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Sunday, December 3, 2023

Israeli forces take big risks to avoid harming Gaza civilians

 With Israel and Hamas returning to arms Friday after the terror group ended a weeklong pause in the fighting across the Gaza Strip, the Jewish state is again under international pressure to halt its war to eliminate the jihadists who brutally slaughtered more than 1,200 people — including 33 Americans — on Oct. 7.

But how, exactly, can the Israel Defense Forces avoid harming civilians when its enemy hides behind innocents, directing its operations from the most sacred of safe spaces – including hospitals – in violation of the international rules of war?

“[Hamas’] M.O. is deliberately to use the civilian realm for their own human shield protection in the most cynical ways,” IDF Lt. Col. Amnon Shefler told reporters at the Israeli embassy in Washington this week.

“I can show you endless amounts of pictures and videos of how rockets are being manufactured in schools, hosted in schools, shot from schools, mosques and homes. We’ve found rockets and ammunition underneath baby girls’ beds and also in hospitals, sadly,” he added.

National Security Council spokesman John Kirby emphasized Hamas’ apparent lack of care for Palestinian civilians Friday, noting that by declining to release further hostages, they stopped humanitarian aid from getting into Gaza.

“The people who suffer the most because of that are the people of Gaza, the Palestinian people,” he said. “So if Hamas truly – as they claim to – do care about Palestinians, they’ll do what they can to come up with a list of hostages that can be exchanged, so that that aid can continue to flow.”

A Palestinian man inspecting damage after Israeli air strikes in Khan Yunis in the Gaza Strip on Dec. 3, 2023.Photo by Ahmad Hasaballah/Getty Images

An unfair fight

Secretary of State Antony Blinken demanded Thursday that Israel not the restart the fighting until it established a “clear plan” to avoid civilian harm – and threatened to withdraw support should it not comply with “humanitarian law.”

But hours later, Hamas terrorists opened fire at a Jerusalem bus stop, killing three civilians and Blinken’s aspirations in one fell swoop.

Despite accusations that Israel’s forces have caused the deaths of thousands of Gazans in the nearly two-month-old war, Shefler said the IDF is “the leading military in the world” at fighting in dense, urban environments while minimizing civilian casualties.

A Palestinian boy crying after being brought to Nasser hospital after an air strike on Dec. 3, 2023.REUTERS/Ibraheem Abu Mustafa

“For years, we’ve been building capabilities, first out of necessity, and on top of that, because that’s what we believe in,” he said. “That in fighting these kinds of complicated battles, we need to find the best ways to stand up for morals and to our values, and also to the Law of Armed Conflict.”

The problem, however, is that when only one side abides by international conflict standards – or cares about saving civilian lives at all – the law itself can become a handicap.

“It was probably written in many ways [to support moral fighting], but it was not written to deal with these kinds of circumstances – dealing with terrorist organizations,” Shefler said. “That’s why we’re finding ourselves in a very, very complicated space of a war zone with a deeply embedded terrorist organization within all this [civilian] infrastructure and underneath the ground.”

Footage of the Oct. 7 attack reviewed by The Post shows Hamas terrorists slaughtering children, beheading the dead and encouraging each other to “play with” the bodies.

Palestinians gathered at a crater in Rafah after an Israeli strike in Gaza on Dec. 3, 2023.Photo by SAID KHATIB/AFP via Getty Images

But the terror did not end there. Until the fighting briefly stopped Nov. 24, Shefler said Hamas was “firing more than 10,500 rockets at Israeli civilians, schools, hospitals, at religious institutions” in Israel each day.

“They did everything that they can with the aim to kill as many civilians as possible,” he said.

Mitigating harm by assuming risk

The terror group’s war-crime strategy makes it nearly impossible for Israel to defend itself without more casualties. But that doesn’t mean they don’t try to avert losses.

“How does one deal with a terrorist infrastructure that is underneath the hospital? We can strike it from the air, but of course that has its implications – and that’s why we chose not to do it,” Shefler said.

The military leader also detailed multiple other creative strategies the IDF uses to mitigate harm to Gazans – from technology use to more rudimentary tactics – putting its own soldiers at greater risk to do so.

An injured Palestinian woman getting rushed to Nasser hospital in Khan Younis.REUTERS/Ibraheem Abu Mustafa

For example, the IDF has sent ground forces to clear Hamas hubs hidden in civilian infrastructure and below ground – a strategy the Israeli military has learned as a best practice from previous clashes.

“For many years, we have been building our special forces to be able to carry out these kinds of missions based on very accurate intelligence,” he said. “Going to very, very specific areas to find those arms, those infrastructure that need to be dismantled, sending in these units with Arabic speakers, with medical teams, and that’s how we were able [mitigate harm,]” he added.

The IDF is also open to learning from others’ experiences – and mistakes. For example, Shefler said Israeli leaders have daily contact with the US military, which has been offering advice on close-quarters fighting in urban environments learned from its 20 years fighting in Afghanistan and Iraq.

Israel has also used information sharing as a tactic in culling unintended deaths. In the war’s early days, the IDF used pamphlets to urge civilians to move south to safety ahead of its intended strikes on Hamas in north Gaza.

Since then, the Israeli military has rolled out a texting feature that gives civilians in soon-to-be targeted areas a heads up before strikes are conducted.

“In the beginning, the civilians did not listen to us to leave a house where we know terrorists were [when we told them] we were going to strike, but they learned to trust us,” Shefler said.

Now, Palestinians have learned to trust IDF messages so much that “you can find so many videos of Palestinians standing outside of buildings that they had been told to leave, filming the strike from their own phone standing there because they know that we’re going to hit.

An Israeli soldier in a tunnel underneath Al Shifa hospital in Gaza City on Nov. 22, 2023.REUTERS/Ronen Zvulun/File Photo

“They also know now to trust when we ask them to move to different areas that they should listen to us, and we hope that that’s another level of mutual learning that is happening how to deal with this really catastrophic situation,” he added.

While the strategy has saved countless lives, it comes as a cost to the IDF, Shefler said. For example, the Israelis gave advance notice to the Al-Shifa hospital in Gaza ahead of its raid last month, presenting a danger to troops by giving a potential heads-up to terrorists hidden in tunnels below.

“That’s a lot of threats to our forces without using a very important tool: military surprise,” he said, adding that the Israelis had scored a coup by “telling in advance that we’re coming, and then going in and finding that all that infrastructure is there, and not even having one person being hurt – one civilian, one patient or one doctor on the grounds.”

Inside the hospital, the IDF discovered that Hamas had “booby trapped” a vehicle in the center of the facility meant to “kill civilians and to kill the soldiers that would come to the table,” Shefler said.

“Had we [launched a strike] from the air, then it would have exploded. But being on the ground, [we] are allowed to dismantle it and not to allow it to explode,” he said.

It’s another lesson learned from previous experiences in unfair fights.

“Many times when we strike other buildings there are explosives and rockets inside that explode with it and create a lot of collateral damage by themselves,” he said. “So we needed to risk sending our troops being there for a lot of things, risk them dealing with these ammunition, with these booby traps, with the potential of Hamas fighters jumping in from different shafts.”

Still, Shefler admitting there is more Israel can do to prevent more civilians from becoming collateral damage. The IDF spent the week-long pause brainstorming additional ways to mitigate harm, and continues to analyze past operations for lessons learned, he said.

“Can we do better? Always. Can we debrief and learn? Absolutely,” Shefler said. “Can we bring other things that aid the situation? Definitely.”

https://nypost.com/2023/12/03/news/how-israeli-forces-take-big-risks-to-avoid-harming-civilians/

'Overweight hampers the body's immune response to SARS-CoV-2'

 University of Queensland-led research shows being overweight can impair the body's antibody response to SARS-CoV-2 infection but not to the protection offered by vaccination.

Research lead, School of Chemistry and Molecular Biosciences Ph.D. candidate Marcus Tong, said the finding built on the team's existing research on how COVID-19 affects people who are overweight. The research is published in Clinical & Translational Immunology.

"We've previously shown that being overweight—not just being obese—increases the severity of SARS-CoV-2," Mr. Tong said.

"But this work shows that being overweight creates an impaired antibody response to SARS-CoV-2 infection but not to vaccination."

The research team collected  from people who had recovered from COVID-19 and not been reinfected during the study period, approximately three months and 13 months post-infection.

"At three months post-infection, an elevated BMI was associated with reduced antibody levels," Mr. Tong said.

"And at 13 months post-infection, an elevated BMI was associated with both reduced antibody activity and a reduced percentage of the relevant B cells, a type of cell that helps build these COVID-fighting antibodies."

In , an elevated BMI had no effect on the antibody response to COVID-19 vaccination at approximately six months after the second  was administered.

Associate Professor Kirsty Short said the results should help shape  moving forward.

"If infection is associated with an increased risk of severe disease and an impaired immune response for the overweight, this group has a potentially increased risk of reinfection," Dr. Short said.

"It makes it more important than ever for this group to ensure they're vaccinated."

Dr. Short said from a public health perspective, this data draws into question policies around boosters and lockdowns.

"We'd suggest that more personalized recommendations are needed for , both for ongoing COVID-19 management and future pandemics," she said.

"Finally, the data provides an added impetus to improve SARS-CoV-2 vaccination in low-income countries, where there's a high percentage of people who are overweight and are dependent on infection-induced immunity."

More information: Elevated BMI reduces the humoral response to SARS-CoV-2 infection, Clinical & Translational Immunology (2023).


https://medicalxpress.com/news/2023-12-overweight-hampers-body-immune-response.html

Venezuela voters back creation of new state from Guyana territory

 Voters in Venezuela have rejected the International Court of Justice's jurisdiction over the country's territorial dispute with Guyana and backed the creation of a new state in the potential oil-rich Esequibo region in a referendum.

The court this week barred Venezuela from taking any action which would change the status quo in the area, which is the subject of an active case before the ICJ, but President Nicolas Maduro's government went ahead with a five-question "consultative" referendum on Sunday.

All questions passed with more than 95 per cent approval, according to electoral authority president Elvis Amoroso, who said at least 10.5 million votes were cast for 'yes' but did not confirm the number of voters.

Some political and security analysts have called the referendum a show of strength by Maduro and a test of support for his government ahead of a planned 2024 presidential election.

The court said in April it had jurisdiction, though a final ruling on the matter could be years away. Venezuela has said the issue should be resolved by the two countries.

Maduro cheered the "total success" of the vote late on Sunday.

"The Venezuelan people have spoken loudly and clearly," he told a cheering crowd.

At issue is a 160,000sqkm region that is mostly thick jungle. Venezuela reactivated its claim over the territory in recent years after the discovery of offshore oil and gas.

"The purpose of (Maduro's) government is to send a message of strength to Guyana," Central University of Venezuela politics professor Ricardo Sucre said, adding Maduro is also thinking of potential oil and gas developments.

The maritime border between the two countries is also in dispute.

There was no organised campaign against the referendum and analysts expected voters who opposed it to stay home.

There are more than 20 million eligible voters in Venezuela.

Reuters witnesses visited voting centres across the country - many had few or no people waiting in line.

How will the Supreme Court reshape US opioid epidemic relief?

 The U.S. Supreme Court is set on Monday to hear arguments over the legality of a roughly $6 billion bankruptcy settlement involving Purdue Pharma, maker of the powerful and highly addictive pain medication OxyContin that played a key role in the country's opioid epidemic.

If the justices allow the deal to proceed, it could lead to billions of dollars being poured into addiction-treatment and other relief efforts. The settlement also would shield the Stamford, Connecticut-based pharmaceutical company's wealthy Sackler family owners from lawsuits brought by opioid victims.

Here is an explanation of the settlement and its consequences.

HOW WOULD THE SETTLEMENT HELP PEOPLE AFFECTED BY OPIOIDS?

An opioid epidemic has caused more than a half million U.S. overdose deaths over a period spanning more than two decades. Purdue introduced OxyContin in 1996, and marketed and promoted it aggressively. OxyContin helped kickstart the epidemic, various plaintiffs have argued in thousands of lawsuits against Purdue. The litigation prompted Purdue in 2019 to file for Chapter 11 bankruptcy to address its debts.

Purdue reached a bankruptcy settlement with creditors, including various state attorneys general, local governments and the U.S. Justice Department's criminal and civil divisions. Under the deal, Purdue would transform into a nonprofit and dedicate its assets to addressing the harms of opioid addiction in the United States.

A U.S. bankruptcy court approved that restructuring plan in 2021. It was revised in 2022 to include more money from the Sacklers after the attorneys general of eight states and the District of Columbia successfully appealed the bankruptcy court approval.

The revised deal is supported by all financial stakeholders in the case, including all state attorneys general, but is opposed by the Justice Department's bankruptcy watchdog and some individual opioid plaintiffs.


Safety Flags of Newer Atopic Dermatitis Treatments

 MedPage Today brought together three expert leaders for a virtual roundtable discussion on atopic dermatitis : Moderator Peter Lio, MD, of Northwestern University Feinberg School of Medicine in Chicago, is joined by Linda Stein Gold, MD, of the Henry Ford Health System in Detroit, and Alexandra Golant, MD, of the Icahn School of Medicine at Mount Sinai in New York City.

This third of four exclusive episodes explores safety monitoring of treatments for the condition. Click here to watch other videosopens in a new tab or window from this roundtable series.

Following is a transcript of their discussion:

Lio: This brings us to our third question, which is really all about the pitfalls and the monitoring, and this is a perfect segue. So Dr. Golant, I've heard you talk very beautifully before on the black box warning on the JAK [Janus kinase] inhibitors, and I'm wondering if you could sort of summarize that for us here, what you might say to your patient when they say, "But doesn't this have a scary warning on it? What am I supposed to do with this?"

Golant: That's a great question, and I've heard you speak beautifully on it too, so I'd be curious to know how you deliver it. But I generally say that, "this entire class of medication," including the topical that's approved or topical JAK inhibitor that Linda mentioned, ruxolitinib [Opzelura], "has a boxed warning. This came from a higher risk patient population with a different JAK inhibitor that was thought to be more immunosuppressive."

"But in that study there was a higher rate of," and I go through the five kind of categories that are on that box warning, which are infection, mortality, cardiovascular events, clots, and malignancy. Then I say, "In the actual clinical trials of this medication I'm talking to you about in an atopic dermatitis population, what seemed to be a true signal, meaning thought to have correlation or cause-effect with the drug in a patient like you, really was limited to infections, particularly shingles and non-melanoma skin cancer."

That conversation lives best after having taken a really detailed history from your patients. So to Linda's point, are they 65 and up? Have they had a cardiovascular event or unprovoked clot? Are they a smoker? What else is going on in their life? Do they have an active malignancy? There are definitely buckets where you would think twice. I liked how Linda said that it's not a "never use," it's a "use your best judgment" and sometimes reach out to the other care teams to get their thoughts about it too. That's kind of how I approach it usually.

Lio: I couldn't agree more, and I love that idea that it's -- forced is strong, but it's true -- it's forced me to reach out to other care team members, which I think in dermatology we don't like to do as much. We tend to be kind of an island and we don't really love communicating as much as we should, but it has been great. I'll talk to the cardiologist, I'll talk to the oncologist. I'll say, "Listen, this is where we're at. These are our options." And I think for some patients the answer is going to be, no, we have to do something else, but for others it's going to be this still is the best choice, even though yes, there may be a higher risk profile, but we're going to do monitoring.

So Dr. Stein Gold, I'll turn it over to you. What, and understanding that the JAK inhibitor guidelines for monitoring, of course these are for the oral agents; there's no specific monitoring recommended for the topical ruxolitinib. But for the orals, it's a little bit vague; they give us kind of a leash. So I'm just curious personally, how do you usually go about it and what kinds of things are you thinking about when you're telling a patient how you're going to monitor?

Stein Gold: And I think that the fact that it's a little bit loose is a good thing, and because it might be different for each patient depending on their particular history, but I do get complete ... monitoring at baseline. You want to make sure their patients are not pregnant. You advise them it's not a good idea to get pregnant while taking an oral JAK inhibitor. Certainly the TB [tuberculosis] tests. But all baseline labs are done initially. And then you can look... and I've learned that all these young healthy people who come into your office are not young, healthy people. You pick up a lot of things on baseline labs that patients had no idea that they had. So I think that baseline monitoring is a great thing for patients in general.

And then often what I'll do, it depends really. With one of the oral medications, we can start to see changes within the first month, with the other one, it's within the first 3 months. So it really depends. But what I've found is, similar to what we did in the clinical trials -- and we've studied all of these agents in clinical trials so I'm fairly comfortable seeing these agents over the course of many years at this point -- but I'll tend to monitor heavier upfront, maybe at baseline, and then 3 months and then another 3 months, then see where things go. But in general, I'll probably, if somebody is on the medication and stable, I might check blood work twice a year.

Lio: That is so helpful, and it's just so great to have your wisdom and experience because I mean, obviously you treat a lot of serious dermatologic conditions and JAK inhibitors are a powerful member of this family. But maybe they're not even the most dangerous. I often think about how prednisone, cyclosporine, methotrexate, azathioprine, those are pretty big guns too, and arguably in some ways more dangerous than the JAKs. So we have this sort of apples to oranges. But I also don't want to totally blow over the biologics. I kind of said the biologics are an easier sell, but as you pointed out, they're not always an easy sell. Maybe easier but not easy.

So Dr. Golant, when you're talking to a patient about biologics, what kinds of safety and tolerability points do you bring up? And people still ask me this to this day -- I don't do any monitoring, but, do you or is there any monitoring you would do for a biologic patient?

Golant: I do not do any monitoring, and that was a departure for me. When they first were approved, I was doing monitoring just because I was so used to doing monitoring with our biologics for which we had biologics for psoriasis at that point, and then you end up finding things that don't preclude you from using the medication. So I said, no more. And that's per their label, right? I really do feel strongly we should be listening to the label. No immunosuppression, no box warning, no monitoring.

I think for both classes, for biologics and the JAK inhibitors, the patient's understanding of why you're talking to them about these medications lands best when you explain why we're talking to you about a systemic medication in general, because we understand atopic dermatitis is a systemic disease. And just like any other chronic condition -- high cholesterol, hypertension, you name it -- sometimes we need to intervene in a systemic way. That is usually my transition point to saying this is our menu. When I counsel about the biologics, usually from a risk or safety profile, I do mention no immunosuppression; this is not a steroid, probably like you've had before. Most of our biologics come with some elevated risk of not just conjunctivitis, but just overall ocular symptomatology: dry eye, itchy eye, irritated eye, red eye. So I talk through that. Sometimes I'll mention slight increase in herpes viral infections, which we're seen in many of the trials. Injection site reactions certainly.

But once you get to safety with the biologics, like you said, Peter, there's not that much to speak about. So that part usually goes pretty quickly once they have the buy-in of "Why are you talking to me about this medication in the first place?"

Lio: I love it. And since we have a couple of extra minutes, I'd love to just pick your brain. So you mentioned the eye issue, so conjunctivitis, keratitis, eye pruritus, dry eye, blepharitis, we see that kind of cluster. What about the face and neck dermatitis? Are you seeing that a lot?

Stein Gold: I don't see it that commonly, but I certainly do see it. And I have had patients that... and that's the reason why I have to take them off their biologic agent, and that's a time when I might consider going to an oral JAK. Because facial dermatitis can be really a problem. It's something that they think about every day. They walk into a room, their face is red, their eyes might be kind of red and swollen. It can be an issue. Again, I don't see it that commonly, but when I do see it, often it is an issue.

Golant: Yeah, I was just going to say I completely agree, and when I have a patient with predominant disease on the head and the neck, I will often say, especially for the biologics, "The trickiest areas to clear sometimes is this part of you [indicates face and neck]. So this is our starting point, but know there are other options if this doesn't become our final solution."

Lio: And then on the other side, with the JAKs, what are kind of the common things that come up? Dr. Stein Gold? Do you feel that the acne, and are there some other things that maybe are more tolerability things that might pop up for a patient?

Stein Gold: You think about the acne, the headache, a little bit of nausea early on, but for most of my patients, they really tolerate it quite well.

But I want to go back to one thing that you brought up. So I'm not sure what the incidence of the facial erythema is going to be with our newer biologic agents, with tralo [tralokinumab; Adbry] and with lebri [lebrikizumab]. I haven't seen it yet in my clinical trials with either of those or with lebri in real life. So that's something I think is still a little bit up in the air.

Lio: That is one of the most compelling things too because right, we've kind of lumped everything together, but they really are different drugs, and particularly the biologics. I mean, they're binding in slightly different areas, so dupilumab, tralo, and lebri, they're all the same pathway, but not fully, right? [Dupilumab] gets the IL-4 as well, so I'll be curious. It seems like the conjunctivitis signal is out there, and now it may be differential in terms of how common it is, but it seems like clinically it'll be comparable, but the face and neck maybe will be different, which would be wild.

For the JAKs, I feel like, again, they're pretty similar, but they're also different drugs. So yeah, I think that there may be some... I wish we had more biomarkers. I wish we had more insight into this so we could give more precision approach, but right now, I don't think it's crazy when someone says, "I failed this biologic, can I try another?" It's not necessarily ridiculous. They're not truly the same, especially if they've responded -- at least in my experience -- if they've responded to it in terms of their eczema but maybe had an adverse event, then I think it could definitely be worth switching to another biologic. If they didn't respond at all, then I feel like maybe it's time to switch categories and go to the JAK inhibitor. Would you guys agree with that?

Golant: I would. I would also add that I've seen the similar or same thing with the JAK inhibitors. I've seen a patient that might've had a partial not complete response to one, do very, very well on the other. So that surprised me too.

Stein Gold: Yeah, I think we're still learning so much, and I think the longer these medications are available, the more we'll truly understand. There have been some case reports of patients who were non-responders on one biologic or responded to the other one, but I think time will tell and we'll really get a better handle on how to approach these patients.

https://www.medpagetoday.com/video-coverage/atopic-derm-expert-video-roundtable/107637