Frequency of Restless Legs Syndrome in Pakistani Patients With Type 2 Diabetes Mellitus.

Objective To determine the frequency of restless legs syndrome (RLS) among Pakistani patients with type 2 diabetes mellitus. Methods This observational cross-sectional study was carried out in the Department of Medicine at Bahawal Victoria Hospital, Quaid-e-Azam Medical College, Bahawalpur, Pakistan, from January 2024 to May 2024. The National Institute of Health (NIH) diagnostic criteria were used to diagnose RLS. Type 2 diabetes mellitus was defined as patients with an HbA1c greater than 7.0%, two random blood glucose readings of ≥200 mg/dL, a previous history of diabetes diagnosis, or those taking anti-hyperglycemic medicines. Patients with a history of leg surgery or amputation, iron deficiency anemia, alcoholism, end-stage kidney disease, chronic liver disease, those on hemodialysis, and pregnant women were excluded from the study. After ethical approval and informed consent were obtained, 255 patients with type 2 diabetes mellitus were included in the study using a non-probability consecutive sampling technique. Demographic information including age, gender, and duration of diabetes was noted, and patients were assessed for diabetes control, peripheral neuropathy, retinopathy, and RLS Patient records were assessed for HbA1c levels and urine examination to diagnose nephropathy. All data were entered into SPSS version 23. A Chi-Square test was applied post-stratification using a p-value of less than 0.05 as significant. Results The mean age was 53.5 ± 12.8 years with 140 (54.9%) females. The mean duration of the disease and mean HbA1c were 6.8 ± 5.4 years and 9.8 ± 2.5%, respectively, with 191 (74.9%) patients having poor control of diabetes. Peripheral neuropathy was seen in 131 (51.4%) patients, retinopathy in 58 (22.7%), and nephropathy in 23 (9.0%). RLS was present in 34 (13.3%) patients with type 2 diabetes mellitus, showing a significant association with diabetes control (p-value = 0.001), peripheral neuropathy (p-value = 0.016), retinopathy (p-value = 0.006), and nephropathy (p-value = 0.011), but not with age (p-value = 0.122), gender (p-value = 0.217), or duration of diabetes (p-value = 0.922). Conclusion RLS was not an uncommon finding in patients with type 2 diabetes mellitus, being more common among those with poor diabetes control and the presence of other complications such as neuropathy, nephropathy, and retinopathy.

Diagnosis and evaluation of prognosis of myelofibrosis: a British Society for Haematology guideline

This document represents an update of the British Society for Haematology (BSH) guideline on myelofibrosis (MF) first published in 2012 and updated in 2015.1 This guideline aims to provide healthcare professionals with clear guidance on the diagnosis and prognostic evaluation of primary my-elofibrosis (PMF), as well as post-polycythaemia vera myelo-fibrosis (post-PV MF) and post-essential thrombocythaemia myelofibrosis (post-ET MF). A section on prefibrotic MF is also included. A separate BSH Guideline covers the manage-ment of MF and is published alongside this guideline.

The management of myelofibrosis: a British Society for Haematology guideline

This document represents an update of the British Society for Haematology guideline on Myelofibrosis first published in 2012 and updated in 2015 These guidelines aim to pro-vide healthcare professionals with clear guidance on stratified management for primary myelofibrosis (PMF), as well as post-polycythaemia myelofibrosis (post-PV MF) and postessential thrombocythaemia myelofibrosis (post-ET MF). A separate BSH guideline covers the diagnosis and prognostic evaluation of myelofibrosis and is published alongside this guideline

Tamoxifen for the treatment of myeloproliferative neoplasms: A Phase II clinical trial and exploratory analysis.

Current therapies for myeloproliferative neoplasms (MPNs) improve symptoms but have limited effect on tumor size. In preclinical studies, tamoxifen restored normal apoptosis in mutated hematopoietic stem/progenitor cells (HSPCs). TAMARIN Phase-II, multicenter, single-arm clinical trial assessed tamoxifen's safety and activity in patients with stable MPNs, no prior thrombotic events and mutated JAK2V617F, CALRins5 or CALRdel52 peripheral blood allele burden ≥20% (EudraCT 2015-005497-38). 38 patients were recruited over 112w and 32 completed 24w-treatment. The study's A'herns success criteria were met as the primary outcome ( ≥ 50% reduction in mutant allele burden at 24w) was observed in 3/38 patients. Secondary outcomes included ≥25% reduction at 24w (5/38), ≥50% reduction at 12w (0/38), thrombotic events (2/38), toxicities, hematological response, proportion of patients in each IWG-MRT response category and ELN response criteria. As exploratory outcomes, baseline analysis of HSPC transcriptome segregates responders and non-responders, suggesting a predictive signature. In responder HSPCs, longitudinal analysis shows high baseline expression of JAK-STAT signaling and oxidative phosphorylation genes, which are downregulated by tamoxifen. We further demonstrate in preclinical studies that in JAK2V617F+ cells, 4-hydroxytamoxifen inhibits mitochondrial complex-I, activates integrated stress response and decreases pathogenic JAK2-signaling. These results warrant further investigation of tamoxifen in MPN, with careful consideration of thrombotic risk.

Proteus Syndrome: A Rare Disease Of Disproportionate And Asymmetric Overgrowth Of Connective Tissue.

Proteus syndrome is a rare disease manifested by progressive segmental overgrowth involving the skeletal, Cutaneous, subcutaneous, and nervous systems. We report the case of a 24-year-old female who was born with no obvious abnormality at birth. From the age of 1 year, she developed asymmetric enlargement of her left upper limb and bilateral lower limbs leading to enlargement of the right-hand phalanges with radial deviation, enlargement of the right big toe, lateral deviation of left foot, and discrepancy in the length of lower extremities and kyphoscoliosis. She had become bed-bound for the last few years due to increasing disability. She was diagnosed with Proteus syndrome based on clinical features of progressive course, mosaic distribution, and sporadic occurrence of the lesions.

Eosinophilic Granulomatosis with Polyangiitis (EGPA): A case report with atypical presentation.

A 72-year-old asthmatic gentleman with a history of recurrent sinusitis and chronic bronchitis presented with shortness of breath and progressively worsening hypoxemic respiratory failure. His CT chest demonstrated airspace disease bilaterally with ground-glass opacifications. He had peripheral eosinophilia with raised inflammatory markers but negative work up of infection. On further investigation, ANA was positive, titer 1:160, speckled pattern and both pANCA and cANCA were present. The patient was diagnosed with Eosinophilic Granulomatosis with Polyangiitis (EGPA) and started on intravenous steroids and cyclophosphamide. A rare multi-organ vasculitis, EGPA is hallmarked by asthma, sinusitis and eosinophilia. In initial stages vasculitic involvement is not usually seen thereby making EGPA a diagnostic challenge.

Avapritinib versus Placebo in Indolent Systemic Mastocytosis.

BACKGROUND: Indolent systemic mastocytosis (ISM) is a clonal mast-cell disease driven by the KIT D816V mutation. We assessed the efficacy and safety of avapritinib versus placebo, both with best supportive care, in patients with ISM. METHODS: We randomized patients with moderate to severe ISM (total symptom score [TSS] of ≥28; scores range from 0 to 110, with higher numbers indicating more severe symptoms) two to one to avapritinib 25 mg once daily (n=141) or placebo (n=71). The primary end point was mean change in TSS based on the 14-day average of patient-reported severity of 11 symptoms. Secondary end points included reductions in serum tryptase and blood KIT D816V variant allele fraction (≥50%), reductions in TSS (≥50% and ≥30%), reduction in bone marrow mast cells (≥50%), and quality of life measures. RESULTS: From baseline to week 24, avapritinib-treated patients had a decrease of 15.6 points (95% CI, −18.6 to −12.6) in TSS compared to a decrease of 9.2 points (−13.1 to −5.2) in the placebo group; P<0.003. From baseline to Week 24, 76/141 patients (54%; 45% to 62%) in the avapritinib group compared to 0/71 patients in the placebo group achieved a ≥50% reduction in serum tryptase level; P<0.001. Edema and increases in alkaline phosphatase were more common with avapritinib than placebo; there were few treatment discontinuations because of adverse events. CONCLUSIONS: In this trial, avapritinib was superior to placebo in reducing uncontrolled symptoms and mast-cell burden in patients with ISM. The long-term safety and efficacy of this approach for patients with ISM remain the focus of the ongoing trial. (Funded by Blueprint Medicines Corporation; ClinicalTrials.gov number, NCT03731260.)

Lupus Vasculitis.

We present the case of a 30-year-old woman who presented with 8-month history of intermittent fever, joint pains with morning stiffness, recurrent oral ulcers, photosensitivity, weight loss and hair fall. For the last 2 months, she had developed a dry cough with progressive shortening of breath. On examination, a cachexic lady with malar hyperpigmentation, alopecia, pallor, nail dystrophy and erythema over her hands and feet were noted. There were multiple punched-out skin ulcers of variable size over legs, arms and abdomen usually round in shape with well-defined even wound margins and scant serous discharge. Musculoskeletal examination revealed synovitis of both elbows and a few metacarpophalangeal and proximal interphalangeal joints. Chest X-ray and HRCT showed bilateral ground-glass opacification. Anti-Nuclear Antibody (ANA) was positive, 1:320, homogenous nuclear pattern. Anti-Ro antibody was highly positive and serum complement (C3, C4) levels were reduced. She was diagnosed with Lupus Vasculitis and started on steroids, mycophenolate mofetil and hydroxychloroquine.

Refractory Sarcoidosis.

A multi-organ granulomatous disease with characteristic lung manifestations, sarcoidosis generally responds well to glucocorticoid therapy but 10% of cases are refractory necessitating immunosuppressive therapy. A 58-year-old lady presented with a dry cough and progressively worsening shortness of breath for the last 12 months. On investigation, her ESR was raised but cultures, malignancy screen and TB quantiferon were negative. HRCT chest demonstrated multiple pulmonary nodules with hilar lymphadenopathy and CT guided biopsy revealed non-caseating granuloma. She was diagnosed with Pulmonary Sarcoidosis and started on oral steroids with minimal improvement. Azathioprine was added but due to gastric intolerance switched to methotrexate. Her disease however continued to worsen and infliximab was started but she developed a severe allergic reaction. She was then started on mycophenolate mofetil but her chest imaging continued to worsen. After failing prednisone, azathioprine, methotrexate, infliximab and mycophenolate mofetil, the patient was started on rituximab.

Prostatitis As An Initial Presentation For Granulomatosis With Polyangiitis.

Granulomatosis with polyangiitis (GPA) is an uncommon pauci-immune small-vessel necrotising granulomatous vasculitis mostly seen in age 45-60 years. We present the case of a formerly healthy 44 years old male presenting with dysuria and intermittent urinary retention for 8 months, not responding to empirical antibiotic therapy and TURP. A prostate biopsy showed necrotising granulomatous prostatitis. Urinalysis demonstrated persistent pyuria and haematuria, but cultures showed no growth. Subsequently he complained of fever, cough, dyspnoea and skin ulcers. CT of the chest showed multiple cavitatory lesions and pleural effusion. On work up, c-ANCA was positive and a diagnosis of granulomatosis with polyangiitis was established. This depicts a rarely seen presentation of prostatitis as the initial feature of GPA.

A retrospective real-world study of the current treatment pathways for myelofibrosis in the United Kingdom: the REALISM UK study.

Background: Myelofibrosis (MF) is a blood cancer associated with splenomegaly, blood count abnormalities, reduced life expectancy and high prevalence of disease-associated symptoms. Current treatment options for MF are diverse, with limited data on management strategies in real-world practice in the United Kingdom. Methods: The REALISM UK study was a multi-center, retrospective, non-interventional study, which documented the early management of patients with MF. The primary endpoint was the time from diagnosis to active treatment. Discussion: Two hundred patients were included (63% [n = 126/200] with primary MF; 37% [n = 74/200] with secondary MF). Symptoms and prognostic scores at diagnosis were poorly documented, with infrequent use of patient reported outcome measures. 'Watch and wait' was the first management strategy for 53.5% (n = 107/200) of patients, while the most commonly used active treatments were hydroxycarbamide and ruxolitinib. Only 5% of patients proceeded to allogeneic transplant. The median (IQR) time to first active treatment was 46 days (0-350); patients with higher risk disease were prescribed active treatment sooner. Conclusion: These results provide insight into real-world clinical practice for patients with MF in the United Kingdom. Despite the known high prevalence of disease-associated symptoms in MF, symptoms were poorly documented. Most patients were initially observed or received hydroxycarbamide, and ruxolitinib was used as first-line management strategy in only a minority of patients. Plain Language Summary: Background: Myelofibrosis is a rare blood cancer associated with symptoms that can seriously affect a patient's daily life, such as enlarged spleen and decreased white and red blood cells. Although several treatments are available for patients with myelofibrosis, it is not clear which ones clinicians use most frequently.Methods: We aimed to review which treatments are usually given to patients with myelofibrosis in the UK, by collecting information from the medical records of 200 patients with myelofibrosis treated in different centres across the UK.Results: The results showed that the symptoms patients experienced were not always written down in the medical records. Similarly, clinical scores based on patient characteristics (which clinicians use to try to predict if a patient will respond to treatment well or not) were also missing from the medical records. Clinicians also rarely asked patients to complete questionnaires that try to measure the impact of myelofibrosis and its treatment on their health. The most common approach for patients with myelofibrosis in the UK was 'watch and wait', which over half of patients received. The most common drugs used for treatment were hydroxycarbamide and ruxolitinib; only a very small proportion of patients received a bone marrow transplant. On average, patients waited for 46 days before receiving a treatment, although patients considered to have a more aggressive type of disease received treatment sooner.Conclusion: The results of this study suggest that medical records can be missing key information, which is needed to decide which is the best way to treat a patient with myelofibrosis. They also suggest that clinicians in the UK prefer observation to treatment for a large number of patients with myelofibrosis. This could mean that the approach used for many patients with myelofibrosis does not help them to control symptoms that have an impact on their daily lives.

Thin flexible lab-on-a-film for impedimetric sensing in biomedical applications.

Microfluidic cytometers based on coulter principle have recently shown a great potential for point of care biosensors for medical diagnostics. Here, we explore the design of an impedimetric microfluidic cytometer on flexible substrate. Two coplanar microfluidic geometries are compared to highlight the sensitivity of the device to the microelectrode positions relative to the detection volume. We show that the microelectrodes surface area and the geometry of the sensing volume for the cells strongly influence the output response of the sensor. Reducing the sensing volume decreases the pulse width but increases the overall pulse amplitude with an enhanced signal-to-noise ratio (~ max. SNR = 38.78 dB). For the proposed design, the SNR was adequate to enable good detection and differentiation of 10 µm diameter polystyrene beads and leukemia cells (~ 6-21 µm). Also, a systematic approach for irreversible & strong bond strength between the thin flexible surfaces that make up the biochip is explored in this work. We observed the changes in surface wettability due to various methods of surface treatment can be a valuable metric for determining bond strength. We observed permanent bonding between microelectrode defined polypropylene surface and microchannel carved PDMS due to polar/silanol groups formed by plasma treatment and consequent covalent crosslinking by amine groups. These experimental insights provide valuable design guidelines for enhancing the sensitivity of coulter based flexible lab-on-a-chip devices which have a wide range of applications in point of care diagnostics.

Prevalence Of FLT-3 Mutation In Acute Myeloid Leukaemia.

BACKGROUND: FLT-3 mutation is a valuable prognostic marker in patients of AML being related with bad prognosis and poor clinical response to conventional chemotherapeutic agents. Frequency of FLT-3 mutation in AML varies from 25% to 35%. The objective of this study was to determine prevalence of FLT-3 mutation in patients with Acute Myeloid Leukaemia. METHODS: This observational cross-sectional Study was conducted in Department of Oncology, Jinnah Hospital Lahore from 1st October 2018 to 31st March 2019. Patients with acute myeloid leukaemia, aged 15-60 years, of both genders were included. After taking consent, demographic data was noted. Three ml of sample of blood was obtained from each patient and sent for detection of FLT-3 mutation. Data was analysed using SPSS version 20.0. Chi square test was applied, pvalue <0.05 significant. RESULTS: A total of 180 patients were enrolled in this study. The mean±SD age of patients was 34.72±14.3 years, among which 38.3% were female and 61.7% male. The mean±SD duration of disease was 3.39±2.8 months. The mean±SD haemoglobin level, TLC and platelet counts were 7.2±2.3 g/dl, 30,913±63,573 per cm and 58.6±52.3×103 per cm. The blast cell (%) count was 69.6±19.8. FLT-3 mutation was present in 18.9%. CONCLUSIONS: We conclude that FLT-3 mutation to be present in only a minority of patients with Acute Myeloid Leukaemia having no significant association with age, sex, haemoglobin, WBCs and blast counts.

Circular shaped microelectrodes for single cell electrical measurements for lab-on-a-chip applications.

The impedimetric sensing techniques for single cell characterization have witnessed growing interest due to their high sensitivity and widespread applications. However, adapting the method to different biological measurements in microfluidic environments under various input conditions can result in feeble signal detection leading to a drastic decrease in the sensor sensitivity. The reduced signal-to-noise ratio (SNR) hinders the signal differentiation, sensor accuracy and prohibits fully integrated point-of-care applications. Here, we address the sensitivity enhancement for microfluidic impedimetric sensing of micron and submicron-sized microparticles by exploring novel circular shape electrodes in a simulation study. The influence of radial electrode parameters on differential electrical signal is systematically analyzed in COMSOL Multiphysics using spherical particles ranging from 0.75 µm to 5 µm in diameter. Detailed analysis revealed the strong impact of the circular shape microelectrode geometry and the electrode gap on the signal strength, resulting SNR, and device sensitivity for multiple bioparticles detection. Specifically, ˃ 50 dB improvement in SNR was enabled by optimizing the circular electrode geometrical parameters. Our proposed sensing modality can be adapted for nanoparticles detection by further optimizing the microfluidic device parameters.

Biochip with multi-planar electrodes geometry for differentiation of non-spherical bioparticles in a microchannel.

A biosensor capable of differentiating cells or other microparticles based on morphology finds significant biomedical applications. Examples may include morphological determination in the cellular division process, differentiation of bacterial cells, and cellular morphological variation in inflammation and cancer etc. Here, we present a novel integrated multi-planar microelectrodes geometry design that can distinguish a non-spherical individual particle flowing along a microchannel based on its electrical signature. We simulated multi-planar electrodes design in COMSOL Multiphysics and have shown that the changes in electrical field intensity corresponding to multiple particle morphologies can be distinguished. Our initial investigation has shown that top-bottom electrodes configuration produces significantly enhanced signal strength for a spherical particle as compared to co-planar configuration. Next, we integrated the co-planar and top-bottom configurations to develop a multi-planar microelectrode design capable of electrical impedance measurement at different spatial planes inside a microchannel by collecting multiple output signatures. We tested our integrated multi-planar electrode design with particles of different elliptical morphologies by gradually changing spherical particle dimensions to the non-spherical. The computed electrical signal ratio of non-spherical to spherical particle shows a very good correlation to predict the particle morphology. The biochip sensitivity is also found be independent of orientation of the particle flowing in the microchannel. Our integrated design will help develop the technology that will allow morphological analysis of various bioparticles in a microfluidic channel in the future.

Exceedingly Sensitive Restructured Electrodes Design for Pathogen Morphology Detection using Impedance Flow Cytometry.

The cellular morphology is a vital biological characteristic for determining explicit information about its physiological state. Monitoring real-time cell shape is of great importance in infectious pathogen detection. Here, we designed a highly sensitive coplanar electrode sensing system and merged it with planar electrodes for simultaneous impedance signals in two dimensions. We simulated the proposed design in this study for the detection of different single cell pathogens based on their morphology. The optimized design has a great potential to monitor and characterize different bacteria based on their sizes and shapes. In this report, spherical and rod shaped particles were used to illustrate the device performance. This simple and extremely sensitive modified electrode design is very promising for bacterial detection and will serve as a future guiding tool for discriminating different morphologies of singular cells.

Is anaemia frequent in HIV/AIDS patients presenting to a tertiary care hospital?

OBJECTIVE: To determine the frequency of anaemia among patients with human immune-deficiency virus / acquired immunodeficiency syndrome. METHODS: The descriptive cross-sectional single-blind study was conducted at Jinnah Hospital, Lahore, Pakistan, from June 25 to December 25, 2016, and comprised human immune-deficiency virus / acquire immunodeficiency syndrome patients diagnosed at least 3 months earlier. Demographic information was obtained along with sample of patient's blood for haemoglobin level estimation. Anaemia was defined as haemoglobin <13 g/dL in males and <12 g/dL in females. Data was analysed using SPSS 20. RESULTS: Of the 230 patients, 100(43.7%) were females and 130(56.5%) were males. The overall mean age was 37.99±14.48 years. The mean haemoglobin level was 11.08±2.44 g/dl; 113(49.1%) 8 12 g/dl, 26(11.3%) <8g/dl, and 91(39.6%) >12g/dl. Overall, 152(66.1%) patients were anaemic and 78(33.9%) were normal. Age and socioeconomic status were significantly associated with anaemia status (p<0.05). CONCLUSIONS: Anaemia was a common finding among human immune deficiency virus / acquired immunodeficiency syndrome patients.

Is Lactulose Plus Rifaximin Better than Lactulose Alone in the Management of Hepatic Encephalopathy?

OBJECTIVE: To compare the efficacy of lactulose plus rifaximin with efficacy of lactulose alone in the treatment of hepatic encephalopathy. STUDY DESIGN: A randomized controlled trial. PLACE AND DURATION OF STUDY: Department of Medicine, Jinnah Hospital, Lahore, from December 2014 to June 2015. METHODOLOGY: All patients who presented with hepatic encephalopathy due to decompensated chronic liver disease were randomly divided into two groups of 65 patients each. One group was given 30 ml thrice daily lactulose alone and the other lactulose plus rifaximin 550 mg twice daily for 10 days. Informed consents were taken from the participants' attendants. Grades II-IV hepatic encephalopathy was noted according to West-Haven Classification. All subjects were followed until 10 days after admission. RESULTS: The mean age of patients was 56.06 +11.2 years, among which 46.9% were females and 53.1% were males. After ten days of follow-up, reversal was seen in 58.46% in lactulose alone group and 67.69% in lactulose plus rifaximin group (Chi-square p=0.276). CONCLUSION: There was no difference in effectiveness of lactulose plus rifaximin and lactulose alone in treatment of hepatic encephalopathy.