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Aim: To find the correlation between subtalar varus angle & disability in patients with patellofemoral arthritis. Methods: A total of 30 subjects aged (48.86±5.74) referred to the department of physiotherapy, with patellofemoral arthritis and fulfilling the criteria of inclusion were recruited for the study, sampling method being convenient sampling. Disability score was measured of each patient by WOMAC index (Western Ontario and McMaster Universities Index of Osteoarthritis) disability questionnaire and subtalar varus angle was measured in non weight bearing position in prone lying. Results: Pearson’s correlation coefficient test showed a highly significant (p=0.000) positive correlation (r=0.821) between disability scores and subtalar varus angle. Conclusion: There is a highly significant relation between disabilities due to patellofemoral pain in patellofemoral arthritis patients and sub talar varus angle.

Introduction: Standard-of-care first-line treatments for paroxysmal nocturnal hemoglobinuria (PNH) include the anti-C5 therapies eculizumab and ravulizumab. However, persistent anemia, likely due to extravascular hemolysis, and reduced quality of life (QoL) due to frequent infusions remain concerns. Iptacopan is a first-in-class oral proximal complement inhibitor that targets factor B in the alternative pathway (upstream of C5), limiting intravascular and extravascular hemolysis., Areas Covered: In patients previously treated with anti-C5 therapies or naive to complement inhibitors, iptacopan 200 mg twice daily resulted in clinically meaningful results in the pivotal phase 3 APPLY-PNH (NCT04558918) and APPOINT-PNH (NCT04820530) trials. Treatment with iptacopan was safe, and no treatment-related adverse events led to discontinuation., Expert Opinion: APPLY-PNH and APPOINT-PNH reported clinically meaningful improvements in hemoglobin, bilirubin, and lactate dehydrogenase levels; transfusion avoidance; reticulocyte count; and fatigue. Iptacopan's safety profile was comparable to other complement inhibitors. Oral iptacopan therapy allows patients to avoid infusions, limit clinical visits, decrease medical costs, improve anemia that persists with other complement inhibitors, and improve QoL. Long-term follow-up will further assess infections, thrombosis, and breakthrough hemolysis. Before treatment, physicians need to discuss current therapeutic options with patients for shared decision-making. Guidelines are being created to assist healthcare professionals in this advancing field.

Abstract: Severe aplastic anemia (SAA) is a rare hematologic condition for which there is no clear management algorithm. A panel of 11 experts on adult and pediatric aplastic anemia was assembled and, using the RAND/University of California, Los Angeles modified Delphi panel method, evaluated >600 varying patient care scenarios to develop clinical recommendations for the initial and subsequent management of patients of all ages with SAA. Here, we present the panel's recommendations to rule out inherited bone marrow failure syndromes, on supportive care before and during first-line therapy, and on first-line (initial management) and second-line (subsequent management) therapy of acquired SAA, focusing on when transplant vs medical therapy is most appropriate. These recommendations represent the consensus of 11 experts informed by published literature and experience. They are intended only as general guidance for experienced clinicians who treat patients with SAA and are in no way intended to supersede individual physician and patient decision making. Current and future research should validate this consensus using clinical data. Once validated, we hope these expert panel recommendations will improve outcomes for patients with SAA., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Abstract: Thrombophilia is one of the principal features of paroxysmal nocturnal hemoglobinuria (PNH) and constitutes the main cause of disease morbidity/mortality. Anticomplement treatment has revolutionized the natural history of PNH, with control of the hemolytic process and abolition of thrombotic events (TEs). However, no guidelines exist for the management of thromboembolic complications in this setting, with type and duration of anticoagulation depending on individual practices. Besides, a scarcity of data is present on the efficacy of direct oral anticoagulants (DOACs). Herein, we accrued a large real-world cohort of patients with PNH from 4 US centers to explore features, predictors of TE, and anticoagulation strategies. Among 267 patients followed up for a total of 2043 patient-years, 56 (21%) developed TEs. These occurred at disease onset in 43% of cases, involving more frequently the venous system, typically as Budd-Chiari syndrome. Rate of TEs was halved in patients receiving complement inhibitors (21 vs 40 TEs per 1000 patient-years in untreated cases, with a 2-year cumulative incidence of thrombosis of 3.9% vs 18.3%, respectively), and varied according to PNH granulocytes and erythrocytes clone size, type, disease activity parameters, as well as number (≥2 mutations, or less) and variant allelic frequency of PIGA mutations. Anticoagulation with warfarin (39%), DOACs (37%), and low-molecular weight heparin (16%) was administered for a median of 29 months (interquartile range [IQR], 9-61.8). No thrombotic recurrence was observed in 19 patients treated with DOACs at a median observation of 17.1 months (IQR, 8.9-45) whereas 14 cases discontinued anticoagulation without TE recurrence at a median time of 51.4 months (IQR, 29.9-86.8)., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Haematological profile of patients with oral sub mucous fibrosis (OSMF) and its correlation with the severity of OSMF is evaluated. The study comprised of sixty participants with clinical diagnoses. They were divided into smaller groups based on the OSMF stage. Sixty age and gender matched healthy controls were chosen among patients presenting for routine hematological examinations and free of systemic illnesses. Assessment of iron, hemoglobin, and red cell indices in all study participants was carried out. It was observed that the values of haematological tests like (Hb (g/dL), PCV, MCV (fl), MCH, MCHC, Iron (mg/dL) and Vitamin B12 (pg/Ml) was greater in normal subjects as compared to OSMF patients. Values were found to decrease further as the severity (staging) of OSMF increased among OSMF patients. The findings were statistically significant showing decrease in the values of different haematological parameters as the stage of OSMF progressed from stage I to stage III., (© 2024 Biomedical Informatics.)

Immuno-histochemical evaluation of CD34 in oral lichen planus (OLP) and Oral Submucous Fibrosis (OSMF) is of interest to dentist.20 specimens of normal oral mucosa (buccal mucosa/gingiva tissue) from patients who had extractions performed as part of orthodontic treatment comprised Group I, the control group. Group II comprised 30 individuals with a diagnosis of oral lichen planus. 30 OSMF cases with diagnoses is Group III. These 80 specimens were all given consideration when choosing for CD34immuno-histochemical staining. The CD34 was greater in all categories of OLP and OSMF when compared to normal controls. Maximum CD34 expression was observed in erosive OLP (147.41±17.60) followed by OSMF (116.01 ±11.72) and reticular OLP (105.01±11.62). Data was statistically significant (p<0.001).Immunohistochemistry of CD34 evaluation is a potential diagnostic marker for OLP and OSMF., (© 2024 Biomedical Informatics.)

Background: To compare and correlate the relationship between body mass index (BMI) and blood and salivary glucose (mean values) in patients with diabetes and non-diabetic control group patients., Materials and Methods: In the study, 100 patients were included, 50 patients each-patients with diabetes and non-diabetic control group. Each patient had their BMI measured as well as unstimulated whole saliva collected and blood drawn., Results: When compared to BMI, blood glucose (mean), and salivary glucose (mean) in healthy controls, BMI, blood glucose, and salivary glucose values in diabetic patients were considerably higher., Conclusion: Patients who have a higher BMI are more likely to develop diabetes., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Genomic mutations drive the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia. While morphological and clinical features have dominated the classical criteria for diagnosis and classification, incorporation of molecular data can illuminate functional pathobiology. Here we show that unsupervised machine learning can identify functional objective molecular clusters, irrespective of anamnestic clinico-morphological features, despite the complexity of the molecular alterations in myeloid neoplasia. Our approach reflects disease evolution, informed classification, prognostication, and molecular interactions. We apply machine learning methods on 3588 patients with myelodysplastic syndromes and secondary acute myeloid leukemia to identify 14 molecularly distinct clusters. Remarkably, our model shows clinical implications in terms of overall survival and response to treatment even after adjusting to the molecular international prognostic scoring system (IPSS-M). In addition, the model is validated on an external cohort of 412 patients. Our subclassification model is available via a web-based open-access resource ( https://drmz.shinyapps.io/mds&#95;latent )., (© 2023. The Author(s).)

Even if local anesthetic is still the mainstay of pain management in dentistry, research will keep striving for novel and effective pain management techniques. The majority of research efforts are focused on improving anesthetic medications, delivery systems, and related methods. There are more recent technologies available that can assist the dentist in providing better pain relief with fewer unpleasant injections and fewer negative adverse effects. The purpose of the current review of the literature is to compile evidence that will convince dentists to employ modern local anesthetics, as well as other methods and techniques to reduce patient discomfort while administering anesthesia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Patel et al.)

Purpose: Secondary myeloid neoplasms (sMNs) remain the most serious long-term complications in patients with aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). However, sMNs lack specific predictors, dedicated surveillance measures, and early therapeutic interventions., Patients and Methods: We studied a multicenter, retrospective cohort of 1,008 patients (median follow-up 8.6 years) with AA and PNH to assess clinical and molecular determinants of clonal evolution., Results: Although none of the patients transplanted upfront (n = 117) developed clonal complications (either sMN or secondary PNH), the 10-year cumulative incidence of sMN in nontransplanted cases was 11.6%. In severe AA, older age at presentation and lack of response to immunosuppressive therapy were independently associated with increased risk of sMN, whereas untreated patients had the highest risk among nonsevere cases. The elapsed time from AA to sMN was 4.5 years. sMN developed in 94 patients. The 5-year overall survival reached 40% and was independently associated with bone marrow blasts at sMN onset. Myelodysplastic syndrome with high-risk phenotypes, del7/7q, and ASXL1 , SETBP1 , RUNX1 , and RAS pathway gene mutations were the most frequent characteristics. Cross-sectional studies of clonal dynamics from baseline to evolution revealed that PIGA/ human leukocyte antigen lesions decreased over time, being replaced by clones with myeloid hits. PIGA and BCOR/L1 mutation carriers had a lower risk of sMN progression, whereas myeloid driver lesions marked the group with a higher risk., Conclusion: The risk of sMN in AA is associated with disease severity, lack of response to treatment, and patients' age. sMNs display high-risk morphological, karyotypic, and molecular features. The landscape of acquired somatic mutations is complex and incompletely understood and should be considered with caution in medical management.

Introduction: Currently available treatments for chronic lower back pain (CLBP) do not adequately address both nociceptive and neuropathic components of pain. We evaluated efficacy and safety of fixed-dose combination (FDC) of low-dose pregabalin prolonged release 75 mg-etoricoxib 60 mg to address both pain components., Methods: This randomized phase 3 trial conducted at 12 centres across India evaluated efficacy (based on mean change in numeric rating scale [NRS], Roland-Morris disability questionnaire [RDQ], visual analogue scale [VAS], patient global impression of improvement [PGI-I], clinical global impression of improvement [CGI-I] and rescue medication consumption) and safety of FDC in comparison to etoricoxib alone in adult patients with CLBP. Treatment duration was 8 weeks., Results: Of the 371 patients screened, 319 were randomized and considered for efficacy and safety analysis. Both treatment groups had no significant difference in terms of demography and baseline disease characteristics. Significantly better outcomes with FDC compared to etoricoxib were observed at week 4 onwards. At week 8, both groups showed significant reduction in mean NRS score from baseline (- 4.00 ± 1.65 in FDC; - 2.92 ± 1.59 in etoricoxib) with mean NRS score being significantly less in the FDC group compared to etoricoxib group (3.26 ± 1.56 vs 4.31 ± 1.56; p < 0.0001). The FDC was more effective than etoricoxib in terms of significantly greater reduction in RDQ score (- 9.28 ± 4.48 vs - 6.78 ± 4.34; p < 0.0001) and VAS score (- 37.66 ± 18.7 vs - 28.50 ± 16.31; p < 0.0001) at week 8. The FDC was also better in terms of significantly more patients reporting their condition as 'very much better' (36.9% vs 5.0%; p < 0.0001) and clinicians reporting patient's condition as 'very much improved' (36.3% vs 5.7%; p < 0.0001). Overall, study medications were well tolerated., Conclusion: FDC of pregabalin and etoricoxib provided significant benefits in reducing pain and improving functional status compared with etoricoxib alone in patients with CLBP. Pregabalin prolonged release-etoricoxib FDC could be one of the treatment options for early and sustained pain relief and improvement in quality-of-life in treating CLBP as it addresses both neuropathic and nociceptive components of pain., Trial Registration: CTRI/2018/10/015886., (© 2022. The Author(s).)

Idiopathic aplastic anemia (IAA) is a rare autoimmune bone marrow failure (BMF) disorder initiated by a human leukocyte antigen (HLA)-restricted T-cell response to unknown antigens. As in other autoimmune disorders, the predilection for certain HLA profiles seems to represent an etiologic factor; however, the structure-function patterns involved in the self-presentation in this disease remain unclear. Herein, we analyzed the molecular landscape of HLA complexes of a cohort of 300 IAA patients and almost 3000 healthy and disease controls by deeply dissecting their genotypic configurations, functional divergence, self-antigen binding capabilities, and T-cell receptor (TCR) repertoire specificities. Specifically, analysis of the evolutionary divergence of HLA genotypes (HED) showed that IAA patients carried class II HLA molecules whose antigen-binding sites were characterized by a high level of structural homology, only partially explained by specific risk allele profiles. This pattern implies reduced HLA binding capabilities, confirmed by binding analysis of hematopoietic stem cell (HSC)-derived self-peptides. IAA phenotype was associated with the enrichment in a few amino acids at specific positions within the peptide-binding groove of DRB1 molecules, affecting the interface HLA-antigen-TCR β and potentially constituting the basis of T-cell dysfunction and autoreactivity. When analyzing associations with clinical outcomes, low HED was associated with risk of malignant progression and worse survival, underlying reduced tumor surveillance in clearing potential neoantigens derived from mechanisms of clonal hematopoiesis. Our data shed light on the immunogenetic risk associated with IAA etiology and clonal evolution and on general pathophysiological mechanisms potentially involved in other autoimmune disorders., (© 2021 by The American Society of Hematology.)

Background: Effective skin graft fixation is vital in preventing sheering forces, seroma, and hematoma from compromising graft take. Yet, selecting the ideal technique for securing skin grafts remains a contentious subject, with significant variation in practice existing between surgeons. There is, therefore, benefit to be derived from assessing the literature for evidence-based recommendations to guide the decision-making process., Methods: A search of Medline and Embase was performed using appropriate key terms, yielding 419 articles. Reference lists were analyzed. Inclusion and exclusion criteria were composed. Level I to III studies, as defined by the Centre for Evidence-Based Medicine, that compared skin graft fixation methods were analyzed. Rayyan QCRI was used for abstract and title screening. After full text screening, 41 studies were included for qualitative analysis. All included randomized control trials (RCTs) were assessed for risk of bias using the Cochrane Risk-of-Bias 2 (ROB2) tool., Results: We identified 4 groups of fixation technique: "tie-over bolster" (TOB), "no TOB," "adhesive glues," and "negative pressure wound therapy" (NPWT). Twelve studies compared TOB with no TOB, with no difference in graft take demonstrated. Sixteen studies compared adhesive glues with traditional methods, with no difference in graft take demonstrated. Thirteen studies compared NPWT with traditional methods, with enhanced graft take demonstrated. Risk of bias was deemed low in 1 of 13 RCTs., Conclusions: Based on the current evidence, only NPWT is associated with enhanced graft take. However, there is a scarcity of robust level I evidence comparing different fixation techniques, meaning that strong recommendations cannot be made. We propose examples of hypothesis-driven RCTs, in predetermined clinical settings, based on the theoretical benefits of the techniques that would add value to clinical practice., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Using a range of health-related quality of life (HRQoL) instruments, most - but not all - studies of myelodysplastic syndromes (MDS) have reported that lower hemoglobin levels and red blood cell transfusion dependency are associated with worse HRQoL. In addition, some MDS treatments may significantly improve HRQoL, particularly among those patients who respond to therapy; however, the majority of these studies were underpowered for this secondary endpoint. Furthermore, decreased HRQoL has been associated with worse survival outcomes, and HRQoL scores can be used to refine classical prognostic systems. Despite the subjective nature of HRQoL, the importance and validity of measuring it in trials and clinical practice are increasingly being recognized, but properly validated MDS-specific instruments are required. We describe what is currently known about HRQoL in patients with MDS, and the limitations of measuring HRQoL, and we provide some recommendations to improve the measurement of this outcome in future trials., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

TCR repertoire diversification constitutes a foundation for successful immune reconstitution after allogeneic hematopoietic cell transplantation (allo-HCT). Deep TCR Vβ sequencing of 135 serial specimens from a cohort of 35 allo-HCT recipients/donors was performed to dissect posttransplant TCR architecture and dynamics. Paired analysis of clonotypic repertoires showed a minimal overlap with donor expansions. Rarefied and hyperexpanded clonotypic patterns were hallmarks of T cell reconstitution and influenced clinical outcomes. Donor and pretransplant TCR diversity as well as divergence of class I human leukocyte antigen genotypes were major predictors of recipient TCR repertoire recovery. Complementary determining region 3-based specificity spectrum analysis indicated a predominant expansion of pathogen- and tumor-associated clonotypes in the late post-allo-HCT phase, while autoreactive clones were more expanded in the case of graft-versus-host disease occurrence. These findings shed light on post-allo-HCT adaptive immune reconstitution processes and possibly help in tracking alloreactive responses.

Application of next generation sequencing (NGS) has shed light on the molecular heterogeneity of hematological malignancies. NGS panels targeting recurrent mutations have become common in many large centers and commercial laboratories. However, its impact in clinical practice is unclear. We sought to characterize the use of NGS at a tertiary care center in an observational study of 343 patients with suspected hematological malignancies. We found that NGS changed or refined the clinical and pathologic diagnosis in 9% of patients and affected management decisions in 65% (including clinical trial eligibility, targeted therapy selection, and consideration for stem cell transplantation). This study emphasizes early incorporation of NGS in clinical practice while also highlighting the present limitations. As our understanding of these disorders increases and more clinically relevant genetic targets emerge, it will be important to refine the molecular testing strategy to deliver personalized medicine given the high cost associated with this technology.

While red blood cells (RBCs) and granulocytes have been more studied, platelets and reticulocytes are not commonly used in paroxysmal nocturnal hemoglobinuria (PNH) flow-cytometry and less is known about susceptibility to complement-mediated destruction and effects of anti-complement therapy on these populations. We performed flow-cytometry of RBCs and granulocytes in 90 PNH patients and of platelets and reticulocytes in a subgroup (N = 36), to unveil perturbations of these populations during PNH disease course before and after anti-complement treatment. We found that platelets and reticulocytes were less sensitive to complement-mediated lysis than RBCs but not as resistant as granulocytes, as shown by mean sensitive fraction (difference in a given PNH population vs. PNH granulocyte clone size). In treated patients, reticulocytes, platelets, RBCs (with differences between type II and III) and granulocytes significantly increased post-treatment, confirming the role of PNH hematopoiesis within the context of anti-complement therapy. Moreover, we found that PNH platelet clone size reflects PNH granulocyte clone size. Finally, we established correlations between sensitive fraction of PNH cell-types and thrombosis. In sum, we applied a flow-cytometry panel for investigation of PNH peripheral blood populations' perturbations before and after eculizumab treatment to explore complement-sensitivity and kinetics of these cells during the disease course., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Approval of hypomethylating agents in patients with chronic myelomonocytic leukaemia is based on trials done in patients with myelodysplastic syndromes. We aimed to investigate whether hypomethylating agents provide a benefit in subgroups of patients with chronic myelomonocytic leukaemia compared with other treatments., Methods: For this retrospective cohort study, data were retrieved between Nov 30, 2017, and Jan 5, 2019, from 38 centres in the USA and Europe. We included non-selected, consecutive patients diagnosed with chronic myelomonocytic leukaemia, who received chronic myelomonocytic leukaemia-directed therapy. Patients with acute myeloid leukaemia according to 2016 WHO criteria at initial diagnosis (ie, ≥20% blasts in the bone marrow or peripheral blood) or with unavailability of treatment data were excluded. Outcomes assessed included overall survival, time to next treatment, and time to transformation to acute myeloid leukaemia. Analyses were adjusted by age, sex, platelet count, and Chronic myelomonocytic leukaemia-Specific Prognostic Scoring System (CPSS). Patients were grouped by first received treatment with either hydroxyurea, hypomethylating agents, or intensive chemotherapy, and stratified by risk according to blast count, French-American-British subtype, CPSS, WHO 2016 subtype, and the eligibility criteria of the DACOTA trial (NCT02214407)., Findings: 949 patients diagnosed with chronic myelomonocytic leukaemia between April 13, 1981, and Oct 26, 2018, were included. Median follow-up was 23·4 months (IQR 11·5-42·3) from diagnosis and 16·2 months (6·6-31·6) from start of first-line treatment. 412 (43%) of 949 patients received hypomethylating agents as first treatment, 391 (41%) hydroxyurea, and 83 (9%) intensive chemotherapy. Adjusted median overall survival for patients treated with hydroxyurea versus hypomethylating agents was 15·6 months (95% CI 13·1-17·3) versus 20·7 months (17·9-23·4); hazard ratio (HR) 1·39 (1·17-1·65; p=0·0002) and 14·0 months (9·8-17·2) versus 20·7 months (17·9-23·4; HR 1·55 [1·16-2·05]; p=0·0027) for those treated with intensive chemotherapy versus hypomethylating agents. In patients with myeloproliferative chronic myelomonocytic leukaemia (myeloproliferative CMML), median overall survival was 12·6 months (10·7-15·0) versus 17·6 months (14·8-21·5; HR 1·38 [1·12-1·70]; p=0·0027) for patients treated with hydroxyurea versus hypomethylating agents, and 12·3 months (8·4-16·6) versus 17·6 months (14·8-21·5; HR 1·44 [1·02-2·03]; p=0·040) for intensive chemotherapy versus hypomethylating agents. Hypomethylating agents did not confer an overall survival advantage for patients classified as having lower-risk disease (ie, myelodysplastic chronic myelomonocytic leukaemia with <10% blasts, CMML-0, or lower-risk CPSS)., Interpretation: These data suggest hypomethylating agents as the preferred therapy for patients with higher-risk chronic myelomonocytic leukaemia and those with myeloproliferative CMML. Our findings also suggest that CPSS is a valuable tool to identify patients who are most likely to benefit from hypomethylating agents. Further evidence from prospective cohorts would be desirable., Funding: The Austrian Group for Medical Tumor Therapy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The therapy algorithm for severe aplastic anaemia (sAA) is established but moderate AA (mAA), which likely reflects a more diverse pathogenic mechanism, often represents a treatment/management conundrum. A cohort of AA patients (n = 325) was queried for those with non-severe disease using stringent criteria including bone marrow hypocellularity and chronic persistence of moderately depressed blood counts. As a result, we have identified and analyzed pathological and clinical features in 85 mAA patients. Progression to sAA and direct clonal evolution (paroxysmal nocturnal haemoglobinuria/acute myeloid leukaemia; PNH/AML) occurred in 16%, 11% and 1% of mAA cases respectively. Of the mAA patients who received immunosuppressive therapy, 67% responded irrespective of time of initiation of therapy while conservatively managed patients showed no spontaneous remissions. Genomic analysis of mAA identified evidence of clonal haematopoiesis with both persisting and remitting patterns at low allelic frequencies; with more pronounced mutational burden in sAA. Most of the mAA patients have autoimmune pathogenesis similar to those with sAA, but mAA contains a mix of patients with diverse aetiologies. Although progression rates differed between mAA and sAA (P = 0·003), cumulative incidences of mortalities were only marginally different (P = 0·095). Our results provide guidance for diagnosis/management of mAA, a condition for which no current standard of care is established., (© 2020 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Purpose of Review: The lack of fully effective therapies to alter the natural course of myelodysplastic syndromes (MDS) leads to chronic morbidity, mortality and affects quality of life (QoL). Since existing therapies outside of hematopoietic cell transplantation (HCT) are not curative, there is a growing interest in incorporating patient-reported outcomes (PROs) as meaningful endpoints for these patients in research and clinical practice., Recent Findings: Currently, there are limited numbers of studies reporting the impact of MDS therapeutics on PROs to guide clinical decision-making and increase patient satisfaction. However, clinical trials that have incorporated QoL outcomes have demonstrated positive results with the use of growth factors, hypomethylating agents, and lenalidomide. Here we review and highlight the importance of harnessing the power of PROs as part of a comprehensive efficacy evaluation to ultimately deliver superior patient-centered care across the spectrum of MDS. As our understanding of MDS continues to increase, adapting the metrics of these outcome measurements will be equally important as the alteration of the natural history in developing new therapies.

The nucleoside analogue decitabine can deplete the epigenetic regulator DNA methyltransferase 1 (DNMT1), an effect that occurs, and is saturated at, low concentrations/doses. A reason to pursue this molecular-targeted effect instead of the DNA damage/cytotoxicity produced with high concentrations/doses, is that non-cytotoxic DNMT1-depletion can cytoreduce even p53-null myeloid malignancies while sparing normal haematopoiesis. We thus identified minimum doses of decitabine (0·1-0·2 mg/kg) that deplete DNMT1 without off-target anti-metabolite effects/cytotoxicity, and then administered these well-tolerated doses frequently 1-2X/week to increase S-phase dependent DNMT1-depletion, and used a Myeloid Malignancy Registry to evaluate long-term outcomes in 69 patients treated this way. Consistent with the scientific rationale, treatment was well-tolerated and durable responses were produced (~40%) in genetically heterogeneous disease and the very elderly., (© 2019 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: There are approximately 2.1 million recreational surfers in the United States. However, little has been reported on surfing-related injuries and, to date, no study has utilized magnetic resonance imaging (MRI) to characterize injury patterns., Objective: To use MRI to perform a descriptive analysis of surfing injuries in patients who presented to an urban tertiary care musculoskeletal hospital. This was not a hypothesis-driven study., Study Design: Case series., Level of Evidence: Level 4., Methods: A retrospective review of the picture archiving and communication system as well as the electronic medical record was performed to identify patients with surfing-related injuries who presented to a tertiary care musculoskeletal hospital for treatment. The search included participants over a 10-year period who presented between January 1, 2009, and August 1, 2018. Descriptive data analyses were performed to determine frequency of body part injured, diagnosis, and operative versus nonoperative treatment., Results: The search yielded 109 patients with surfing-related injuries and MRIs. A total of 90 patients presented within 6 months of their surfing injury and were included in the final analysis. The median age was 36 years (range, 12-66 years). A majority of the patients included were male (74%; n = 67). Acute surfing injuries were diagnosed via imaging in 72% (n = 65) of patients. The joints injured most commonly were the shoulder (46%; n = 30) and the knee (28%; n = 18). Only 17% (n = 11) of acute surfing injuries required surgery, while 83% (n = 54) were treated nonoperatively., Conclusion: The most common surfing-related injuries occurred in the shoulder and knee., Clinical Relevance: This study helps characterize the risk of injury for surfers and informs healthcare providers on common surfing injuries.

Lower-risk myelodysplastic syndromes are defined using prognostic scoring systems that incorporate data on bone marrow blast percentage, degree and numbers of cytopenias, and cytogenetic abnormalities. Increasingly, these are incorporating molecular abnormalities to further refine risk. Therapy is geared toward predominating cytopenias, with erythropoiesis-stimulating agents luspatercept and lenalidomide used to ameliorate anemia, romiplostim and eltrombopag tackling thrombocytopenia, and hypomethylating agents and antithymocyte globulin palliating pancytopenia. Newer agents on the horizon are abrogating the downstream sequelae of specific molecular mutations. One challenge for the future is in further modifying response criteria to align with improvements that are clinically meaningful to patients., Competing Interests: Conflict-of-interest disclosure: M.A.S. has served on advisory boards for Celgene and Millennium/Takeda. B.J.P. declares no competing financial interests., (© 2019 by The American Society of Hematology. All rights reserved.)

For chronic malignant and benign ureteral obstruction, the metal construction of the Resonance ureteral stent has been developed to maintain ureteral patency for up to 12 months, obviating the need for the frequent exchange required for conventional plastic ureteral stents. We report our experience placing tandem Resonance stents (TRS) in a single ureter of patients who failed management with a single Resonance stent. A retrospective review of patients who had TRS for management of ureteral obstruction between February 2014 and May 2017 was performed. Seven renal units from four patients with a median age of 62 years were managed with TRS. All but one renal unit was successfully managed with TRS initially. Hydronephrosis resolved in 80% of renal units at a median of 33 days, and creatinine reached its nadir a median of 38 days after placement, with a median improvement of 0.68 ng/mL. However, the median length of management with TRS was only 123.5 days with one exchange, and there was an overall success rate of 28.5% at 1 year. TRS placement is a feasible option for short-term management in a challenging population that would like to avoid nephrostomy and has failed other modalities., (Copyright © 2019 Baylor University Medical Center.)

In recent past, the respiratory infection has emerged as a great challenge to the poultry farmers. Various pathogens including Avian pneumovirus (APV), Avian influenza virus (AIV), Infectious bronchitis virus (IBV) and Newcastle disease virus (NDV), Avibacterium paragallinarum, Ornithobacterium rhinotracheale (ORT), Mycoplasma synoviae (MS), Mycoplasma gallisepticum (MG) and Avian pathogenic Escherichia coli (APEC) are involved in the respiratory disease complex in birds [1], [2] (Bradbury, 1984; Roussan et al., 2008). Hence, respiratory disease complex is the most serious disease affecting to poultry and causes heavy economic losses in the poultry industry worldwide [3] (Murthy et al., 2008). In recent years, metagenomics is powerful analyzing tool for detection of pathogens directly from clinical samples without any prior knowledge of the organism in a given sample [4], [5] (Schuster, 2008; Pereira et al., 2010). High throughput Next-Generation-Sequencing technology was used for sequencing the isolated genomic DNA. These data provides an insight about taxonomic and functional status of microorganisms responsible for causing respiratory infection in broiler. The data of these metagenome are available in the BioSample Submission Portal as Bioproject PRJNA339659 and SRA accession number SRR5997823, SRR5992854, SRR6037376, SRR6024702, SRR6012248 and SRR6008913.

Potentially fatal arrhythmias add to the mental health challenges of adolescence. This systematic review sought to summarise current knowledge regarding the mental health of adolescents and pre-adolescents diagnosed with inherited arrhythmia syndromes. Searches combining psychological problems with inherited cardiac arrhythmia diagnoses identified 16 studies with paediatric (<18 years) inherited arrhythmia patients. All studies were cross-sectional; 8/16 required an implantable cardioverter defibrillator. Methods were quantitative (n=11), qualitative (n=4), or mixed (n=1), with 14-100% of participants having an inherited arrhythmia syndrome. Mean/median age in 13/16 studies was 12-16 years. Patients and parents reported lower quality of life, particularly in relation to physical function, social relationships, restriction of peer activities, bodily pain, and mental and emotional health. Self-perceptions and behaviour were similar to healthy populations. Rates of anxiety and depression (15-33% of these patients) were not increased in these studies where patients were assessed 2+ years after diagnosis. Higher mental health risk occurred among patients who have a diagnosed sibling, those with cardiomyopathy, and those who report decreased quality of life. Mental health research among youth with inherited arrhythmias is extremely limited and of low quality. Data, primarily from patients 2-4 years after diagnosis or treatment with an implantable cardioverter defibrillator, indicate that quality of life may be decreased and 15-33% experience mental health issues. Future research is required to examine the mental health and quality of life of paediatric patients with inherited arrhythmia syndromes, whether or not they have an implantable cardioverter defibrillator, from time of diagnosis.

Outcomes of relapsed adult acute lymphoblastic leukemia (ALL) have improved over time with the introduction of new therapies as well as better supportive care. However, there is still a need for easy-to-use and accurate prognostic tools for patients in first relapse. Whether complete response (CR) with incomplete count recovery (CRh) can be grouped with CR in relapsed ALL trials has not been formally studied. We analyzed 106 ALL patients at first relapse who were treated at three academic centers and achieved CR/CRh. White blood cell count at initial diagnosis and receiving hematopoietic cell transplant (HCT) were independent predictors of overall survival after relapse, while minimal residual disease (MRD) positivity and performance of HCT were predictors of relapse free survival (RFS). Patients who achieved MRD negativity and underwent HCT had the best outcomes. Our results suggest that MRD is a more powerful predictor of outcome than CRh.

Using next generation sequencing we have systematically analyzed a large cohort of 489 patients with bone marrow failure (BMF), including myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), aplastic anemia (AA), and related conditions for the presence of germline (GL) alterations in Fanconi Anemia (FA) and telomerase genes. We have detected an increased frequency of heterozygous FA gene mutations in MDS and to lesser degree in AML suggesting that the presence of one normal allele may not be completely protective and indeed heterozygous FA lesions may have a long latency period before hematologic manifestation. In contrast, GL telomerase gene mutations were not associated with increased disease risk. When compared to large control cohorts, we have not detected an increased frequency of damaging variants among telomerase complex genes, including those previously believed to be involved in the pathogenesis of AA. Our results may suggest that while low penetrance and delayed disease onset can confound identification of genetic predisposition factors, GL FA alterations can be also associated with MDS., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

The biology, clinical phenotype and progression rate of chronic myelomonocytic leukemia (CMML) are highly variable due to diverse initiating and secondary clonal genetic events. To determine the effects of molecular features including clonal hierarchy in CMML, we studied whole-exome and targeted next-generation sequencing data from 150 patients with robust clinical and molecular annotation assessed cross-sectionally and at serial time points of disease evolution. To identify molecular lesions unique to CMML, we compared it to the related myeloid neoplasms (N=586), including juvenile myelomonocytic leukemia, myelodysplastic syndromes (MDS) and primary monocytic acute myeloid leukemia and discerned distinct molecular profiles despite similar pathomorphological features. Within CMML, mutations in certain pathways correlated with clinical classification, for example, proliferative vs dysplastic features. While most CMML patients (59%) had ancestral (dominant/co-dominant) mutations involving TET2, SRSF2 or ASXL1 genes, secondary subclonal hierarchy correlated with clinical phenotypes or outcomes. For example, progression was associated with acquisition of new expanding clones carrying biallelic TET2 mutations or RAS family, or spliceosomal gene mutations. In contrast, dysplastic features correlated with mutations usually encountered in MDS (for example, SF3B1 and U2AF1). Classification of CMML based on hierarchies of ancestral and subclonal mutational events may correlate strongly with clinical features and prognosis.

Psychosocial health issues are common among children with cardiac diagnoses. Understanding parent and child perceptions is important because parents are the primary health information source. Significant discrepancies have been documented between parent/child quality-of-life data but have not been examined among psychosocial diagnostic instruments. This study examined agreement and discrepancies between parent and child reports of psychosocial health and quality of life in the paediatric cardiology population. Children (n=50, 6-14 years) with diagnoses of CHDs (n=38), arrhythmia (n=5), cardiomyopathy (n=4), or infectious disease affecting the heart (n=3) were enrolled, completing one or more outcome measures. Children and their parents completed self-reports and parent proxy reports of quality of life - Pediatric Quality of Life Inventory - and psychosocial health - Behavioral Assessment Scale for Children (Version 2). Patients also completed the Multidimensional Anxiety Scale for Children. Associations (Pearson's correlations, Intraclass Correlation Coefficients) and differences (Student's t-tests) between parent proxy reports and child self-reports were evaluated. Moderate parent-child correlations were found for physical (R=0.33, p=0.03), school (R=0.43, p<0.01), social (R=0.36, p=0.02), and overall psychosocial (R=0.43, p<0.01) quality of life. Parent-child reports of externalising behaviour problems, for example aggression, were strongly correlated (R=0.70, p<0.01). No significant parent-child associations were found for emotional quality of life (R=0.25, p=0.10), internalising problems (R=0.17, p=0.56), personal adjustment/adaptation skills (R=0.23, p=0.42), or anxiety (R=0.07, p=0.72). Our data suggest that clinicians caring for paediatric cardiac patients should assess both parent and child perspectives, particularly in relation to domains such as anxiety and emotional quality of life, which are more difficult to observe.

Purpose: Cryotherapy and brachytherapy are definitive local treatment options for low- to intermediate-risk prostate cancer. There are both prospective and retrospective data for brachytherapy, but the use of cryotherapy has been limited primarily to single-institution retrospective studies. Currently, no published evidence has compared low-dose-rate brachytherapy versus cryotherapy., Methods and Materials: Institutional review board approval was obtained to conduct a retrospective chart review of consecutive patients treated at our institution from 1990 to 2012. For inclusion, patients must have received a prostate cancer diagnosis and have been considered to have low- to intermediate-risk disease according to the National Comprehensive Cancer Network criteria. All patients received brachytherapy or cryotherapy treatment. Disease specifics and failure details were collected for all patients. Failure was defined as prostate-specific antigen nadir +2 ng/mL., Results: A total of 359 patients were analyzed. The groups comprised 50 low-risk cryotherapy (LRC), 92 intermediate-risk cryotherapy (IRC), 133 low-risk brachytherapy (LRB), and 84 intermediate-risk brachytherapy (IRB) patients. The median prostate-specific antigen follow-up periods were 85.6 months (LRC), 59.2 months (IRC), 74.9 months (LRB), and 59.8 months (IRB). The 5-year biochemical progression-free survival (bPFS) rate was 57.9% in the cryotherapy group versus 89.6% in the brachytherapy group (P<.0001). The 5-year bPFS rate was 70.0% (LRC), 51.4% (IRC), 89.4% (LRB), and 89.7% (IRB). The bPFS rate was significantly different between brachytherapy and cryotherapy for low- and intermediate-risk groups (P<.05). The mean nadir temperature reached for cryotherapy patients was -35°C (range, -96°C to -6°C). Cryotherapy used a median of 2 freeze-thaw cycles (range, 2-4 freeze-thaw cycles)., Conclusions: Results from this study suggest that cryotherapy is inferior to brachytherapy for patients with low- to intermediate-risk prostate cancer. Patient selection criteria for consideration of cryotherapy and brachytherapy are similar in terms of anesthesia candidacy. Therefore, cryotherapy would not be recommended as a first-line local therapy for this particular patient subset., (Copyright © 2017 Elsevier Inc. All rights reserved.)