Preoperative timed single leg standing time is associated with the postoperative activity of daily living in aged disabled patients with end-stage knee osteoarthritis at six-months after undergoing total knee arthroplasty

Objectives: The aim of the present study was to investigate the effect size (ES) of total knee arthroplasty (TKA) for the symptoms and lower limb function and identify preoperative factor(s) associated with the post-operative activity of daily living (ADL) in aged patients with end-stage knee OA undergoing TKA.

Methods: Fifty-nine aged patients with end-stage knee OA (mean age: 74.6 years) were enrolled in this study. The symptoms and lower limb function of the patients were evaluated using the Japanese Knee Osteoarthritis Measure (JKOM), the timed up and go (TUG) test and timed single-legged stance test with eyes open (TSLS) before and after six months from the operation.

Results: While the ES of TKA for the improvement of pain was 2.83, the ES of TKA for the improvement of ADL, TUG and TSLS were 1.30, 0.59, and 0.49, respectively. While the post-operative ADL score was not associated with the preoperative ADL or pain scores, it was associated with the preoperative TUG and TSLS scores. A multiple regression analysis revealed that the one preoperative factor associated with the postoperative ADL was the TSLS.

Conclusion: The preoperative TSLS is associated with the postoperative ADL in aged disabled patients with end-stage knee OA.     

Elevated levels of T-cell immune response cDNA 7 in patients with immune thrombocytopenia

Objectives

This study aimed to investigate the expression levels of T-cell immune response cDNA 7 (TIRC7) in immune thrombocytopenia (ITP) patients before and after high-dose dexamethasone (HD-DXM) treatment.

Methods

Forty-four patients with ITP were enrolled and received dexamethasone (40 mg/day) for 4 consecutive days. Patients who had platelet counts more than 50 × 10⁹/l or less were defined as responders or non-responders, respectively. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to measure RNA level and plasma level of TIRC7, respectively.

Results

TIRC7 levels (RNA and plasma level) were significantly higher in ITP than that in control (P < 0.0001). However, after treatment, TIRC7 levels were significantly decreased in responders (P < 0.0001) but not in non-responders (P > 0.05).

Discussions

TIRC7 might be associated with the pathogenesis of ITP, and TIRC7 levels could be used as an indicator to evaluate patients’ response to HD-DXM treatment.     

Selective apoptosis of multiple myeloma cells in primary samples induced by arsenic trioxide

Objectives

Currently, multiple myeloma (MM) is an incurable disease. Despite the fact that arsenic trioxide (ATO) shows promising results in vitro, data from treatment of patients with MM are disappointing. Due to these discrepancies, we compared the efficacy and selectivity of ATO at two different concentrations in samples from MM patients.

Methods

The extent of apoptosis induced by 2 and 5 µM ATO was evaluated by flow cytometry using annexin V. 34 diagnostic bone marrow samples obtained from MM patients were analysed.

Results

5 µM ATO efficiently induced apoptosis in primary samples. Besides efficacy, also selectivity of action on MM cells in comparison to remaining haematopoietic cells was demonstrated for 5 µM ATO but not for 2 µM ATO.

Discussion

Our study on primary samples confirmed that ATO has a potential role in therapeutic management of MM. Further controlled studies on MM patients are needed.     

Influence of age on the correlations of hematological and biochemical variables with the stability of erythrocyte membrane in relation to sodium dodecyl sulfate

Objectives

To evaluate the influence of age on the relationships between biochemical and hematological variables and stability of erythrocyte membrane in relation to the sodium dodecyl sulfate (SDS) in population of 105 female volunteers between 20 and 90 years.

Methods

The stability of RBC membrane was determined by non-linear regression of the dependency of the absorbance of hemoglobin released as a function of SDS concentration, represented by the half-transition point of the curve (D₅₀) and the variation in the concentration of the detergent to promote lysis (dD).

Results

There was an age-dependent increase in the membrane stability in relation to SDS. Analyses by multiple linear regression showed that this stability increase is significantly related to the hematological variable red cell distribution width (RDW) and the biochemical variables blood albumin and cholesterol.

Discussion

The positive association between erythrocyte stability and RDW may reflect one possible mechanism involved in the clinical meaning of this hematological index.     

Risky behaviours of Jamaican adolescents with sickle cell disease

Objectives

To describe the risky behaviours of Jamaican teens with sickle cell disease (SCD) and compare them to a national sample of Jamaican youth.

Methods

One hundred twenty two SCD adolescents, 15–19 years old, completed the standardized questionnaire used in the Jamaican Youth Risk and Resiliency Behaviour Survey (JYRRBS), which was a nationally representative survey of 1317 Jamaican youths. Information was obtained on socio-demographics, smoking, alcohol use, and sexual activity. Secondary data from the JYRRBS were extracted to measure the difference in risky behaviours between the groups.

Results

Almost 50% of SCD and 58% of national teens reported having had sexual intercourse. More SCD teens used alcohol (77.7% vs. 60.7%; P value = 0.001). Risky behaviours tended to coexist and living with a parent (odds ratio: 0.62, P value <0.01) and currently attending school (odds ratio: 0.43, P value <0.001) lowered the likelihood of having had sex.

Discussion

SCD teens engage in many risky behaviours and health care professionals should screen and counsel them at each visit.     

CpG island methylator phenotype and its relationship with prognosis in adult acute leukemia patients

Objective

To investigated the relationship between CpG island methylator phenotype (CIMP) and prognosis in adults with acute leukemia.

Methods

Bone marrow samples from 53 acute myeloid leukemia and 50 acute lymphoblastic leukemia patients were collected. The methylation status of 18 tumor suppressor genes was determined using methylation-specific polymerase chain reaction.

Results

Greater than 30% of acute leukemia patients had methylated p15, p16, CDH1, CDH13, RUNX3, sFRP1, ID4, and DLC-1 genes; methylation of ≥4 were defined as CIMP positive. Age, type of leukemia, white blood cell count, and CIMP status were significantly associated with recurrence-free survival (RFS) and overall survival (OS) (P < 0.05). CIMP status was an independent prognostic factor for OS (hazard ratio: 2.07, 95% confidence interval: 1.03–4.15, P = 0.040). CIMP-negative patients had significantly improved RFS and OS (P < 0.05). p16 and DLC1 methylation was significantly associated with RFS and OS (P < 0.05).

Conclusions

CIMP may serve as an independent risk factor for evaluating the prognosis of patients with acute leukemia.     

Fear of Falling Restricts Activities of Daily Living after Total Hip Arthroplasty: A One-Year Longitudinal Study

Objectives: To determine the prevalence and time course in changes regarding the fear of falling and whether there are consequent restrictions in activities of daily living (ADL) after total hip arthroplasty (THA).

Methods: This is 1-year longitudinal observational study. We recruited ninety-eight patients before and after THA. Fear of falling was assessed for 12 ADLs preoperatively and postoperatively at 3, 6, and 12 months following THA. In addition, we asked patients to answer whether they had refrained from performing each ADL because of fear of falling.

Results: Fifty-two patients were enrolled for the analysis. The total fear of falling score during ADLs decreased with time after THA. The ADLs in which many patients (over 20%) felt fear even at 12 months were using the stairs (25%), sitting and standing from the floor (23%), and walking around the neighborhood (21%). Approximately 10% of patients were restricted in performing ADLs, such as sitting and standing from the floor, because of fear.

Conclusions: Patients undergoing THA frequently experience fear of falling during some ADLs even at 1 year after the operation, which could cause ADL restrictions.

Clinical Implications: Clinicians should evaluate fear of falling and institute rehabilitation programs individually to decrease excessive fear that might lead to ADL restrictions.     

Total knee arthroplasty improves both knee function and disease activity in patients with rheumatoid arthritis

Objective: This study evaluated the effect of TKA with capsulosynovectomy on disease activity and knee function in patients with RA.

Methods: Seventy-six RA patients who underwent primary TKA with more than two years of follow-up were retrospectively reviewed to assess postoperative knee function and disease activity.

Results: Postoperative knee function was significantly improved in all clinical scores, and maintained up to 24 months after surgery. RA disease activity was significantly decreased in DAS28-CRP, CDAI, and serum CRP level, and maintained up to 24 months after surgery. Postoperative knee function was negatively correlated with RA disease activity.

Conclusions: TKA improves both knee function and disease activity in patients with rheumatoid arthritis.     

Recombinant human lipocalin 2 acts as an antibacterial agent to prevent platelet contamination

Background

Bacterial contamination of platelet products is the major infectious risk in blood transfusion medicine, which can result in life-threatening sepsis in recipient. Lipocalin 2 (Lcn2) is an iron-sequestering protein in the antibacterial innate immune response, which inhibit bacterial growth. This study was aimed to evaluate the antibacterial property of Lcn2 in preventing bacterial contamination of platelets.

Methods

Recombinant Lcn2 was expressed in a eukaryotic expression system and following purification and characterization of the recombinant Lcn2, its minimum inhibitory concentration was determined. Then, platelet concentrates were inoculated with various concentrations of Staphylococcus epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Enterococcus faecalis, and the antibacterial effects of Lcn2 was evaluated at 20–24°C.

Results

Results revealed that Lcn2 effectively inhibited the growth of 1.5 × 10⁴ CFU/ml S. epidermidis, P. aeruginosa, K. pneumoniae, E. coli, and E. faecalis at 40 ng/ml. At this concentration, Lcn2 also inhibited the growth of 1.5 × 10³ CFU/ml Staphylococcus aureus and Proteus mirabilis.

Conclusion

Recombinant Lcn2 inhibited growth of a variety of platelet-contaminating bacteria. Therefore, supplementation of platelet concentrates with Lcn2 may reduce bacterial contamination.     

Acute physiological responses to physiotherapy applications pre and post autologous stem cell transplantation: an experimental study

Objective

We aimed to investigate the acute physiological responses (APR) to physiotherapy applications in patients undergoing autologous stem cell transplantation (ASCT), the difference between pre- and post-ASCT according to APR.

Methods

Twenty-six patients who were hospitalized for ASCT attended regular physiotherapy program. APR was recorded in the beginning and at the end of each exercise session. The differences in APR were calculated for each session. The mean values of the differences in APR were computed in pre-conditioning, pre-, and post-ASCT. Daily complete blood counts were also recorded during ASCT.

Results

Hemoglobin and platelet counts were significantly lower pre- and post-ASCT. Neutrophil counts were significantly lower post-ASCT. The difference in systolic blood pressure (SBP) in the beginning and at the end of the exercise sessions was significantly higher post-ASCT in comparison to pre-ASCT.

Conclusion

There was no significant change in APR except the SBP which suggests that similar level of exercise intensity could be tolerated in pre- and post-ASCT periods as well as preconditioning.     

Incidence of internal tandem duplications and D835 mutations of FLT3 gene in chronic myeloid leukemia patients from Southern India

Objective

To screen two important FLT3 mutations (internal tandem duplication (ITD) and D835 point mutations) in chronic myeloid leukemia (CML) patients from Southern India and report their incidence.

Methods

Screened 350 CML patients and 350 controls for the two FLT3/mutations through polymerase chain reaction and restriction fragment length polymorphism methods.

Results

ITDs were detected in 12 of the 350 CML patients (3.4%) and D835 mutations in only four cases (1.14%), relatively low in frequency as compared to those reported earlier from non-Indian populations. None of the cases showed simultaneous occurence of both ITD and D835 mutations.

Discussion

These FLT3 mutations seem to be very rare in CML, and it is possible that these could be found only in a subset of patients who are in the progressive stage and/or with varied drug response. Prospective studies are needed to confirm the role of FLT3 mutations in CML pathogenesis, which may help devising therapeutic interventions.     

Heterogeneity in clinical course of EBV-associated lymphoproliferative disorder after allogeneic stem cell transplantation

Objective and Importance

Post-transplant lymphoproliferative disorder (PTLD) is a severe complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) associated with Epstein–Barr virus (EBV).

Clinical presentations

Among 263 individuals treated with allo-HSCT for severe aplastic anemia, pure white cell aplasia, T-prolymphocytic leukemia, and relapsed Hodgkin lymphoma, we diagnosed EBV-PTLD in 5 patients. Median age was 29 years (range 19–70 years) and four of five patients were EBV-seropositive prior to HSCT. All five had unrelated EBV-positive donors. In all cases, PTLD occurred within the first year post-transplant (median 4 months).

Intervention

There were two rapidly fatal courses with extensive organ involvement. Both patients showed lymphopenia and thrombocytopenia. In contrast, the three surviving patients had higher lymphocytes and normal platelet counts, while PTLD was restricted to one site and resolved after 2–4 cycles of rituximab.

Conclusion

In this case series courses of PTLD showed substantial diversity.     

Optimal length of time of cryopreserved umbilical cord blood infusion after thawing

Objective

Dimethyl sulfoxide (DMSO) can damage hematopoietic progenitor cells (HPCs) at room temperature. To minimize the time of contact between DMSO and the thawed umbilical cord blood (UCB), there is an incentive to infuse the UCB as quickly as possible. However, the infusion of cryopreserved UCB also results in side effects. Currently, it is difficult to determine the optimal length of time for cryopreserved UCB infusion, not only to ensure the maximum effect of engraftment but also to reduce the toxicity of the cord blood infusion.

Methods

Ten units of cord blood were thawed to assess viability, apoptotic events of CD34⁺ cells and CD45⁺ cells, and the number of colony-forming units (CFUs) at four time points: 0, 10, 20, and 30 minutes post-thaw (PT). The infusion time, side effects, and the speed of platelet and neutrophil engraftment of the 10 patients were monitored.

Results

Within 30 minutes, the viability decreased (P < 0.01), the percentage of early apoptotic CD34⁺ cells and CD45⁺ cells was unchanged. At time point PT30, the number of CFUs was decreased compared to PT0 (P < 0.05), but it was unchanged within 20 minutes. All the 10 UCB cells engrafted well in patients.

Conclusion

This study indicates that post-thawed UCB HPCs are preserved for less than 30 minutes at room temperature; thus, the optimal length of time of cryopreserved cord blood infusion should be no more than 20 minutes after thawing.     

Nucleostemin knocking-down causes cell cycle arrest and apoptosis in human T-cell acute lymphoblastic leukemia MOLT-4 cells via p53 and p21Waf1/Cip1 up-regulation

Objectives

Nucleostemin (NS), a recently discovered nucleolar protein, is essential for maintaining self-renewal and proliferation of embryonic and adult stem cells as well as cancerous cells. The aim of this study was to determine biological function of NS in MOLT-4 cells as a human T-cell acute lymphocytic leukemia (T-ALL) model.

Methods

Efficacy of a specific small interference RNA on NS depletion was studied by quantitative polymerase chain reaction and western blotting. The growth rate and viability were analyzed by trypan blue exclusion test. Fluorescent microscopy was used for detecting apoptosis. Cell cycle and apoptosis were mechanistically studied by flow cytometry and western blotting.

Results

Knockdown of NS inhibited proliferation, arrested the cell cycle, and induced apoptosis through p53 and p21^Waf1/Cip1 pathways in MOLT-4 cells.

Discussion

These findings demonstrate critical roles of NS in MOLT-4 cells and may implicate on its therapeutic potential in this human T-ALL model.     

Compliance and satisfaction with deferasirox (Exjade®) compared with deferoxamine in patients with transfusion-dependent beta-thalassemia

Objective

The current standard option for iron chelation therapy (ICT) in transfusion-dependent patients with beta-thalassemia is deferoxamine (DFO). We aimed to compare the compliance with DFO vs. deferasirox (Exjade^®), a novel oral iron chelator, in patients with transfusion-dependent beta-thalassemia.

Methods

In this cross-sectional study, 220 patients from Southern Iran who were receiving DFO or Exjade^® for the last 2 years were investigated in 2012. Satisfaction, compliance, convenience, and life disturbances of the patients with ICT were evaluated. Assessments were performed at four different occasions during 1 year.

Results

According to the results, 114 patients received treatment with DFO and 106 patients were treated with Exjade^®. In comparison with the patients who were treated with DFO, those receiving Exjade^® reported a significantly higher rate of compliance and convenience (P < 0.05). However, no significant difference was observed between the two groups regarding their satisfaction (P > 0.05). In the DFO group, 44.9% of the patients reported irritation and pain at the injection site.

Conclusions

Considering higher rate of compliance and convenience with Exjade^® and the comparable efficacy of these two modalities of ICT documented in previous studies, Exjade^® can be used as a preferable choice of ICT in iron-overload patients with beta-thalassemia.     

Brain abscess caused by Nocardia cyriacigeorgica in two patients with multiple myeloma: novel agents,new spectrum of infections

Objective and importance

Introduction of high-dose chemotherapy and the novel agents including bortezomib, Lenalidomide, and Thalidomide has provided a significant progress in the treatment of multiple myeloma (MM) with an increase in median overall survival up to 6–8 years. However, the advances in myeloma treatment comes at a price with new spectrum of treatment-related infectious complications which should be taken into consideration while treating these patients.

Clinical presentation

We report here two patients with Ig G λ MM presenting with intracerebral mass lesions in the abscence of constitutional symptoms that would suggest an infectious etiology. Both patients had severe hypogammaglobulinemia and lymphopenia, which was attributed to treatment regimens including bortezomib.

Intervention

The surgical intervention-revealed abscess in both cases caused by Nocardia cyriacigeorgica, a relatively new pathogen which rarely causes infections in humans and also an unexpected pathogen in myeloma patients.

Conclusion

Although every aspect of immune system is known to be affected in MM, humoral immune deficiency is the hallmark of the inherent immune defect in this disease. Introduction of the novel agents, bortezomib in particular seems to have changed the characteristics of the immune dysfunction and the spectrum of the opportunistic infections by causing qualitative and quantitative changes in cellular immunity. The new spectrum of infectious agents might not be limited to hepatitis B and herpes zoster. Monitoring lymphopenia and administration of prophylactic antimicrobial agents accordingly could be considered in patients treated with bortezomib.     

XPD gene polymorphisms and the effects of induction chemotherapy in cytogenetically normal de novo acute myeloid leukemia patients

Background

Cytogenetically normal acute myeloid leukemia (AML) represents nearly half of newly diagnosed de novo AML cases. XPD is one of the DNA repair proteins, whose genetic polymorphisms are thought to affect their function as regards response to chemotherapeutic drugs and chemotherapy-induced toxicities.

Subjects and methods

We investigated the XPD Asp312Asn and Lys751Gln polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in 51 newly diagnosed cytogenetically normal de novo AML patients. The response to the standard induction chemotherapy protocol and chemotherapy-induced toxicities were monitored.

Results

The XPD Asp312Asn GG genotype was the most frequent (57%) followed by the GA variant (37%), and the AA variant was the least frequent (6%). As regards the XPD Lys751Gln polymorphism, the AA genotype was the most frequent (49%), followed by the AC (39%) and CC (12%) variants. These variants were not associated with age, sex, FAB subtype, CNS infiltration, chemotherapy-induced hepatotoxicity, nephrotoxicity, or metabolic toxicity. The XPD Lys751Gln CC polymorphic variant was associated with chemotherapy-induced cardiotoxicity and lower chance to achieve response to induction chemotherapy.

Conclusion

XPD Lys751Gln and not Asp312Asn polymorphism was associated with chemotherapy-induced cardiotoxicity and response to induction chemotherapy in newly diagnosed cytogenetically normal AML patients. Pretreatment assay of XPD Lys751Gln may help to anticipate cardiotoxicity in those at risk. Moreover, it may be considered a prognostic marker in AML cases. However, further large scale research is needed to verify its usefulness.     

Association of MDR1 gene polymorphism (G2677T) with imatinib response in Egyptian chronic myeloid leukemia patients

Background

Despite the excellent efficacy results of imatinib treatment in CML patients, resistance to imatinib has emerged as a significant problem. Genetic variations in genes involved in drug transportation might influence the pharmacokinetic and metabolism of imatinib. The genotype of a patient is increasingly recognized in influencing the response to the treatment.

Aim

To investigate the genotype frequencies of single nucleotide polymorphisms (SNPs) G2677T in CML patients undergoing imatinib treatment to determine whether different genotype pattern of these SNPs have any influence in mediating response to imatinib.

Methods

A total of 96 CML and 90 control samples were analyzed for the human multidrug resistance gene 1 (MDR1) gene polymorphism (G2677T) using polymerase chain reaction-restriction fragment length polymorphism technique.

Results

Genotype distribution revealed a significant lower frequency of TT genotype in CML patients and non-significant difference in the GG, GT genotype frequencies between patients and controls (P = 0.004, 0.138, 0.210, respectively). GG genotype was significantly higher in chronic phase (P = 0.046), while GT genotype was significantly higher in Blastic crisis phase (P = 0.002). There was a significant difference in genotype frequency of G2677T among patients showing response and resistance to imatinib in chronic phase (P = 0.02). TT genotype was associated with complete hematological response (P = 0.01), complete cytogenetic response (P < 0.001), and better molecular response with a significant association (P < 0.001). GT genotype was associated with partial hematological response (P = 0.01) and minor cytogenetic response (P < 0.001). Optimal and suboptimal responses were observed for patients with TT genotype (P = 0.003). Failure of drug response was associated with GT genotype (P = 0.02); however, GG had no association with drug response. Multivariate analysis considered GT genotype as independent risk factor for resistance (P = 0.037), while TT genotype as protective factor against resistance to imatinib (P = 0.008).

Conclusion

Determination of MDR1 polymorphisms (G2677T) might be useful in response prediction to therapy with imatinib in patients with CML.     

A self-controlled comparative clinical trial to explore the effectiveness of three topical hemostatic agents for stopping severe epistaxis in pediatrics with inherited coagulopathies

Objective

The aim of this study was to assess the effectiveness of localized treatments to persistently stop epistaxis in patients with inherited bleeding disorders.

Methods

In a self-controlled comparative clinical trial, to offer the best solution to stop epistaxis at home (within 10 minutes), patients with inherited bleeding disorders were treated using three different topical hemostatic agents, including Tranexamic acid impregnated tampon, EpiCell tampon prepared from oxidized regenerated cellulose pad, and ChitoHem tampon (reinforced with chitosan). The results of using these different products on three groups of randomly selected patients were ultimately compared using the χ² and Fisher's exact test statistics.

Results

A total of 31 patients, 5 females and 26 males with a mean age of 5.6 years, were included in the study. Twenty-three patients had Glanzmann disease, four had von-Willebrand disease, two had Bernard soulier syndrome, two had activated factor VII deficiency, and one patient had impaired secretion of adenosine deaminase. The study exhibited that statistically there was no significant difference between EpiCell tampon and Tranexamic acid impregnated tampon treatments with respect to the hemostasis duration. However, ChitoHem tampon was more efficient than Tranexamic acid impregnated tampon (P value <0.001) and EpiCell tampon (P value < 0.05).

Conclusion

ChitoHem tampon, the chitosan-reinforced product, was the best therapy solution to stop epistaxis. We recommend further research on the use of other hemostatic agents for localized bleeding in patients with inherited bleeding disorders.