Clinical and neuroradiographic features of fentanyl inhalation-induced leukoencephalopathy.

A man in his late 40s with no known past medical history was unresponsive for an unknown period of time. Crushed pills and white residue were found on a nearby table. On presentation he was obtunded and unresponsive to verbal commands but withdrawing to painful stimuli. The initial urine drug screen was negative, but a urine fentanyl screen was subsequently positive with a level of 137.3 ng/mL. MRI of the brain showed reduced diffusivity and fluid attenuated inversion recovery (FLAIR) hyperintensity symmetrically in the bilateral supratentorial white matter, cerebellum and globus pallidus. Alternative diagnoses such as infection were considered, but ultimately the history and workup led to a diagnosis of fentanyl-induced leukoencephalopathy. Three days after admission the patient became able to track, respond to voice and follow basic one-step commands. The patient does not recall the mechanism of inhalation. While there are case reports of heroin-induced leukoencephalopathy following inhaled heroin use and many routes of fentanyl, this is the first reported case of a similar phenomenon due to fentanyl inhalation.

Evaluation of the quality of information online for arthroscopic Bankart repair.

PURPOSE: The purpose of this study was to evaluate the quality and readability of information online for patients searching terms related to arthroscopic Bankart repair (ABR). METHODS: Google, Yahoo and Bing were searched with terms related to ABR. The quality of information was assessed using the Journal of the American Medical Association (JAMA) Benchmark criteria, DISCERN Score, and the Flesch-Kincaid Reading Ease & Grade Level. The presence of the HONcode marker was noted. Additionally, we used a scoring system specific to content relating to the ABR (AB score), a 1-20 Likert scale. Websites were also categorised according to the source: academic institution, physician, allied healthcare, commercial, media or social media. Statistical analysis was performed using GraphPad Prism. RESULTS: Ninety-six unique websites were evaluated, with the most common website category being physician websites (52) and academic institution websites (24). There were nine websites with the HONcode marker. The average JAMA Benchmark criteria score was 1.95 (1-4), the average DISCERN score was 48.8 (20-78), with an average Flesch-Kincaid reading ease of 50.9 (11-96) and grade level of 8 (1-18). The average AB score was 5.9 (0-18), and there was a strong correlation with a higher DISCERN score (r=0.57), but not JAMA score (r=0.18) or Flesch-Kincaid grade (r=0.16). Websites with the HONcode marker did not score higher in any criteria than those without it (p>0.05). The quality of information on physician websites was better than (statistically insignificant) non-physician websites; however, the readability of information in the former was poorer (statistically significant) than the latter. CONCLUSION: There was wide variability in the quality and readability online of the information on ABR, and the AB scoring system was shown to correlate strongly with increased quality.

Detailed analysis of in-hospital transmission of SARS-CoV-2 using whole genome sequencing.

BACKGROUND: Hospital transmission of SARS-CoV-2 has proved difficult to control, with healthcare-associated infections troublesome throughout. AIM: To understand factors contributing to hospital transmission of infections, which is necessary for containing spread. METHODS: An outbreak of 56 staff and patient cases of COVID-19 over a 31-day period in a tertiary referral unit is presented, with at least a further 29 cases identified outside of the unit and the hospital by whole genome sequencing (WGS). FINDINGS: Transmission is documented from staff to staff, staff to patients, and patients to staff, showing disruption of a tertiary referral service, despite implementation of nationally recommended control measures, superior ventilation, and use of personal protective equipment. There was extensive spread from the index case, despite this patient spending only 10 h bed bound on the ward in strict cubicle isolation and with an initial single target low level (CT = 32) polymerase chain reaction test. CONCLUSION: This investigation highlights how effectively and rapidly SARS-CoV-2 can spread in certain circumstances. It raises questions about infection control measures in place at the time and calls into question the premise that transmissibility can be reliably detected by using lower sensitivity rapid antigen lateral flow tests. We also highlight the value of early intervention in reducing impact as well as the value of WGS in understanding outbreaks.

Analysis of Adverse Events and Intravenous Iron Infusion Formulations in Adults With and Without Prior Infusion Reactions.

Importance: Although iron deficiency is common, it remains unclear which iron repletion strategy is associated with the lowest rate of infusion-related adverse events, and how patients with history of infusion reaction should be managed. Objective: To evaluate rates of infusion reactions among 4 commonly used intravenous iron repletion strategies and determine how readministration was managed in patients with history of reaction. Design, Setting, and Participants: This cohort study included all patients receiving intravenous iron infusion from January 1, 2015, to September 7, 2021, at 6 centers in Portland, Oregon. Participants included a total of 12 237 patients with iron deficiency, not restricted by etiology. Statistical analysis was performed from September to October 2021. Exposures: Type of intravenous iron formulation and concurrent administration of diphenhydramine, epinephrine, famotidine, and/or hydrocortisone, used as surrogate maker of infusion reaction. Main Outcomes and Measures: Incidence of adverse events, including severe events requiring epinephrine, stratified by type of iron formulation, and in patients who received premedication or with history of infusion-related reaction receiving subsequent doses. Results: Among 35 737 unique iron infusions (12 237 patients [9480 (77.5%) women; 717 (5.9%) Black; 10 250 (83.7%) White; mean (SD) age of 51 (20) years]), comprising 22 309 iron sucrose doses, 9067 iron dextran total doses (1771 preceded by test dose, 56 test doses alone), 3147 ferumoxytol doses, and 1214 ferric carboxymaltose doses, incidence of adverse events was 3.9% (n = 1389; 95% CI, 3.7%-4.1%). Rate of infusion events differed among iron formulations: 4.3% (n = 970; 95% CI, 4.1%-4.6%) iron sucrose, 3.8% (n = 345, 95% CI: 3.4%-4.2%) iron dextran (test and full doses or test dose alone), 1.8% (n = 57; 95% CI, 1.4%-2.3%) ferumoxytol, and 1.4% (n = 17, 95% CI, 0.8%-2.3%) ferric carboxymaltose (P < .001). Severe adverse events were exceedingly rare with only 2 documented epinephrine administrations, both associated with iron dextran. Incidence of adverse events among those who received premedication was 23-fold higher compared with those who did not (38.6% vs 1.7%, χ21 = 7324.8; P < .001). Among 873 patients with history of infusion reaction who underwent readministration, the majority received the same formulation, which was associated with significantly higher reaction rate particularly if premedication was administered (68% [95% CI, 64%-72%] vs 32% [95% CI, 26%-41%], respectively), compared with those who received an alternate formulation (21% [95% CI, 11%-35%] vs 5% [95% CI, 2%-12%], respectively) (P < .001). Conclusions and Relevance: These data, and the preponderance of published evidence, suggest that intravenous iron is generally well tolerated with exceedingly low risk of severe reaction, use of premedication and test doses are unnecessary, and that optimal prevention and management of infusion-related reactions warrant further study.

A Comprehensive Analysis of Hyperbolical Fluids in Modified Gravity.

This paper is devoted to understanding a few characteristics of static irrotational matter content that assumes hyperbolical symmetry. For this purpose, we use metric f(R) gravity to carry out our analysis. It is noticed that the matter distribution cannot fill the region close to the center of symmetry, thereby implying the existence of an empty core. Moreover, the evaluation of the effective energy density reveals that it is inevitably negative, which could have utmost relevance in understanding various quantum field events. To derive the structure scalars, we perform the orthogonal splitting of the Riemann tensor in this modified gravity. Few relationships among matter variables and both Tolman and Misner Sharp are determined. Through two generating functions, some hyperbolically symmetric cosmological models, as well as their physical interpretations, are studied. To delve deeply into the role of f(R) terms, the model of the less-complex relativistic system of Einstein gravity is presented.

Frequency of CD34 and CD10 Expression in Adolescent and Young Adult Patients Having Precursor B-cell Acute Lymphoblastic Leukemia and Its Correlation With Clinical Outcomes: A Single-Center Study.

BACKGROUND: The clinical outcomes of CD34 and CD10 antigens expression in adolescent and young adult (AYA) precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) is not still well established. In the present study, we analyzed the laboratory characteristics and clinical outcomes of 123 AYA pre-B-ALL patients in order to evaluate the possible clinical significance of these markers. MATERIALS AND METHODS: In the current study clinical data of 123 consecutive AYA pre-B-ALL patients aged 18-39 years old, enrolled in adult hematology-oncology unit from December 2014 to April 2019 was analyzed. Patient clinical outcome was calculated as overall survival and disease-free survival. RESULTS: Overall, 76.4% of patients showed CD34 expression and CD10 expression was found in 90.2%. CD34 and CD10 expression was associated with higher total leucocyte count, increased peripheral blood blast percentage, and decreased platelet count. Overall survival and disease-free survival were both significantly better in CD34 negative and CD10 negative patients compared to their CD34 positive and CD10 positive counterparts. INTERPRETATION AND CONCLUSION: Expressions of CD34 and CD10 are adverse prognostic factors in AYA pre-B-ALL patients and the presence of these antigens influences the clinical outcome of these patients.

The role of Platelet Rich Plasma and other orthobiologics in bone healing and fracture management: A systematic review.

BACKGROUND: Treatment of large bone defects and fracture healing complications (delayed and non-union) presents a substantial challenge for orthopaedic surgeons. Given that bone healing requires mechanical stability as well as a favourable biological microenvironment, orthobiologics such as Platelet-Rich Plasma (PRP) may have a significant clinical role to play. AIMS: To perform a systematic review of the available literature to assess the clinical effect of PRP, with or without other orthobiologics, on bone healing. METHOD: Two independent reviewers performed the literature search based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Clinical studies of any evidence, assessing effect of PRP with or without other orthobiologics on bone healing, were included. A qualitative analysis was carried out on the clinical and radiological outcomes reported. RESULT: 27 articles with 1631 patients (mean age = 43.56, 57.1% male, mean follow-up = 17.27 months) were included in the qualitative. Of the 27 studies, 13 dealt with fracture complications (delayed or non-unions), 7 with acute fracture healing, 4 with tibial osteotomies and lengthening procedures and 3 with lumbar spine pathology. 18/27 studies showed a clinical benefit of PRP, 8/27 showed no significant effect, and 1/27 showed a worse outcome with PRP. CONCLUSION: Our review suggests PRP may play a clinical role in bone healing but further randomised controlled trials (RCTs) using standardised outcomes should be performed to establish its efficacy.

Hematological Parameters and Demographic Distribution of Hemoglobinopathies and Various Hemoglobin Variants.

Background The study was conducted to find the prevalence of hemoglobinopathies along with their geographical/ethnic distribution to highlight the region of high prevalence that can be used to guide screening. Method Results of blood samples received for hemoglobin variants determination by high-performance liquid chromatography (HPLC) were retrospectively analyzed at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore. Blood samples were assayed for CBC (complete blood count), red blood cell morphology, and hemoglobin analysis by HPLC. CBC was performed on Sysmex XN 9000 analyzer (Sysmex, Kobe Japan), peripheral smears to review RBC morphology were stained with Wright-Giemsa stain, and HPLC was performed on BIO-RAD variant II (Bio-Rad Laboratories, Hercules, USA). Results Hemoglobinopathies were identified in 9.7% (n=997) out of 10,297 samples. Beta thalassemia trait was the most common hemoglobinopathy recognized with a prevalence of 5% (n=516), with the maximum number of cases in the Lahore district of Punjab province. The next most common hemoglobinopathy identified was sickle cell disease with a frequency of 1.43% (n=148) and the maximum cases from the Dera Ismail Khan district of the Khyber Pakhtunkhwa province. The additional important hemoglobinopathies found were sickle cell trait, hemoglobin-D Punjab trait, and compound heterozygote for sickle and beta thalassemia. Conclusion Hemoglobinopathies are the most common inherited disorders in Pakistan and worldwide. Screening for hemoglobinopathies is recommended in high-prevalence districts of Pakistan. Sickle cell screening is also recommended in newborns in the high prevalence area of Pakistan, such as the northwest regions.

Mortality and AIDS-defining events among young people following transition from paediatric to adult HIV care in the UK.

OBJECTIVES: To investigate risk of AIDS and mortality after transition from paediatric to adult care in a UK cohort of young people with perinatally acquired HIV. METHODS: Records of people aged ≥ 13 years on 31 December 2015 in the UK paediatric HIV cohort (Collaborative HIV Paediatric Study) were linked to those of adults in the UK Collaborative HIV Cohort (CHIC) cohort. We calculated time from transition to a new AIDS event/death, with follow-up censored at the last visit or 31 December 2015, whichever was the earliest. Cumulative incidence of and risk factors for AIDS/mortality were assessed using Kaplan-Meier and Cox regression. RESULTS: At the final paediatric visit, the 474 participants [51% female, 80% black, 60% born outside the UK, median (interquartile range) age at antiretroviral therapy (ART) initiation = 9 (5-13) years] had a median age of 18 (17-19) years and CD4 count of 471 (280-663) cell/µL; 89% were prescribed ART and 60% overall had a viral load ≤ 400 copies/mL. Over median follow-up in adult care of 3 (2-6) years, 35 (8%) experienced a new AIDS event (n = 25) or death (n = 14) (incidence = 1.8/100 person-years). In multivariable analyses, lower CD4 count at the last paediatric visit [adjusted hazard ratio = 0.8 (95% confidence interval: 0.7-1.0)/100 cells/µL increment] and AIDS diagnosis in paediatric care [2.7 (1.4-5.5)] were associated with a new AIDS event/mortality in adult care. CONCLUSIONS: Young people with perinatally acquired HIV transitioning to adult care with markers of disease progression in paediatric care experienced poorer outcomes in adult care. Increased investment in multidisciplinary specialized services is required to support this population at high risk of morbidity and mortality.

Health Care Workers and Patients as Trojan Horses: a COVID19 ward outbreak.

BACKGROUND: Transmission in healthcare settings can result in significant infections in healthcare workers and patients. Understanding infection dynamics has important implications for methods employed in hospitals to prevent nosocomial transmission events. METHODS: In this case series report we describe a cluster of COVID-19 (Coronavirus disease 2019) in a tertiary care university hospital, in the early phases of the epidemic, after hospital visiting had been stopped and when the UK lockdown was in place. FINDINGS: A 48 year old patient developed COVID-19 31 days post-admission and four days after admission to a medical ward from ITU. Infection was likely acquired from an asymptomatic or minimally symptomatic healthcare worker (HCW). Subsequent investigation over a 14 day period revealed symptoms in 23 staff members and five linked cases in patients on the same ward.Nine of the 23 affected staff members provided care for and had direct exposure with the index case. Four staff reported caring for the index case without use of personal protective equipment. One was coughed on directly by the patient 24 hours prior to the onset of symptoms. CONCLUSION: SARS CoV2 infection can be introduced to a ward area by asymptomatic and minimally symptomatic healthcare workers. Staff members and patients can act as Trojan horses carrying infection into and around the hospital, setting up unexpected transmission events.Transmission of infection from pre-symptomatic, asymptomatic and minimally symptomatic individuals means that universal use of measures to prevent transmission is required for successful reduction of transmission events in the hospital setting.

Actomyosin and vimentin cytoskeletal networks regulate nuclear shape, mechanics and chromatin organization.

The regulation of nuclear state by the cytoskeleton is an important part of cellular function. Actomyosin stress fibres, microtubules and intermediate filaments have distinct and complementary roles in integrating the nucleus into its environment and influencing its mechanical state. However, the interconnectedness of cytoskeletal networks makes it difficult to dissect their individual effects on the nucleus. We use simple image analysis approaches to characterize nuclear state, estimating nuclear volume, Poisson's ratio, apparent elastic modulus and chromatin condensation. By combining them with cytoskeletal quantification, we assess how cytoskeletal organization regulates nuclear state. We report for a number of cell types that nuclei display auxetic properties. Furthermore, stress fibres and intermediate filaments modulate the mechanical properties of the nucleus and also chromatin condensation. Conversely, nuclear volume and its gross morphology are regulated by intracellular outward pulling forces exerted by myosin. The modulation exerted by the cytoskeleton onto the nucleus results in changes that are of similar magnitude to those observed when the nucleus is altered intrinsically, inducing chromatin decondensation or cell differentiation. Our approach allows pinpointing the contribution of distinct cytoskeletal proteins to nuclear mechanical state in physio- and pathological conditions, furthering our understanding of a key aspect of cellular behaviour.

Study of genetic variation of eggplant cultivars by using RAPD-PCR molecular markers and the relationship with Phomopsis blight disease reaction.

Disease susceptibility and genetic variability in 10 eggplant genotypes were studied after inoculating Phomopsis vexans under confined field conditions. Random amplified polymorphic DNA (RAPD) markers were used to assess genetic variation and relationships among eggplant genotypes. The disease index of leaves ranged 0.208-13.79%, while fruit infection ranged 2.15-42.76%. Two varieties, Dohazari G and Laffa S, were found to be susceptible, 6 were moderately resistant, 1 was moderately susceptible, and BAU Begun-1 was resistant to P. vexans. Amplification of genomic DNA by using 3 RAPD primers produced 20 bands: 14 (70%) were polymorphic and 6 (30%) were monomorphic. The highest intra-variety similarity indices values were found in ISD 006, Ishurdi L, Jessore L, and BAU Begun-1 (100%), while the lowest was in Dohazari G (90%). The lowest genetic distance (0.0513) and the highest genetic identity (0.9500) were observed between the ISD 006 and Ishurdi L combinations. A comparatively higher genetic distance (0.3724) and the lowest genetic identity (0.6891) were observed between the ISD 006 and Dohazari G combinations. A dendogram was constructed based on Nei's genetic distance, which produced 2 main clusters of the genotypes - Cluster I: ISD 006, Ishurdi L, Marich begun L, BAU Begun-1, Marich begun S, and Chega and Cluster 2: Laffa S, Dohazari G, Jessore L, and Singhnath. Genetic variation and its relationship with disease susceptibility were assessed using RAPD markers, to develop disease-resistant varieties and improve eggplant crops.

Spot morning urine protein creatinine ratio and 24 hour urinary total protein excretion rate.

Proteinuria helps to establish the diagnosis of most renal diseases and also to predict the outcome of such diseases. Proteinuria is biochemically represented by measuring the protein concentration in timed collection of 24 hour urine. But, 24-hour timed urine collection is time consuming, cumbersome and often unreliable due to collection errors and also results in undue delay on diagnostic process. An alternate approach avoiding arduous and inaccurate timed urine collection can be the measurement of protein creatinine ratio in spot morning urine. This study was aimed to evaluate whether the spot morning urine protein creatinine ratio can be a reliable alternative to 24-hour urinary total protein (UTP) estimation. The study was carried out in the department of Biochemistry, Bangabandhu Sheikh Mujib Medical University, Dhaka on 50 (fifty) non-diabetic Chronic Renal Disease (CRD) patients with an age ranging from 18 -70 years. The study subjects were grouped into mild, moderate and severe CRD on the basis of GFR. Urinary protein and creatinine concentrations were measured in spot morning urine samples and their ratios were calculated. Urinary protein measured in 24-hour timed collected urine samples gave the 24-hour UTP excretion rate. In our study, spot morning urine protein creatinine ratio significantly correlated with 24-hour UTP excretion rate in all CRD patients. Severe CRD patients gave significant positive correlation (p<0.05), whereas mild and moderate CRD patients gave very highly significant positive correlation (p<0.001). Therefore, it may be suggested that protein creatinine ratio in spot morning urine can be accepted as a reliable and alternative to 24-hour UTP excretion rate in non-diabetic chronic renal disease patients. This simple and inexpensive procedure will thus simplify the way of establishing the severity of renal disease along with its prognosis.