Spontaneous tumor lysis syndrome in a patient with chronic myeloid leukemia treated successfully with allopurinol.

BACKGROUND: Tumor Lysis Syndrome (TLS) is an oncologic emergency that may occur in any patient with a hematologic malignancy, even prior to initiation of chemotherapy. Spontaneous TLS massive tumor cell destruction with intracellular electrolyte release prior to the initiation of chemotherapy. Spontaneous tumor lysis syndrome is a rare presentation, mainly occurring in Acute Leukemia and non-Hodgkin Lymphoma. Chronic Myeloid Leukemia (CML) is a low-risk disease based on TLS risk stratification. To the best of our knowledge, spontaneous TLS in the chronic phase of CML successfully treated with allopurinol and aggressive hydration has yet to be reported in the literature. A case report is described regarding a 67 year old Jamaican female with a history of hypertension who presented to the emergency department with abdominal pain, nausea, and vomiting for 1 day. The patient was found to have leukocytosis to 344,000 with 4% Blasts, hyperuricemia, and acute kidney injury. A peripheral blood smear confirmed the diagnosis of CML. Bone marrow biopsy was performed with evidence of the chronic phase of CML. The patient met clinical criteria for spontaneous tumor lysis syndrome. The patient was started on aggressive intravenous hydration, allopurinol, hydroxyurea and imatinib. Creatinine and uric acid level improved on this regimen within 48 h of initiation.

Fossil dermal denticles reveal the preexploitation baseline of a Caribbean coral reef shark community.

Preexploitation shark baselines and the history of human impact on coral reef-associated shark communities in the Caribbean are tpoorly understood. We recovered shark dermal denticles from mid-Holocene (∼7 ky ago) and modern reef sediments in Bocas del Toro, Caribbean Panama, to reconstruct an empirical shark baseline before major human impact and to quantify how much the modern shark community in the region had shifted from this historical reference point. We found that denticle accumulation rates, a proxy for shark abundance, declined by 71% since the mid-Holocene. All denticle morphotypes, which reflect shark community composition, experienced significant losses, but those morphotypes found on fast-swimming, pelagic sharks (e.g., families Carcharhinidae and Sphyrnidae) declined the most. An analysis of historical records suggested that the steepest decline in shark abundance occurred in the late 20th century, coinciding with the advent of a targeted shark fishery in Panama. Although the disproportionate loss of denticles characterizing pelagic sharks was consistent with overfishing, the large reduction in denticles characterizing demersal species with low commercial value (i.e., the nurse shark Ginglymostoma cirratum) indicated that other stressors could have exacerbated these declines. We demonstrate that the denticle record can reveal changes in shark communities over long ecological timescales, helping to contextualize contemporary abundances and inform shark management and ecology.

SPG7 Is an Essential and Conserved Component of the Mitochondrial Permeability Transition Pore.

Mitochondrial permeability transition is a phenomenon in which the mitochondrial permeability transition pore (PTP) abruptly opens, resulting in mitochondrial membrane potential (ΔΨm) dissipation, loss of ATP production, and cell death. Several genetic candidates have been proposed to form the PTP complex, however, the core component is unknown. We identified a necessary and conserved role for spastic paraplegia 7 (SPG7) in Ca(2+)- and ROS-induced PTP opening using RNAi-based screening. Loss of SPG7 resulted in higher mitochondrial Ca(2+) retention, similar to cyclophilin D (CypD, PPIF) knockdown with sustained ΔΨm during both Ca(2+) and ROS stress. Biochemical analyses revealed that the PTP is a heterooligomeric complex composed of VDAC, SPG7, and CypD. Silencing or disruption of SPG7-CypD binding prevented Ca(2+)- and ROS-induced ΔΨm depolarization and cell death. This study identifies an ubiquitously expressed IMM integral protein, SPG7, as a core component of the PTP at the OMM and IMM contact site.

Xanthogranulomatous Pyelonephritis: A Complicated Febrile Urinary Tract Infection Detected by Point-of-Care Ultrasound in the Emergency Department.

BACKGROUND: Febrile urinary tract infections (UTIs) include a spectrum of pathologies from uncomplicated pyelonephritis to urosepsis, including xanthogranulomatous pyelonephritis (XGP). Most febrile UTIs are treated with antibiotics alone, but studies indicate nearly 12% of cases of presumed simple pyelonephritis require emergent urologic intervention. How to identify these individuals, while limiting unnecessary advanced imaging and delays in diagnosis, challenges all emergency providers. We review the diagnosis and management of XGP, as well as the evidence regarding the role of renal ultrasound in the identification of complicated presentations of febrile UTIs. CASE REPORT: We present a case of XGP, a complicated febrile UTI requiring immediate urologic intervention, diagnosed by point-of-care ultrasound. A 40-year-old female presented in severe sepsis and complaining of flank pain. Prompt bedside ultrasound demonstrated hydronephrosis, expediting definitive urologic treatment via percutaneous nephrostomy tube placement. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: With a mortality rate exceeding 40%, obstructed pyonephrosis requires prompt decompression. Given its exceptional sensitivity for identifying hydronephrosis and ability to detect abscesses and emphysematous changes, we advocate a point-of-care ultrasound-first approach to screen for cases of complicated febrile UTIs in order to expedite treatment and limit radiation in uncomplicated presentations.

Tracking Childhood Lead Exposure in Early Industrial Romanians.

Childhood lead exposure has been linked to severe adverse health outcomes throughout life. Measurements of lead in teeth have established that individuals living in contaminated environments show higher levels compared to individuals living further away, although less is known about when individuals are most susceptible to these exposures. We examined lead (Pb208) concentrations (ppm) in teeth over the first 2.5 years of life in 16 children born in the late 19th to early 20th century throughout Romania. This period of intense industrialization was characterized by increases in mining, coal burning, and oil refining-activities that contaminate air, water, and food with Pb. We hypothesized the distance from an operational mine or oil refinery, or being born in a city, would be positively associated with cumulative dentine Pb exposure (CDPE). We also predicted that Pb exposures would peak in the first six months of life when gastrointestinal (GI) absorption of Pb is likely highest. Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) of sectioned tooth dentine followed by Bayesian statistical analyses revealed that living 30 km or more from a mine or oil refinery did not explain CDPE. However, being born in a city explained 42% of CDPE. All individuals showed maximum Pb exposures after six months of age, likely due to contaminated solid food and/or non-milk liquids. This research demonstrates how tooth formation can be coupled with comprehensive elemental mapping to analyse the context and timing of early-life neurotoxicant exposures, which may be extended to well-preserved teeth from clinical and historic populations.

Coral carbonate-bound isotopes reveal monsoonal influence on nitrogen sources in Southeastern China's Greater Bay Area from the mid-Holocene until the Anthropocene.

Most anthropogenic nitrogen (N) reaches coastal waters via rivers carrying increasing loads of sewage, fertilizer, and sediments. To understand anthropogenic N impacts, we need to understand historical N-dynamics before human influence. Stable isotope ratios of N preserved in carbonates are one way to create temporal N records. However, records that span periods of human occupation are scarce, limiting our ability to contextualize modern N dynamics. Here, we produce a fossil-bound N-record using coral subfossils, spanning 6700 years in China's Greater Bay Area (GBA). We found that during the mid-to-late Holocene, the GBA's coastal N was dominated by fluvial sources. The weakening of the Asia monsoon throughout the late-Holocene decreased river outflow, leading to a relative increase of marine nitrate. This source shift from riverine-to-ocean dominance was overprinted by anthropogenic N. During the late 1980s to early 1990s, human development and associated effluent inundated the coastal system, contributing to the decline of coral communities.

Histologic features of allograft livers in patients treated for rejection before biopsy.

Liver biopsy is essential for management in liver transplant patients with clinical features suspicious for acute cellular rejection (ACR). As more patients are transplanted for noninfectious indications, it has become increasingly common for them to receive treatment for presumed ACR before biopsy. The effect of pretreatment on the classic histologic triad of ACR's mixed portal inflammation, endothelialitis, and bile duct damage is not well described. Here we report a retrospective study of 70 liver transplant biopsies performed on 53 patients for suspected ACR between 2018 and 2021. Thirty-seven biopsies had a clinical diagnosis of ACR after biopsy. Pretreatment with steroids, antithymocyte globulin, or other increased immunosuppression was given before biopsy in 17 of 37 cases; 20 not-pretreated cases acted as controls. A representative hematoxylin and eosin-stained slide from each biopsy was reviewed independently in a blinded fashion by 3 hepatic pathologists, graded according to the Banff system, assigned a Rejection Activity Index (RAI), and assessed for other histologic features. We found that pretreated biopsies had significantly less portal inflammation (P < .001), less endothelialitis (P < .001), lower RAI (P < .001), and less prominent eosinophils (P = .048) compared to not-pretreated biopsies. There was no significant difference for the other examined variables, including bile duct inflammation/damage (P = .32). Our findings suggest that portal inflammation and endothelialitis become less prominent with pretreatment, whereas bile duct inflammation/damage may take longer to resolve. When evaluating biopsies for suspected ACR, the finding of bile duct inflammation/damage should raise the possibility of partially treated ACR, even in the absence of endothelialitis and portal inflammation.

Reef accumulation is decoupled from recent degradation in the central and southern Red Sea.

Reefs are biogenic structures that result in three-dimensional accumulations of calcium carbonate. Over geological timescales, a positive balance between the production and accumulation of calcium carbonate versus erosional and off-reef transport processes maintains positive net accretion on reefs. Yet, how ecological processes occurring over decadal timescales translate to the accumulation of geological structures is poorly understood, in part due to a lack of studies with detailed time-constrained chronologies of reef accretion over decades to centuries. Here, we combined ecological surveys of living reefs with palaeoecological reconstructions and high-precision radiometric (U-Th) age-dating of fossil reefs represented in both reef sediment cores and surficial dead in situ corals, to reconstruct the history of community composition and carbonate accumulation across the central and southern Saudi Arabian Red Sea throughout the late Holocene. We found that reefs were primarily comprised of thermally tolerant massive Porites colonies, creating a consolidated coral framework, with unconsolidated branching coral rubble accumulating among massive corals on shallow (5-8 m depth) exposed (windward), and gently sloping reef slopes. These unconsolidated reef rubble fields were formed primarily from ex situ Acropora and Pocillopora coral fragments, infilled post deposition within a sedimentary matrix. Bayesian age-depth models revealed a process of punctuated deposition of post-mortem coral fragments transported from adjacent reef environments. That a large portion of Saudi Arabian Red Sea reef slopes is driven by allochthonous deposition (transportation) has important implications for modeling carbonate budgets and reef growth. In addition, a multi-decadal lag exists between the time of death for branching in situ coral and incorporation into the unconsolidated reef rubble. This indicates that recent climate related degradation in the 21st century has not had an immediately negative effect on reef building processes affecting a large portion of the reef area in the Saudi Arabian Red Sea.

Giant Gastric Folds in Juvenile Polyposis.

To advance the diagnostic accuracy of juvenile polyposis syndrome, an important yet often difficult diagnosis, we describe in detail a new and medically significant presentation. This hereditary and high-risk GI cancer syndrome is often associated with hereditary hemorrhagic telangiectasia, as in this 47-year-old female patient with a SMAD4 germline pathogenic mutation. Total gastrectomy revealed giant gastric folds with inflamed foveolar hyperplasia consuming most of the gastric cardia and body but sparing the antrum. Together, this gross and histologic pathology mimics Ménétrier's disease, an exceedingly rare and acquired protein-losing hypertrophic gastropathy. Classical gastric juvenile polyposis almost always and principally involves the antrum with multiple distinctive inflammatory polyps rather than the newly illustrated giant gastric folds of this case. No reports of giant gastric folds in juvenile polyposis have appeared in the literature. The distinction between juvenile polyposis and Ménétrier's disease is essential due to their disparate clinical outcomes and management. The differential considerations for giant gastric folds and inflamed gastric foveolar hyperplasia are fully reviewed. On the basis of this report, the differential for giant gastric folds must now expand to include juvenile polyposis syndrome. Genetic testing for pathogenic germline mutations of the 2 known causative genes of this syndrome, namely SMAD4 and BMPR1A, are readily available and should become part of the evaluation of giant gastric folds, particularly in view of the neoplastic and hereditary aspects of juvenile polyposis syndrome.

Imaging Modalities in Genitourinary Emergencies.

Emergency physicians rely on a multitude of different imaging modalities in the diagnosis of genitourinary emergencies. There are many considerations to be taken into account when deciding which imaging modality should be used first, as oftentimes several diagnostic tools can be used for the same pathologic condition. These factors include radiation exposure, sensitivity, specificity, age of patient, availability of resources, cost, and timeliness of completion. In this review, the strengths and weaknesses of different imaging tools in the evaluation of genitourinary emergencies are discussed.

Impact of Traditional Versus Flavored Tongue Depressors on Pediatric Oropharynx Exam.

We compared patient-reported discomfort associated with oropharynx examination using traditional (unflavored) versus flavored tongue depressors among pediatric patients presenting to the emergency department in a single-blinded, placebo-controlled randomized trial using a convenience sample ages 3 to 12 years. Our primary outcome was patient discomfort. Secondary outcomes included provider perceptions of patient discomfort, provider-reported examination ease, and caregiver perceptions of patient discomfort. Of 96 recruited patients, 92 (95.8%) completed the study. Forty-six (50%) were randomized to a traditional tongue depressor. Mean patient-reported oropharynx examination discomfort scores were 2.3 cm (95% confidence interval = 1.4-3.2 cm) with traditional tongue depressors versus 1.9 cm (95% confidence interval = 1.0-2.8 cm) with flavored tongue depressors ( P = .72). There were similarly no significant differences between the 2 arms with regard to any of the secondary outcomes. We conclude that the use of flavored tongue depressors does not appear to significantly alleviate discomfort associated with examination of the oropharynx in pediatric patients.

Historical photographs revisited: A case study for dating and characterizing recent loss of coral cover on the inshore Great Barrier Reef.

Long-term data with high-precision chronology are essential to elucidate past ecological changes on coral reefs beyond the period of modern-day monitoring programs. In 2012 we revisited two inshore reefs within the central Great Barrier Reef, where a series of historical photographs document a loss of hard coral cover between c.1890-1994 AD. Here we use an integrated approach that includes high-precision U-Th dating specifically tailored for determining the age of extremely young corals to provide a robust, objective characterisation of ecological transition. The timing of mortality for most of the dead in situ corals sampled from the historical photograph locations was found to coincide with major flood events in 1990-1991 at Bramston Reef and 1970 and 2008 at Stone Island. Evidence of some recovery was found at Bramston Reef with living coral genera similar to what was described in c.1890 present in 2012. In contrast, very little sign of coral re-establishment was found at Stone Island suggesting delayed recovery. These results provide a valuable reference point for managers to continue monitoring the recovery (or lack thereof) of coral communities at these reefs.

Intracranial hemorrhage in newborns with hemophilia: the role of screening radiologic studies in the first 7 days of life.

In newborns with hemophilia, intracranial hemorrhage (ICH) is a potentially life-threatening event and in those who survive, there is a risk of long-term neurologic sequelae. A single-center retrospective chart review was performed to look at the utility of central nervous system screening of babies who were diagnosed with moderate or severe hemophilia in the first 7 days of life. Twenty of the twenty-two eligible babies had either a head ultrasound or computerized tomography of the head performed as soon as possible after the diagnosis of hemophilia was confirmed. ICH was found in 3 of the 20 newborns. All patients with ICH had instrument-assisted deliveries with extracranial signs of bleeding/trauma. On the basis of this series we found screening to be safe and effective in recognizing ICH. As a result of this approach, all ICHs were found when they were radiographically small and before the babies had neurologic symptoms.