The face of remission induction

Acute myeloid leukaemia (AML) is a heterogeneous disease in which prognosis is determined by cytogenetic and molecular aberrations as well as patient-related factors, including age, prior haematologic disorders, and comorbidities. Despite the diverse disease biology, the standard of care for remission induction therapy has changed very little since its inception in 1973. Next generation sequencing has helped to increase our knowledge of the disease pathogenesis, allowing us to develop targeted and possibly more effective treatment options. Seven new agents have been approved for the treatment of AML since 2017, all of which are directed toward a specific molecular subtype or patient population. With the advent of these therapies, a more optimal, patient-specific approach rather than the historical ‘one-size fits all’ model can be utilised. This review will discuss the role of these novel therapies in the remission induction setting.     

Comparative evaluation of 2-point vs 3-point fixation in the treatment of zygomaticomaxillary complex fractures – A systematic review

BackgroundThe zygomaticomaxillary complex (ZMC) functions as the main buttress for the lateral portion of the middle third of the facial skeleton and because of its prominent position & convex shape, it is frequently fractured, alone or along with other bones of the midface. The management of the ZMC fractures is debatable as the literature is saturated with various theories. A number of techniques, from closed reduction to open reduction and internal fixation can be effectively used to manage these fractures. Controversies lie right from the amount of fixation (1-, 2-, 3- or 4- point fixation) required to the ideal approach, and there is no conclusive view on its ideal line of management.ObjectiveTo compare Malar asymmetry after 2-point vs 3-point fixation in the treatment of zygomaticomaxillary complex fractures.Data sourceElectronic search of Pub Med, Google Scholar, Institutional Library, Email to authors and manual search of various journals.Study eligibility criteriaThe following criteria were used to select the studies on 2- point and 3-point fixation methods in Zygomaticomaxillary complex fractures. Inclusion criteria had articles that included clinical studies published in the English language or those having sufficient data in English on 2-point or 3-point fixation in the treatment of zygomaticomaxillary complex fractures between the period of 1st January 2008 to 30th September 2018. While exclusion criteria were articles not published in the English language before 1st January 2008 and after 30th September 2018, any reviews, abstracts, letters to editors, editorials and in vitro studies were excluded. Studies that included patients with craniofacial and secondary deformities were also excluded.InterventionOpen reduction and internal fixation using 2-point and 3-point fixation methods in the treatment of Zygomaticomaxillary complex fractures.ResultsPreliminary screening consisted of 757 studies and additional records identified through other sources of 272 studies. Amongst these 1029 studies, 837 studies were excluded after reviewing the titles. A review of abstract further excluded 71 studies, so 34 studies that remained were evaluated to fit the eligibility criteria. On the basis of information on fixation methods and parameters of evaluation of fixation method, 26 studies were further excluded. Thus 8 studies with a total of 823 estimates were included in qualitative synthesis.LimitationsParameters assessed by all the authors varied and hence a standardisation for comparison could not be done.ConclusionFive out of eight studies showed that the use of 3-point fixation in the treatment of zygomaticomaxillary complex fractures was superior than 2-point fixation for the same. Hence it can be concluded that 3-point fixation is superior than 2-point fixation in reducing malar asymmetry in zygomaticomaxillary complex fractures.Future implicationsFuture studies with uniform parameters being assessed can be done. 3-point fixation can be used as a standard treatment modality in the effective management of Zygomaticomaxillary complex fractures.     

Diabetic foot ulcers—where do we stand microbiologically?

Foot ulcers in diabetics are prone to polymicrobial infection by bacteria as well as fungi. Infection retards healing of ulcers leading to gangrene and ultimately, amputation of the extremity. The choice of empiric antibiotic therapy is extrapolated from results of studies from other regions, western literature or infection at other sites which may be inappropriate. Thus, a study was conducted to determine microbial aetiology of diabetic foot ulcers and their susceptibility patterns. Pus aspirates or wound swabs were collected from foot ulcers of 70 diabetics at the time of admission and processed for isolation of bacteria (aerobic and anaerobic) and fungi according to standard protocols. Organisms were identified upto species level. Antimicrobial susceptibility testing was performed by Kirby Bauer disk diffusion method as per CLSI standards. One hundred forty-seven organisms were isolated from 70 specimens. Seventy-three percent showed polymicrobial growth. The proportion of Gram negative bacilli, Gram positive cocci, anaerobes and fungi were 57 %, 27 %, 4 % and 12 % respectively. Enterobacteriaceae were the predominant Gram negative bacilli and S.aureus, the predominant Gram positive cocci. Clostridium and Candida species were the commonest among anaerobes and fungi respectively. Twenty-three percent of S.aureus were MRSA and 23 % of Enterobacteriaceae were ESBL producers. Ps.aeruginosa strains demonstrated good susceptibility to antipseudomonal antimicrobials and 16.5 % strains were meropenem resistant. Due to the associated risk of increased morbidity and mortality in infected diabetic ulcers, the wide spectrum of organisms associated with it and their differing susceptibility profile, treatment should be individualised based on microbial culture and antimicrobial susceptibility results.     

Laboratory misdiagnosis of von Willebrand disease in post-menarchal females: A multi-center study

Increased awareness of von Willebrand Disease (VWD) has led to more frequent diagnostic laboratory testing, which insurers often dictate be performed at a facility with off-site laboratory processing, instead of a coagulation facility with onsite processing. Off-site processing is more prone to preanalytical variables causing falsely low levels of von Willebrand Factor (VWF) due to the additional transport required. Our aim was to determine the percentage of discordance between off-site and onsite specimen processing for VWD in this multicenter, retrospective study. We enrolled females aged 12 to 50 years who had off-site specimen processing for VWF assays, and repeat testing performed at a consulting institution with onsite coagulation phlebotomy and processing. A total of 263 females from 17 institutions were included in the analysis. There were 251 subjects with both off-site and onsite VWF antigen (VWF:Ag) processing with 96 (38%) being low off-site and 56 (22%) low onsite; 223 subjects had VWF ristocetin co-factor (VWF:RCo), 122 (55%) were low off-site and 71 (32%) were low onsite. Similarly, 229 subjects had a Factor VIII (FVIII) assay, and 67 (29%) were low off-site with less than half, 29 (13%) confirmed low with onsite processing. Higher proportions of patients demonstrated low VWF:Ag, VWF:RCo, and/or FVIII with off-site processing compared to onsite (McNemarʼs test P-value <.0005, for all assays). These results emphasize the need to decrease delays from sample procurement to processing for VWF assays. The VWF assays should ideally be collected and processed at the same site under the guidance of a hematologist.     

Rasch analysis of clinical outcome measures in spinal muscular atrophy

Introduction: Trial design for SMA depends on meaningful rating scales to assess outcomes. In this study Rasch methodology was applied to 9 motor scales in spinal muscular atrophy (SMA). Methods: Data from all 3 SMA types were provided by research groups for 9 commonly used scales. Rasch methodology assessed the ordering of response option thresholds, tests of fit, spread of item locations, residual correlations, and person separation index. Results: Each scale had good reliability. However, several issues impacting scale validity were identified, including the extent that items defined clinically meaningful constructs and how well each scale measured performance across the SMA spectrum. Conclusions: The sensitivity and potential utility of each SMA scale as outcome measures for trials could be improved by establishing clear definitions of what is measured, reconsidering items that misfit and items whose response categories have reversed thresholds, and adding new items at the extremes of scale ranges. Muscle Nerve 49 :422–430, 2014     

Sibling concordance for clinical features of Duchenne and Becker muscular dystrophies

Introduction: The correlation of markers of disease severity among brothers with Duchenne or Becker muscular dystrophy has implications for clinical guidance and clinical trials. Methods: Sibling pairs with Duchenne or Becker muscular dystrophy (n = 60) were compared for ages when they reached clinical milestones of disease progression, including ceased ambulation, scoliosis of ≥ 20°, and development of cardiomyopathy. Results: The median age at which younger brothers reached each milestone, compared with their older brothers ranged from 25 months younger for development of cardiomyopathy to 2 months older for ceased ambulation. For each additional month of ambulation by the older brother, the hazard of ceased ambulation by the younger brother decreased by 4%. Conclusions: The ages when siblings reach clinical milestones of disease vary widely between siblings. However, the time to ceased ambulation for older brothers predicts the time to ceased ambulation for their younger brothers. Muscle Nerve 49 : 814–821, 2014     

Phenazopyridine associated acute interstitial nephritis and review of literature

Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration, hepatitis and acute renal failure. Various case reports with phenazopyridine associated acute renal failure secondary to acute tubular necrosis have been reported in the literature. Acute kidney injury in these patients is caused by either direct injury to renal tubular epithelial cells or secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury from phenazopyridine-induced methemoglobinemia has been well documented. We report a case of biopsy proven acute interstitial nephritis, associated with therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or other mechanism of renal injury. Clinicians should be aware of the toxicity of this commonly used drug and should look closely for signs of renal insufficiency. Identifying and stopping the offending medication stays as the first step, but recent studies indicate that early steroid administration improves renal recovery, as well as decreasing the risk of progression to chronic kidney disease with fibrosis and consequent permanent renal damage.     

Estimating the seroprevalence of chikungunya virus exposure in Shimoga district,Karnataka state: A hospital-based study during 2014-2018

Chikungunya fever is a viral disease transmitted to humans by the bite of infected mosquitoes. The disease is characterized by fever, headache, rash, severe joint, and muscle pain. To evaluate the disease burden in the population and the effectiveness of public health measures, periodic seroprevalence surveys are essential. Chikungunya outbreaks were reported from many Asian countries since 2005, after more than three decades of disappearance. The study aimed to estimate the seroprevalence of the chikungunya virus in southern parts of Karnataka state, through demonstrating chikungunya virus-specific neutralizing antibodies. A cross-sectional study was carried out using 509 archived blood samples from a hospital-based acute febrile illness surveillance project, representative of the period between June 2014 and 2018. The study reported a 3.7% seroprevalence of chikungunya virus-neutralizing antibodies in Thirthahalli and Hosanagara taluks of South Karnataka. The low prevalence of chikungunya-neutralizing antibodies indicates that a major population is unexposed and prone to future outbreaks.     

Association of FADS2 rs174575 gene polymorphism and insulin resistance in type 2 diabetes mellitus

BackgroundMany risk factors contribute to the pathogenesis of diabetes. Gene and lifestyle factors are considered to be the major contributors. A dietary pattern is attributed to be one of the lifestyle risk factors favoring diabetes. The present study aims to find an association between fatty acid desaturase (FADS) gene polymorphism and glycemic profile in type 2 diabetes mellitus (T2DM).MethodologyA total of 429 subjects were included in the study on the basis of inclusion and exclusion criteria, of which 213 and 216 subjects were diabetic and control, respectively. Body mass index was calculated. Fasting plasma glucose, glycated hemoglobin (HbA1c) and insulin were measured using commercially available kits. rs174575 of FADS2 was selected based on previous publications and identified using the dbSNP database. To compare the biochemical parameters with the genotype, the following three models were used: additive model (CC vs CG vs GG), dominant model (CC + CG vs GG), and recessive model (CC vs CG + GG).Results and DiscussionFBS, HbA1c, insulin, HOMA-IR, and HOMA-B exhibited a high and statistically significant difference between subjects and controls. The three models exhibited a statistically significant difference between FBS, HOMA-IR, and HOMA- B (p<0.05).ConclusionThe distribution of rs174575 genotype differed significantly between the subjects and controls in the present study. The study revealed that genetic variation in FADS2 is an additional facet to consider while studying the risk factors of T2DM.