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FDA staff flags eye safety risks for GSK's blood cancer drug – Reuters
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Christian Bale steps out with family for daughters Rome fashion show
Christian Bale made a rare public appearance with his family in Rome on July 14, showing support for his daughter Luka Bale as she walked the runway at Dolce & Gabbana’s Alta Moda fashion show.
The actor, known for keeping his personal life out of the spotlight, attended the event alongside his wife, Sibi Blazic, and their 11-year-old son, Rex.
Wearing a sharp all-black suit, Bale arrived hand in hand with Blazic, whom he married in 2000. Their son Rex followed close behind, also dressed in a dark suit, matching the family’s polished look.
As in snaps shared by Just Jared on social media, the group later posed for a photo with designer Domenico Dolce, who wore his usual black attire and wide-rimmed glasses.
The moment marked a rare family outing for Bale, who rarely steps into the public eye with his children.
For years, fans believed his son’s name was Joseph, a rumor that his rep shut down in May 2024, clarifying, “His name isn’t Joseph. That was made up by the internet.”
Rex was credited under his real name for his cameo in Bale’s 2022 film Thor: Love and Thunder.
Luka’s name was also kept mostly private until her credit in Bale’s 2016 film Ford v Ferrari. She later appeared briefly in Thor: Love and Thunder as well, and stepped into the modeling world with Dolce & Gabbana in 2021.
Sunday’s event served as a proud and stylish moment for the family, one that gave fans a rare glimpse into the actor’s private life while celebrating Luka’s rise in the fashion industry.
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Tony Gilroy on ‘Andor’ Emmy nominations, ‘spooky’ real-life parallels
“Andor” has been the “seminal creative experience” of Tony Gilroy’s life.
The filmmaker spent over five years steeped in the world of the “Star Wars” prequel series, which follows resistance fighter Cassian Andor (portrayed by Diego Luna) during the nascent days of the Rebellion. On Tuesday, “Andor” earned 14 Emmy nominations for its second and final season, including in the marquee race for drama series.
“It’s hard to imagine that I’ll ever be as deeply invested with as much and so submerged with so many people in such a huge endeavor,” Gilroy said via Zoom after the nominations announcement. “It’s a life experience as much as anything else. Everybody on this show really came away with a deeper sense of community and affection than they went in with.”
In addition to drama series, “Andor” was nominated for its directing, writing, cinematography, production design, costume, editing, score, original music, sound editing, sound mixing and special effects. Performances by Forest Whitaker (guest actor) and Alan Tudyk (character voice-over) were also recognized.
A grounded, political spy thriller, “Andor” is set during the five years leading up to the events of “Rogue One: A Star Wars story,” the 2016 film on which Gilroy is credited as one of the writers. The series has been hailed by critics and audiences since its 2022 debut, captivating both longtime “Star Wars” fans as well as those who don’t know an Ewok from a Wookiee.
Cassian Andor (Diego Luna) and K-2SO (Alan Tudyk) in “Andor.”
(Lucasfilm Ltd)
The show’s second season, which unfolds over the span of four years, provided key glimpses into the Galactic Empire’s operations as well as the origins of the Rebel Alliance. And while the show is inspired by revolutions past, Gilroy admits it has been “spooky” to see current events parallel moments from the show.
In an interview with The Times, Gilroy discussed “Andor’s” nominations, real-life parallels and more. The conversation edited for length and clarity.
Congratulations on the 14 nominations! How are you feeling?
I’m trying to find a word that everybody you’re calling doesn’t use. I feel affirmed. It’s very exciting, obviously.
Where were you and what were you doing when you heard the news?
I waited and I took a ride and took a shower and got out and saw my phone was hot. I waited to see if my phone was hot.
Is there an “Andor” group chat where you all can chat in a thread together?
No. Well, maybe there is and I’m not on it. It’s more text mania. Then you have to figure out who’s on WhatsApp, who’s on this, who’s on that. Everybody’s on different s—. It’s actually really f— complicated, to be honest. Now I’ve got emails to answer, WhatsApps to answer.
What has it been like for you to be on this ride with this show as real-life events start to parallel what happened on the show? It feels like we’re living through so much of it now.
It’s been spooky. We had to do a very interesting thing, I think, and figure out how to sell the show while this was all happening without us getting confused, or the world getting confused, or anything else. So I’m really proud. We went all around the world and really sold it really hard. It’s hard to get a large audience to watch “Star Wars” — it’s strange, but it’s really difficult. Along the way I think we managed through the relevancy and the politics of it as successfully as we could. I think now things are a little bit looser. We’re a little bit more free with how we want to speak now so that’s a little bit liberating.
How hard is it to hold some of that in while you’re trying to appeal to an audience?
There wasn’t anything really cynical about it. Everything we said was legit. The historical model is truly what we were doing, and we’re not espousing an ideology in the show or anything like that. But we were also quite taken aback as things went along, at the amount of things that started rhyming with what was going on. Watching Sen. [Alex] Padilla get [handcuffed] while we’re watching the Ghorman senate — there’s things we did not expect to see lining up. It’s really tough and it should be obvious what people think about it.
One of the show’s nominations was writing for Episode 9.
Dan Gilroy, nominated!
How does it feel to be able to share this moment with your brother?
All three Gilroy brothers were nominated today! It’s very pleasing to see that. There’s so many things on here that really, really, really, make me smile. It’s really great that [production designer] Luke [Hull] and [costume designer] Michael Wilkinson [were nominated]. All the technical things that came in for us today were really satisfying. All these awards are community property no matter how people talk about it. You know how many people it takes to stand behind every one of these episodes. They’re just epic, the amount of people that are involved.
As you’re picking these individual episodes, how did Episode 9 stand out? What made it special for you?
We were really torn about what to [submit]. We had three candidates that we really were really interested in. In the end, people felt — direction wise — that the Ghorman massacre, Episode 8, was such a powerhouse. It’s such a strong flavor and so memorable that we could not have that beat for direction. And we also felt that [Episode] 9, it’s just so sophisticated. The spy writing and the sleekness of the politics and the sleekness of the storytelling in there and the scale of the issues for the characters that came up. That was always the favorite for script.
Since you mention Ghorman, what was memorable about working on that episode for you?
It’s always an experiment to see if you’re going to get the power out of things that you think you’re going to get. [So,] to watch that expand beyond where we thought it was going to be, and to have it affect us, the people making it, more than we expected. To have the extras walk off the set on the final day of shooting, when they were finally released, all the people in that square after months and they went off singing the Ghorman national anthem on their own on the way out of Pinewood [Studios]. I’m very proud of it.
That anthem is also nominated.
That’s really all I care about, Tracy. I’ve written a national anthem and it’s been nominated for an Emmy. [Laughs.]
Dedra Meero (Denise Gough) and Grymish (Kurt Egyiawan) in “Andor.”
(Lucasfilm Ltd)
Your time with “Star Wars” is pretty much wrapped up. What has it been like for you, being steeped in this world for so long?
“Rogue [One]” aside, just being on this show the last five and a half, six years, this is the seminal creative experience, I’m imagining, of my life. It’s hard to imagine that I’ll ever be as deeply invested with as much and so submerged with so many people in such a huge endeavor. I can’t imagine that will ever happen again. It’s a life experience as much as anything else. Everybody on this show really came away with a deeper sense of community and affection than they went in with. To make a great show, and we’re really proud of it, and to come away feeling the way that we feel about each other and what everybody did, I’m as proud of that as anything.
How are you going to celebrate?
I’m going to roll these calls and I’m going to go back to prepping the movie that I’m supposed to start shooting. I’ve got homework to do. I’m going to try and get an hour or two of work done before I go out for dinner with my wife. But I’ll have an extra cherry in my old fashioned tonight.
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Broccoli, The Surprising Veg That Helps Regulate Hormonal Health
If the words fiber, florets, and sulforaphane don’t already inspire thoughts of a hormonal superfood, well… they’re about to. Because broccoli (which possesses all three) is one of the most underrated foods for better hormonal health. In fact, the unassuming (and if you’re a child, maligned) green vegetable is so beneficial, I’ve scarcely gone a day without eating it for the past five years.
Below, I’ve picked the brain of Hannah Alderson—registered nutritionist, hormone specialist, and author of Everything I Know About Hormones: Six Steps to Optimal Health & Happiness—to find out exactly how broccoli can help with everything from detoxing excess estrogen to supporting healthy liver function (the key, you’ll discover, for almost everything hormonal), and helping better regulate hormone metabolism. Here are the three reasons why I incorporate it into my diet every single day.
Broccoli helps get rid of excess estrogen
Broccoli and broccoli sprouts are both part of the cruciferous vegetable family, meaning they contain a compound called indole-3-carbinol (or I3C). “When digested, I3C converts into diindolylmethane (DIM), which helps support the liver’s breakdown of estrogen into safer, more easily excreted metabolites,” Alderson explains.
This metabolization of estrogen is incredibly important, as too much of the hormone can lead to heavy and painful periods, tender breasts during the luteal phase, bloating, PMS, mood swings, fatigue, and much more. The compound I3C helps to properly break it down, which makes it easier for the body to then get rid of it.
There is a hierarchy of broccoli, though. Normal broccoli—chunky, with one stalk and lots of florets—has lots of benefits, including soluble and insoluble fiber, both highly beneficial for gut health and gut motility (digestion). Broccoli sprouts, on the other hand, contain much higher levels of sulforaphane, which is a powerful detoxifying compound that helps to support the liver.
“Think of sprouts as the concentrated version. They’re great in small doses and can be a fantastic daily addition to salads or smoothies, or for anyone looking to give their detoxifying pathways a little extra love,” says Alderson. Available in most grocery stores, broccoli sprouts are also an easy grow-at-home job, too.
Broccoli supports liver function
The liver is the body’s in-built filtration system, and good liver function is the key to better hormonal function, being able to fight infection, and to efficiently remove toxins. The compounds present in broccoli sprouts and broccoli help to maintain the healthy functioning of the liver. “Raw or lightly steamed broccoli may also up-regulate an important liver enzyme known as CYP1A1,” Alderson tells me.
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A Comatose Patient’s Urgent Return to the ED
Editor’s Note:
The Case Challenge series includes difficult-to-diagnose conditions, some of which are not frequently encountered by most clinicians, but are nonetheless important to accurately recognize. Test your diagnostic and treatment skills using the following patient scenario and corresponding questions. If you have a case that you would like to suggest for a future Case Challenge, please email us at ccsuggestions@medscape.com with the subject line “Case Challenge Suggestion.” We look forward to hearing from you.Background
A 42-year-old comatose man is brought to the emergency department (ED) by ambulance. He had recently been hospitalized for decompensated hepatitis C virus liver cirrhosis at another hospital, from which he left against medical advice. In the hours before admission to the ED, the patient experienced two witnessed episodes of loss of consciousness associated with urinary incontinence and myoclonic jerks.
The patient’s prescribed medications include abacavir, lamivudine, and zidovudine daily for HIV infection. He also takes furosemide (50 mg), potassium canrenoate (an aldosterone antagonist), lorazepam, and methadone (90 mg); the latter is for the management of heroin addiction.
Physical Examination and Workup
Upon physical examination, the patient is lethargic, and his Glasgow Coma Scale score is 6 (eye opening response, 1; verbal response, 1; motor response, 4). His pupils are normal in size and bilaterally reactive to light. He has a temperature of 96.8°F (36.5°C), a blood pressure of 90/54 mm Hg, and a pulse rate of 86 beats/min. His respiratory rate is 18 breaths/min, and he has an oxygen saturation of 98% while breathing room air.
Upon auscultation, the lung fields are clear bilaterally, and normal heart sounds are heard. His peripheral pulses are palpable; however, bilateral lower extremity pitting edema is present. The abdomen is distended, tense, and with ascites. His sclerae are noted to be icteric.
Laboratory tests are ordered, with pertinent findings that include a hemoglobin level of 11.1 g/dL (reference range, 13.5-17.5 g/dL) and a platelet count of 24 × 109/L (reference range, 136-436 × 109/L).
A chemistry panel reveals the following:
- Sodium level: 134 mEq/L (134 mmol/L; reference range, 135-145 mEq/L)
- Potassium level: 3.2 mEq/L (3.2 mmol/L; reference range, 3.5-5 mEq/L)
- Creatinine level: 0.6 mg/dL (53.04 µmol/L; reference range, 0.7-1.2 mg/dL)
- Glucose level: 148 mg/dL (8.21 mmol/L; reference range, <140 mg/dL)
- Bilirubin level: 4.7 mg/dL (80.37 µmol/L; reference range, 0.3-1 mg/dL)
- Magnesium level: 1.3 mg/dL (0.53 mmol/L; reference range, 1.5-2.5 mg/dL)
- Ammonium level: 153.3 µg/dL (90 μmol/L; reference range, 11-79 µg/dL)
- Ionized calcium level: 3.96 mg/dL (0.99 mmol/L; reference range 4.6-5.6 mg/dL)
His troponin level is 0.07 ng/mL (0.07 μg/L; reference range, <0.12 ng/mL). Serum alcohol testing results are negative, and a urine toxicology screen is negative for cannabinoids, cocaine, and opiates (note that methadone usage may not cause a positive opiate result). A CT scan of the brain is negative for acute abnormalities.
The patient is initially thought to have had a seizure and is cautiously given benzodiazepines to prevent a recurrence.
An electrocardiogram (ECG) is then performed (Figure 1). Soon afterwards, an abnormal tracing is seen on the cardiac monitor (Figure 2), and the patient becomes pulseless and apneic and requires cardiopulmonary resuscitation.
Figure 1.
Figure 2.
Discussion
The cardiac rhythm strip (Figure 2) demonstrated torsade de pointes (French for “twisting of the points”), otherwise known as simply “torsades” or polymorphic ventricular tachycardia.
Figure 2.
The initial ECG (Figure 1), which was obtained before the development of the torsades, revealed a prolonged QT interval and notched T waves. A prolonged QT interval is often noted incidentally on an ECG in an asymptomatic patient; however, in a patient who presents with palpitations, presyncope, syncope, or cardiac arrest, the presence of a prolonged QT interval should raise particular concern for torsade de pointes.
Figure 1.
QT prolongation can be either acquired or congenital. A thorough clinical history-taking and knowledge of the patient’s current medications is very important for this differentiation. Congenital long QT syndrome (LQTS) is a disorder characterized by abnormal QT-interval prolongation on the ECG caused by cardiac myocyte ion channel gene mutations, with a propensity to ventricular tachyarrhythmias. Patients are typically young and may present with syncope or sudden death.[1,2,3,4]
Acquired QT interval prolongation may be drug-induced, or it may be caused by certain electrolyte derangements, such as hypomagnesemia, hypokalemia, and hypocalcemia. Many drugs have been implicated, including class 1A antiarrhythmic drugs such as quinidine and procainamide and class III antiarrhythmics such as amiodarone and sotalol. Other drugs that have been implicated include antihistamines (terfenadine, astemizole), macrolide antibiotics (erythromycin, clarithromycin, clindamycin, azithromycin), pentamidine, serotonin receptor antagonists (ketanserin), diuretics (indapamide), certain fluoroquinolone antibiotics, tricyclic antidepressants, antipsychotics (phenothiazines, haloperidol, mesoridazine, pimozide, thioridazine, ziprasidone), gastrointestinal motility enhancers (cisapride, domperidone), inotropes (amrinone, milrinone), antimalarials (chloroquine, hydroxychloroquine), toxins (organophosphates, arsenic), protease inhibitors, and methadone.[1,5,6,7,8,9]
Drug-induced prolongation of the QT interval is directly linked to a modification in myocardial cell repolarization, which is mediated by the efflux of potassium ions. The shape of the action potential depends on the balance between sodium and calcium inflow and potassium outflow. Two subtypes of the delayed rectifier K+ current, IKr (rapid) and IKs (slow), are responsible for repolarization. The human ether-a-go-go related gene (hERG; also termed KCNH2) codes for a protein known as the Kv 11.1 potassium ion channel, which mediates the repolarizing potassium current IKr.
Blockage of the hERG-encoded potassium channels has been implicated as a cause of drug-induced QT prolongation. A strong correlation is noted between IKr blockade and ventricular arrhythmia or sudden death. Drugs that block the IKr channel increase the QT interval and allow inward current, particularly calcium, to reactivate, leading to early after-depolarizations in cardiac tissue that may result in torsades. Other drugs implicated in QT prolongation have no effect on the potassium channels; therefore, additional cardiac mechanisms can play a significant role.[2,5]
Some medications prolong the QT interval at specific doses, whereas others may act at any dose. The patient’s underlying decompensated hepatitis C virus liver cirrhosis is a significant predisposing factor for QT interval prolongation and the development of torsades.[4] Many medications that prolong the QT interval, including methadone, are metabolized by the hepatic cytochrome P450 3A4 (CYP3A4) system. Therefore, hepatic dysfunction can alter drug metabolism and increase plasma concentrations of QT-prolonging drugs, thereby contributing to QT prolongation. This risk is further exacerbated by potential drug-drug interactions involving CYP3A4 inhibitors.
When administering a drug that potentially prolongs the QT interval, numerous predisposing factors for torsades development must be considered, including advanced age, obesity, poor nutrition (anorexia nervosa, starvation diets, alcoholism), bradycardia (<50 beats/min), cerebrovascular disease (intracranial and subarachnoid hemorrhage, stroke, intracranial trauma, thalamic hematoma), congenital long QT syndrome, heart failure (cardiomyopathy, dilated or hypertrophic), hypoglycemia, hypothermia, hypothyroidism, myocardial ischemia or infarction, organophosphate exposure, pheochromocytoma, pituitary insufficiency, coadministration of other QT prolonging agents, and hypoxia.
If a drug-to-drug interaction is suspected, the drug should be withdrawn. Ehret and colleagues[9] studied a population of active or former intravenous drug abusers and suggested that methadone (even at low doses), CYP3A4 inhibitors, and hepatic dysfunction contributed to prolongation of QT. Methadone delays cardiac repolarization by blocking the flow of potassium ions through the hERG channels, but no evidence suggests interaction between this drug and nucleoside reverse transcriptase inhibitors.[5,7,9,10]
Torsade de pointes is characterized by QRS complexes that vary in axis and amplitude over the isoelectric line (“twisting around the points,” as the name implies). Other associated characteristics include the presence of long and short beat-to-beat (RR) interval onset after an early premature ventricular contraction.
A relationship between the degree of QT interval prolongation and the development of torsades is noted. The QT interval varies directly with heart rate, and a correction is required in order to compensate for heart rate. A commonly used correction (QTc) is the Bazett correction (QTc=QT/√RR), wherein QT is the longest QT interval measured on the ECG, and RR is an average RR interval. QT measurement should be made manually from a 12-lead ECG, and it is calculated from the beginning of the QRS complex to the end of the T wave and averaged over three to five beats in a single lead. Prominent U waves should be included in the measurement if they merge into the T wave. It is advisable to assess QT during peak plasma concentration of any ingested QT-prolonging substances and to correct it for heart rate while looking for other warning signs, including the appearance of prominent U waves, extrasystoles, and U wave augmentation after extrasystole.
Corrected QT is considered prolonged if it is beyond 440 msec for adult males, 460 msec for adult females, and 500 msec in the presence of ventricular depolarization abnormalities (ie, bundle branch blocks or intraventricular conduction delay greater than 120 msec). The uncorrected QT interval should also be considered, however, as a very long QT (>600 msec) after drug exposure is a marker of an increased risk for torsades.[1,5,11]
The patient in this case was initially treated with 2 g of intravenous magnesium sulfate and 1 g of calcium chloride. Despite this, he developed recurrent torsade de pointes. He underwent repeated defibrillation followed by irregular rhythms, including premature atrial complexes and ventricular bigeminy. The recurrent episodes of torsade de pointes were then treated with an intravenous bolus of lidocaine followed by a 2-mg/min infusion. Normal sinus rhythm then returned, and the patient slowly improved and regained consciousness.
In this case, the cause of the patient’s QT prolongation was likely multifactorial and probably included the chronic use of methadone and electrolyte derangement. Slight hypomagnesemia, hypocalcemia, and hypokalemia were noted. These mild electrolyte abnormalities alone are not sufficient to result in torsade de pointes, as evidenced by the persistence of episodic torsade de pointes despite electrolyte replacement. Once the methadone was withdrawn, however, no further episodes of torsade de pointes occurred, and the QT interval normalized.
Cirrhotic cardiomyopathy is often associated with QT interval prolongation and is an important consideration in the differential diagnosis of acquired QTc prolongation.[12,13] However, in this patient’s case, the arrhythmogenic effect was more likely medication-related than a direct consequence of cirrhosis, given the resolution of QTc prolongation following methadone withdrawal.
Treatment of Torsade de Pointes
The immediate and primary treatment for torsades is intravenous magnesium sulfate, typically as a 2-g bolus followed by an infusion of 2-4 mg/min. This therapy is recommended regardless of the patient’s serum magnesium levels.[3] Repeated doses may be needed, titrated to suppress ectopy and nonsustained ventricular tachycardia episodes while precipitating factors are corrected.[3] Magnesium is not contraindicated in liver disease, although caution may be necessary in severe renal failure.
For patients experiencing hemodynamically unstable torsades, or if the arrhythmia persists or degenerates into ventricular fibrillation (VF), immediate unsynchronized defibrillation (direct current cardioversion) is indicated.[3,4]
Correction of electrolyte abnormalities is crucial. Serum potassium levels should be maintained in the high-normal range (4.5-5 mmol/L).[3,4] Hypokalemia and hypomagnesemia are recognized factors that can trigger ventricular arrhythmias, including torsades. If both magnesium and potassium levels are low, magnesium should be repleted first to facilitate potassium replacement.
For recurrent torsades, particularly in patients with acquired long QT syndrome and bradycardia that is refractory to magnesium, rate-increasing therapies are recommended to shorten the QT interval and prevent recurrences. These therapies include the following:
- Overdrive transvenous pacing: Pacing with a slightly higher rate than the baseline rhythm can temporarily suppress slow recurrent or incessant VT.
- Isoproterenol infusion: Isoproterenol works by increasing heart rate and abolishing the post-extrasystolic pauses that can precipitate torsades. However, it is contraindicated in patients with congenital long QT syndrome and ischemic heart disease.[3,4] Maintaining a heart rate greater than 70 beats/min protects against drug-induced torsades.[2,3,4]
Any offending QT-prolonging medications should be discontinued whenever drug-induced arrhythmias are suspected. Medications such as amiodarone and procainamide, which prolong the QT interval, should not be used for torsades or arrhythmic storm associated with a prolonged QT, as they can worsen the condition.[2,3] Patients who require a potentially arrhythmia-inducing drug should undergo regular ECG and other tests based on their profile and the drug’s characteristics.[4]
While not a first-line approach to acutely terminate torsades, beta-blockade is a component of the multifaceted approach to managing arrhythmic storm (which can include torsades).[2] Nonselective beta-blockers (eg, propranolol) are preferred and often used in combination with intravenous amiodarone in patients with structural heart disease (SHD) and electrical storm, unless contraindicated.[2,3,4]
Lidocaine, a class IB antiarrhythmic, blocks fast inward sodium currents and can slightly shorten the QTc interval. It is included in some guidelines for torsades and electrical storm management and is considered beneficial for 4 cardiac arrest due to shock-refractory VF or polymorphic VT.[3,4] It may be considered if beta-blockers and amiodarone are ineffective.[4]
Long-term management and prevention of sudden cardiac death in patients susceptible to torsades and other ventricular arrhythmias primarily involves implantable cardioverter-defibrillators (ICDs) and comprehensive medical strategies.[2,3,4]
This case illustrates an incident of likely drug-induced torsade de pointes resulting from methadone usage in the setting of electrolyte abnormalities. The case highlights the need for an evaluation for potential cardiogenic causes of syncope in patients who present with an abnormal ECG.
Acquired QT interval prolongation may be drug-induced, or it may be caused by certain electrolyte derangements, such as hypomagnesemia, hypokalemia, and hypocalcemia. Many drugs have been implicated, including class 1A antiarrhythmic drugs such as quinidine and procainamide and class III antiarrhythmics such as amiodarone and sotalol. Other drugs that have been implicated include antihistamines (terfenadine, astemizole), macrolide antibiotics (erythromycin, clarithromycin, azithromycin, clindamycin), pentamidine, serotonin receptor antagonists (ketanserin), diuretics (indapamide), certain fluoroquinolone antibiotics, tricyclic antidepressants, antipsychotics (phenothiazines, haloperidol, mesoridazine, pimozide, thioridazine, ziprasidone), gastrointestinal motility enhancers (cisapride, domperidone), inotropes (amrinone, milrinone), antimalarials (chloroquine, hydroxychloroquine), toxins (organophosphates, arsenic), protease inhibitors, and methadone.
Immediate treatment for patients who develop torsades can be categorized into pharmacologic and nonpharmacologic approaches. Intravenous magnesium sulfate (2-g bolus followed by an infusion of 2-4 mg/min) is the initial therapy, regardless of the serum levels of magnesium.
Editor’s Note: This article was created using several editorial tools, including generative AI models, as part of the process. Human review and editing of this content were performed prior to publication.
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Cheers To TNA Wrestling & Markovic Estates, Delivering A Slammiversary Sangria on July 20th at UBS Arena in New York – TNA Wrestling
Cheers To TNA Wrestling & Markovic Estates, Delivering A Slammiversary Sangria on July 20th at UBS Arena in New York
TNA Wrestling today announced a partnership with Markovic Estates, kicking off with a special Slammiversary Sangria on Sunday, July 20, at TNA’s biggest event of the year, which will be held at UBS Arena in New York and air live around the world on pay-per-view.
Markovic Estates bridges generations and continents through meticulously crafted wines and spirits that date back to 1815, bringing the timeless elegance of French winemaking and the vibrant spirit of Eastern European tradition to your glass.
With Slammiversary rolling into New York, teaming with Markovic Estates is a perfect, natural fit, with Markovic Estates roots in Queens, New York. The founders of Markovic Estates raised their family in New York – and the business remains family-owned and operated.
“Markovic Estates is authentic, family-run and fearless—just like the TNA roster,” said TNA SVP of Sales Nicole Racine. “All of their products use natural, old-school technique. I can’t wait for the Slammiversary crowd to thrill to the in-ring wrestling action, with a glass of Slammiversary Sangria from Markovic Estates by their side.
“Sangria is fun, fresh and real. Over ice, it’s the kind of drink you can sip throughout Slammiversary. And it punches way above its weight.”
Markovic Estates is already on tap at Citi Field, home of the New York Mets. Now it’s stepping into the ring with TNA Wrestling.
“We’re a proud New York family business, rooted here and committed to our craft,” said Lazar Markovic, Brand Director, Markovic Estates. “At Markovic Estates, we bring together the elegance of French winemaking and the spirit of our Eastern European heritage – and we’re excited to share that with the TNA fans at Slammiversary. It’s an honor to bring our sangrias to Slammiversary and share what we do with their fans.”
The Slammiversary Sangria will deliver a world champion kick, a distinctive mix of red wine, chopped fruit and other ingredients.
# # #
About TNA Wrestling:
A subsidiary of Anthem Sports & Entertainment Inc. and a division of Anthem Sports Group, Total Nonstop Action (TNA) Wrestling® is one of the world’s top wrestling brands, producing over 200 hours of original content annually and televised in 200 countries including AXS TV in the United States. Founded in 2002, TNA Wrestling’s deep library of premium content is streamed across the world on key OTT platforms including Pluto TV, Roku SamsungTV Plus and its own on-demand subscription service TNA+©. TNA Wrestling has a powerful social media presence with over 10 million engaged followers across all major services. Ancillary businesses include live events, merchandise, licensing, and sponsorship.
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Do we really need a tetanus-diphtheria booster every 10 years? New research says maybe not
For generations, adults in the U.S. have been told to roll up their sleeves for a tetanus and diphtheria booster every 10 years. But new research from Oregon Health & Science University suggests this long-standing advice may be outdated — and unnecessarily costly.
In a study published Tuesday, OHSU scientists argue that adults who completed their childhood vaccinations may not need tetanus or diphtheria boosters nearly as often as previously thought. Their findings suggest protection lasts far longer for most healthy adults — at least 30 years, and possibly for life.
“Why keep vaccinating adults every 10 years? It’s just burned into our brains when the evidence shows you don’t have to,” said lead author Dr. Mark K. Slifka, a professor at OHSU’s Oregon National Primate Research Center.
The U.S. has recommended a 10-year booster schedule for tetanus-diphtheria since the 1960s. But Slifka said this guidance hasn’t kept pace with mounting evidence that immunity to these diseases — now rare in the U.S. thanks to widespread childhood vaccination — doesn’t require such frequent upkeep.
“Tetanus and diphtheria are among our most successful vaccines,” he said. “Their effectiveness has virtually eliminated these diseases in countries with high childhood vaccination coverage.”
Tetanus, a severe bacterial disease caused by spores commonly found in soil, manure or dust, now occurs in the U.S. at a rate of less than one case per 10 million people annually. Diphtheria, a highly contagious bacterial infection, is even more rare, with just seven cases reported nationwide over the past 20 years.
Oregon’s last tetanus case occurred in 2017, when an unvaccinated 6-year-old boy nearly died after scraping his forehead. Before that, the state hadn’t seen a case in 30 years.
Slifka’s latest study, published in the journal Clinical Microbiology Reviews, builds on nearly two decades of research tracking immunity in individuals and across populations. His findings suggest that for adults who received the standard five-dose childhood vaccine series, immunity often lasts for life — making routine boosters largely unnecessary.
Based on the evidence, the researchers propose a simpler, age-based schedule: a booster at age 30 and another at 60. They say that would eliminate the confusion and burden of trying to recall the date of one’s last shot every decade.
Slifka said “this idea isn’t a radical change,” as similar policies exist abroad. The United Kingdom, for example, doesn’t recommend routine adult boosters and has maintained low rates of both diseases, even during a 2022 influx of more than 70 diphtheria cases.
The World Health Organization dropped its recommendation for routine adult boosters in 2017, advising them only in specific circumstances such as pregnancy, travel, or wound care.
Meanwhile, more than 18 million Americans receive these boosters annually, costing over $1 billion. The researchers say a 30-year schedule could cut vaccination costs by two-thirds, saving around $280 million each year.
Slifka said eliminating unnecessary boosters — while continuing vaccinations for pregnant women, people with wounds and those with uncertain vaccine history — could free up resources for other public health priorities.
“If we could use some of these funds that we save and use it to deal with vaccine hesitancy and vaccine education, then I think we could really put that money to good use,” he said.
Slifka said that while the study suggests boosters may not be needed as often, it should not be seen as a reason to overlook the importance of childhood vaccinations.
“Vaccines work, and they work for a long time,” he said. “By maintaining strong, consistent childhood vaccination programs, we’re able to reduce or eliminate these booster vaccinations for adults.”
Changes to official guidelines would require review by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices, the group responsible for setting vaccine policy in the U.S.
Slifka hopes this new evidence sparks a fresh look.
“The wheels of science turn slowly,” he said. “But we think it’s time to bring this back up for discussion.”
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Kirkland Advises Northleaf and AVALT on Acquisition of WASH | News
Kirkland & Ellis advised Northleaf Capital Partners, a global private markets investment firm, and AVALT, a Boston-based investment firm, in a transaction whereby funds managed by Northleaf, alongside AVALT, have signed definitive agreements to acquire WASH Multifamily Holdings Inc, a leading North American route-based laundry infrastructure services company, from EQT, a purpose-driven global investment organization. The transaction is expected to close in the third quarter of 2025 upon receipt of customary regulatory approvals.
Read Northleaf’s press release
The Kirkland team included corporate lawyers John Kaercher, Jennifer Gasser and Chandler Spinks; tax lawyers Mike Greenberg, Steve Butler and Liz Ji; and debt finance lawyers Lucas Spivey, Osaro Aifuwa and Kirby Swartz.
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‘Back to the Dawn’ Mixes Animal Farm With Prison Break for an Interesting and Intriguing RPG Experience
They say it’s a dog-eat-dog world out there, but what if you’re a fox? Back to the Dawn doesn’t skip out on the formalities, and it throws players into the thick of it straight away. As either Thomas the Fox or Bob the Black Panther, the story of a potential life behind bars begins to unfold. Rather than just roaming the halls of this prison, wasting away until our trial begins, we have a chance to make a name for ourselves. Become something bigger than what we are. No matter if I’m shanking a fellow inmate in a bid for supremacy, or I’m working in the laundry room to live an honest life, this RPG is much deeper than I may have given it credit for at the start.
Screenshot: Shaun Cichacki Even Trying To Live an Honest Life Is Difficult in ‘Back to the Dawn’
Booting up the game, I wanted to experience the story of Thomas the Fox before anything else. A reporter by trade, he’s been working diligently to expose the Mayor of their fine town for corruption. Yet, he finds himself stuck between a rock and a hard place. Inside a coffee shop, Back to the Dawn cuts to Thomas speaking to someone named “The Eraser”. It isn’t difficult to imagine that this wolf isn’t wearing sheep’s clothing, and he means business. His associate, Kong, brandishes a briefcase full of funds for Thomas to drop the investigation. I could take it and likely move along my merry way. Or, I could deny it and see where that leads me. Thomas is a good fox, so he denies the cash and leaves the shop. Before he can get into his car, however, all hell breaks loose.
Looks like The Eraser has the local police in his pocket, as a cop car screeches to a halt in front of my vehicle. An “anonymous tipster” told them that I’m harboring illegal substances in my car. Surprise, surprise, there’s a baggie of some white powder in the trunk of my ride. I know that isn’t mine, and so do these corrupt cops. But they don’t care, they’re eager to throw another person behind bars for a crime they didn’t commit. That’s when I’m introduced to the Prison for the first time. A sprawling locale, filled with a variety of different animals that are eager to befriend me or behoove me. I have to do what I can to survive, so I resort to my animalistic tendencies and sniff around, speaking to different characters to peel back the veil of what a day here is like.
Before anything else, I need to use my one phone call. There’s a problem, however. This world, somehow more capitalistic than our own, requests $100 before I can even dial out. I knew inflation was bad, but back in my day? A phone call only cost a quarter. I have to see what I can do.
Screenshot: Shaun Cichacki Working in the Laundry Room. Working Out. Trying To Survive in ‘Back to the Dawn’ Is Harder Than It Seems
At this point, I need to do something. I have to talk to my lawyer to let them know what happened. But seeing as I don’t have anywhere close to $100 on my person, I have to get a little creative. Job postings will regularly go up in the prison, and I’m granted… laundry duty. So, I swallow my pride and head into the laundry room after getting a physical. Just to prove that I’m able to do the job correctly. Back to the Dawn shares a lot in common with games like The Escapists, but with a much stronger emphasis on narrative progression. Seeing as Bob the Black Panther is the star of his own DLC story, his story is expertly woven into the main narrative, giving players juicy details before they embark on his quest.
All in the span of the first day, I befriended a number of inmates. Worked out in the yard after paying one of the three gangs some cash. Considered joining one of the gangs. Spoke to a crooked guard who puts on the facade of being damn-near militaristic in their approach to the inmates. Ate some apple pie and shared it with a new friend. Got my lunch money stolen by a crocodile. So much more happened in between, but every day is a new adventure in this prison. I expected Back to the Dawn to coast by on its stylish 2D-HD look and soundtrack. But at this point, I’m fully invested. The story is already incredibly juicy, and it seems like it can only continue ramping up from here.
The mixture of dice rolls, witty and interesting dialogue, daring adventure, and RPG elements has all been mixed together expertly. This is one that I’m struggling to put down, and I’m very intrigued to see how it’s going to turn out at the end of the day. Thomas may be sly as a fox, but that means nothing when you’re fighting against an ox.
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Playing an instrument may help protect brain against ageing, study finds
Playing a musical instrument could help protect the brain against age-related decline, new research has suggested.
Older adults with long-term musical training performed better at understanding speech in noisy environments and showed brain connectivity patterns closer to younger people, according to a study published in the journal PLOS Biology.
Researchers from Baycrest Academy for Research and Education in Canada and the Chinese Academy of Sciences used functional MRI scans to compare brain activity in 25 older musicians, 25 older non-musicians and 24 young non-musicians.
The participants were asked to identify syllables masked by background noise, a task that typically becomes harder with age.
While older non-musicians showed the usual age-related increase in neural activity and connectivity – a sign that the brain is working harder to compensate for decline – older musicians maintained a more “youth-like” pattern.
The strength of connections in certain brain networks also correlated with better performance on the speech-in-noise task, the study found.
Older adults with long-term musical training performed better at understanding speech in noisy environments and showed brain connectivity patterns closer to younger people (Getty Images) Older adults with long-term musical training performed better at understanding speech in noisy environments and showed brain connectivity patterns closer to younger people (Getty Images)
The findings support what the researchers call the “Hold-Back Upregulation” hypothesis. This is when the cognitive reserve built through musical training helps the brain hold onto its younger functional features, instead of simply compensating for loss.
Dr Yi Du, co-author of the study, said: “Just like a well-tuned instrument doesn’t need to be played louder to be heard, the brains of older musicians stay finely tuned thanks to years of training.
“Our study shows that this musical experience builds cognitive reserve, helping their brains avoid the usual age-related overexertion when trying to understand speech in noisy places.”
The authors said that although the study cannot prove cause and effect, it adds to growing evidence that positive lifestyle choices, such as musical training, higher education and bilingualism, can help the brain cope better with ageing.
Dr Lei Zhang, another co-author, added: “A positive lifestyle helps older adults cope better with cognitive ageing, and it is never too late to take up, and stick with, a rewarding hobby such as learning an instrument.”
The scientists are now planning to explore whether other activities, such as exercise and multilingualism, could offer similar benefits.
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