Clinical factors associated with autologous stem cell transplantation outcomes in multiple myeloma: upfront transplant with MEL200 remains the standard of care.

Autologous stem cell transplantation (ASCT) remains the mainstay of the treatment in newly diagnosed transplant-eligible multiple myeloma (MM) patients. This retrospective study was performed to investigate the potential prognostic markers which may modify transplant course in a total of 256 ASCT recipients [median age: 58 (30-74) years; male/female: 138/118], including pretransplant (PET0) and day + 60 (PET2) PET/CT assessments and comparative analysis of melphalan (Mel) dose. Better responses with significantly higher complete response/very good partial response rates were achieved in patients who proceeded to transplant within 301 days from diagnosis (p < 0.001). Patients who had received < 1.5 lines of treatment prior to transplant had significantly higher probability of overall survival (OS) (p = 0.004) and progression-free survival (PFS) (p < 0.001). The probability of OS was significantly higher in patients with low Eastern Cooperative Oncology Group (ECOG) performance score (PS = 0-1) (p = 0.003) and HCT-Comorbidity Index (HCT-CI = 0) (p = 0.011). The number of involved areas (p = 0.028) and maximum standardized uptake value (SUVmax) (p = 0.021) in PET0 represented significant impact on OS. The probabilities of OS (p < 0.001) and PFS (p = 0.01) were significantly better with Mel200 mg/m2 conditioning compared to Mel140 mg/m2. Conditioning with Mel200 mg/m2, early and upfront ASCT and low pretransplant treatment burden were found to be significantly associated with ASCT outcome in MM patients. Despite its predictor impact on survival and prognosis, further studies are warranted to standardize PET/CT-based response assessments before being used as a guide for treatment decisions in clinical practice.

A metagenomic survey of bacterial communities from kurut: The fermented cow milk in Kyrgyzstan.

Kurut is a traditional dry dairy product mostly consumed in Central Asia. In this study, the distribution of the dominant bacteria present in kurut samples (n=84) originated from seven (Chuy, Issyk-Kul, Talas, Naryn, Jalal-Abad, Osh, and Batken) regions in Kyrgyzstan were analyzed with Illumina iSeq100 platform. The dominant phylum detected was Firmicutes followed by Proteobacteria, Actinobacteria, Cyanobacteria/Chloroplast, and Tenericutes. The most abundant family detected was Lactobacillaceae followed by Streptococcaceae, Enterococcaceae, Chloroplast, and Leuconostocaceae. At the genus level, Lactobacillus was the predominant one in samples and Streptococcus, Enterococcus, Lactococcus, and Streptophyta followed this. Further comprehensive characterization analyses in kurut samples may have potential applications both in industrial starter culture developments and also future therapeutic approaches based on potential strains with probiotic properties.

Allogeneic hematopoietic cell transplantation in patients with chronic phase chronic myeloid leukemia in the era of third generation tyrosine kinase inhibitors: A retrospective study by the chronic malignancies working party of the EBMT.

Following the introduction of tyrosine kinase inhibitors (TKI), the number of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for chronic phase (CP) chronic myeloid leukemia (CML) has dramatically decreased. Imatinib was the first TKI introduced to the clinical arena, predominantly utilized in the first line setting. In cases of insufficient response, resistance, or intolerance, CML patients can subsequently be treated with either a second or third generation TKI. Between 2006 and 2016, we analyzed the impact of the use of 1, 2, or 3 TKI prior to allo-HCT for CP CML in 904 patients. A total of 323-, 371-, and 210 patients had 1, 2, or 3 TKI prior to transplant, respectively; imatinib (n = 778), dasatinib (n = 508), nilotinib (n = 353), bosutinib (n = 12), and ponatinib (n = 44). The majority had imatinib as first TKI (n = 747, 96%). Transplants were performed in CP1, n = 549, CP2, n = 306, and CP3, n = 49. With a median follow-up of 52 months, 5-year OS for the entire population was 64.4% (95% CI 60.9-67.9%), PFS 50% (95% CI 46.3-53.7%), RI 28.7% (95% CI 25.4-32.0%), and NRM 21.3% (95% CI 18.3-24.2%). No difference in OS, PFS, RI, or NRM was evident related to the number of TKI prior to allo-HCT or to the type of TKI (p = ns). Significant factors influencing OS and PFS were > CP1 versus CP1 and Karnofsky performance (KPS) score > 80 versus ≤80, highlighting CP1 patients undergoing allo-HCT have improved survival compared to >CP1 and the importance of careful allo-HCT candidate selection.

Elevated expression levels of COX-2, IL-8 and VEGF in colon adenocarcinoma.

There is growing evidence of a connection between inflammation and tumor development and NF-κB is an important transcription factor in the inflammation pathway. Genetic approaches have proven the role of NF-κB responsive genes in tumorigenesis. The NF-κB responsive genes products such as IL-8, VEGF and COX-2 are the key components of angiogenesis. MMP-2 and MMP-9 are playing important roles in the disruption of the extracellular matrix that may contribute to the metastasis of tumor cells. This study aimed to investigate gene expression levels of COX-2, IL-8, VEGF, MMP-2 and MMP-9 in colon tumors. A total of 34 fresh colon carcinoma specimens and paired normal adjacent tissues (NAT) were collected during the surgery and RNA isolations were carried out from specimens. Synthesis of cDNA was carried out from these RNAs with oligo dT18 primers. The transcribed cDNA was used for PCR amplification reactions for the investigated genes with ß-actin being the internal reference via the semi-quantitative RT-PCR method. A statistically significant difference was observed for COX-2, IL-8 and VEGF which were all upregulated in colon tumors compared with adjacent normal tissues (p<0.05). However, MMP-2 and MMP-9 expression levels did not change between tumor and normal tissues (p>0.05). Upregulated expression levels of COX-2, IL-8 and VEGF might occur in the early stages of tumorigenesis and detection of these mRNA levels may be beneficial for early diagnosis and management of colon tumors.

Determination of Bacterial Diversity of Propolis Microbiota.

Propolis is a natural resinous mixture produced by the excretions of honeybees. PCR amplification of the 16S rRNA gene region was achieved using DNA of pre-enriched propolis samples collected from Apis mellifera production hives (n=37) in Eastern Türkiye (Bingöl and its regions). Next-generation sequencing and metabarcoding techniques were used to identify bacterial communities in propolis samples. Firmicutes dominated the phylum structure, with Proteobacteria, Actinobacteria, Tenericutes, and Spirochaetes following. The top three bacterial families were Bacillaceae, Enterobacteriaceae, and Enterococcaceae. Bacillus (dominantly B. badius and B. thermolactis at the species level) was recognized at the genus level, followed by Enterococcus and Clostridium sensu stricto. Our study comprehensively identified the bacterial diversity of propolis samples. Further investigations targeting to enlighten the microbiota of propolis and its potential application fields are required to gain better insight into ecological, nutritional, and medicinal perspectives.

[Comparison of the Results of Galactomannan and Beta Glucan Antigen Tests in the Suspicion of Invasive Pulmonary Aspergillosis]. / Invaziv Pulmoner Aspergilloz Süpheli Hastalarda Galaktomannan ve Beta Glukan Antijen Testlerinin Karsilastirilmasi.

Opportunistic fungal infections are an important cause of morbidity and mortality in immunocompromised patients. Invasive aspergillosis (IA) has an important place among these infections with ~ 250.000 cases annually. Reducing the mortality rate due to invasive aspergillosis is possible with early diagnosis and treatment of the disease. Because of the low sensitivity in microscopic examination, the time consuming of culture growth, and the difficulties in distinguishing colonization/infection, serological methods are frequently used in the diagnosis of invasive aspergillosis. The aim of this study was to determine the diagnostic performance of galactomannan and beta glucan tests for the diagnosis of invasive pulmonary aspergillosis (IPA). Sixty patients, followed up with the suspicion of invasive pulmonary aspergillosis in Gazi University Hospital were included in the study. The clinical classification of the patients was made according to the revised European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) criteria. A total of 10 patients were classified as probable invasive aspergillosis and 20 patients were classified as possible invasive fungal disease. Demographic data of the patients and various risk factors were recorded. One hundred and thirty serum and nine bronchoalveolar lavage (BAL) fluid samples were studied with Plateliaᵀᴹ Aspergillus Ag (Bio-Rad, France), Dynamiker Aspergillus Galactomannan and Dynamiker Fungus (1-3)-beta-D-Glucan (Dynamiker, China) kits. Sensitivity and specificity values were calculated according to U.S. Food and Drug Administration (FDA) approved Plateliaᵀᴹ Aspergillus Ag test. According to this study, the most important risk factors in the development of IPA were the use of steroids and immunomodulatory drugs. The sensitivity of the galactomannan test in the probable group was 77.8%, the specificity was 96.7%, the sensitivity of the beta glucan test was 61.1%, and the specificity was 92.6%. When these two tests were evaluated together, it was observed that the sensitivity in the probable group increased to 83.3% and the specificity decreased to 89.3%. The combined use of galactomannan and beta glucan tests increases the diagnostic sensitivity. Although the presence of prolonged neutropenia is an important risk factor for IA, the use of steroids and immunomodulatory drugs should be kept in mind in non-neutropenic patients.

Risk factors for ICU mortality in patients with hematological malignancies: a singlecenter, retrospective cohort study from Turkey.

BACKGROUND: Patients with hematological malignancies (HM) often require admission to the intensive care unit (ICU) due to organ failure, disease progression or treatment-related complications, and they generally have a poor prognosis. Therefore, understanding the factors affecting ICU mortality in HM patients is important. In this study, we aimed to identify the risk factors for ICU mortality in our critically ill HM patients. METHODS: We retrospectively reviewed the medical records of HM patients who were hospitalized in our medical ICU between January 1, 2010 and December 31, 2018. We recorded some parameters of these patients and compared these parameters by statistically between survivors and nonsurvivors to determine the risk factors for ICU mortality. RESULTS: The study included 368 critically ill HM patients who were admitted to our medical ICU during a 9-year period. The median age was 58 (49-67) years and 63.3% of the patients were male. Most of the patients (43.2%) had acute leukemia. Hematopoietic stem cell transplantation (HSCT) was performed in 153 (41.6%) patients. The ICU mortality rate was 51.4%. According to univariable analyses, a lot of parameters (e.g., admission APACHE II and SOFA scores, length of ICU stay, some laboratory parameters at the ICU admission, the reason for ICU admission, comorbidities, type of HM, type of HSCT, infections on ICU admission and during ICU stay, etc.) were significantly different between survivors and nonsurvivors. However, only high SOFA scores at ICU admission (OR:1.281, p = 0.004), presence of septic shock (OR:17.123, p = 0.0001), acute kidney injury (OR:48.284, p = 0.0001), and requirement of invasive mechanical ventilation support during ICU stay (OR:23.118, p = 0.0001) were independent risk factors for ICU mortality. DISCUSSION: In our cohort, critically ill HM patients had high ICU mortality. We found four independent predictors for ICU mortality. Yet, there is still a need for further research to better understand poor outcome predictors in critically ill HM patients.

Comparison of daily oral iron replacement therapy with every other day treatment in female reproductive age patients with iron-deficiency anemia.

Iron-deficiency anemia (IDA) is accepted as the most common cause of anemia in the world. The main goals of iron replacement therapy are to normalize the hemoglobin level and to replace iron stores. Current guidelines for treating iron deficiency recommend daily divided doses of iron to increase absorption. Hepcidin is a key regulator of systemic iron balance and acts in harmony with intracellular iron metabolism. Daily dosing and divided doses may increase serum hepcidin and decrease iron absorption. In this study, it was aimed to compare the effectiveness of daily and every other day oral iron replacement therapy in women of reproductive age with iron-deficiency anemia. We included premenopausal female patients aged between 18 and 50 years with iron-deficiency anemia. Forty patients were given oral iron therapy at a daily dose of 2*80 mg (iron sulfate). Forty-three patients were given iron treatment at a dose of 2*80 mg (iron sulfate) every other day. After 2 months of oral iron therapy, there was a significant improvement in hemoglobin, mean corpuscular volume, serum iron, total iron-binding capacity, and transferrin saturation in both groups. The values of hemoglobin, serum iron, transferrin saturation, and ferritin significantly increased at the end of the treatment for both groups. Although the median hepcidin level on the 15th-day measurement in the every other day treatment group was higher than that in the daily treatment group, there was no significant difference. As a result, the patients' compliance with the treatment can be increased by offering treatment every other day instead of daily, since it provides similar treatment effectiveness.

Is comprehensive geriatric testing guiding in the identification of multiple myeloma patients who are candidates for autologous stem cell transplantation? A prospective analysis.

Multiple myeloma (MM) is a hematological malignancy of older adults. This study aimed to investigate the differences in performance, comorbidity scores, and comprehensive geriatric assessment (CGA) before and after induction therapy in newly diagnosed MM patients, as well as the factors that may be associated with improved performance status after induction therapy. Thirty-seven consecutive patients aged 50 years and older, who were newly diagnosed with MM, were included in the study. The patients underwent performance status evaluation and CGA when first diagnosed and after 4 cycles of induction chemotherapy. The performance status of 11 patients (40.7%) changed after induction therapy. Improvement in performance status was significantly lower in patients who were frail according to the Fried frailty criteria and IMWG scores (60% vs. 25%, p = 0.04), (30.0% vs. 6.2%, p = 0.02), taking more than 2 medications due to comorbidities (p = 0.01, confidence interval 0.06-0.09) and those with renal involvement (80.0% vs. 18.7%, p = 0.002). Those with bone involvement were more prevalent among the patients whose performance status improved (87.5% and 50.0%, p = 0.03). This study demonstrated that performance status might improve after induction therapy. Results suggest that CGA before induction therapy can predict performance status change. These results might have implications for predicting at the time of diagnosis, whether an MM patient can be a transplant candidate after induction therapy.

Variable impact of graft CD3+ cell content on graft versus host disease in hematopoietic stem cell transplant recipients: Is the role of donor CD3+ cells overestimated?

Graft cellular composition is considered as a significant determinant of transplant outcome. Donor CD3+ cells were shown to have a significant association with the development of graft vs host disease (GvHD). The aim of this study was to investigate the impact of graft CD3+ cell content on transplant outcome, particularly in terms of GvHD and relapse. We retrospectively analysed the records of 515 allo-HCT recipients [median age: 37(15-71) years; male/female: 323/192]. The optimal threshold of infused CD3+ cell count for acute GvHD development was estimated to be 197.5 × 106/kg (AUC: 0.572; 95 % CI: 0.513-0.631; p = 0.018) and 198.5 × 106/kg (AUC: 0.6; 95 % CI: 0.520-0.679; p = 0.019) for the general population and reduced-intensity conditioning (RIC) subgroup, respectively. Acute GvHD was more frequent in low-CD3+ group in the whole study population, particularly in RIC transplants. The incidence of cytomegalovirus reactivation was higher in low-CD3+ group and neutrophil engraftment occured earlier in the same group of patients. Overall survival and non-relapse mortality were comparable between high and low-CD3+ groups. Age, ECOG performance status, hypogammaglobulinemia, chronic GvHD and post-transplant relapse were found to predict prognosis in multivariate analysis. By focusing mainly on donor T cells, the potential role of host immune cells in the early post-transplant milieu may have been underestimated. Drawing a more detailed profile of graft and host immune cells in the joint microenvironment may elucidate our way to a better understanding of GvHD pathogenesis. By this way a comprehensive pre-transplant risk assessment could be improved to generate more personalized approaches.

A medical and molecular approach to kefir as a therapeutic agent of human microbiota.

The imbalanced microbial composition called as dysbiosis constitutes a tendency related to different kind of human diseases. To overcome the disadvantages of dysbiosis, the consumption of probiotics is an emerging and promising topic of the last decade. Kefir is a probiotic fermented beverage produced from the fermentation of kefir grains with changing varieties of milk and displays a symbiotic association of bacteria and yeast. The discovery of the concept that fermented foods/beverages such as kefir could modify gut microbiota in humans has widened the borders of precision medicine and now microbiome therapeutics can be considered as a significant part of this field. Kefir seems to have potential to guide and manipulate future replacement/complementary therapies with a variety of beneficial biological/medical properties it has. The aim of this review was a comprehensive recapitulation of probiotic beverage kefir's significant properties mainly focusing of antioxidative, immunomodulatory, apoptotic, antitumor, neuroprotective. Apoptotic/antimetastatic effects are regulated at the molecular level by increases in TGF-ß1, caspase-3, p53, Bax, Bax:Bcl-2 ratio, p21 and decreases in TGF-α, Bcl-2 and MMP polarization. Neuroprotective effects are revealed upon upregulation of SOD/catalase and anti-inflammatory Treg cells, decreases in repetitive behavior and modulation of apoptotic genes. Besides these significant features that may offer quite advantages in supplementary cancer therapies, the scope was also extended to recent emerging medical topics and also discussed and evaluated the concept of "psychobiotics". The therapeutic potential of psychobiotic effect is majorly attributed to the increased ratios of Clostridium butyricum, Lactobacillus and Bifidobacterium.

Predictive value of KRAS/NRAS, IL-4 VNTR and HPV alterations in metastases of colorectal cancer.

PURPOSE: The main aim of the study was to evaluate the potential roles of KRAS/NRAS proto-oncogenes, IL-4 VNTR variants and HPV prevalence in colorectal cancer metastasis. As the second aim, the interactions of the analyzed genes and viral sequences with both clinicopathological variables and each other were targeted. METHODS: DNA was extracted using AmoyDx FFPE DNA Extraction kit from paraffin-embedded colorectal tumor tissue samples (n = 60). NRAS/KRAS mutational profiles were determined with real-time polymerase chain reaction using AmoyDx KRAS/NRAS Mutation Detection Kit. Genotyping of IL-4 VNTR was made with PCR. HPV detection was analyzed by PCR with both GP5+/GP6+ consensus primers and type-specific primers for HPV-16 and HPV-18. SPSS v22 (IBM) statistics software was used for all statistical analyses. RESULTS: From the demographical/clinicopathological parameters, age and biopsy specimens revealed an association with metastasis. KRAS mutation rate was as high as 65 % in the patients and the most prevalent mutation type was G12D. Metastasis risk was 3.19-fold increased in KRAS-mutated patients compared to KRAS-negative ones. IL-4 VNTR genotypes/alleles were not associated with metastasis in our analysis.  The frequency of HPVs in our colorectal cancer cohort was 36.7 %, but HPV positivity was not found to be associated with metastasis.  A significant association was found between HPV and NRAS mutations; NRAS wild-type status acted as a protective factor by 7.5-fold for HPV negativity. CONCLUSION: Our study comprehensively and concomitantly evaluated several potential molecular risk factors. Future studies designed in such combined approaches will substantially contribute to better manage colorectal cancer tumorigenesis from molecular biological perspective (Tab. 6, Fig. 2, Ref. 40).

Seasonal Human Coronavirus Respiratory Tract Infection in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Little is known about characteristics of seasonal human coronaviruses (HCoVs) (NL63, 229E, OC43, and HKU1) after allogeneic stem cell transplantation (allo-HSCT). METHODS: This was a collaborative Spanish and European bone marrow transplantation retrospective multicenter study, which included allo-HSCT recipients (adults and children) with upper respiratory tract disease (URTD) and/or lower respiratory tract disease (LRTD) caused by seasonal HCoV diagnosed through multiplex polymerase chain reaction assays from January 2012 to January 2019. RESULTS: We included 402 allo-HSCT recipients who developed 449 HCoV URTD/LRTD episodes. Median age of recipients was 46 years (range, 0.3-73.8 years). HCoV episodes were diagnosed at a median of 222 days after transplantation. The most common HCoV subtype was OC43 (n = 170 [38%]). LRTD involvement occurred in 121 episodes (27%). HCoV infection frequently required hospitalization (18%), oxygen administration (13%), and intensive care unit (ICU) admission (3%). Three-month overall mortality after HCoV detection was 7% in the whole cohort and 16% in those with LRTD. We identified 3 conditions associated with higher mortality in recipients with LRTD: absolute lymphocyte count <0.1 × 109/mL, corticosteroid use, and ICU admission (hazard ratios: 10.8, 4.68, and 8.22, respectively; P < .01). CONCLUSIONS: Seasonal HCoV after allo-HSCT may involve LRTD in many instances, leading to a significant morbidity.

Can treating critically-ill haematological malignancy patients in a separate intensive care unit decrease intensive care unit mortality?

Background/aim: The aim of the study was to investigate whether treating haematological malignancy (HM) patients in a separate intensive care unit (ICU) would reduce ICU mortality. Materials and methods: HM patients treated by the same ICU team in a general medical ICU (GM-ICU) and a separate haematology ICU (H-ICU) were included in this study. Patients' demographic characteristics and ICU data were recorded retrospectively. Differences in the ICU course and prognosis between these two groups were determined. Results: A total of 251 patients (102 from GM-ICU, 149 from H-ICU) were included in this study. The disease severity and organ failure scores at ICU admission and underlying HMs were not different between the two groups. Patients waited longer for admission to GM- ICU. Therapeutic procedures were performed significantly more frequently in GM-ICU. ICU complications were not different between the groups. ICU mortality rates were higher in GM-ICU (59.8% vs 37.6%, p = 0.006). Conclusion: A separate ICU allocated for haematology patients will allow timely and rapid admission of HM patients to ICU. Thus, mortality rates of HM patients needing ICU care will decline.

Retrospective analysis of the association of the expression and single nucleotide polymorphisms (SNPs) of the TLR4, PTX3 and Dectin-1 (CLEC/A) genes with development of invasive aspergillosis among haematopoietic stem cell transplant recipients with oncohaematological disorders.

OBJECTIVES: Several studies described single nucleotide polymorphisms (SNPs) on pattern recognition receptor (PRR) such as toll-like receptors (TLRs), dendritic cell-associated C-type lectin-1 (Dectin-1/CLEC7A) genes of patients with invasive fungal infections (IFIs) caused by Candida and Aspergillus. We screened TLR4, Dectin-1 and PTX3 polymorphisms in a Turkish population with invasive aspergillosis (IA) underlying haematological malignancies. METHODS: In this case-control study, a cohort of 59 patients with haematological malignancies were included. There were 26 IA patients assigned by the EORTC-MSG criteria and 33 patients with no evidence of fungal disease. DNA and RNA were isolated from frozen bone marrow and serum samples. RNA levels and polymorphisms of TLR4 (rs4986790, rs4986791), Dectin-1 (rs16910526, rs7309123) and PTX3 (rs2305619, rs3816527) were determined. The odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated by unconditional logistic regression analysis. RESULTS AND CONCLUSIONS: TLR4, PTX3 and Dectin-1 genes were downregulated in aspergillosis cohort under similar haematological conditions. TLR4 expression was 0.0626 ± 0.032 in controls when compared to IA patients as 0.0077 ± 0.014, and the difference was significant (P = .026). There was a difference in also the PTX3 gene among IA (0.0043 ± 0.004) and control (0.5265 ± 0.0043) groups (P = .035). The Dectin-1 (CLEC/A) expression was downregulated in IA group (0.1887 ± 0.072 & 0.0655 ± 0.010) but not statistically significant (P > .05). Conditional logistic regression analyses indicated that the GT genotype of rs16910526 polymorphism in Dectin-1 gene was associated with lower risk of IA (odds ratio = 3.635, 95% confidence interval = 0.690-3.138, P = .04).

Recombinant Zoster Vaccine Significantly Reduces the Impact on Quality of Life Caused by Herpes Zoster in Adult Autologous Hematopoietic Stem Cell Transplant Recipients: A Randomized Placebo-Controlled Trial (ZOE-HSCT).

Herpes zoster (HZ) can have a substantial impact on quality of life (QoL). The vaccine efficacy (VE) of a recombinant zoster vaccine (RZV) was 68.2% (95% confidence interval [CI], 55.6% to 77.5%) in a phase 3 study in adult autologous hematopoietic stem cell transplant (HSCT) recipients (NCT01610414). Herein, we report the impact of RZV on patients' QoL. Autologous HSCT recipients were randomized 1:1 to receive 2 doses of RZV or placebo, given 1 to 2 months apart. QoL was measured by the Short Form Survey-36 and Euro-QoL-5 Dimension at baseline, 1 month, and 1 year postdose 2 and during suspected HZ episodes with the Zoster Brief Pain Inventory (ZBPI). The RZV impact on ZBPI burden of illness and burden of interference scores was estimated. The 2 scores were calculated from the area under the curve (days 0 to 182) of the ZBPI worst pain and ZBPI activities of daily living scores, respectively, assuming a score of 0 for patients not having a confirmed HZ episode. The ZBPI maximum worst pain score was significantly lower in the RZV than placebo group (mean: 5.8 versus 7.1, P = .011). Consequently, the VE estimates for HZ burden of illness (82.5%; 95% CI, 73.6 to 91.4) and burden of interference (82.8%; 95% CI, 73.3 to 92.3) were higher than the HZ VE estimate (ie, 68.2%). RZV showed significantly better QoL scores than placebo 1 week following rash onset among patients with confirmed HZ. In addition to reducing the risk of HZ and its complications, RZV significantly reduced the impact of HZ on patients' QoL in those who developed breakthrough disease.

Expression profiles of proto-oncogene TWIST1 and tumor metastasis suppressor gene LASS2 in bladder cancer.

Transcription factor proto-oncogene TWIST1 and tumor metastasis suppressor gene LASS2 have been reported to be involved in various carcinomas but their expression profiles and prognostic significances in bladder cancer are largely unknown. We aimed to determine these genes' expression levels both at mRNA and protein level in bladder cancer. mRNA expression levels of TWIST1 and LASS2 genes were examined using real-time quantitative PCR (qPCR) in human bladder tumors and paired normal adjacent tissues obtained from 44 patients. Protein expression profiles of both genes were detected by immunohistochemical staining in formalin-fixed and paraffin-embedded tissues from the same patients. The expression profiles of TWIST1 mRNA in bladder tumors were significantly lower than the normal adjacent tissues and linked to both the stage and the grade. The expression profiles of LASS2 mRNA in bladder tumors were also significantly lower than the normal adjacent tissues reflecting the potential tumor suppressor profile of the gene, independently from stage or grade. By immunohistochemistry, TWIST1 and LASS2 positive expression rates were found as 14.3% (6/42) and 38.1% (16/42), respectively. As potential molecular markers for bladder carcinoma, both TWIST1 and LASS2 transcripts seem to play role during the tumorigenesis and development of bladder cancer. Lack of a functional link and/or weak inverse link between TWIST1 and LASS2 transcripts and immunohistochemical findings may reflect the potential associations of transcription regulation mechanisms and merit further investigations. To the best of our knowledge, this is the first report investigating the combined expression profile of TWIST1 and LASS2 in bladder cancer both at mRNA and protein level.

Comparison of conditioning regimen toxicities among autologous stem cell transplantation eligible multiple myeloma patients: High-dose melphalan versus high-dose melphalan and bortezomib.

Background Autologous hematopoietic stem cell transplantation (AHSCT) remains the standard of care for younger patients with multiple myeloma (MM). Currently, high-dose melphalan (HDM) is recommended as conditioning regimen before AHSCT. Preclinical data suggest that combining bortezomib and melphalan has synergistic effect against multiple myeloma cells. Bortezomib and HDM (Bor-HDM) combination as conditioning regimen has been investigated by many other investigators. Objective In this retrospective study, we aimed to compare transplant-related toxicities and hematologic recovery of HDM and Bor-HDM conditioning regimens. Method We retrospectively evaluated hematologic recovery and toxicity profile in patients with MM who received AHSCT with either HDM ( n = 114) or Bor-HDM ( n = 53) conditioning regimen. Results Nonhematologic toxicities were comparable between HDM and Bor-HDM conditioning regimen, except mucositis and diarrhea being more frequent in the Bor-HDM group. Neutrophil and platelet engraftment time and duration of hospital stay were significantly shorter for HDM regimen. Conclusions In this retrospective analysis, we observed engraftment kinetics and duration of hospitalization were significantly worse in Bor-HDM conditioning regimen with manageable toxicities. Randomized studies are needed to further compare Bor- HDM regimen to HDM in terms of response rates, toxicities, and transplant-related mortality.

Factors affecting hematopoietic stem cell mobilization and apheresis in allogeneic donors: The role of iron status.

Infused CD34 cell count has a significant impact on transplant outcome. In this retrospective study, we aimed to analyze the impact of donor iron parameters on peripheral blood stem cell (PBSC) collection. A total of 303 related donors were included in the study. The mobilization regimen, recombinant G-CSF, was given for four consecutive days. A CD34+ cell count below 2×106/kg was defined as mobilization failure which was demonstrated in 23 donors (7.6%). Mobilization failure was more frequent in female donors than male donors (13.7% vs 3.4%). Body mass index, mean corpuscular volume, hemoglobin and ferritin levels were found to be lower in donors with mobilization failure. Body mass index was significantly correlated with PBSC count on the 4th day of G-CSF. Body mass index, male gender, mean corpuscular volume and ferritin levels had significant impact on PBSC count. Although PBSC count was found to be similar between female and male donors, female gender was shown to have an adverse impact on PBSC collection, which may be attributed to lower body weight and concurrent iron deficiency.

Lack of association between MAOA-uVNTR variants and excessive daytime sleepiness.

Sleep disorders are highly prevalent in the population and have dramatic health, social, and economic impacts. However, their treatments may remain symptomatic due to ignorance of molecular factors which may provide fundamental insights into the neurological bases of sleep. Excessive daytime sleepiness (EDS) is a common complaint encountered in neurological practice with significant effects both on individuals and on society. We aimed to investigate the role of monoamine oxidase A (MAOA) as a candidate gene in EDS. Epworth sleepiness scale (ESS) was applied to 221 subjects who were also genotyped for MAOA upstream variable number of tandem repeats (MAOA-uVNTR). Patient group displayed higher ESS values (mean 12.67) when compared with the control group (mean 6.38). However, MAOA-uVNTR genotypes did not show a significant association with ESS scores neither on women nor on men. Finally, these data suggest further replications in different populations. Moreover, the investigation of some other genes together with MAOA and/or some possible regulatory molecular mechanisms may offer a more comprehensive approach in the role of genetic factors contributing to EDS.