Evaluation of the cachexia index using a bioelectrical impedance analysis in elderly patients with non-Hodgkin's lymphoma: A single-center prospective study.

Cancer cachexia is a disorder that affects patient outcomes. The present study prospectively evaluated the prognostic value of the cachexia index (CXI) in elderly patients with non-Hodgkin's lymphoma (NHL). We prospectively analyzed 51 elderly patients who were diagnosed with NHL at our institution. CXI was calculated as follows: CXI = SMI × Alb/NLR (SMI: skeletal muscle index, Alb: serum albumin, NLR: neutrophil-to-lymphocyte ratio). SMI was measured by a bioelectrical impedance analysis (BIA) using the InBody 720. We determined the sex-specific cutoff values of the CXI by a receiver operating characteristic curve analysis and divided all patients into low- and high-CXI groups. The median age at the diagnosis was 78 years (60-93 years), and 28 (55%) were male. The histologic subtypes were B-cell lymphoma in 49 patients and T-cell lymphoma in 2. Twenty-eight (55%) patients were categorized into the high-CXI group, and 23 (45%) were categorized into the low-CXI group. The overall survival (OS) in the low-CXI group was significantly shorter than that in the high-CXI group (3-year OS, 70.4% vs. 95.7%, p = 0.007). Among 23 patients with DLBCL, patients with low-CXI had shorter OS than those with high-CXI (3-year OS, 55.6% vs. 92.9%, p = 0.008). On the other hand, sarcopenia had less impact on the clinical outcome of DLBCL patients. Low-CXI was associated with poor outcomes in elderly NHL and the CXI may be a clinical useful index for predicting prognosis. Further large prospective studies are needed to verify this conclusion.

The prognostic value of the Fibrinogen-Albumin Ratio Index in patients with myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes treated with azacitidine.

Inflammation is a major hallmark of several cancers. The present study evaluated the prognostic value of the Fibrinogen-Albumin Ratio Index (FARI) at the diagnosis in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) treated with azacitidine (AZA). A retrospective study was conducted in a single cohort of 99 patients with de novo MDS and AML-MRC who were treated with AZA between May 2011 and June 2019 in our hospital. Plasma fibrinogen and serum albumin levels were measured before the start of AZA treatment. A total of 99 patients were included in the analysis. The optimal cut-off value of FARI for predicting the 1-year overall survival (OS) was determined by a receiver operating characteristic (ROC) analysis to be 0.079. A total of 59 (60%) and 40 (40%) patients had an FARI ≥0.079 (high-FARI group) and < 0.079 (low-FARI group), respectively. The high-FARI patients had a significantly shorter OS than low-FARI patients (1-year OS, 35.6% vs. 77.5%, p < 0.001). In a multivariate analysis, parameters with independent adverse significance for the OS were a high FARI (≥0.079) (hazard ratio (HR) 2.41, 95% confidence interval (CI), 1.36-4.29; p = 0.006), and Revised-International Prognostic Scoring System (IPSS-R) very high (HR 1.483, 95% CI, 1.12-1.963, p = 0.006). A high FARI was found to be associated with a poor outcome in MDS and AML-MRC patients treated with AZA, and FARI was an independent prognostic factor for the OS in these patients. Further internal and external validations are needed to clarify the prognostic role of the FARI for MDS and AML-MRC patients.

Intravenous itraconazole compared with liposomal amphotericin B as empirical antifungal therapy in patients with neutropaenia and persistent fever.

BACKGROUND: Fungal infections are a major complication of neutropaenia following chemotherapy. Their early diagnosis is difficult, and empirical antifungal treatment is widely used, and uses of less toxic drugs that reduce breakthrough infection are required. OBJECTIVE: We conducted a multicentre, open-label, randomised, non-inferiority trial to compare the safety and efficacy of intravenous itraconazole (ivITCZ) and liposomal amphotericin B (LAmB) as empirical antifungal therapy in patients with haematological malignancies with neutropaenia and persistent fever. METHODS: Patients with haematological malignancies who developed fever refractory to broad-spectrum antibacterial agents under neutropaenia conditions were enrolled. Patients were randomised for treatment with LAmB (3.0 mg/kg/d) or ivITCZ (induction: 400 mg/d, maintenance: 200 mg/d). RESULTS: Observed overall favourable response rates of 17/52 (32.7%) and 18/50 (36.0%) in the LAmB and ivITCZ groups, with a model-based estimate of a 4% difference (90% CI, -12% to 20%), did not fulfil the statistical non-inferiority criterion. In the LAmB group, there were two cases of breakthrough infection and five cases of probable invasive fungal disease, whereas in the itraconazole group, neither breakthrough infection nor probable invasive fungal disease occurred. Patients in the ivITCZ group had significantly fewer grade 3-4 hypokalaemia-related events than LAmB group patients (P < .01). The overall incidence of adverse events tended to be lower in the ivITCZ group (P = .07). CONCLUSION: ivITCZ showed similar efficacy and safety as LAmB as empirical antifungal therapy in haematological malignancy patients with febrile neutropaenia, although the small sample size and various limitations prevented demonstration of its non-inferiority.

The prognostic value of the controlling nutritional status score in patients with multiple myeloma.

The Controlling Nutritional Status (CONUT) score predicts the prognosis in several tumors. However, its prognostic significance in multiple myeloma (MM) remains unclear. The present study investigated the correlation between the CONUT score and the survival outcomes of MM patients. A total of 178 patients newly diagnosed with MM were retrospectively enrolled. Patients with a high CONUT score (≥5) had a significantly shorter median overall survival (OS) than those with a low CONUT score (≤4) (33 vs. 57 months, p < .001). In a multivariate analysis among patients with International Staging System (ISS) score of ≤2, a high CONUT score was an independent prognostic covariate for the OS after adjusting for other significant factors (hazard ratio 2.364; 95% confidence interval 1.324-4.220, p = .004). Our results suggest that the CONUT score is a predictor of a poor outcome in patients with MM, particularly in low-ISS-score cases.

Aspergillus meningitis in a patient with chronic lymphocytic leukemia.

Central nervous system aspergillosis is relatively rare and difficult to diagnose. Here, we report a case of 90-year-old man with chronic lymphocytic leukemia who presented with a month-long gradually worsening headache followed by 3 days of low-grade fever associated with altered mental status. Aspergillus meningitis diagnosed using Aspergillus galactomannan antigen in the cerebrospinal fluid and treated with voriconazole. Delayed diagnosis and treatment of Aspergillus meningitis is typically associated with high mortality; therefore, it is imperative to include this disease in the differential diagnoses of subacute meningitis.

Prognostic Impact of ABO Blood Group on Survival in Patients With Malignant Lymphoma.

BACKGROUND: The ABO blood group is reported to be associated with survival for several types of malignancy. We conducted a retrospective study to evaluate the prognostic significance of the ABO blood group in patients with malignant lymphoma. PATIENTS AND METHODS: A total of 523 patients with malignant lymphoma were included in this study. The primary outcome measured was the association between the ABO blood group and survival. RESULTS: Patients with blood group B had shorter 5-year overall survival (OS) than patients with non-B blood groups (40.9% vs. 57.3%; P < .01). Among 240 patients with diffuse large B-cell lymphoma (DLBCL), patients with blood group B had shorter 5-year OS in comparison with patients with non-B blood groups (36.3% vs. 56.9%; P < .01). Among male patients with DLBCL, those with blood group B had significantly shorter 5-year OS than those with non-B blood groups (27.5% vs. 55.8%; P = .003). On the other hand, there was no significant difference in the survival between female patients with blood group B and those with non-B blood groups (5-year OS: 49.2% vs. 58.2%; P = .67). A multivariate analysis demonstrated that blood group B (hazard ratio, 1.83; 95% confidence interval, 1.21-2.78; P = .04) was an independent predictor of shorter OS in male patients with DLBCL. CONCLUSION: The ABO blood group is associated with survival in patients with lymphoma. Interestingly, only male patients with DLBCL with blood group B had significantly shorter OS than those male patients with DLBCL with non-B blood groups.

Calculus pyelonephritis associated with ureterocutaneostomy.

A 79-year-old woman with a history of total hysterectomy for cervical cancer with ureterocutaneostomy presented with high fever. She had tenderness and a hard lump around the ureterocutaneostomy site. Computed tomography scan revealed 1.5 cm ureteral calculus in ureterocutaneous fistula (Fig. 1A) associated with bilateral hydronephrosis (Fig. 1B) and we performed a transureteral stent insertion. Blood culture grew methicillin-sensitive Staphylococcus aureus (MSSA), Haemophilus parainfluenzae, Veillonella species and Bacteroides fragilis and urine culture revealed Escherichia coli, MSSA, and Enterococcus faecalis. The patient's clinical signs and symptoms gradually improved with ampicillin/sulbactam. Patients with urinary diversions including ureterocutaneostomy and iliac conduits are at increased risk of urolithiasis (1), which can cause sepsis, pyelonephritis, and renal insufficiency (2). Since most patients become colonized with a multitude of bacteria including Enterobacteriaceae and skin flora such as Staphylococcus aureus and Streptococcus spp., we should empirically treat with broad-spectrum antimicrobials until the culture results are available. Early diagnosis and urological intervention are required because it can be life-threatening with delayed treatment.

[Acute myeloid leukemia with sudden onset bilateral lower extremity paralysis caused by disseminated mucormycosis following unrelated bone marrow transplantation].

A 63-year-old woman was admitted to our hospital with relapsed acute myeloid leukemia. On day10 after reinduction therapy, she became febrile. Computed tomography on day15 revealed right upper lobe consolidation. Because the ß-D glucan and Aspergillus galactomannan antigen tests were negative, we considered pulmonary mucormycosis as a breakthrough infection under voriconazole administration. Liposomal amphotericin B was initiated, and the patient underwent unrelated bone marrow transplantation although not in complete remission. She developed right shoulder pain on day1, and her pneumonia worsened on day3. She reported right lower extremity paralysis on day15, and developed bilateral lower extremity motor and sensory paralysis the next day. T2-enhanced magnetic resonance imaging revealed hyperdense lesions in the spinal cord at Th11. Transverse myelitis was diagnosed, and she underwent antiviral therapy. After engraftment, she died of pneumonia on day24. Postmortem examination revealed disseminated mucormycosis involving the lungs, liver, diaphragm, blood vessels, and dura matter of the spinal cord; it also revealed that the sudden bilateral lower extremity paralysis was caused by disseminated mucormycosis. This case stresses the possibility of mucormycosis, particularly in prolonged neutropenic patients with pain, fever, and focal neurological findings.

Possible relationship between organizing pneumonia and chronic pulmonary aspergillosis: A case report and literature review.

Organizing pneumonia (OP) is a nonspecific response to various forms of lung injury and has been reported in association with several infectious agents. However, little is known about the relationship between OP and chronic pulmonary aspergillosis, and the mechanism of this linkage has not been elucidated. Here, we present a case of chronic pulmonary aspergillosis that led to the development of OP, which was successfully treated with corticosteroid and surgical intervention. In a review of the literature, we aim to highlight the possible relationship between OP and chronic pulmonary aspergillosis.

Multiple granulomatous lung lesions in a patient with Epstein-Barr-virus-induced mononucleosis and new-onset systemic lupus erythematosus: a case report.

INTRODUCTION: Granulomatous lesions are commonly encountered abnormalities in pulmonary pathology, and often pose a diagnostic challenge. We report an unusual case of granulomatous lung disease with uncommon characteristics, which developed following Epstein-Barr-virus-induced mononucleosis and new-onset systemic lupus erythematosus. We aim to highlight a diagnostic approach for the condition and to raise awareness of the possibility of it being related to the immunological reaction caused by Epstein-Barr virus infection. CASE PRESENTATION: A 36-year-old Japanese man, who had been diagnosed with Epstein-Barr-virus-induced infectious mononucleosis, new-onset systemic lupus erythematosus, and secondary Sjögren's syndrome three weeks previously, presented to our facility with fever and diffuse pulmonary infiltrates. A computed tomography scan of the chest revealed multiple small nodules in both lungs. Fiberoptic bronchoscopy with bronchoalveolar lavage revealed lymphocytosis with predominance of T lymphocytes. A histological examination of a lung biopsy taken during video-assisted thoracic surgery showed randomly distributed tiny granulomatous lesions with infiltration of eosinophils. The differential diagnoses included hypersensitivity pneumonitis, sarcoidosis, and pulmonary involvement of Crohn's disease, systemic lupus erythematosus, and Sjögren's syndrome, but the clinical and pathological findings were not consistent with any of these. Our patient's condition did not improve; therefore, prednisolone therapy was started because of the possibility of specific immunological reactions associated with Epstein-Barr virus infection. After steroid treatment, our patient showed radiological and clinical improvement. CONCLUSIONS: To the best of our knowledge, this is the first case of a patient developing randomly distributed multiple granulomatous lung lesions with eosinophilic infiltrates after Epstein-Barr virus infection and systemic lupus erythematosus. On the basis of our data, we hypothesize that Epstein-Barr virus infection altered the immune response of our predisposed patient and contributed to the pathogenesis of the lung lesions. Our patient's clinical response to steroid treatment was excellent.

Association between breast cancer risk and the wild-type allele of human ABC transporter ABCC11.

BACKGROUND: International mortality and frequency rates for breast cancer have been associated with the wet type of human earwax. It was recently found that earwax type is determined by a single nucleotide polymorphism (SNP), 538G>A (Gly180Arg), in ABCC11. The G allele determines the wet type of earwax as a Mendelian trait with a dominant phenotype. The present study examined the association between the frequency rate of breast cancer and the frequency of the G allele of ABCC11. PATIENTS AND METHODS: Using blood samples from patients with invasive breast cancer (n = 270) and control volunteers (n = 273), the 538G>A SNP in ABCC11 was genotyped using the SmartAmp method. RESULTS: The frequency of the G allele in breast cancer patients was higher than that in healthy controls. The odds ratio for the genotypes (G/G+G/A) to develop breast cancer was estimated to be 1.63 (p-value = 0.026), suggesting that the G allele in ABCC11 is associated with breast cancer risk. CONCLUSION: This study showed that Japanese women with wet earwax have a higher relative risk of developing breast cancer than those with dry earwax. The ABCC11 SNPs that determine these phenotypes should be further investigated in order to obtain insights into the mechanisms by which breast cancer develops and progresses.

Emerging new technologies in Pharmacogenomics: rapid SNP detection, molecular dynamic simulation, and QSAR analysis methods to validate clinically important genetic variants of human ABC Transporter ABCB1 (P-gp/MDR1).

Pharmacogenomics, the study of the influence of genetic factors on drug action, is increasingly important for predicting pharmacokinetics profiles and/or adverse reactions to drugs. Drug transporters as well as drug-metabolism play pivotal roles in determining the pharmacokinetic profiles of drugs and, by extension, their overall pharmacological effects. There are an increasing number of reports addressing genetic polymorphisms of drug transporters. A key requirement for the development of individualized medicine or personalized therapy is the ability to rapidly and conveniently test patients for genetic polymorphisms and/or mutations. We have recently developed a rapid and cost-effective method for single nucleotide polymorphism (SNP) detection, named Smart Amplification Process 2 (SmartAmp2), which enables us to detect genetic polymorphisms or mutations in 30 to 45min under isothermal conditions without DNA isolation and PCR amplification. Furthermore, high-speed functional screening, quantitative structure-activity relationship (QSAR) analysis, and molecular dynamic (MD) simulation methods have been developed to study the substrate specificity of ABC transporters and to evaluate the effect of genetic polymorphisms on their function and substrate specificity. These methods would provide powerful and practical tools for screening synthetic and natural compounds, and the deduced data can be applied to the molecular design of new drugs. This review addresses such new methods for validating genetic polymorphisms of human ABC transporter ABCB1 (P-gp/MDR1) which is critically involved in the pharmacokinetics of drugs.

Earwax, osmidrosis, and breast cancer: why does one SNP (538G>A) in the human ABC transporter ABCC11 gene determine earwax type?

One single-nucleotide polymorphism (SNP), 538G>A (Gly180Arg), in the ABCC11 gene determines the type of earwax. The G/G and G/A genotypes correspond to the wet type of earwax, whereas A/A corresponds to the dry type. Wide ethnic differences exist in the frequencies of those alleles, reflecting global migratory waves of the ancestors of humankind. We herein provide the evidence that this genetic polymorphism has an effect on the N-linked glycosylation of ABCC11, intracellular sorting, and proteasomal degradation of the variant protein. Immunohistochemical studies with cerumen gland-containing tissue specimens revealed that the ABCC11 WT protein was localized in intracellular granules and large vacuoles, as well as at the luminal membrane of secretory cells in the cerumen gland, whereas granular or vacuolar localization was not detected for the SNP (Arg180) variant. This SNP variant lacking N-linked glycosylation is recognized as a misfolded protein in the endoplasmic reticulum and readily undergoes ubiquitination and proteasomal degradation, which determines the dry type of earwax as a mendelian trait with a recessive phenotype. For rapid genetic diagnosis of axillary osmidrosis and potential risk of breast cancer, we developed specific primers for the SmartAmp method that enabled us to clinically genotype the ABCC11 gene within 30 min.