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Monday, November 4, 2024

Short-Course Vasoconstrictors After EVL: Time for a New Standard of Care?

 New research challenges the traditional practice of continuing vasoconstrictor therapy for 5 days after endoscopic variceal ligation (EVL) for acute variceal bleeding, finding that a shorter course of 1-3 days may suffice, without raising the risk for rebleeding, if the initial ligation successfully controls bleeding.

“This approach would allow earlier discharge from the hospital and reduce the risk of adverse events, all without sacrificing treatment efficacy or compromising patient safety,” Sushrut Ingawale, MD, MBBS, Quinnipiac University School of Medicine, North Haven, and St. Vincent’s Medical Center, Bridgeport, Connecticut, said in a presentation at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

Ingawale called for a “re-evaluation of existing protocols, emphasizing the potential to update current protocols to reflect shorter, more personalized” duration of vasoconstrictor therapy in these patients.

Commenting on this research, Nancy Reau, MD, of Rush University in Chicago, said, “We should always question the standard of care.”

“Vasoconstrictors for 5 days is the standard of care, but this could lead to prolonged hospitalization in patients who are otherwise doing well after endoscopic intervention. Recognizing that a shorter course of vasoconstrictor treatment may have equal outcome is very important though it may not be appropriate for all patients, especially those at high risk for rebleeding,” said Reau.

Outdated Guidelines?

In his presentation, Ingawale noted that current guidelines that recommend continuing vasoconstrictors, like octreotide or terlipressin, for at least 3-5 days after EVL for acute variceal bleeding are based primarily on old studies in which sclerotherapy was the primary hemostatic method.

The study team assessed comparative outcomes based on the duration of vasoconstrictors after EVL for acute variceal bleeding in a systematic review and network meta-analysis of 11 randomized controlled trials.

The studies had a total of 816 patients who were grouped based on the duration vasoconstrictor therapy: 24 hours or less (group 1), 24-72 hours (group 2), and 72-120 hours (group 3).

There was no significant difference in the risk for rebleeding in group 1 (risk ratio [RR], 1.36; 95% CI, 0.48-3.52) and group 2 (RR, 1.34; 95% CI, 0.42-4.54) vs group 3.

“This finding was even consistent when we compared individual durations” of 0, 12, 24, 48, and 72 hours vs 120 hours, Ingawale said.

There was also no statistically significant difference in the 5-day mortality risk between group 1 (RR, 0.66; 95% CI, 0.09-2.52) and group 2 (RR, 1.08; 95% CI, 0.15-6.43) or the 30-day mortality risk between group 1 (RR, 1.18; 95% CI, 0.51-2.51) and group 2 (RR, 0.98; 95% CI, 0.36-2.52) vs group 3.

Rapidly Evolving Area

“Our network meta-analysis did not show any benefit of continuing vasoconstrictors after EVL,” the researchers wrote in their conference abstract. Despite historical precedent, shorter durations may be adequate, “potentially enabling earlier hospital discharge without compromising patient outcomes,” they said.

Ingawale suggested future research should look to identify the subset of patients at a risk for failure to control bleeding who might benefit from the continuation of vasoconstrictors.

Reau told Medscape Medical News, “Management of complications of portal hypertension are rapidly evolving and this study will add to the data that drives our guidelines. Seeing this data in a peer reviewed publication will add the necessary validity to impact a change in the treatment paradigm.”

The study had no specific funding. Ingawale had no relevant financial relationships. Reau disclosed various relationships with AbbVie, Gilead, Arbutus, Intercept, and Salix.

https://www.medscape.com/viewarticle/short-course-vasoconstrictors-after-evl-time-new-standard-2024a1000k3b

Federal Judge Rules Iowa Officials Can Challenge Ballots Of Potential Noncitizen Voters

 by Aldgra Fredly via The Epoch Times (emphasis ours),

A federal judge ruled on Sunday that Iowa election officials may continue to follow Secretary of State Paul Pate’s directive to challenge the ballots of 2,176 registered voters who have been identified as possible noncitizens.

A voter fills out a ballot at a polling station in Des Moines, Iowa on Nov. 6, 2018. Joshua Lott/Getty Images

The ruling came as a recent Des Moines Register/Mediacom Iowa poll forecast Vice President Kamala Harris leading in Iowa by three points over former President Donald Trump, while other polling organizations estimate that Trump is still ahead in what has been a safely Republican state in recent years.

The American Civil Liberties Union (ACLU) of Iowa filed a lawsuit on behalf of four naturalized citizens on Oct. 30, alleging that Pate’s directive to check registered voters’ citizenship status violated the equal protection clause of the U.S. Constitution.

On Oct. 22, Pate directed Iowa county auditors to challenge the ballots of voters who had previously identified themselves as noncitizens to the Iowa Department of Transportation (DOT).

In its lawsuit, the ACLU argued that Pate’s list of voters whose ballots would be challenged was based on outdated DOT records, and that many of those listed have already been proven to be citizens.

It alleged that the secretary’s directive places “severe burdens” on the voting rights of the affected voters by keeping the list secret, which it said could undermine their ability to resolve their eligibility.

Pate responded that voters will be allowed to cast a provisional ballot instead, which will be counted if they can prove their citizenship.

U.S. District Judge Stephen Locher declined to grant a preliminary injunction, citing the finding that “some portion” of the registered voter names on Pate’s list have indeed been confirmed to be non-citizens.

“This portion appears to be relatively small—no more than 12 percent—but, still, the injunctive relief requested by Plaintiffs effectively would force local election officials to permit those individuals to vote,” Locher stated in a Nov. 3 ruling.

The plaintiffs had argued that Pate’s directive violates the National Voter Registration Act (NVRA), which requires that states complete any program for removing ineligible voters within 90 days before an election.

However, Locher ruled that the NVRA was not implicated in this case because the state had not removed any voters from the voter rolls, and was only requiring them to cast provisional ballots.

Secretary Pate’s letter is likely to impose a modest additional burden on at least some voters who should not have to bear that burden. All the same, those voters are still permitted to vote and have their ballots counted. The harm is therefore not irreparable,” the judge stated.

Pate last week had blamed the federal government for blocking his office from meeting the 90-day rule, saying that the audit was delayed to October by a lack of cooperation by the Department of Transport, which did not grant access to the U.S. Citizenship and Immigration Services’ Systematic Alien Verification for Entitlements (SAVE) database for confirming citizenship.

In a statement, Pate hailed the court’s ruling as a “win for Iowa’s election integrity,” emphasizing the importance of ensuring that only eligible voters can participate in Iowa’s election process.

He said that his office would continue to seek clarity on the citizenship status of voters who had previously self-reported to be noncitizens, while urging the U.S. Citizenship and Immigration Services office to allow the Iowa field office to release information about those voters.

Iowa Attorney General Brenna Bird stated on X that the ruling ensured that Iowans’ votes will not be canceled out by illegal votes.

I was glad to lead the fight in court to defend Iowa’s long-standing election integrity laws. Only American citizens can vote in Iowa elections,” she said in a statement.

The Epoch Times has reached out to the ACLU for comment but did not hear back by publication time.

https://www.zerohedge.com/political/federal-judge-rules-iowa-officials-can-challenge-ballots-potential-noncitizen-voters

Cranberry, Antibiotic May Help Kids with Recurrent UTI

 For children with a history of recurrent urinary tract infection (RUTI), the antibiotic nitrofurantoin and cranberry products appeared to decrease the incidence of symptomatic episodes, a meta-analysis suggested.

Across 23 randomized controlled trials involving 3,335 participants, nitrofurantoin took top place in significantly lowering odds of symptomatic UTI episodes during prophylaxis, whether compared with controls (OR 0.21, 95% CI 0.07-0.65, P=0.007) or compared with either trimethoprim or sulfamethoxazole antibiotics (OR 0.29, 95% CI 0.10-0.82, P=0.02) or trimethoprim alone (OR 0.23, 95% CI 0.08-0.66, P<0.01).

However, prophylaxis with cranberry juice or tablets also yielded 59% lower odds of symptomatic UTI episodes compared with controls (OR 0.41, 95% CI 0.23-0.74, P=0.003), reported Nikolaos Gkiourtzis, MD, MSc, of Aristotle University of Thessaloniki in Greece, and colleagues writing in Pediatricsopens in a new tab or window.

In a commentaryopens in a new tab or window accompanying the study, Joshua Watson, MD, and Jason Newland, MD, MEd, both of Nationwide Children's Hospital in Columbus, Ohio, wrote that "negative consequences related to antibiotic prophylaxis makes the non-antibiotic options for preventing RUTI an exciting area of research," and thus the finding of benefit from cranberry products was "encouraging."

The literature has supported "some benefit" of low-dose antibiotics in preventing repeated episodes of UTI in vulnerable children by inhibiting bacterial growth that causes acute pyelonephritis and kidney scarring, Gkiourtzis's group wrote. "Nevertheless, according to a recent Cochrane Systematic Review, long-term antibiotic prophylaxis may have a small impact on UTI prevention with a concurrent increase in the risk for antibiotic resistance, concluding that they should be reserved only for children at risk for RUTI."

Although nitrofurantoin and cranberry products "may decrease the incidence of symptomatic UTI episodes in pediatric patients with a history of RUTI," Gkiourtzis and colleagues noted, "[n]o prophylaxis option can lead to a reduction of the risk of kidney scarring after RUTI."

"Febrile UTI and acute pyelonephritis in children may contribute to kidney scar formation with the subsequent risk of future complications," Gkiourtzis and colleagues wrote, adding that a recent post hoc analysis of data from two multicenter studies showed kidney scarring incidence of 2.8% after one febrile UTI, 25.7% after two febrile UTIs, and 28.6% after three or more febrile UTIs.

The study by Gkiourtzis and colleagues compared nine interventions, including placebo, cephadroxil (Duricef), lactobacillus, vitamin D, and cefprozil (Cefzil), for a total of 18 theoretical comparisons.

"Although other interventions had clinical significance, with respect to reducing UTI incidence, they did not reach statistical significance in this analysis," Gkiourtzis and colleagues noted. Additionally, "nitrofurantoin was ranked as the best intervention for reducing UTI incidence as compared with all available interventions."

Among the studies, the mean age of participants ranged from 3.8 to 14.7 years. More than half of the included studies were conducted in Europe. Others were from Asia, the U.S., Argentina, and Australia.

The studies were conducted between 1975 and 2023, and treatment and follow-up ranged from 2 months to 3 years. Fourteen of the studies were deemed to be of "high risk of bias."

The researchers called for studies to elucidate the optimal formulation, dose, and patient population where these products achieve their maximal benefit.

Meanwhile, decisions about treatment "should be individualized based on the patients' profile," they added. "Future studies with optimal methodology, studying non-antibiotic prophylaxis options, focusing on children with RUTI, and the risk for kidney scarring are needed to draw further conclusions."

Other options might hold potential as well, Watson and Newland noted: "Several other antibiotic alternatives have not yet been adequately studied in children, including probiotics, methenamine, and D-mannose. ... Additionally, vaccine development is underway and, if successful, may be a powerful tool for RUTI prevention."

Disclosures

Neither the authors nor the editorialists reported any relevant conflicts of interest.

Primary Source

Pediatrics

Source Reference: opens in a new tab or windowGkiourtzis N, et al "Prophylaxis options in children with a history of recurrent urinary tract infections: a systematic review" Pediatrics 2024; DOI: 10.1542/peds.2024-066758.

Secondary Source

Pediatrics

Source Reference: opens in a new tab or windowWatson JR, Newland JG "Recurrent urinary tract infection prevention: progress and challenges" Pediatrics 2024; DOI: 10.1542/peds.2024-068728.

https://www.medpagetoday.com/pediatrics/generalpediatrics/112733

Missouri sues to block Justice Department from sending poll monitors

  The Republican-led state of Missouri asked a judge on Monday to block the U.S. Justice Department from sending lawyers to St. Louis on Election Day to monitor for compliance with federal voting rights laws, even after the city's election board agreed to permit it.

The lawsuit, which was filed in the U.S. District Court for the Eastern District of Missouri by the state's attorney general and secretary of state, accuses the Justice Department of making an 11th hour plan that intends to "displace state election authorities" by sending poll monitors on Tuesday to locations throughout St. Louis.

Republican former President Donald Trump, who faces Democratic Vice President Kamala Harris in Tuesday's U.S. presidential election, continues to falsely claim that his 2020 defeat was the result of widespread fraud. He has urged his supporters to turn out at polling places to watch for suspected fraud.

Missouri is one of 27 states the Justice Department said on Friday it would send staff out to monitor voting locations, as it has done regularly during national elections.

The only location in Missouri it is sending poll monitors to is St. Louis, which in January 2021 reached a settlement with the Justice Department over concerns about architectural barriers and other problems that could have hindered voting by people with disabilities.

As part of that settlement, the city's Board of Election Commissioners agreed to allow the Justice Department to monitor for compliance. This included the monitoring of polling places on Election Day.

The settlement was completed at the very end of the Trump administration, when Eric Dreiband previously served as the Assistant Attorney General for the Civil Rights Division.

The Justice Department declined to comment on the lawsuit.

While some of the locations the Justice Department will monitor on Election Day include key counties in the seven battleground states expected to help decide the election, the Justice Department is also sending personnel to a variety of other locations such as counties in Texas, Massachusetts, Alaska, South Dakota and New Jersey.

Missouri is not one of the seven battleground states.

The Justice Department is responsible for enforcing a variety of federal voting rights laws, such as one that requires states to accommodate voters with disabilities and another that requires states to allow U.S. citizens and military members who reside overseas to vote by absentee ballot in federal elections.

In 2022, both Florida and Missouri resisted efforts by the Justice Department to send poll monitors to locations including Miami-Dade and Broward County, Florida.

Florida, in a letter to the Justice Department that year, said state law prohibited department employees from being inside polling places unless they were on a list of permitted personnel.

In response to the concerns, the Justice Department had its staff stationed outside polling locations in Florida and Missouri for the 2022 election.

https://www.marketscreener.com/news/latest/Missouri-sues-to-block-Justice-Department-from-sending-poll-monitors-48249310/

Biden, Harris, Pfizer, and Moderna smacked with MASSIVE lawsuit for anti-human crimes

 10 Shocking Stories the Media Buried This Week

#10 - Biden, Harris, Pfizer, and Moderna smacked with MASSIVE lawsuit for anti-human crimes. The lawsuit, which has been filed in the Southern District of Texas, demands an end to: • The COVID-19 injections. • The “poisoning of our skies” that people refer to as chemtrails. • And other toxic practices deemed harmful to human beings. Shelby Hosana, one of the multiple plaintiffs in the lawsuit, call this “a whole lot of evil put into one hefty lawsuit.” She explained that “every single thing in the lawsuit was based on a constitutional statute,” emphasizing their focus on constitutional violations that will be tough for the court to dismiss. Going further, Hosana added, “If enough people... join this lawsuit as a plaintiff, we can actually turn it into class action status, meaning the lawsuit could represent a larger group of individuals, creating a collective force that the court cannot easily ignore. “So we can overwhelm the Texas district court, and they'll have no choice but to turn it into a class action.” If you know someone injured by the jabs, direct them to HUMANITY SUIT DOT COM to become a plaintiff. (See 9 More Revealing Stories Below)

Singular Genomics presentation Nov. 9

 

We are thrilled to introduce 2 posters next week at #SITC2024 showcasing the latest data generated on the G4X. The posters will be presented on Saturday November 9th and will highlight the novel Direct-Seq technology and the G4X's high-resolution in situ multiomic capabilities.

BioNTech Handily Beats Q3 Expectations, Trims Full-Year Revenue Guidance

 

Driven by the early approval of its updated COVID-19 vaccine, BioNTech far exceeded analysts’ expectations in the third quarter and reported its first quarterly profit in 2024. However, the German biotech also cut its outlook for the year.

BioNTech released its third-quarter earnings report on Monday, finally stemming its losses this year and reporting strong year-over-year growth driven by its variant-adapted COVID-19 vaccine.

In Q3, the company generated $1.36 billion in sales, up from nearly $940 million during the same period in 2023—and far ahead of the consensus forecast, which expected that BioNTech would bring in nearly $652 million in Q3, according to analytics firm Zacks Equity Research.

BioNTech reported net profit in the quarter of $216 million—the first time it’s done so this year, after sustaining more than $340 million and almost $885 million in losses in the first and second quarters, respectively. On a per-share basis, BioNTech’s profit was $0.88, while analysts forecasted a loss of $2.01 per share

The biotech attributed the strong performance in Q3 to the “earlier” approval for its variant-adapted COVID-19 shot, compared with the later regulatory nod the company secured in 2023. The FDA greenlit BioNTech’s vaccine in August 2024, allowing its use for the Omicron KP.2 variant for the 2024–2025 season. Last year, the FDA’s approval came in September.

Still, 2024 has been difficult for BioNTech overall, reflected in its nine-month revenue of $1.7 billion, down from $2.55 billion during the same period last year. And despite recording its first quarterly profit this year, the biotech has still suffered more than $1 billion in losses in 2024 so far.

Reflecting its financial challenges, BioNTech on Monday lowered its total revenue guidance for the year. The company now expects it to be in the lower end of its previously announced forecast range of $2.73 billion to $3.38 billion.

BioNTech’s adjusted guidance reflects expectations regarding the uptake of its updated COVID-19 vaccine, as well as potential inventory write-downs and other charges associated with its partnership with Pfizer.

In an investor call on Monday, CEO Ugur Sahin struck an optimistic note and focused on the company’s prospects in the coming years, touting the biotech’s progress in oncology development—particularly regarding its lead cancer candidate BNT327, a bispecific antibody that binds to PD-L1 and VEGF-A, both validated targets in cancer.

“BioNTech was established with the ambition to revolutionize cancer treatment through the development of mRNA-based immunotherapies, particularly personalized cancer vaccines” Sahin said during the call. With its oncology pipeline, the biotech is looking to leverage its COVID-19 success to advance a portfolio of next-generation cancer treatments, “aiming to tailor therapies to the individual genetic make-up of each patient tumor.”

Last month, BioNTech dosed the first patient in the Phase II study testing BNT327, in combination with chemotherapy, for the first- and second-line treatment of patients with locally advanced or metastatic triple-negative breast cancer. Data from this study will help the biotech launch a Phase III program for the bispecific, set to begin in 2025.

BioNTech is also developing BNT327 for non-small cell lung cancer and at the 2024 European Society for Medical Oncology Congress in September 2024, the biotech unveiled Phase II data showing a 57.8% confirmed objective response rate in patients carrying EGFR mutations.

In addition to BNT327, BioNTech is working on the anti-CTLA-4 monoclonal antibody BNT316, dubbed as gotistobart, for the treatment of NSCLC and platinum-resistant ovarian cancer. The company is also advancing a portfolio of mRNA cancer vaccines, which are in mid-stage studies.

“We are entering a catalyst-rich period for our company, in particular for our oncology portfolio,” Chief Strategy Officer Ryan Richardson said during Monday’s earnings call, noting that BioNTech currently has more than 10 Phase II and III trials ongoing across various cancer types. “In the next 18 months, we expect multiple clinical data updates from these trials and we’ll initiate several additional trials with registrational potential.”

https://www.biospace.com/business/biontech-handily-beats-q3-expectations-trims-full-year-revenue-guidance