Dermatitis Mouse Model.

Malnutrition is not only regarded as a complication of rheumatoid arthritis and inflammatory bowel disease but also that of inflammatory skin disease; however, the mechanisms and efficacy of its treatment have not been elucidated. Using a mouse model of dermatitis, we investigated the pathophysiology of malnutrition in inflammatory skin conditions and efficacy of its treatment. We employed spontaneous skin inflammation mice models overexpressing human caspase-1 in the epidermal keratinocytes. Body weight, nutrition level, and α1-antitrypsin fecal concentration were measured. The gastrointestinal tract was histologically and functionally investigated. Fluorescein isothiocyanate (FITC)-dextran was forcibly fed on an empty stomach, and plasma FITC-dextran was measured. The treatment efficacy of antibodies against tumor necrosis factor-α (TNF-α) and interleukin (IL)-α/ß as well as Janus kinase (JAK) inhibitors was investigated. Compared with wild-type littermates, the inflammatory skin mice models showed a lowered body weight, reduction of serum albumin level, amyloid deposition in the stomach, small intestine, and large intestine, and increased α1-antitrypsin fecal concentration. However, the plasma FITC-dextran was unchanged between the dermatitis models and wild-type littermates. The over-produced serum amyloid A1 in the liver was detected in the plasma in the dermatitis model. Antibodies against TNF-α and IL-α/ß showed partial effects on amyloid deposition; however, JAK inhibitors improved gastrointestinal amyloidosis with the improvement of skin symptoms. Chronic dermatitis is closely related to secondary amyloidosis in the gastrointestinal tract, resulting in hypoalbuminemia. Therefore, active control of skin inflammation is essential for preventing gastrointestinal complications.

Tolerability of Highly Protein Bound Targeted Oral Oncolytic Drugs in Patients With Hypoalbuminemia: A Retrospective Analysis.

BACKGROUND: Hypoalbuminemia is commonly observed in cancer patients. Given the pharmacokinetic interactions between serum proteins and protein bound medications, administration of highly protein bound targeted oral oncolytic drugs may result in elevated unbound drug levels and decreased tolerability in those with hypoalbuminemia. OBJECTIVE: To describe the impact of hypoalbuminemia on oral oncolytic drug tolerability. METHODS: A retrospective study was conducted of adult patients receiving treatment with targeted oral oncolytic drugs with ≥95% protein binding. The primary end point of this study was to compare time to discontinuation resulting from documented toxicity in those with and without hypoalbuminemia. RESULTS: The study included 143 patients receiving 16 targeted oral oncolytic drugs (42% with hypoalbuminemia, 58% without hypoalbuminemia). Adverse events were common, with similar incidence among patients with and without hypoalbuminemia (73% vs 76%, respectively; P = 0.727). Median time to therapy discontinuation resulting from documented toxicity was significantly shorter in those with hypoalbuminemia (22 months vs not reached; P = 0.003). Cox regression demonstrated that hypoalbuminemia was the only significant risk factor for shorter time to discontinuation resulting from documented adverse effects (hazard ratio = 3.0; 95% CI = 1.15-8.0; P = 0.025). CONCLUSION AND RELEVANCE: This represents the first report of the impact of hypoalbuminemia on tolerability of highly protein bound oral oncolytic drugs, demonstrating that patients with hypoalbuminemia may be at increased risk for early discontinuation resulting from toxicity. Given the importance of maintaining dose intensity in patients receiving oncolytic therapy, albumin levels should be monitored throughout treatment and supportive care maximized in those developing hypoalbuminemia.

Cronkhite-Canada syndrome: report of a rare case and review of the literature.

Cronkhite-Canada syndrome is rarely encountered in clinical practice. Notably, most patients with Cronkhite-Canada syndrome exhibit hypoalbuminemia. Because the cause of Cronkhite-Canada syndrome is unknown, no specific treatment method has been established. Here, we describe a 59-year-old woman with Cronkhite-Canada syndrome in whom clinical manifestations were considerably relieved after treatment with prednisone.

Impact of serum albumin levels on the body fluid response to tolvaptan in chronic kidney disease patients.

PURPOSE: Tolvaptan exerts an aquaretic effect by blocking vasopressin V2 receptor. Although tolvaptan ameliorates body fluid retention even in patients with chronic kidney disease (CKD), predictors of body fluid reduction induced by tolvaptan remain unclear. We, therefore, examined the clinical parameters associated with the effect of tolvaptan on fluid volume in CKD patients. METHODS: Twelve CKD patients (stage 3-5) with fluid retention were treated with tolvaptan in addition to conventional diuretic treatment. Patients were divided into low and high responders by the median change in total body water (TBW) for 1 week measured by a bioimpedance analysis (BIA) device, and clinical parameters were compared between the groups. RESULTS: The body weight significantly decreased by 2.0 ± 2.3 kg (p = 0.005), but the estimated glomerular filtration rate (eGFR) was not significantly changed (16.9 ± 11.9 vs. 17.4 ± 12.4 mL/min/1.73 m2, p = 0.139) after 1 week. The BIA showed that the intracellular water (ICW) decreased by 6.0% ± 4.7% (p < 0.001), the extracellular water (ECW) decreased by 6.7% ± 5.4% (p = 0.001), and the TBW decreased by 6.3% ± 4.9% (median value - 6.02%, p < 0.001). The serum albumin level in the high responders was significantly lower than in the low responders (2.3 ± 0.5 vs. 3.3 ± 0.8 g/dL, p = 0.013). Significant partial correlations adjusted for the eGFR were observed between the baseline serum albumin level and changes in the ICW (r = 0.440, p = 0.048), ECW (r = 0.593, p = 0.009) and TBW (r = 0.520, p = 0.020). CONCLUSIONS: Serum albumin levels predict the body fluid response to tolvaptan in CKD patients. Tolvaptan may be a promising therapeutic option for ameliorating body fluid retention, especially in patients with hypoalbuminemia.

Collagenous gastritis: An unusual cause of generalized oedema in a child.

Collagenous gastritis is an uncommon gastrointestinal disease in children. Its cause remains uncertain. It may present as severe hypoproteinaemia manifesting as generalized oedema. We report a 15 months old female who presented with pica, generalized body oedema and diarrhoea. Diagnostic workup revealed gastric replacement of the lamina propria by hyalinized collagen on histology. This case seeks to highlight the need for early paediatric gastroenterology referral including oesophagogastroduodenoscopy with multiple tissue biopsies as part of a broad diagnostic workup in children with non-specific gastrointestinal symptoms to improve diagnostic yield and enable accurate histologic diagnosis, so that appropriate therapy can be timeously applied.

A rapid ultra-performance LC-MS/MS assay for determination of serum unbound fraction of voriconazole in cancer patients.

BACKGROUND: Voriconazole (VOR), an antifungal agent, is clinically monitored to guide therapeutic dosing and avoid toxicity. It is believed that measurement of serum unbound VOR provides more accurate information, especially in hypoalbuminemia patients. We developed and validated an accurate, simple and fast test with ultrafiltration and ultra-performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS) to measure unbound VOR in human serum. METHODS: The Agilent UPLC system coupled with a SCIEX QTRAP4000 MS with a positive ionization mode was developed and validated for VOR analysis. RESULTS: A good linearity was demonstrated from 0.02 to 2.5 µg/ml for unbound VOR (r2 = 0.9969). The within-run and between-run accuracy and precision was <5% and < 6%. The levels of total VOR were well correlated with reference laboratory results. Serum unbound VOR levels were correlated with the total VOR levels (r = 0.78, p < 0.0001). There was a reverse correlation between unbound VOR fractions and plasma albumin levels (p < 0.05). In hypoalbuminemia patients, the unbound VOR levels were increased to a higher degree than total VOR. CONCLUSION: This assay is suitable for monitoring both unbound and bound VOR in cancer patients especially in those with hypoalbuminemia in clinical laboratories. Measurement of unbound VOR offers a better approach in prediction of VOR toxicity.

New Insights About Albumin and Liver Disease.

Decompensated liver cirrhosis has a dismal prognosis, with an overall survival of 2-4 years, which is worse than for many oncological diseases. Albumin is an important tool in the management of patients with cirrhosis, since it decreases for less than half the risk for post-paracentesis cardiocirculatory dysfunction and mortality associated with spontaneous bacterial infection, as well as, it triplicates the response to terlipressin in patients with hepatorenal syndrome. Recently, research on albumin has been a hot topic, with important new insights such as the characterization of the pleiotropic effects of albumin (which surpass its oncotic properties) and the concept of effective albumin concentration. In fact, patients with liver cirrhosis present posttranslational modifications on albumin that compromises its function. Those modified albumin forms were proved to have prognostic value and its knowledge may change the paradigm of albumin treatment. In this review, we critically summarize the latest evidence on the potential benefits of albumin in patients with end-stage liver disease.