Mortality in Innu communities in Labrador, 1993-2018: a cross-sectional study of causes and location of death.

In Canada, most people prefer to die at home. However, the proportion of deaths that occur in hospital has increased over time. This study examined mortality rates and proportionate mortality in Innu communities in Labrador, and compared patterns to other communities in Labrador and Newfoundland. We conducted a cross-sectional ecological study with mortality data from the vital statistics system. This included information about all deaths in Newfoundland and Labrador from 1993 to 2018. We used descriptive statistics and rates to examine patterns by age, sex, cause and location. During the 2003 to 2018 period the leading cause of death in the Innu communities (excluding external causes) was cancer, followed by circulatory disease and respiratory disease. Between 1993 and 2018, there was a lower percentage of hospital deaths and a higher percentage of at home deaths in Innu communities than in the rest of the province. The majority of deaths among Innu were due to cancer and chronic diseases. We found a higher percentage of at home deaths in Innu communities compared to the rest of the province.

Geometric and dosimetric evaluation for breast and regional nodal auto-segmentation structures.

The accuracy of artificial intelligence (AI) generated contours for intact-breast and post-mastectomy radiotherapy plans was evaluated. Geometric and dosimetric comparisons were performed between auto-contours (ACs) and manual-contours (MCs) produced by physicians for target structures. Breast and regional nodal structures were manually delineated on 66 breast cancer patients. ACs were retrospectively generated. The characteristics of the breast/post-mastectomy chestwall (CW) and regional nodal structures (axillary [AxN], supraclavicular [SC], internal mammary [IM]) were geometrically evaluated by Dice similarity coefficient (DSC), mean surface distance, and Hausdorff Distance. The structures were also evaluated dosimetrically by superimposing the MC clinically delivered plans onto the ACs to assess the impact of utilizing ACs with target dose (Vx%) evaluation. Positive geometric correlations between volume and DSC for intact-breast, AxN, and CW were observed. Little or anti correlations between volume and DSC for IM and SC were shown. For intact-breast plans, insignificant dosimetric differences between ACs and MCs were observed for AxNV95% (p = 0.17) and SCV95% (p = 0.16), while IMNV90% ACs and MCs were significantly different. The average V95% for intact-breast MCs (98.4%) and ACs (97.1%) were comparable but statistically different (p = 0.02). For post-mastectomy plans, AxNV95% (p = 0.35) and SCV95% (p = 0.08) were consistent between ACs and MCs, while IMNV90% was significantly different. Additionally, 94.1% of AC-breasts met ΔV95% variation <5% when DSC > 0.7. However, only 62.5% AC-CWs achieved the same metrics, despite AC-CWV95% (p = 0.43) being statistically insignificant. The AC intact-breast structure was dosimetrically similar to MCs. The AC AxN and SC may require manual adjustments. Careful review should be performed for AC post-mastectomy CW and IMN before treatment planning. The findings of this study may guide the clinical decision-making process for the utilization of AI-driven ACs for intact-breast and post-mastectomy plans. Before clinical implementation of this auto-segmentation software, an in-depth assessment of agreement with each local facilities MCs is needed.

Myelographic Techniques for the Localization of CSF-Venous Fistulas: Updates in 2024.

CSF-venous fistulas (CVFs) are a common cause of spontaneous intracranial hypotension. Despite their relatively frequent occurrence, they can be exceedingly difficult to detect on imaging. Since the initial description of CVFs in 2014, the recognition and diagnosis of this type of CSF leak has continually increased. As a result of multi-institutional efforts, a wide spectrum of imaging modalities and specialized techniques for CVF detection is now available. It is important for radiologists to be familiar with the multitude of available techniques, because each has unique advantages and drawbacks. In this article, we review the spectrum of imaging modalities available for the detection of CVFs, explain the advantages and disadvantages of each, provide typical imaging examples, and discuss provocative maneuvers that may improve the conspicuity of CVFs. Discussed modalities include conventional CT myelography, dynamic myelography, digital subtraction myelography, conebeam CT myelography, decubitus CT myelography by using conventional energy-integrating detector scanners, decubitus photon counting CT myelography, and intrathecal gadolinium MR myelography. Additional topics to be discussed include optimal patient positioning, respiratory techniques, and intrathecal pressure augmentation.

The BAHD and the bold: the mitochondria's role in alkaloid artistry.

In a recent study, Zeng et al. uncovered 3ß-tigloyloxytropane synthase (TS) in Atropa belladonna, characterizing its mitochondrial localization and substrate specificity. The discovery of this enzyme opens up new bioengineering possibilities for tropane alkaloids (TAs), enhancing the potential for sustainable agriculture and expanding our knowledge of TA biosynthesis.

Discrepancies of centric occlusion located by using a conventional method and four intraoral scanners combined with a computer-aided design program: A pilot investigation.

STATEMENT OF PROBLEM: Intraoral scanners (IOSs) can be used to record the maxillomandibular relationship at centric relation (CR). The articulated digital scans can be imported into a dental computer-aided design (CAD) program and used to locate centric occlusion (CO); however, the accuracy of the CO recorded by using IOSs and a dental CAD program remains unknown. PURPOSE: The purpose of this clinical study was to compare the position of the CO located by using a conventional method and 4 IOSs combined with a dental CAD program. MATERIAL AND METHODS: A patient volunteered to participate in this study. Conventional diagnostic stone casts were obtained. A facebow record (Kois Dentofacial Analyzer) was used to transfer the maxillary cast into a semi-adjustable articulator (Panadent PCH Articulator). A Kois deprogrammer (KD) was used to record the maxillomandibular relationship at CR and to transfer the mandibular cast into the articulator. Afterwards, CO was located in the articulated casts by removing the incisal pin and using an 8-µm articulating foil. CO was marked in the casts by using a blue articulating paper (control). Three groups were created based on the IOS used: TRIOS 4, iTero Element 5D Plus, i700, and Primescan. In each IOS group, a maxillary and mandibular scan were obtained. The scans were duplicated 10 times. Afterwards, a bilateral occlusal record captured with the KD was used to articulate each pair of duplicated scans. Each articulated specimen was imported into a CAD program (DentalCAD) and CO was virtually located. The teeth contacting at the CO of each specimen were compared with the control group. Categorical data were analyzed by using the chi-squared test (α=.05). RESULTS: The chi-squared test revealed a significant association between the IOS system and the location of the CO (P=.004). The highest association was found between the TRIOS 4 and CO position, in which 100% of the specimens obtained the same CO position as in the conventional group. The lowest association was found between the i700 and CO position. In the i700 group, 20% of the specimens showed the same CO position as in the control group. A similar outcome was obtained in the iTero and Primescan groups. In both groups, 60% of the specimens demonstrated the same CO position as the control group. CONCLUSIONS: The IOS system used to acquire articulated scans at CR impacted the CO position located by using the evaluated digital methods. The TRIOS 4 system was the only IOS that consistently reproduced the same CO position as the conventional method.

Case Report: The effect of automated manual lymphatic drainage therapy on lymphatic contractility in 4 distinct cases.

Introduction: Automated manual lymphatic drainage therapy (AMLDT) is available for home use in the form of a pneumatic mat of 16 pressurized air channels that inflate and deflate to mimic the stretch and release action of manual lymphatic drainage therapy. Four cases (a patient with complex regional pain syndrome and lymphedema, a healthy patient, a breast cancer survivor with chronic pain, and a patient with a history of abdominal surgery) underwent near-infrared fluorescence lymphatic imaging (NIRFLI) with AMLDT to evaluate the effect of AMLDT on lymphatic pumping and pain. Methods: Each patient received 32-36 injections of 25 µg indocyanine green (ICG) on the anterior and posterior sides of their body and underwent 1 h of NIRFLI to assess the drainage of ICG laden lymph toward regional nodal basins at baseline. Each patient lay supine on the mat for 1 h of AMLDT with NIRFLI to assess lymphatic flow during treatment. A final NIFRFLI assessment was done 30-60 min posttreatment with the patient in the supine and prone position. Patients reported baseline and posttreatment pain using the Visual Analogue Scale. An imager analyzed NIRFLI images using ImageJ (US National Institutes of Health). Using time stamps of the first and last images to determine time lapsed and the number of pulses observed in a timeframe, pulsing frequency (pulses/min) was obtained to assess lymphatic function. Results: All 4 cases completed the NIRFLI and AMLDT without complications; all 3 patients with baseline pain reported reduced pain posttreatment. AMLDT appeared to alter lymphatic contractility, with both increased and decreased pulsing frequencies observed, including in nonaffected limbs. Pulsing frequencies were very heterogeneous among patients and varied within anatomic regions of the same patient. Discussion: This proof-of-concept study suggests that AMLDT may impact lymphatic contractility. Further research on its effect on lymphatic function is warranted.

The Evolving Role of Genetic Testing in Monogenic Kidney Stone Disease: Spotlight on Primary Hyperoxaluria.

Multiple factors are thought to give rise to common, recurrent kidney stone disease, but for monogenic stone disorders a firm diagnosis is possible through genetic testing. The autosomal recessive primary hyperoxalurias (PH) are rare but important forms of monogenic kidney stone disease. All 3 types of PH are caused by inborn errors of glyoxylate metabolism in the liver, leading to hepatic oxalate overproduction and excessive renal urinary oxalate excretion. The conditions are characterized by kidney stones, nephrocalcinosis, progressive chronic kidney disease (CKD), and eventually kidney failure. Systemic oxalosis, the extra-renal deposition of oxalate resulting in severe morbidity and mortality, occurs in the setting of CKD when oxalate clearance by the kidneys declines. Novel small interfering RNA-based therapeutics targeting the liver to reduce urinary oxalate excretion have been approved, introducing precision medicine to treat primary hyperoxaluria type 1 (PH1). Increased access to genetic testing facilitates early detection of PH and other monogenic causes of kidney stone disease so that individualized care can be instituted promptly. This narrative review addresses the benefits and practicalities of genetic testing for suspected monogenic kidney stone disease and the critical roles of a multidisciplinary team. We share our procedures, education, training, and workflows to help other clinicians integrate genetic assessment into their diagnostic routines. This information may ensure more timely diagnoses so that patients with suspected monogenic kidney stone disease gain access to an expanded range of services and enrollment in clinical trials and registries.

Acute Migraine Treatment with Timolol 0.5% Nasal Spray - Compounding Pharmacists Have an Important Role.

For the foreseeable future, timolol 0.5% nasal spray prepared by compounding pharmacists will be the only source for a potentially dramatic new paradigm in the treatment of acute migraine.1 It is also likely other medical conditions can be treated with the compounded timolol nasal spray that need extremely rapid therapeutic beta blocker blood levels when IV infusion is not possible or practical. This manuscript will review the research and development of compounded timolol medication over the past dozen years and reference previous articles in IJPC detailing how the pharmaceutical compounded product is prepared.2 A final goal is to engage physicians in a beneficial working relationship with compounding pharmacies to make immediately available to patients a nasal spray formulation of the beta blocker timolol 0.5% in solution. It has recently been demonstrated for the first time to benefit acute migraine treatment.

Distinct mitochondrial respiration profiles in pediatric patients with febrile illness versus sepsis.

OBJECTIVE: Mitochondrial dysfunction, linked to sepsis-related organ failure, is unknown in febrile illness. METHODS: Prospective study of children in an Emergency Department (ED) with febrile illness or without infection (ED controls); secondary analysis of ICU patients with sepsis or without infection (ICU controls). Mitochondrial oxygen consumption measured in peripheral blood mononuclear cells using respirometry, with primary outcome of spare respiratory capacity (SRC). Mitochondrial content measured as citrate synthase (CS: febrile illness and ED controls) and mitochondrial to nuclear DNA ratio (mtDNA:nDNA: all groups). RESULTS: SRC was lower in febrile illness (6.7 ± 3.0 pmol/sec/106 cells) and sepsis (5.7 ± 4.7) than ED/PICU controls (8.5 ± 3.7; both p < 0.05), but not different between febrile illness and sepsis (p = 0.26). Low SRC was driven by increased basal respiration in febrile illness and decreased maximal uncoupled respiration in sepsis. Differences were no longer significant after adjustment for patient demographics. Febrile illness demonstrated lower CS activity than ED controls (p = 0.07) and lower mtDNA:nDNA than both ED/PICU controls and sepsis (both p < 0.05). CONCLUSION: Mitochondrial SRC was reduced in both febrile illness and sepsis, but due to distinct mitochondrial profiles and impacted by demographics. Further work is needed to determine if mitochondrial profiles could differentiate febrile illness from early sepsis. IMPACT STATEMENT: Mitochondrial dysfunction has been linked to organ failure in sepsis, but whether mitochondrial alterations are evident in febrile illness without sepsis is unknown. In our study, while mitochondrial spare respiratory capacity (SRC), an index of cellular bioenergetic reserve under stress, was reduced in children with both febrile illness and sepsis compared to children without infections, low SRC was driven by increased basal respiration in febrile illness compared with decreased maximal uncoupled respiration in sepsis. Additional research is needed to understand if distinct mitochondrial profiles could be used to differentiate febrile illness from early sepsis in children.

Absence of Cerebrospinal Fluid Pleocytosis in Encephalitis.

BACKGROUND: Early diagnosis of encephalitis involves identifying signs of neuroinflammation, including cerebrospinal fluid (CSF) pleocytosis. However, absence of CSF pleocytosis in encephalitis has been described, most notably in autoimmune encephalitis. We examined clinical characteristics and outcomes associated with the absence or presence of CSF white blood cell pleocytosis (≥ 5 cells/µL), to inform timely diagnosis and management of encephalitis. METHODS: This retrospective study compares initial CSF profiles in 597 adult patients with all-cause encephalitis. RESULTS: Of the 597 patients, 446 (74.7%) had CSF pleocytosis while 151 (25.3%) did not. CSF pleocytosis occurred more commonly in infectious cases (200/446, 44.8%), along with 59 (13.2%) autoimmune cases, comprised chiefly of anti-NMDAR encephalitis (37/59, 62.7%). Notably, the group without pleocytosis was comprised of similar proportions of infectious (47/151, 31.1%) and autoimmune (38/151, 25.92%; p>0.05) encephalitis. Among those with infectious encephalitis, 47/247 (19%) had absent pleocytosis, including 18/76 (23.7%) with HSV-1 encephalitis. The absence of pleocytosis was associated with a decreased rate of acyclovir administration (47.7% in patients without pleocytosis vs. 71.1% in patients with pleocytosis, p<0.001). Despite pleocytosis being associated with some measures of clinical severity at admission such as a Full Outline of UnResponsiveness (FOUR) score ≤14, it was not associated with mortality or prolonged hospitalization. CONCLUSION: CSF pleocytosis is an important criterion for encephalitis diagnosis, but 25.3% of patients with all-cause encephalitis and 23.7% of those with HSV-1 encephalitis exhibit absence of pleocytosis on initial LP. Acyclovir initiation should not be delayed in the absence of pleocytosis in patients with suspected encephalitis.

Amplified warming of North American cold extremes linked to human-induced changes in temperature variability.

How global warming is impacting winter cold extremes is uncertain. Previous work has found decreasing winter temperature variability over North America which suggests a reduction in frequency and intensity of cold extremes relative to mean changes. However, others argue that cold air outbreaks are becoming more likely because of Arctic-induced changes in atmospheric circulation. Here we show that cold extremes over North America have warmed substantially faster than the winter mean temperature since 1980. This amplified warming is linked to both decreasing variance and changes in higher moments of the temperature distributions. Climate model simulations with historical forcings robustly capture the observed trends in extremes and variability. A pattern-based detection and attribution analysis shows that the changes in variability are detectable in observations and can be attributed to human influence. Our results highlight that human emissions are warming North American extreme cold temperatures beyond only shifting the winter mean temperature.

Cross-sectional and longitudinal changes in mind-wandering in older adulthood.

Age-related declines in the frequency of mind-wandering are well established. Theories of mind-wandering have attempted to explain why this decline occurs, but no one theory firmly predicts such changes. One problem with these theoretical views, and the studies that have grown out of them, is their reliance on cross-sectional methods, which do not account for within-person changes over time in mind-wandering, and it is well-documented that cross-sectional and longitudinal changes in some cognitive domains do not align. We present a novel analysis of longitudinal change in subjective and objective indicators of mind-wandering during a sustained attention task. Cognitively normal adults (N = 277, age range 42-94) completed a sustained attention task with thought probes to measure mind-wandering repeatedly over several years. Linear mixed effect models revealed baseline differences in subjective mind-wandering reports among middle-aged and older adults. However, longitudinally, middle-aged participants showed a significant increase in subjective mind-wandering, whereas older participants showed no change. Changes in mind-wandering could not be explained by attentional control ability or contemporaneous estimates of interest and perceived difficulty, but they were explained by baseline levels of conscientiousness. Objective measures of mind-wandering did not show these same patterns and were largely only associated with participants perceived difficulty. Our results build on previous cross-sectional research and suggest that incorporating longitudinal analyses into theories of ageing and mind-wandering and mind-wandering more broadly is important for refining these theories. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Eukaryotic Pif1 helicase unwinds G-quadruplex and dsDNA using a conserved wedge.

G-quadruplexes (G4s) formed by guanine-rich nucleic acids induce genome instability through impeding DNA replication fork progression. G4s are stable DNA structures, the unfolding of which require the functions of DNA helicases. Pif1 helicase binds preferentially to G4 DNA and plays multiple roles in maintaining genome stability, but the mechanism by which Pif1 unfolds G4s is poorly understood. Here we report the co-crystal structure of Saccharomyces cerevisiae Pif1 (ScPif1) bound to a G4 DNA with a 5' single-stranded DNA (ssDNA) segment. Unlike the Thermus oshimai Pif1-G4 structure, in which the 1B and 2B domains confer G4 recognition, ScPif1 recognizes G4 mainly through the wedge region in the 1A domain that contacts the 5' most G-tetrad directly. A conserved Arg residue in the wedge is required for Okazaki fragment processing but not for mitochondrial function or for suppression of gross chromosomal rearrangements. Multiple substitutions at this position have similar effects on resolution of DNA duplexes and G4s, suggesting that ScPif1 may use the same wedge to unwind G4 and dsDNA. Our results reveal the mechanism governing dsDNA unwinding and G4 unfolding by ScPif1 helicase that can potentially be generalized to other eukaryotic Pif1 helicases and beyond.

Evaluating the safety profile of semaglutide: an updated meta-analysis.

BACKGROUND: Semaglutide is increasingly used in the management of type 2 diabetes mellitus and obesity. Ensuring the safety of this medication is crucial for its clinical use. This meta-analysis evaluates the safety profile of semaglutide across patient populations and treatment durations. METHODS: Randomized controlled trials assessing the safety of semaglutide vs. placebo, with specified treatment durations were identified. The primary outcome was occurrence of any cardiovascular adverse events. Secondary outcomes included sudden cardiac death, adverse events leading to death, adverse events, gastrointestinal side effects, occurrence of hypoglycemia, and new-onset neoplasm. RESULTS: A total of 23 studies met the inclusion criteria with a combined sample size of 57,911 participants. The meta-analysis revealed that the adverse event associated with semaglutide is gastrointestinal in nature (nausea and vomiting). No significant differences were observed between semaglutide and comparator groups. CONCLUSION: Semaglutide appears to have a favorable safety profile across diverse patient populations and treatment durations, supporting its continued use in the management of type 2 diabetes mellitus and obesity. It is generally well-tolerated, with a low incidence of adverse events. Clinicians should be aware of these findings and monitor patients accordingly. Further long-term studies are warranted to assess the safety of semaglutide in clinical practice.

Treatment of Locally Recurrent Rectal Cancer: A Review.

ABSTRACT: Up to 10% of patients with locally advanced rectal cancer will experience locoregional recurrence. In the setting of prior surgery and often radiation and chemotherapy, these represent uniquely challenging cases. When feasible, surgical resection offers the best chance for oncologic control yet risks significant morbidity. Studies have consistently indicated that a negative surgical resection margin is the strongest predictor of oncologic outcomes. Chemoradiation is often recommended to increase the chance of an R0 resection, and in cases of close/positive margins, intraoperative radiation/brachytherapy can be utilized. In patients who are not surgical candidates, radiation can provide symptomatic relief. Ongoing phase III trials are aiming to address questions regarding the role of reirradiation and induction multiagent chemotherapy regimens in this population.

Real-world effectiveness of sotrovimab in preventing hospitalization and mortality in high-risk patients with COVID-19 in the United States: A cohort study from the Mayo Clinic electronic health records.

BACKGROUND: To describe outcomes of high-risk patients with coronavirus disease 2019 (COVID-19) treated with sotrovimab, other monoclonal antibodies (mAbs), or antivirals, and patients who did not receive early COVID-19 treatment. We also evaluate the comparative effectiveness of sotrovimab versus no treatment in preventing severe clinical outcomes. METHODS: This observational retrospective cohort study analyzed Mayo Clinic electronic health records. Non-hospitalized adult patients diagnosed with COVID-19 from May 26, 2021 and April 23, 2022 and at high risk of COVID-19 progression were eligible. The primary outcome was 29-day all-cause hospitalization and/or death. Outcomes were described for patients treated with sotrovimab, other mAbs, or antivirals, and eligible but untreated patients, and compared between sotrovimab-treated and propensity score (PS)-matched untreated cohorts. RESULTS: We included 35,485 patients (sotrovimab, 1369; other mAbs, 6488; antivirals, 133; high-risk untreated, 27,495). A low proportion of patients treated with sotrovimab (n = 33/1369, 2.4%), other mAbs (n = 147/6488, 2.3%), or antivirals (n = 2/133, 1.5%) experienced all-cause hospitalization or death. Among high-risk untreated patients, the percentage of all-cause hospitalization or death was 3.3% (n = 910/27,495). In the PS-matched analysis, 2.5% (n = 21/854) of sotrovimab-treated patients experienced all-cause hospitalization and/or death versus 2.8% (n = 48/1708) of untreated patients (difference, -0.4%; p = 0.66). Significantly fewer sotrovimab-treated patients required intensive care unit admission (0.5% vs 1.8%; difference, -1.3%; p = 0.002) or respiratory support (3.5% vs 8.7%; difference, -5.2%; p < 0.001). CONCLUSIONS: There was no significant difference in the proportion of sotrovimab-treated and PS-matched untreated patients experiencing 29-day all-cause hospitalization or mortality, although significantly fewer sotrovimab-treated patients required intensive care unit admission or respiratory support.

The effect of histopathologic analysis and tissue cultures on inpatient management of cellulitis: a randomized control trial.

BACKGROUND: In the absence of a gold-standard diagnostic modality for cellulitis, sterile inflammatory disorders may be misdiagnosed as cellulitis. OBJECTIVE: To determine the utility of skin biopsy and tissue culture for the diagnosis and management of patients admitted with a diagnosis of presumed cellulitis. DESIGN: Pilot single-blind parallel group randomized controlled clinical trial in 56 patients with a primary diagnosis of presumed cellulitis. In the intervention group only, skin biopsy and tissue culture results were made available to the primary care team to guide diagnosis and management. Length of hospital stay and antibiotic use were evaluated as outcome measures. RESULTS: Length of stay showed the greatest opportunity for further study as a primary outcome (intervention: 4, IQR (2-6) vs. control: 5 IQR (3-8) days; p = 0.124). LIMITATIONS: The COVID-19 pandemic placed limitations on participant enrollment and study duration; in addition, data was collected from a single medical center. CONCLUSION: This study demonstrates that length of stay and anti-pseudomonal antibiotic de-escalation are endpoints that may be influenced by biopsy and tissue culture results in presumed cellulitis patients; these outcomes warrant further study.

Core socioDemographic data variables in ICU Trials (CoDe-IT): a protocol for generating core data variables using a Delphi consensus process.

INTRODUCTION: Sociodemographic variables influence health outcomes, either directly (ie, gender identity) or indirectly (eg, structural/systemic racism based on ethnoracial group). Identification of how sociodemographic variables can impact the health of critically ill adults is important to guide care and research design for this population. However, despite the growing recognition of the importance of collecting sociodemographic measures that influence health outcomes, insufficient and inconsistent data collection of sociodemographic variables persists in critical care studies. We aim to develop a set of core data variables (CoDaV) for social determinants of health specific to studies involving critically ill adults. METHODS AND ANALYSIS: We will conduct a scoping review to generate a list of possible sociodemographic measures to be used for round 1 of the modified Delphi processes. We will engage relevant knowledge users (previous intensive care unit patients and family members, critical care researchers, critical care clinicians and research co-ordinators) to participate in the modified Delphi consensus survey to identify the CoDaV. A final consensus meeting will be held with knowledge user representatives to discuss the final CoDaV, how each sociodemographic variable will be collected (eg, level of granularity) and how to disseminate the CoDaV for use in critical care studies. ETHICS AND DISSEMINATION: The University of Calgary conjoint health research ethics board has approved this study protocol (REB22-1648).

Significant pituitary siderosis is common in transfusion dependent sickle cell disease.

Chronically transfused sickle cell patients typically don't exhibit iron-mediated extrahepatic toxicity. However, we demonstrate that the pituitary gland is vulnerable to iron deposition, and it occurs regardless of other extrahepatic involvement. Severe pituitary siderosis is associated with early organ dysfunction.

RANDOMIZED TRIAL COMPARING MICROSERRATED VERSUS CONVENTIONAL INTERNAL LIMITING MEMBRANE FORCEPS FOR INTERNAL LIMITING MEMBRANE PEELING.

PURPOSE: To evaluate anatomic outcomes and surgeon response following the use of microserrated (Sharkskin, Alcon, Forth Worth, TX) internal limiting membrane (ILM) forceps compared with conventional (Grieshaber; Alcon) ILM forceps for peeling of the ILM. METHODS: Patients were prospectively assigned in a 1:1 randomized fashion to undergo ILM peeling using microserrated forceps or conventional forceps. Rates of retinal hemorrhages, deep retinal grasps, ILM regrasping, time to ILM removal, and surgeon questionnaire comparing the use of microserrated and conventional ILM forceps were analyzed. RESULTS: A total of 90 eyes of 90 patients were included in this study. The mean number of deep retinal grasps was higher in the conventional forceps group (1.51 ± 1.70 vs. 0.33 ± 0.56, respectively [P < 0.0001]). The mean number of failed ILM grasps was higher with conventional forceps (6.62 ± 3.51 vs. 5.18 ± 2.06 [P = 0.019]). Microserrated forceps provided more comfortability (lower number) in initiating the ILM flap (2.16 ± 0.85 vs. 1.56 ± 0.76, P < 0.001), comfortability in regrasping the ILM flap (2.51 ± 1.01 vs. 1.98 ± 0.89, P = 0.01), and comfortability in completing the ILM flap (2.42 ± 1.03 vs. 1.84 ± 1.02, P = 0.01). CONCLUSION: Surgeons utilizing the microserrated forceps experienced fewer deep retina grasps and fewer failed ILM grasps compared with conventional ILM forceps. The microserrated forceps was also a more favorable experience subjectively among the surgeons.