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Labrad : Vol 49, Issue 1 - June 2024, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• EDITORIAL
• ARTICLES
• Empowering Donors Through Technology
• Impact of Clinical Laboratories on Greenhouse gas emissions
• Embracing Digitalization and Sustainability: Streamlining Laboratory Reporting
• Accelerating Productivity and Performance: Transition from Transcribers to Working with Speech Recognition.
• ECO-Friendly Molecular Pathology Laboratory Practices
• Let’s Work to Build A Sustainable Histopathology Lab
• Laboratory Sustainability -Things to Promote Eco-Conscious Laboratory Environment
• A Guide to Develop the current and future Eco-Friendly Molecular Lab practices
• The Role of Microbiology Laboratories in Seaweed Reduction and Sustainable Agar Production
• The Role of Behavioral Change in Reducing Energy Use in Microbiology Laboratories
• Reducing Pathology’s Environmental Impact – What can we do?
• Water …

Two Decades Of Research Capacity Strengthening And Reciprocal Learning On Sexual And Reproductive Health In East Africa – A Point Of (No) Return, Caroline Frisendahl, Emelie Looft-Trägårdh, Amanda Cleeve, Susan Atuhairwe, Elin Larsson, Othman Kakaire, Herbert Kayiga, Annette Aronsson, Anne Kihara, Marleen Temmerman

Obstetrics and Gynaecology, East Africa

As the world is facing challenges such as pandemics, climate change, conflicts, and changing political landscapes, the need to secure access to safe and high-quality abortion care is more urgent than ever. On 27th of June 2023, the Swedish government decided to cut funding resources available for developmental research, which has played a fundamental role in the advancement of sexual and reproductive health and rights (SRHR) globally, including abortion care. Withdrawal of this funding not only threatens the fulfilment of the United Nations sustainable development goals (SDGS) – target 3.7 on ensuring universal access to SRHR and target 5 on …

Reversal Of Propofol-Induced Depression Of The Hypoxic Ventilatory Response By Bk-Channel Blocker Ena-001: A Randomized Controlled Trial, Simone Jansen, Maarten Van Lemmen, Erik Olofsen, Laurence Moss, Joseph Pergolizzi, Thomas Miller, Robert Colucci, Monique Van Velzen, Philip Kremer, Albert Dahan, Rutger Van Der Schrier, Marieke Niesters

Department of Medicine Faculty Papers

BACKGROUND: The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory stimulants that increase respiratory drive irrespective of its cause. The authors tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion. They hypothesize that ENA-001 is able to fully restore the hypoxic ventilatory response.

METHODS: In this randomized, double-blind crossover trial, 14 male and female healthy volunteers were randomized to receive placebo and low- and high-dose ENA-001 on three …

Effect Of Home-Based Transcranial Direct Current Stimulation On Cognitive Function In Patients With Mild Cognitive Impairment: A Two-Week Intervention, Jaesub Park, Kyungmi Chung, Yoonkyung Oh, Kwang Joon Kim, Chang Oh Kim, Jin Young Park

Faculty, Staff and Student Publications

PURPOSE: Repeated transcranial direct current stimulation (tDCS) is expected to have the potential to improve cognitive function in patients with mild cognitive impairment (MCI). We aimed to evaluate the efficacy and safety of at-home tDCS for elderly patients with MCI.

MATERIALS AND METHODS: Patients aged 60-80 years, who maintained normal daily living but reported objective memory impairments, were enrolled. Active or sham stimulations were applied to the dorsal frontal cortex (left: anode; right: cathode) at home for 2 weeks. Changes in cognitive function were assessed using visual recognition tasks and the Mini-Mental State Exam (MMSE), and safety and efficacy were …

Jak-Stat Signaling And Beyond In The Pathogenesis Of Spondyloarthritis And Their Clinical Significance, Siba P Raychaudhuri, Ruchi J Shah, Sneha Banerjee, Smriti K Raychaudhuri

Faculty, Staff and Student Publications

Purpose of Review

Janus kinase–signal transducers and activators of transcription cell signaling proteins (JAK-STATs) play a key regulatory role in functioning of several inflammatory cytokines. JAK-STAT signaling proteins are the key regulators of the cytokine/cytokine receptor system involved in the pathogenesis of various autoimmune disease including spondyloarthritis (SpA). This article mainly highlights the JAK-STAT signaling system, its association with the relevant cytokine/cytokine-receptor system, and its regulatory role in pathogenesis of SpA. Also, we have briefly addressed the principle for the use JAKi in SpA and the current status of use of JAK inhibitors (JAKi) in SpA.

Recent Findings

Recent developments …

Polygenic Liability For Anxiety In Association With Comorbid Anxiety In Multiple Sclerosis, Kaarina Kowalec, Arvid Harder, Casandra Dolovich, Kathryn C Fitzgerald, Amber Salter, Yi Lu, Charles N Bernstein, James M Bolton, Gary Cutter, John D Fisk, Joel Gelernter, Lesley A Graff, Sara Hägg, Carol A Hitchon, Daniel F Levey, Fred D Lublin, Kyla A Mckay, Scott Patten, Amit Patki, Murray B Stein, Hemant K Tiwari, Jerry S Wolinsky, Ruth A Marrie

Faculty, Staff and Student Publications

OBJECTIVE: Comorbid anxiety occurs often in MS and is associated with disability progression. Polygenic scores offer a possible means of anxiety risk prediction but often have not been validated outside the original discovery population. We aimed to investigate the association between the Generalized Anxiety Disorder 2-item scale polygenic score with anxiety in MS.

METHODS: Using a case-control design, participants from Canadian, UK Biobank, and United States cohorts were grouped into cases (MS/comorbid anxiety) or controls (MS/no anxiety, anxiety/no immune disease or healthy). We used multiple anxiety measures: current symptoms, lifetime interview-diagnosed, and lifetime self-report physician-diagnosed. The polygenic score was computed …

Nutritional Supplementation In Children With Severe Pneumonia In Uganda And Kenya (Coast-Nutrition): A Phase 2 Randomised Controlled Trial, Sarah Kiguli, Peter Olupot-Olupot, Mainga Hamaluba, Elisa Giallongo, Karen Thomas, Florence Alaroker, Robert Opoka, Abner Tagoola, Shela Oyella, Damalie Nalwanga

Paediatrics and Child Health, East Africa

Background Severe pneumonia in African children results in poor long-term outcomes (deaths/readmissions) with undernutrition as a key risk factor. We hypothesised additional energy/protein-rich Ready-to-Use Therapeutic Foods (RUTF) would meet additional nutritional requirements and improve outcomes.

Methods COAST-Nutrition was an open-label Phase 2 randomised controlled trial in children (aged 6 months-12 years) hospitalised with severe pneumonia (and hypoxaemia, SpO2 <92%) in Mbale, Soroti, Jinja, Masaka Regional Referral Hospitals, Uganda and Kilifi County Hospital, Kenya (ISRCTN10829073 (registered 6th June 2018) PACTR202106635355751 (registered 2nd June 2021)). Children were randomised (ratio 1:1) to enhanced nutritional supplementation with RUTF (plus usual diet) for 56 days vs usual diet (control). The primary outcome was change in mid-upper arm circumference (MUAC) at 90 days as a composite with mortality. Secondary outcomes include anthropometric status, mortality, and readmissions at Days 28, 90 and 180.

Findings Between 12 August 2018 and 22 April 2022, 846 eligible children were randomised, 424 to RUTF and 422 to usual diet, and followed for 180-days [12 (1%) lost-to-follow-up]. RUTF supplement was initiated in 417/419 (>99%). By Day 90, there was …

International Consensus On Standard Outcome Measures For Neurodevelopmental Disorders: A Consensus Statement, Melissa Mulraney, Umanga De Silva, Andria Joseph, Maria Da Luz Sousa Fialho, Iain Dutia, Natalie Munro, Jonathan M. Payne, Tobias Banaschewski, Cláudia Bandeira De Lima, Susan Wamithi

Paediatrics and Child Health, East Africa

Importance: The use of evidence-based standardized outcome measures is increasingly recognized as key to guiding clinical decision-making in mental health. Implementation of these measures into clinical practice has been hampered by lack of clarity on what to measure and how to do this in a reliable and standardized way.

Objective: To develop a core set of outcome measures for specific neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactivity disorder (ADHD), communication disorders, specific learning disorders, and motor disorders, that may be used across a range of geographic and cultural settings.

Evidence Review: An international working group composed of clinical and research experts …

Thyroid Cartilage Metastases From Prostate Cancer On 18f Psma Pet Ct: A Case Series, Poonamjeet Loyal, Samuel Gitau, Khalid Makhdomi

Imaging & Diagnostic Radiology, East Africa

Prostate cancer metastases to the thyroid cartilage is an extremely rare phenomenon. We report three cases of advanced prostate carcinoma with metastases to the thyroid cartilage identified on 18F prostate-specific membrane antigen-1007 (PSMA-1007) positron emission tomography (PET)/computed tomography (CT). The pathophysiology and possibility for under-reporting are also discussed. Prostate cancer metastases to the larynx should be considered in the differential diagnosis of thyroid cartilage lesions in patients with advanced prostate cancer and is associated with poor prognosis.

A Case Of Charcot-Marie-Tooth Disease Type 2o (Cmt 20) Associated With Dync1h1 And Slc12a6 Mutations, Tehreem Arshad, Muhammad Jawad Hassan, Arsalan Ahmad

Pakistan Journal of Neurological Sciences (PJNS)

Charcot-Marie-Tooth disease (Charcot Marie-Tooth) comprises of a variety of hereditary diseases affecting the peripheral nervous system. Charcot Marie-Tooth2 is a subgroup caused by defects in the axon of the peripheral nerve cells. Charcot Marie-Tooth Type 2O is an uncommon type that affects less than one in a million people and is linked to specific genetic abnormalities. We report a case study of a 66-year-old individual with Charcot Marie-Tooth Type 2O, diagnosed on clinical presentation and identified through genetic analysis. Electromyography and nerve conduction studies supported the diagnosis of an axonal sensorineural neuropathy. A comprehensive genetic neuropathies panel led to the …

Hurdles In Diagnosis Of Familial Amyotrophic Lateral Sclerosis With Anticipation Catastrophe Across Three Generations: A Case Report, Sana Ghous, Alam Ibrahim Siddiqui

Pakistan Journal of Neurological Sciences (PJNS)

Familial amyotrophic lateral sclerosis (F-ALS), a rare hereditary variant of ALS, is characterized by a genetic predisposition to the disease. In this case report, we reveal a compelling instance of F-ALS within a three-generation family, involving a grandfather, son, and grandson, all manifesting early-onset symptoms and progressive upper and lower motor neuron findings. The clinical diagnosis was confirmed through electromyography fulfilling El Escorial criteria of ALS. Our investigation highlights the familial connection in this case, emphasizing the hereditary aspect of ALS. This report underscores the significance of considering familial ALS in cases of successive generational involvement with early onset, a …

Rare Presentation Of Central Nervous System Tuberculosis With Bilateral Anterior Cerebral Artery Aneurysm: A Case Report, Maryam Khalil, Mansoor Iqbal, Samer Naik, Ayma Khan Khan, Zakir Jan, Mazhar Badshah

Pakistan Journal of Neurological Sciences (PJNS)

Central Nervous System tuberculosis (CNS TB) with intracranial aneurysms is rare and needs prompt diagnosis and early management. The presence of un-ruptured or ruptured aneurysms in the presence of CNS infection is difficult to treat in both acute settings and long-term management because of possible complications prevention. A female of 70 years of age presented with a history of fever, headache, vomiting, and altered sensorium for one week with GCS of 13/15, later developing paraparesis. She was diagnosed to have CNS tuberculosis with complicating bilateral anterior communicating artery (ACA) aneurysms. She was managed conservatively in our hospital and was referred …

End Of Life, Children's Mercy Kansas City

Clinical Pathways

No abstract provided.

3d Bioprinting The Tumor Microenvironment For Immunotherapy Development, Molly Leyda, Tykeem Manor, John Szarejko, Douglas Myers, John M. Perry

Posters

The tumor microenvironment (TME) is a complex system that plays a crucial role in tumor progression, immune evasion, and therapy resistance. The TME is composed of various cell types, including tumor cells, stromal cells, and immune cells such as macrophages. Macrophages are versatile myeloid cells which can exhibit both pro-tumoral and anti-tumoral functions, depending on their phenotype and the TME context. M1 macrophages have demonstrated promising pro-inflammatory and anti-tumor effects, while tumor associated M2 macrophages (TAMs) play an anti-inflammatory role and promote tumor immune escape. Understanding the complex interactions between TAMs and the TME is, therefore, essential for developing effective …

Predictive Capacity Of Immune-Related Adverse Events And Cytokine Profiling In Neoadjuvant Immune Checkpoint Inhibitor Trials For Head And Neck Squamous Cell Carcinoma, Angela Alnemri, Sruti Tekumalla, Annie Moroco, Ioannis Vathiotis, Madalina Tuluc, Stacey Gargano, Tingting Zhan, David Cognetti, Joseph Curry, Athanassios Argiris, Alban Linnenbach, Andrew South, Larry Harshyne, Jennifer Johnson, Adam Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status.

METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival …

Statin Utilization And Cardiovascular Outcomes In A Real-World Primary Prevention Cohort Of Older Adults, Aaron J. Walker, Jianhui Zhu, Floyd Thoma, Oscar Marroquin, Amber Makani, Martha Gulati, Eugenia Gianos, Salim S. Virani, Fatima Rodriguez, Steven E. Reis, Christie Ballantyne

Office of the Provost

Background: Statins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years).
Objective: Investigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network.
Methods: We included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and 'moderate or high' intensity statins with a follow up period of ∼7 years. Cox regression models were used to …

Rates Of Urinary Tract Infection In Transgender Women Postvaginoplasty Vs Cisgender Women: A Retrospective Cohort Study In A Large Us Health Network, David Gilbert, Aishwarya Gautam, Tomasz Tabernacki, Megan Mcnamara, Rachel Pope, Shubham Gupta, Kirtishri Mishra

Student Scholarship

Objective: To describe urinary tract infection (UTI) risk 3-month postvaginoplasty (VP) in transgender women (TW) compared to cis women (CW). Methods: Using TriNetX (TriNetX, Inc, Cambridge, MA), we built cohorts of 2041 TW and 48,374,745 CW. Outcomes were ≥1 instance of UTI or Cystitis, and assessed from 3-6, 3-12, 3-36 months, and 3 months-10 years post-VP. TW and CW were age-cohorted (18-39, 40-59, 60-74) and compared at each time interval. Kaplan-Meier was used to account for loss to follow-up, along with hazard ratios and log-rank tests to determine significance (P <.05). Results: For all time intervals and age ranges, TW had a significantly (P <.0001-P = .0088) higher probability of developing a UTI compared to CW. The largest difference was ages 40-59 ten-year post-VP. In this analysis, CW and TW had a 12.96% and 29.34% cumulative outcome incidence, respectively. Cox proportional hazard analysis demonstrated increased hazard for TW compared to CW. Hazard ratios between CW and TW ranged from 1.363 (ages 18-39 at 10 years, 95%CI: 1.119,1.660) to 3.522 (ages 60-74 at 12 months, 95%CI: 1.951,6.360). Conclusion: We found a significantly higher probability of TW developing UTIs compared to age-cohorted CW. Contributing factors may include difficulties with neovaginal perineal hygiene, lack of commensal bacteria and vaginal mucosa, larger urethral meatus, high rates of meatal stenosis, and nonnative bacteria introduced through dilators and douching. These findings may help improve quality of postoperative care in TW.

Practical Guidance On Establishing A Molecular Testing Pathway For Alterations In Homologous Recombination Repair Genes In Clinical Practice For Patients With Metastatic Prostate Cancer, Martin Schostak, Angela Bradbury, Alberto Briganti, David Gonzalez, Leonard Gomella, Joaquin Mateo, Frédérique Penault-Llorca, Albrecht Stenzinger, Alexander Wyatt, Anders Bjartell

Department of Urology Faculty Papers

CONTEXT: Prostate cancer is a molecularly heterogeneous disease that is amenable to diagnostic testing to identify patients potentially eligible for personalised treatments inform familial risk and provide relevant information about potential prognosis. Several guidelines support the integration of genomic testing in a shared decision-making framework so that both health care professionals (HCPs) and patients are involved in determining the best treatment approach.

OBJECTIVE: To review current guidelines on molecular diagnostic testing for homologous recombination repair (HRR) gene alterations in patients with metastatic prostate cancer, with the aim of providing practical considerations for effective guideline implementation and establishment of an appropriate …

Introducing A Novel Innovative Technique For The Recording And Interpretation Of Dynamic Coronary Angiography, Thach Nguyen, Duc Khiem Ngo, Tri Loc Vu, Hien Q. Nguyen, Dat H. Pham, Mihas Kodenchery, Gianluca Rigatelli, Aravinda Nanjundappa, Michael Gibson

School of Medicine Publications

In the study of coronary artery disease (CAD), the mechanism of plaque formation and development is still an important subject for investigation. A limitation of current coronary angiography (CAG) is that it can only show static images of the narrowing of arterial channels without identifying the mechanism of the disease or predicting its progression or regression. To address this limitation, the CAG technique has been modified. The new approach emphasizes identifying and analyzing blood flow patterns, employing methodologies akin to those used by hydraulic engineers for fluid or gas movement through domestic or industrial pipes and pumps. With the new …

The Internist's Post V.1 N.4, The University Of Texas Rio Grande Valley. School Of Medicine, Jian Garcia Cruz, Diana Othon Martinez, Edgar Dorsey Trevino, Eunbee Cho, Barbara Malaga-Espinoza, Roque Mifuji, Martha Solis, Cesar Gutierrez

School of Medicine Publications

No abstract provided.

Polymer-Based Drug-Eluting Stent Treatment Extends The Time To Reintervention For Patients With Symptomatic Femoropopliteal Artery Disease: Clinical Evidence And Potential Economic Value, William Gray, Yoshimitsu Soga, Masahiko Fujihara, Osamu Iida, Anvar Babaev, Daizo Kawasaki, Thomas Zeller, David O'Connor, Michael Jaff, Anna Chavez, Stefan Müller-Hülsbeck

Department of Medicine Faculty Papers

Aim: Use long-term follow-up data from the IMPERIAL study to determine whether drug-eluting polymer-based nitinol stent treatment can delay the time to repeat intervention for femoropopliteal artery disease and how such a delay may result in cost savings in a value-based episode of care. Patients & methods: The IMPERIAL randomized controlled trial was an international study of a paclitaxel-eluting polymer-coated stent (Eluvia, Boston Scientific, MA, USA) versus a polymer-free paclitaxel-coated stent (Zilver PTX, Cook Corporation, IN, USA) for treating lesions of the femoropopliteal arterial segment. Study patients (n = 465) had symptomatic lower limb ischemia. Safety and efficacy assessments were …

Ocrelizumab In Multiple Sclerosis:Real-World Experience From Baluchistan, Pakistan, Ahmed Wali, Sajid Hameed, Hazar Khan, Amara Ahmed, Madiha Malik

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Multiple sclerosis (MS) is an autoimmune demyelinating disorder affecting the central nervous system. Ocrelizumab, a disease-modifying drug for MS, is funded by Bait ul Maal Pakistan for economically disadvantaged patients in Balochistan. The objective of this study was to evaluate the treatment response of Ocrelizumab in our population.

Methods: This prospective observational study enrolled 22 patients from three tertiary care hospitals in Balochistan from July 2021 to June 2022. Patients aged 18–50 years diagnosed with MS and without contraindications for Ocrelizumab were included. The Expanded Disability Status Scale (EDSS) was calculated at baseline and at three, six, …

Erdheim-Chester Disease Presenting In The Foramen Magnum With Mass Effect Of A 39-Year-Old Male, Joseph Fullmer, Brandon Metcalf, Casey Schukow

Conference Presentation Abstracts

Background: Erdheim-Chester disease (ECD) is a rare clonal histiocytosis neoplastic condition. This condition is characterized by a non-specific infiltration of foamy macrophages in multiple organs, such as the bone or skeletal system (>95%), retroperitoneum, kidneys, and heart, resulting in inappropriate inflammation, fibrosis, and multi-end organ dysfunction. central nervous system (CNS) is present in a minority of cases. This condition is extremely rare with only a few hundred cases reported in medical literature. Methods: We present a case of ECD in a 39-year-old male with past medical history for type-2 diabetes mellitus, neuropathy, and low testosterone on replacement therapy who …

Evaluation Of Aluminum Exposure In Neonates Receiving Parenteral Nutrition, Emma Sedarski

2024 Swedish Learning and Celebration Day

No abstract provided.

Naloxone: From Legislation To Distribution, Kailyn Elliot, Emily Stewart, John Delfeld

2024 Swedish Learning and Celebration Day

No abstract provided.

Safety And Efficacy Of Empiric De-Escalation Of Antibiotics For Pneumonia In The Intensive Care Unit, Brandon Carron

2024 Swedish Learning and Celebration Day

No abstract provided.

Polyvagal Theory For Kids: A Brain-Based Teaching Tool To Promote Coping, Katy Tenhulzen

2024 Swedish Learning and Celebration Day

No abstract provided.

A Multisite Initiative To Increase Utilization Of Clinical Pathways In The Selection Of Systemic Cancer Treatment, Kate Hough

2024 Swedish Learning and Celebration Day

No abstract provided.

Safety Of Ketamine Use For Rapid Control Of Agitation In The Emergency Department, Rosa Hong Trieu

2024 Swedish Learning and Celebration Day

No abstract provided.

Neurocognitive Outcome Following Tuberculous Meningitis Treatment: A Systematic Review, Muhammad Ilham Dhiya Rakasiwi, Erlina Burhan, Afid Brilliana Putra, Ihya Fakhrurizal Amin, Nadhif Wiratara

Pakistan Journal of Neurological Sciences (PJNS)

Background and objective: Tuberculous meningitis (TBM) is an infectious disease of the central nervous system that remains to be a global health challenge. Patients who survive after experiencing TBM have a risk of developing functional, cognitive and psychological disorders that can affect daily activities. The objective of this study is to present a comprehensive review of data on cognitive outcome after TBM infection.

Method: We conducted a systematic literature search to identify studies addressing cognitive outcomes in adult TBM patients. Following a systematic literature search (PubMed, Scopus, EBSCO), studies were reviewed by independent reviewers to assess eligibility for inclusion. Three …