Effect of QT interval prolongation on cardiac arrest following liver transplantation and derivation of a risk index

Liver transplantation (LT) has a 4-fold higher risk of periprocedural cardiac arrest and ventricular arrhythmias (CA/VAs) compared with other noncardiac surgeries. Prolongation of the corrected QT interval (QTc) is common in patients with liver cirrhosis. Whether it is associated with an increased risk of CA/VAs following LT is unclear. Rates of 30-day CA/VAs post-LT were assessed in consecutive adults undergoing LT between 2010 and 2017. Pretransplant QTc was measured by a cardiologist blinded to clinical outcomes. Among 408 patients included, CA/VAs occurred in 26 patients (6.4%). QTc was significantly longer in CA/VA patients (475 ± 34 vs 450 ± 34 ms, P < .001). Optimal QTc cut-off for prediction of CA/VAs was ≥480 ms. After adjustment, QTc ≥480 ms remained the strongest predictor for the occurrence of CA/VAs (odds ratio [OR] 5.2, 95% confidence interval [CI] 2.2-12.6). A point-based cardiac arrest risk index (CARI) was derived with the bootstrap method for yielding optimism-corrected coefficients (2 points: QTc ≥480, 1 point: Model for End-Stage Liver Disease [MELD] ≥30, 1 point: age ≥65, and 1 point: male). CARI score ≥3 demonstrated moderate discrimination (c-statistic 0.79, optimism-corrected c-statistic 0.77) with appropriate calibration. QTc ≥480 ms was associated with a 5-fold increase in the risk of CA/VAs. The CARI score may identify patients at higher risk of these events. Whether heightened perioperative cardiac surveillance, avoidance of QT prolonging medications, or beta blockers could mitigate the risk of CA/VAs in this population merits further study.     

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.     

Selective transperineal prostate biopsy for fluoroquinolone-resistance patients reduces sepsis and cost

Background:Urosepsis is a recognized complication of transrectal ultrasound-guided prostate biopsy (TRUS-Bx). Pre-biopsy rectal swabs have been used to identify patients with microorganisms in the rectal flora resistant to the conventionally used empirical prophylaxis. The transperineal route of biopsy (TP-Bx) has a lower complication risk but comes at an increased cost.Materials and methods:Retrospective cohort study including patients undergoing prostate biopsies between October/2015 and April/2018. The intervention cohort, a rectal swab was performed, the result of which dictated the biopsy route; TRUS-Bx against TP-Bx. TP-Bx for patients with fluoroquinolone resistance or extended-spectrum β-lactamase. The control cohort underwent TRUS without a rectal swab receiving empirical antibiotics—oral ciprofloxacin and intravenous gentamicin.Results:Total 1000 patients were included in which 500 underwent a swab, 14 (2.8%) developed post-TRUS biopsy infective complications with 3 having positive bacteremia (0.6%); 500 had no swab, 47 (9.4%) developed post-TRUS biopsy infective complications with 22 (4.4%, p < 0.05) having positive bacteremia. Three patients (0.6%) of patients who underwent swab developed urinary tract infection symptoms whilst 12 (2.4%) had urinary tract infection in the control group. In those patients that underwent a swab, 14 required hospitalization with mean length of stay of 2.5 days versus 43 patients of the control with 3.6 days. Cost analysis concluded savings of this strategy was £18,711.Conclusions:We have demonstrated a protocol that reserves template biopsies for higher risk patients and can significantly reduce sepsis and other infectious complication rates whilst also proving to be a cost-efficient strategy. We recommend that units not utilizing rectal swabs to uncover the fluoroquinolone resistance rate by introducing them. We advocate units that already utilize rectal swabs, to introduce transperineal biopsy for their higher risk patients.     

Anatomic and experimental basis for the insertion of a screw at the first sacral vertebra

Summary The authors present the anatomic and experimental basis of an original technique for screwing at the first sacral level employed in lumbosacral fusion. The anatomic studies were based on specimens from the anatomy museum, frozen sections of the sacrum and CT examinations with three-dimensional reconstruction and assessment of the density of the different structures of S1 in Hounsfield units (HU). The findings were that the ala and lateral portions of S1 contain yellow marrow forming what amounts to a fatty sphere bounded by the cortical bone of the sacroiliac joint, the linea terminalis and the spongy bone of the pedicles and of the body of S1. The experimental study was made by avulsion of sacral screws (system of Cotrel Dubousset), each of 7mm diameter. No screw perforated the sacral cortex. Three directions were tested. The insertion of a screw through the pedicle and body of S1 is advised, with the point of insertion below and lateral to the articular process of S1 and an oblique course forward and inward at an angle of 10° to the sagittal plane. This internal obliquity is limited by the posterior prominence of the iliac ala.

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Bases anatomiques et expérimentales de la mise en place d'une vis d'ostéosynthèse au niveau de la première vertèbre sacrée

Résumé Les auteurs présentent les bases anatomiques et expérimentales d'une technique originale de vissage en S1 employée pour les ostéosynthèses lombo-sacrées. Les études anatomiques portent sur des pièces du musée d'Anatomie, sur des coupes congelées de sacrum, des examens tomodensitométriques computérisés avec reconstruction en 3 dimensions et appréciation de la densité exprimée en unité Hounsfield (uH) des différentes structures de S1. Les constatations sont les suivantes : les ailerons et la partie latérale de S1 continennent de la moëlle jaune formant une véritable boule graisseuse limitée latéralement par l'os cortical de l'articulation sacro-iliaque, médialement par l'os spongieux des pédicules et du corps de S1, ventralement et dorsalement par les corticales de la partie latérale de S1. L'étude expérimentale est faite par arrachement de vis sacrées (matériel de Cotrel Dubousset), faisant chacune 7mm de diamètre. Aucune vis ne perfore la corticale sacrée. Trois directions sont testées. Nous conseillons la mise en place d'une vis pédiculo-corporéale en S 1 ; le point d'introduction est au-dessous et en dehors du processus articulaire de S 1, le trajet est oblique en avant et en dedans faisant 10° avec le plan sagittal. Cette obliquité interne est limitée par la saillie postérieure de l'aile iliaque.

     

Synthesis of new xanthenone derivatives of expected antibilharzial activity

Some new 9H-thioxanthen-9-one incorporated into heterocyclic systems such as pyridone8, pyrazoline9, pyranone11, iminopyrane12, furopyrimidine17, imidazothiazole19, thiazole21, triazine24 and other related compounds through a para imminophenyl grouping at position-1 of the thioxanthenone ring were synthesized and tested as antitumor agents, against L 1210 leukemia in mice. Some of the new compounds showed considerable antitumor activity.     

Synthesis of 1-(heterocyclic substituted anilino)-9H-thioxanthon-9-ones and their antitumor activity

Some new 9H-thioxanthen-9-one incorporated into heterocyclic systems such as pyridone8, pyrazoline9, pyranone11, iminopyrane12, furopyrimidine17, imidazothiazole19, thiazole21, triazine24 and other related compounds through a para imminophenyl grouping at position-1 of the thioxanthenone ring were synthesized and tested as antitumor agents, against L 1210 leukemia in mice. Some of the new compounds showed considerable antitumor activity.     

Differential effects of zidovudine and zidovudine triphosphate on mitochondrial permeability transition and oxidative phosphorylation

1. The effects of zidovudine (ZDV) and zidovudine triphosphate (ZDV-3P) on Ca²⁺-induced mitochondrial permeability transition (MPT), respiratory control ratio (RCR) and ATP synthesis have been investigated on isolated rat liver mitochondria.
2. ZDV slightly but significantly decreased RCR and ATP synthesis but was ineffective in inhibiting MPT. In contrast, ZDV-3P did not alter RCR and ATP synthesis but strongly inhibited MPT (IC₅₀=3.0±0.9 μM).
3. The effect of ZDV-3P on mitochondrial swelling required a preincubation time. When incubated 10 min with mitochondria, ZDV-3P (8 μM) totally inhibited the rate of swelling.
4. ADP, ATP and atractyloside, which are agents known to interact with the mitochondrial adenine nucleotide carrier (ANC), antagonized the effect of ZDV-3P on mitochondrial swelling. Indeed, the IC₅₀ value of ZDV-3P increased from 3.0 to 17.4, 93.6 and 66.5 μM, in the presence of 20 μM, ADP, ATP or atractyloside, respectively.
5. ZDV-3P did not displace [³H]-ATP from its mitochondrial binding site(s) whereas ADP and atractyloside did, suggesting that ZDV-3P and [³H]-ATP do not share the same binding sites.
6. ZDV-3P did not affect either mitochondrial respiration or ATP synthesis but inhibited Ca²⁺-dependent mitochondrial swelling. It was concluded that mitochondrial toxic effects observed during the chronic administration of ZDV cannot be related to its active metabolite (ZDV-3P).

     

Adrenergic,purinergic, and endothelial mediators and modulators of norepinephrine-induced mesenteric autoregulatory escape

We evaluated the effects of potential factors in autoregulatory escape from norepinephrine-induced vasoconstriction in rat anterior mesenteric artery. We determined mesenteric artery blood flow velocity with a pulsed Doppler, sonic flowmeter, and systemic arterial blood pressure with a transducer. A 4-min norepinephrine infusion (0.125–1.0 × 10^–8 M/min) intravenously evoked a dose-dependent, initial vasoconstriction that was followed by rapid escape of blood flow toward or above the control value during sustained norepinephrine administration. Neonatal capsaicin treatment enhanced vasoconstrictor responses to norepinephrine but failed to affect escape parameters. Propranolol decreased norepinephrine-induced escape dose dependently. Adenosine deaminase attenuated escape, and the combination of this enzyme plus propranolol nearly abolished escape from norepinephrine-induced vasoconstriction. Methylene blue also diminished autoregulatory escape. These findings suggest that norepinephrine-induced autoregulatory escape involves simultaneous -adrenoceptor, purinergic, and endothelial mediation. Norepinephrine-evoked mesenteric vasoconstriction appears to involve predominantly ₂-adrenoceptors and is modulated by peptidergic sensory nerves and adenosine.NIH grant number supporting these studies: USPHS # DK37050.     

Three cases of dural arteriovenous fistula of the anterior condylar vein within the hypoglossal canal

Dural arteriovenous fistulas (DAVFs) of the anterior condylar vein are an uncommon but important subset of fistulas occurring at the skull base that can be confused with DAVFs of the marginal sinus on angiography. MR angiography source images can document the intraosseous extent and the relationship to the hypoglossal canal of this type of fistula, which can have significant clinical implications. We present the imaging features of angiography, CT, and MR angiography of three cases of DAVFs localized to the anterior condylar vein and within the hypoglossal canal, which were confirmed by source images from MR angiography. Transvenous coil embolization was curative in two of three cases and would seem to be the treatment of choice when venous access is available.