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Begalka: Events mark military milestones, past and present

Begalka: Events mark military milestones, past and present

It’s special to find a direct descendant of the Revolutionary War with ties to McHenry County, but Sunday will be a special day.

That is when the Kishwaukee Trail Daughters of the American Revolution Chapter will place a bronze marker next to the worn headstone of Phebe Ashley Mead Weed in a ceremony at 1:30 p.m. in old Marengo City Cemetery at 101-199 N. East St.

“In the life of a chapter, it is rare to be able to celebrate and mark a grave of a daughter of a patriot,” said event spokeswoman Claudia Edwards. “Phebe will be the 43rd marking of a daughter of a patriot in the entire state of Illinois. This is rare because so many have already been marked and because so much of the lineage is lost. Women marry and their maiden names are lost or not traced.”

Phebe is related to Fox River Grove native Kathy (Welisek) Hartke. As a child, she accompanied her mother, Betty, and grandmother Marjorie Long, to the Marengo City Cemetery to place flowers on the graves of relatives. About 2007 or 2008, Hartke became interested in finding out more about her forebearers.

Her great-great-great-great-grandmother Phebe, was the daughter of Phebe Howe and Revolutionary War soldier William Ashley. Details remain sketchy, but she learned he enlisted in July or August 1775. Ashley, born in 1758, was a member of the Vermont militia and one of Ethan Allen’s Green Mountain Boys who fought under the command of Gen. Benedict Arnold. He assisted in the evacuation of Fort Ticonderoga in the face of superior British forces.

Hartke is descended from the daughter of Phebe’s first marriage to Amasa Mead in the Forestville area of New York. Hartke’s great-great-great-grandmother Catherine is one of their six children. Phebe later married John Weed and had three more children.

While in New York, Catherine married Frederick Webb. The couple moved to Marengo in the 1850s. Sometime after her second husband died, Phebe moved to Marengo, as well.

Phebe is the third person in McHenry County honored by the DAR with a direct connection to the Revolutionary War. The others are Major Watson and his daughter, Clarissa Watson Down, both buried in the Linn-Hebron Cemetery.

In 2015, Hartke and her husband traveled to Poultney, Vermont, to search for records, but she began “actively” working on this project in 2019. Stops included visits to McHenry County Historical Society’s Research Library, with assistance from DAR member and librarian Arlyn Booth.

“We’ve had a lot of help from all the members of the DAR. It is a very exciting project,” Hartke said. “The more you know, the more you want to know.”

After Sunday’s brief ceremony that includes a color guard dressed in Revolutionary War-period uniforms, light refreshments will be served.

•••

The American Veterans Traveling Tribute comes to Harvard from 8 a.m. to 9 p.m. Sept. 8to 11 at Milky Way Park, 300 Lawrence Road. This nationally recognized traveling tribute honors veterans from every major conflict dating to World War I. Harvard is bringing the entire tribute, which consists of of 212 panels and 58,300 names. An 80% scale replica of the Vietnam Veterans Memorial in Washington, D.C., the wall measures almost 400 feet long. It also includes smaller tribute panels honoring American sacrifices in conflicts through the 20th and 21st centuries, including WWI, WWII, 9-11, Afghanistan and Iraq.

“I have a huge military presence in my background,” Harvard Chamber of Commerce member Crystal Musgrove said. Her husband, father-in-law, son, brother, father, stepfather and nephew either served in the military or currently are on duty.

“I’ve wanted to do this for 15 years, to bring something like that here out of respect for those who served from here,” Musgrove said.

The schedule includes school tours, library-led crafts, an appearance by Harvard historical reenactor Ed O’Brien and performances by Joe Cantafio and country singer Austin Edwards. In 2020, Edwards was part of a duo that claimed first runner-up fame on “America’s Got Talent.”

Musgrove is working to line up additional acts, as well as a cadre of volunteers to oversee this free event. She also is seeking sponsors to help underwrite the cost of bringing the etched aluminum panels to McHenry County, as well as light them and keep the memorial secure. If you can help, call the Chamber at 815-943-4404 or email Musgrove at info@harvcc.net.

“It’s very cool and pretty powerful,” she said. “Our freedom is not free. There is a lot of cost in human life.”

•••

Join Ernest J. Varga project/design engineer with the McHenry County Division of Transportation, as he explores the origins of road names across McHenry County. “A Road By Any Other Name” begins at 2 p.m. Saturday, Aug. 20, at the county history museum, 6422 Main St. in Union. Admission, which includes free museum access, is $5 for society members and $8 for nonmembers. For information visit GotHistory.org.

Kurt Begalka is administrator of the McHenry County Historical Society & Museum. He may be reached at kurt@mchenrycountyhistory.org.

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Expect Kejriwal to be present in future events: LG’s message after Delhi CM skips joint programme

Expect Kejriwal to be present in future events: LG's message after Delhi CM skips joint programme

The feud between Delhi Lieutenant Governor VK Saxena and Chief Minister Arvind Kejriwal escalated after the latter skipped a pre-decided combined programme on Sunday.

The LG said that he expects the Chief Minister to be present in future events “to give a message” that they “want to work together” for the city’s development.

A pre-decided combined programme of tree plantation drive at Asola Bhatti mines was organised, which was skipped by the Chief Minister.

The Delhi government sources said that the government programme was turned into a political BJP programme, because of which Kejriwal decided not to attend the event.

This comes days after Kejriwal skipped the weekly meeting called by the LG on Friday citing ill-health. However, the Aam Aadmi Party alleged that the LG had also skipped one of the meetings on July 8.

“Delhi Police forcefully took over the stage of Van Mohatsav before the programme. It is a Delhi government event, the CM and LG were to attend jointly. Posters showcasing Prime Minister Narendra Modi were put up and the government programme was turned into a political BJP programme. This is the reason Delhi CM and ministers decided not to attend the event,” said the AAP.

However, the Delhi LG said that he wanted Kejriwal to attend the event, adding that all should work together for this tree plantation drive.

“I wanted CM Arvind Kejriwal to attend this event but due to some reasons, he could not. This is a programme where all of us should work together. I expect him to be present in future events to give a message that we want to work together for Delhi’s development,” LG Saxena said during his address.

Earlier in the day, the sources said, “After absenting from the scheduled weekly meeting with Delhi Lieutenant Governor VK Saxena on Friday, citing ill health, Chief Minister Arvind Kejriwal on Sunday again skipped a pre-decided combined programme of tree plantation at Asola Bhatti mines in the national capital gain due to ill health”.

The said programme of tree plantation corresponding with the ‘Van Mahotsav’, was to be undertaken jointly by the Lieutenant Governor and Chief Minister.

A mutual decision in this regard had been taken on July 4, 2022. A total of 1,00,000 trees are planted as a part of the programme, and the Lieutenant Governor and Chief Minister were to launch the same together.

“One is left to wonder if recommending a CBI inquiry into an apparently illegal excise policy is taking the focus of the CM away from Delhi’s environmental concerns,” said LG sources.

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FATHOM EVENTS, UNIVERSAL PICTURES AND DREAMWORKS PICTURES PROUDLY PRESENT GLOBAL COMEDY SENSATION JO KOY IN A ONE-NIGHT-ONLY LIVE IN-PERSON EVENT TO CELEBRATE THE RELEASE OF HIS GROUNDBREAKING NEW FEATURE FILM, EASTER SUNDAY

FATHOM EVENTS, UNIVERSAL PICTURES AND DREAMWORKS PICTURES PROUDLY PRESENT GLOBAL COMEDY SENSATION JO KOY IN A ONE-NIGHT-ONLY LIVE IN-PERSON EVENT TO CELEBRATE THE RELEASE OF HIS GROUNDBREAKING NEW FEATURE FILM, EASTER SUNDAY

Fathom Events’ Easter Sunday: Live with Jo Koy, featuring an exclusive comedic introduction with Jo Koy, takes place on August 4, 2022

Easter Sunday, from Universal Pictures and DreamWorks Pictures, arrives in theaters nationwide August 5.

DENVER, July 12, 2022 /PRNewswire/ — Global stand-up comedy sensation Jo Koy will bring his singular and hilarious take on family matters to theaters nationwide with an exclusive comedic introduction as part of a celebration of his groundbreaking new feature film, Easter Sunday. Ahead of the film’s nationwide release on August 5, Fathom Events will present Koy’s live introduction in more than 850 theaters across the country on August 4, followed immediately by a full screening of the film from Universal Pictures and DreamWorks Pictures.

See trailer HERE.

Koy’s live introduction takes place on Thursday, Aug. 4, at AMC Lincoln Square in New York City and it will play in theaters nationwide LIVE at 8:00 pm ET and 5:00 pm PT and tape-delayed at 8:00 pm CT/MT/ PT.

In Easter Sunday, Koy (Jo Koy: In His ElementsJo Koy: Comin’ in Hot) stars as a man returning home for an Easter celebration with his riotous, bickering, eating, drinking, laughing, loving family in this love letter to his Filipino-American community. 

“Fathom Events is excited to present this exclusive, live introduction from Jo Koy to kick off the debut of Easter Sunday; it’s what Event Cinema is all about,” said Ray Nutt, CEO of Fathom Events. “Jo’s comedy is so hilarious because it’s so relatable. Who doesn’t have crazy holiday traditions with their family?”

Tickets to Easter Sunday and this special live comedic introduction can be purchased online at www.fathomevents.com or at participating theater box offices. For a complete list of theater locations visit the Fathom Events website (theaters and participants are subject to change).

Easter Sunday features an all-star comedic cast that includes Jimmy O. Yang (Silicon Valley series), Tia Carrere (True LiesWayne’s World films), Brandon Wardell (Curb Your Enthusiasm series), Tony nominee Eva Noblezada (Broadway’s Hadestown), Lydia Gaston (Broadway’s The King and I), Asif Ali (WandaVision), Rodney To (Parks and Recreation series), Eugene Cordero (The Good Place series), Jay Chandrasekhar (I Love You, Man), Tiffany Haddish (Girls Trip) and Lou Diamond Phillips (Courage Under Fire).

Easter Sunday, from DreamWorks Pictures, is directed by Jay Chandrasekhar (Super TroopersThe Dukes of Hazzard, I Love You, Man), from a script by Ken Cheng (Sin City Saints series) and Kate Angelo (Sex Tape) based on a story by Ken Cheng.

The film is produced by Rideback’s blockbuster producers Dan Lin (The Lego Movie franchise, It franchise) and Jonathan Eirich (AladdinThe Two Popes), and is executive produced by Nick Reynolds, Joe Meloche, Jo Koy, Jessica Gao, Jimmy O. Yang, Ken Cheng and Seth William Meier

The film is distributed by Universal Pictures domestically. Amblin Partners and Universal share international distribution rights. 

Press Assets: Can be found HERE

About Fathom Events

Fathom is a recognized leader in the entertainment industry as one of the top distributors of content to movie theaters in North America. Owned by AMC Entertainment Inc. (NYSE: AMC); Cinemark Holdings, Inc. (NYSE: CNK); and Regal, a subsidiary of the Cineworld Group (LSE: CINE.L), Fathom operates the largest cinema distribution network, delivering a wide variety of programming and experiences to cinema audiences in all of the top U.S. markets and to more than 45 countries. For more information, visit www.FathomEvents.com.

SOURCE Fathom Events

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Their Voice: Events past, present celebrate those with autism

Their Voice: Events past, present celebrate those with autism


Before we end the month of April, a month designated as Autism Awareness Month, I wanted to share some information about a research project taking place at BYU.

The study is focused on preschool-aged children diagnosed in the autism spectrum. They are asking for mothers of children between the ages of 2-5 years of age to participate in an autism research study. The mothers are required to be available for live virtual meetings on Tuesdays from 6:30-8:30 pm.

Depending on the participation category the study may include parent participation in up to 8 online teaching workshops, assessments and shared reading of provided books. Parents can earn a $25 gift card upon completion.

If you are interested in participating, go to the website https://autismbehaviorlab.byu.edu/current-research to see if you qualify. For any more information, contact Blake Hansen at 801-422-4691.

Speaking of autism, as we wind down from the events, I wanted to give a personal thank you to all of the members of the Autism Resources of Utah County Council (ARUCC) for the very successful 10th Annual Uplifting Celebration on April 16.

According to Laurie Bowen, associate director of the Melisa Nellesen Center for Autism at UVU, there were over 900 people in attendance with over 33 organizations providing food, games and other activities. The group of volunteers this year included many young adults who were on the spectrum.

As a participating sponsor, we provided a table for people to create greeting cards to send to the children in Ukraine. The cards were beautifully done and contained very heartfelt messages of hope, peace and love. It was touching to realize how many individuals in the autism community wanted to do something to send their well wishes. The 53 cards that were made are being sent over to Ukraine with the help of Orem City Police Chief Josh Adams, who recently returned from a humanitarian trip there that he organized with his good friend Jared Turner.

Thanks to all of the ARUCC and all of the organizations who worked so hard to make this day a success.



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Checkpoint Inhibitors Present Unique Adverse Events, Require Careful Management Strategies in Breast Cancer

Checkpoint Inhibitors Present Unique Adverse Events, Require Careful Management Strategies in Breast Cancer

Most, but not all, immunotherapy-related adverse events (irAE) occur throughout the first 12 weeks of treatment, and can affect any organ, according to La-Urshala Brock, FNP-BC, CNM, RNF, a clinical instructor specializing in breast and gynecologic cancers at the Nell Hodgson Woodruff School of Nursing with Emory University.1

Brock recently presented during the 39th Annual Miami Breast Cancer Conference® about immunotherapy-related adverse event management, in a lecture titled, “Immunotherapy Adverse Effects,” which focused specifically on toxicities associated with pembrolizumab (Keytruda).

In July 2021, the PD-L1 inhibitor pembrolizumab was approved by the FDA to treat patients with triple-negative breast cancer (TNBC) in the neoadjuvant meeting in conjunction with chemotherapy, to be continued as an adjuvant monotherapy after surgery.2

The approval for pembrolizumab was supported by findings from the randomized, multicenter, double-blind, placebo-controlled KEYNOTE-522 trial (NCT03036488).3 Results demonstrated a 37% reduction in the risk of disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (HR, 0.63; 95% CI, 0.48-0.82; P = .00031).The recommended dose for intravenous pembrolizumab is 200 mg every 3 weeks.2

Notably, this approval also marked the first immunotherapy to treat patients with high-risk early-stage TNBC. However, the introduction of the agent also opens the door for more toxicity management education for nurses who care for patient with breast cancer.

“Immunotherapies present with a novel spectrum of AEs that differ in important ways from those associated with chemotherapy and targeted agents,” said Brock. “When you’re using immunotherapy, truly any organ can be affected. The median onset is 4 to 5 weeks [after beginning treatment], but adverse events can happen as early as when you start the treatment.”

Atezolizumab (Tecentriq), a PD-L1 inhibitor, was granted accelerated approval for TNBC to be given every 3 weeks with weekly nab-paclitaxel (Abraxane) in 2019, but this agent was withdrawn from market, since it was not shown to improve survival in patients with locally unresectable metastatic, PD-L1–positive disease.4

In her discussion, Brock highlighted a wide range of toxicities that are associated with immune checkpoint inhibitiors (ICI)—particularly for patients with TNBC receiving pembrolizumab. Toxicities of interest include dermatitis, endocrine effects, adrenal insufficiencies, lung effects, colitis, hepatotoxicity, and ocular side effects, in addition to a couple rarer immune-related AEs (irAEs).

Dermatitis

ICIs may induce low-grade rashes in many patients. This can include reticular erythema, papules, and plaques. In more rare cases, Stevens-Johnson syndrome or toxic epidermal necrolysis, palmar–planta dysesthesia may also occur.

Effective management of skin-related toxicities involve frequent photo documentation of the toxicity and follow-up photos to track potential changes, as well as consulting a dermatologist to obtain a biopsy. For low-grade toxicities, symptomatic treatment with antihistamines typically prove to be effective. However, for high-grade toxicities, treatment with topical or oral steroids may be appropriate. In addition, if symptoms progress to grade 3, treatment should be withheld, and if symptoms worsen to grade 4, treatment should be discontinued.5,6,7,8

“We hold at this point,” said Brock. “You could think about using rituximab [Rituxan] for treatment. You want to continue steroids until the blisters have resolved completely and then [once] the blisters have resolved, you want to slowly taper the steroids.”

Endocrine Toxicities

Endocrine toxicities occur in approximately 10% of patients receiving pembrolizumab. Nurses should watch for vision changes, weight gain or weight loss, dizziness, constant chilliness or feeling cold, constipation, and hair loss. Other signs of endocrine toxicities include increased headaches or changes in headache patterns, increased heartbeat, increased urination, increased tiredness, increased thirst or appetite, changes in mood, and increased sweating.8

Patients suspected to be experiencing these toxicities should have their thyroid-stimulating hormone (TSH) and free thyroxine (FT4) checked every 4 to 6 weeks with complete blood count (CBC) and comprehensive metabolic panel (CMP).

Adrenal Insufficiency

Adrenal insufficiency, or Addison’s disease, means that the adrenal glands produce insufficient amounts of the hormone cortisol, Brock explained. Signs and symptoms include extreme fatigue, darkening skin or hyperpigmentation, low blood pressure or fainting, abdominal pain, muscle or joint pain, salt craving, weight loss, depression or behavioral changes, and nausea, vomiting, or diarrhea.

For primary adrenal insufficiency, the workup should include assessing morning cortisone and adrenocorticotropic hormone (ACTH) levels, as well as CMP to assess sodium, glucose, potassium, and carbon dioxide.

If a patient has elevated TSH levels but normal or low FT4, then hypothyroidism is the cause. So long as the toxicity remains a grade 1 (TSH < 10 ml U/L or asymptomatic), they may continue receiving the checkpoint inhibitor with continued TSH and FT4 monitoring.

For hypophysitis, or inflammation of pituitary gland, the workup should include assessing morning cortisone as well as ACTH, TSH, FT4, testosterone in men, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen in premenopausal women, and an MRI of the brain with or without contrast with pituitary cuts.

If the hypothyroidism progresses to a grade 2 (TSH > 10 mIU/L or symptomatic), the ICI should be withheld, an endocrinologist should be consulted, and a thyroid hormone supplementation should be implemented. The patients will continue to require TSH and FT4 checks every 6 weeks, but if the severity reduces to a grade 1 event, they may continue treatment.

In the event of grade 3/4 hypothyroidism, the ICI should be withheld until symptoms resolve to baseline with thyroid supplementation.

If a patient has low TSH and high, normal, or elevated FT4 levels, then this person is experiencing hyperthyroidism. As long as the toxicity remains at grade 1, they may continue receiving the ICI with continued TSH and FT4 checks every 2 to 3 weeks.

If the hyperthyroidism progresses to a grade 2, the ICI should be withheld until symptoms return to baseline and an endocrinologist should be consulted. A beta blocker might also be considered.

For grade 3/4 hyperthyroidism, the ICI will need to be withheld until symptoms resolve to baseline with thyroid supplementation. In addition, at this grade, hospitalization may be required if thyroid storm occurs. Prednisone should be considered at a dosage of 1 to 2 mg/kg daily and then put on a tapering schedule.

“With hyperthyroidism, what I want to mention here is that if someone is experiencing symptoms, we can use a beta blocker, but we also still want to be consulting endocrinology,” Brock highlighted. “One of the risk factors here when we get to grade 4 is the risk for thyroid storm. That is why it is important to have endocrinology involved.”

In less than 1% of patients, ICI-mediated endocrinopathy type 1 diabetes mellitus may occur with rapid onset anytime following therapy initiation.

Management for this toxicity involves monitoring serum glucose at baseline and prior to each cycle of ICI. An endocrinologist should be consulted, and generally, lifelong insulin therapy will be required. Once blood sugar is well controlled, the ICI therapy can be restarted.

Lung Toxicity

Pneumonitis equates to inflammation of the lung parenchyma. This irAE occurs between 0% to 10% of patients, but the odds increase when patients receive combination therapy as opposed to monotherapy, as well as if there has been previous thoracic radiation.9-11 The onset time for lung toxicity can range from 2 to 24 months, however, the median onset time is 3 months.

Cough, fever, dyspnea, and chest pain should be evaluated when monitoring for lung toxicity. Patients who experience these symptoms will need a chest x-ray and CT scan. The threshold for obtaining a CT scan of the chest and a pulmonary consultation should be low, noting that CT findings typically lag patient symptoms.

Management includes routine pulse oximetry checks in addition to potential CT scans, as well as administration of high-dose steroids, starting at 1 to 2 mg/kg daily, and tapering across 45 to 60 days. If symptoms return, the steroids may require retapering.

If within 72 to 96 hours of steroid initiation there is no symptom relief, patients should receive infliximab-axxq (Avsola) at 5 mg/kg. In most cases, the addition of immunosuppressants will help to resolve the issue.Infectious workup should include a nasal swab for potential viral pathogens, including COVID-19.

Notably, lung toxicity has been associated with immune checkpoint inhibitors but is an uncommon AE; less than 5% of patients experience this irAE, and less than 1% report high-grade lung toxicity while receiving this type of immunotherapy. In comparison, lung toxicity tends to present more in patients receiving ipilimumab (Yervoy) plus nivolumab (Opdivo), explained Brock.

Colitis

Colitis occurs in approximately 8% to 27% of patients receiving ICIs. Onset of GI toxicities typically appear about 5 to 10 weeks after treatment begins but can occur months after treatment with the ICI has stopped.

Initial workup for colitis should include CBC, CMP labs to assess TSH, c-reactive protein (CRP), HIV, hepatitis A and B; whereas interferon gamma release assay should be used to look for tuberculosis (TB). In addition, stool cultures to identify C. diff, CMB, ova, and parasites are recommended; lactoferrin should identify inflammation of digestive tracts and calprotectin can determine immune bowel disease (≤80 ug/g) vs inflammation (levels on 80 ≥ 1, 60 ug/g); and a CT scan.

At grade 1 severity, the ICI can either continue or be temporarily withheld. Providers should discuss dietary changes with their patients and review hydration strategies, and antdiarrheal administration may also be effective.

If the inflammation progresses to grade 2 level, the ICI should be withheld until symptoms return to grade 1 or less. A GI specialist should be consulted for an EGD/colonoscopy and prednisone should be administered at a dosage of 1 mg/kg daily. In addition, stools should be checked for inflammatory markers, such as lactoferrin and calprotectin. Once the symptom returns to grade 1, the steroids should be tapered across 4 to 6 weeks.

Grade 3 inflammation requires a hold on the ICI. Hospitalization may be required if there is electrolyte imbalance and dehydration. Providers should rule out CMV via colonoscopy and consult a GI specialist. Corticosteroids given at a dosage of 1 to 2 mg/kg day or infliximab at a dosage of 5 to 10 mg/kg daily should be administered.

“With colitis, there could be another rebound,” said Brock. “Someone could resolve back to a ready to a grade 1; if that occurs then, of course, we restart the steroids or increase the steroids and start again—slowly tapering once the symptoms improve.”

If the severity level reaches a grade 4, it is now life-threatening, and treatment should be discontinued permanently.

Hepatotoxicity/Immune-Mediated Hepatitis

Hepatotoxicity or immune-mediated hepatitis occurs in approximately 2% to 10% of patients receiving pembrolizumab and onset usually occurs between 6 to 12 weeks after treatment initiation. Symptoms include drowsiness, jaundice, right-sided abdominal pain, severe nausea or vomiting, increased bleeding, or bruising, decreased appetite, and abnormal liver blood tests (aspartate aminotransferase [AST], alanine transaminase [ALT], and bilirubin).

For grade 1 inflammation (AST or ASLT > upper limit of normal [ULN] to 3.0 and/or total bilirubin 1.0 ULN > 1.5 ULN), ICI treatment may continue but liver function should be monitored 1 to 2 times weekly. For grade 2 inflammation (ASR or ALT > 3.0 ULN to < 5.0 and/or total bilirubin 1.0 ULN to 3.0 ULN with symptoms), the ICI should be held until severity resolves to a grade 1.

In addition, the liver should be monitored every 3 days if the patient is symptomatic. If the symptom reaches statistical significance, after 3 to 5 days they can receive corticosteroids at a dosage of 0.5 to 1.0 mg/kg daily. This will require tapering over 1 month. Lastly, any hepatoxic medication should be halted.

For grade 3 inflammation (ASR or ALT 5 x 20 x ULN and/or total bilirubin >3-10 x ULN with symptoms such as biopsy-fibrosis or cirrhosis), the ICI should be discontinued permanently, and the patient should be monitored every 1 to 2 days. Corticosteroids should be administered at a dosage of 1 to 2 mg/kg/day, and the patient should be referred to a hepatologist.

If the symptom progresses to grade 4 (ASR or ALT >20 x ULN and/or total bilirubin > 10 x ULN, with symptoms such as ascites or encephalopathy), they will need to be hospitalized with daily lab monitoring and consultation from a hepatitis. They should receive methylprednisone at a dosage of 2 mg/kg daily.

Ocular Symptoms

Ocular symptoms typically occur in less than 1% of patient receiving PD-1/PD-L1 inhibitors alone or in combination. Symptoms include eyelid swelling, blurred vision, double vision, or color vision changes, photophobia, painful eye movement, scotomas, proptosis or bulging eyes, and visual field changes.

If a patient appears to be experiencing an ocular toxicity, they should be referred to an ophthalmologist and receive a slit-lamp exam.

Treatment management for uveitis or inflammation of the middle of the eye, and iritis, or inflammation of the iris, are similar. For grade 1 inflammation, ICI treatment should continue but a referral to an ophthalmologist should be made. For grade 2 inflammation (anterior uveisis), the ICI should be held until ophthalmology evaluation and topical or systematic corticosteroids can be administered. These can continue once the issue resolves or returns to grade 1 and the patient resumes ICI treatment.

If symptoms progress to grade 3 (posterior uveitis), the ICI should be discontinued permanently, and systematic and topical corticosteroids should be administered. Lastly, if symptoms become grade 4, not only should the ICI be discontinued permanently, but the patient may need emergency care.

Rare irAEs

In addition, rare irAEs that may present in patients receiving ICIs include myocarditis and pericarditis; nephritis; pancreatitis; musculoskeletal toxicities such as arthritis, arthralgia, myalgia, and myositis; and neurologic toxicities such as peripheral neuropathy, myasthenia gravis, and Guillain-Barré Syndrome.

General Principles of ICI Toxicity Management

In conclusion, for grade 1 toxicities (mild or asymptomatic toxicities), the patient can continue receiving the ICI without steroids or intervention. Patients with grade 1 toxicities may benefit from antihistamines.

For grade 2 toxicities (moderate toxicities), a specialist should be consulted, and steroids should be considered. The ICI should be withheld until the symptom returns to grade 1; if the grade 2 symptoms persist for more than 12 weeks, the ICI should be discontinued.

If symptoms progress to grade 3, the ICI should be held (or, in the case of pneumonitis, discontinued), and prednisone should be administered. A specialist should be consulted, and hospitalization may become necessary. If these symptoms remain consistent, the ICI should be discontinued.

Grade 4 toxicities are life-threatening. Unless the symptom is endocrine-related, grade 4 toxicities signify that the ICI should be immediately discontinued. The patient will need hospitalization, and to continue receiving prednisone. If the steroid does not yield symptom improvement, infliximab should also be considered.

Other important considerations include using a proton pump inhibitor or H2 blocker for gastritis, sulfamethoxazole/trimethoprim/fluconazole for opportunistic infections, and calcium and vitamin D for osteoporosis, Brock noted.

Furthermore, counseling patients and caregivers should involve setting evidence-based expectations for benefits. Patients may have heard of the drug and have misconceptions based on popular stories in the news. It should be clear that benefits taking longer to emerge with immunotherapy compared with treatments like chemotherapy and targeted therapy. Therefore, patients with significant tumor burden or rapidly progressing disease often cannot afford to elect these types of therapies.

For nurses caring for patients beginning immunotherapy, it is essential to emphasize the importance of monitoring and promptly reporting symptoms.

“Emphasize [the importance] of monitoring and promptly reporting symptoms,” Brock urged. “[Teach them to] contact the oncology care team if [they are] experiencing any new signs or symptoms [and to] report any visits to the emergency department and other healthcare providers.”

In addition, patients should also always always carry an immunotherapy wallet. Lastly, patients need adequate irAE management education.

“Discontinuing ICIs because of AEs does not worsen survival,”12 she noted. “Treating irAEs with steroids does not worsen response or survival.”13,14 

References

  1. Brock LA. Immunotherapy adverse effects. Presented at: 39th Annual Miami Breast Cancer Conference®; March 3-6, 2022; Miami Beach, FL.
  2. This Keytruda combination is the first immunotherapy regimen approved for high-risk early-stage triple-negative breast cancer (TNBC). News release. Merck. July 27, 2021. Accessed March 15, 2022. https://bit.ly/3id6Rou
  3. Schmid P, Cortes J, Dent R, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022;386(6):556-567. doi:10.1056/NEJMoa2112651
  4. Roche provides update on Tecentriq US indication for PD-L1-positive, metastatic triple-negative breast cancer. News release. Roche. August 27, 2021. Accessed August 27, 2021. https://bit.ly/3ypzC6K
  5. Weber JS, Postow M, Lao CD, Schadendorf D. Management of adverse events following treatment with anti-programmed death-1 agents. Oncologist. 2016;21(10):1230-1240. doi:10.1634/theoncologist.2016-0055.
  6. Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [published correction appears in Ann Oncol. 2018;29(suppl 4):iv264-iv266]. Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
  7. Sanlorenzo M, Vujic I, Daud A, et al. Pembrolizumab cutaneous adverse events and their association with disease progression. JAMA Dermatol. 2015;151(11):1206-1212. doi:10.1001/jamadermatol.2015.1916
  8. Freeman-Keller M, Kim Y, Cronin H, Richards A, Gibney G, Weber JS. Nivolumab in resected and unresectable metastatic melanoma: characteristics of immune-related adverse events and association with outcomes. Clin Cancer Res. 2016;22(4):886-894. doi:10.1158/1078-0432.CCR-15-1136
  9. NCCN guidelines for management of immunotherapy-related toxicities. NCCN. Accessed March 18, 2022. https://bit.ly/34TwdEN
  10. Haanen JBAG, Carbonnel F, Robert C, et al. Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [published correction appears in Ann Oncol. 2018 Oct 1;29(Suppl 4):iv264-iv266]. Ann Oncol. 2017;28(suppl_4):iv119-iv142. doi:10.1093/annonc/mdx225
  11. Chen X, Zhang Z, Hou X, et al. Immune-related pneumonitis associated with immune checkpoint inhibitors in lung cancer: a network meta-analysis. J Immunother Cancer. 2020;8(2):e001170. doi:10.1136/jitc-2020-001170
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Synopsys to Present at Upcoming Investor Events

World Series of Poker Announces 2022 Daily Event Schedule

MOUNTAIN VIEW, Calif., March 1, 2022 /PRNewswire/ — Synopsys, Inc. (Nasdaq: SNPS) today announced the following presentations for the investment community.

Morgan Stanley Technology, Media & Telecom Conference

Tuesday, March 8 at 11:30 a.m. PT / 2:30 p.m. ET

Aart de Geus, Synopsys chairman and co-CEO

KeyBanc Emerging Technology Summit

Wednesday, March 9 at 9:30 a.m. PT / 12:30 p.m. ET

Trac Pham, Synopsys chief financial officer

There will be a live audio webcast and a replay will be available following the live event. Both live webcast and replay can be accessed via the Synopsys corporate website at https://www.synopsys.com/company/investor-relations.html.

About Synopsys

Synopsys, Inc. (Nasdaq: SNPS) is the Silicon to Software™ partner for innovative companies developing the electronic products and software applications we rely on every day. As an S&P 500 company, Synopsys has a long history of being a global leader in electronic design automation (EDA) and semiconductor IP and offers the industry’s broadest portfolio of application security testing tools and services. Whether you’re a system-on-chip (SoC) designer creating advanced semiconductors, or a software developer writing more secure, high-quality code, Synopsys has the solutions needed to deliver innovative products. Learn more at www.synopsys.com.

Investor Contact:

Christine Salvi-Sullivan

Synopsys, Inc.

(650) 584-1433

Synopsys-ir@synopsys.com

Cision View original content:https://www.prnewswire.com/news-releases/synopsys-to-present-at-upcoming-investor-events-301493250.html

SOURCE Synopsys, Inc.