Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association

177Lu PSMA Effective After 223Ra In Real-World Patients With MCRPC

Lutetium-177-PSMA-617 (177Lu PSMA) appears effective following treatment with radium 223 (223Ra) in real-world patients with metastatic castration-resistant prostate cancer (mCRPC), a new study finds. Low platelet count may be a useful biomarker of poor response.

In the retrospective study of 233 patients with mCRPC treated with 177Lu PSMA at 5 European centers, 27 patients were previously treated with 223Ra and 206 were not. The overall response rate to 177Lu PSMA was 54% and was similar between the 223Ra-pretreated and radium-naive groups, Isabel Heidegger, MD, PhD, of Medical University Innsbruck in Austria, and colleagues reported in Clinical Genitourinary Cancer. Patients with a greater delay between castration resistance and the initiation of 177Lu PSMA therapy had significantly longer response: median 17 vs 8.5 months in progressors. Multivariate regression analysis showed that lower platelet levels predicted poor response, the investigators reported.

"This highlights the potential utility of incorporating platelet monitoring into clinical practice when assessing the prognosis and adapting therapeutic strategies for patients undergoing 177Lu PSMA therapy," according to Dr Heidegger's team.

The all-cause mortality rate was significantly higher among patients previously treated with 223Ra (86% vs 51%). Prostate cancer was the main cause of death in the overall cohort. The reason for the survival disadvantage is not entirely clear, according to the investigators, but the 223Ra-naive group had a higher proportion of patients who initially received androgen deprivation therapy combined with an androgen receptor signaling inhibitor. Poor ECOG performance status and higher alkaline phosphatase (ALP) levels significantly predicted early mortality, the investigators reported.

Unlike other studies, this cohort included 48% patients who received additional therapies between 223Ra and 177Lu PSMA. According to the investigators, these "results clearly indicate a benefit of delaying radiopharmaceutical therapies." 177Lu PSMA is a beta emitter, whereas 223Ra is an alpha emitter.

No new safety signals emerged with 177Lu PSMA treatment, the investigators noted. Adverse events affected 44.0% of the 223Ra-pretreated group, most commonly anemia. Grade 3 or higher adverse events affected 22.2% of this group, mostly anemia requiring blood transfusion.

"These findings underscore the importance of treatment sequencing and key prognostic markers in optimizing therapy for mCRPC patients," Dr Heidegger's team wrote.

This article originally appeared on Renal and Urology News

Prayers Pour In For Pope Francis, In Critical Condition With Early Kidney Failure But Still Alert

ROME (AP) — Pope Francis remained in critical condition Sunday and blood tests show early kidney failure but he remains alert and "well-oriented," and attended Mass, the Vatican said, as the 88-year-old pontiff battles pneumonia and a complex lung infection.

In a late update, the Vatican said Francis hadn't had any more respiratory crises since Saturday night but was still receiving high flows of supplemental oxygen.

Some blood tests showed "initial, mild, kidney failure," but doctors said it was under control. The decreased platelet count, necessary for clotting, that was first detected Saturday was stable.

READ MORE: Pope Francis in critical condition after asthmatic respiratory crisis, Vatican says

"The complexity of the clinical picture, and the necessary wait for drug therapies to provide some feedback, dictate that the prognosis remains reserved," the doctors concluded.

Prayers for him poured in from around the world, from his native Argentina to the seat of Sunni Islam in Cairo to schoolchildren in Rome.

In New York, Cardinal Timothy Dolan admitted what church leaders in Rome weren't saying publicly: that the Catholic faithful were united "at the bedside of a dying father."

"As our Holy Father Pope Francis is in very, very fragile health, and probably close to death," Dolan said at St. Patrick's Cathedral, without saying if he had independent information about the pope's condition.

Doctors have said Francis' condition is touch-and-go, given his age, fragility and pre-existing lung disease. His condition has revived speculation about what might happen if he becomes unconscious or otherwise incapacitated, and whether he might resign.

Prayers for pope at Vatican

Francis was supposed to have celebrated Mass on Sunday morning in St. Peter's Basilica and ordained deacons as part of the Vatican's yearlong Holy Year commemoration.

The organizer of the Holy Year, Archbishop Rino Fisichella, celebrated the Mass in his place and offered a special prayer for Francis from the altar before delivering the homily the pope had prepared.

"Even though he is in a hospital bed, we feel Pope Francis close to us. We feel him present among us," Fisichella told the hundreds of white-robed deacons.

A pre-written message that had been prepared for Francis to read Sunday but did not deliver said he was "confidently continuing my hospitalization at the Gemelli Hospital, carrying on with the necessary treatment; and rest is also part of the therapy!" The message asked for prayers for him — as he always asks — and noted the upcoming anniversary of Russia's invasion of Ukraine, "a painful and shameful occasion for the whole of humanity."

Meanwhile in Francis' native Argentina, Catholics prayed for the pope at the Buenos Aires cathedral and the city's iconic obelisk was lit up "Francis, the city prays for you."

In Cairo, the grand imam of Al-Azhar, the seat of Sunni learning who forged a close bond with Francis, wished him well.

"I pray to Allah to grant my dear brother, Pope Francis, a swift recovery and to bless him with good health and well-being so that he may continue his journey in serving humanity," Sheikh Ahmed al-Tayeb wrote in a Facebook post.

And school children from around Rome deluged the Gemelli hospital with get-well cards, while Italian bishops led rosary prayers and celebrated special Masses across Italy.

The main threat facing the pope is sepsis

Doctors have warned that the main threat facing Francis is sepsis, a serious infection of the blood that can occur as a complication of pneumonia. As of Friday, there was no evidence of any sepsis, and Francis was responding to the various drugs he is taking, the pope's medical team said in their first in-depth update on the pope's condition.

Francis developed a low platelet count, a condition called platelopenia or thrombocytopenia. Platelets are cell-like fragments that circulate in the blood that help form blood clots to stop bleeding or help wounds heal. Low platelet counts can be caused by a number of things, including side effects from medicines or infections.

Francis, who has chronic lung disease and is prone to bronchitis in winter, was admitted to Gemelli hospital on Feb. 14 after a weeklong bout of bronchitis worsened.

Doctors first diagnosed the complex viral, bacterial and fungal respiratory tract infection and then the onset of pneumonia in both lungs. They prescribed "absolute rest" and a combination of cortisone and antibiotics, along with supplemental oxygen when he needs it.

Francis' recent reforms suggest he knew he was getting older and more fragile

Francis has taken several recent decisions that suggest he was well aware that he was getting old and frail.

Last year, he revised the funeral rites that will be used after he dies, simplifying the rituals to emphasize his role as a mere bishop and allowing for burial outside the Vatican in keeping with his wishes. But the core elements of the rites remain, including the three key moments that must be observed between the death of a pope and his funeral: In his home, in St. Peter's Basilica and in the place of burial.

READ MORE: Pope names 21 new cardinals, expanding pool of electors who will one day pick his successor

In December, Francis created 21 new cardinals. All but one were under age 80 and thus eligible to vote in a conclave to elect his successor. Their additions brought the overall number of voting-age cardinals to 140, well over the 120 limit set by St. John Paul II. But several of the current electors are turning 80 this year, bringing the number down.

Earlier this month, once he was already sick, Francis decided to extend the five-year term of the current dean of the College of Cardinals, Cardinal Giovanni Battista Re, 91, rather than make way for someone new. As depicted in the film "Conclave," the dean of the College of Cardinals plays an important role in the life of the Catholic hierarchy, and is a crucial figure during the transition between one papacy and the next.

Francis also decided to extend the term of the vice-dean, Argentine Cardinal Leonardo Sandri, 81.

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227 A Low Platelet Count Is Associated With Treatment Failurein Preterm Infants Treated With Ibuprofen For Patent Ductus Arteriosus (PDA)

Background: Recent studies have demonstrated that platelet count (PLTc) and function have an important role in promoting spontaneous closure of the PDA in animal models. Aimto evaluate whether response to ibuprofen in premature infants with PDA is influenced by PLTc.

Methods: All infants with GA ≤ 28wks born in our unit between 1/1/2007 and 31/12/2009 were retrospectively studied. Exclusion criteria were: congenital malformations, death within 48 hrs and outborn. All infants had echocardiographic evaluation in 1st DoL. Patients with a hemodynamically significant PDA (HsPDA) were treated with a standard course of ibuprofen. GA, BW, antenatal steroids, gender, type of ventilatory support were analyzed along with PLTc before and after treatment. Associations with HsPDA and treatment response were assessed by univariate and multivariate analysis.

Results: Data from 130 out of 162 newborns (GA 26.2w±1.5, BW 851.2±293g) were analysed. 117 patients showed a PDA at first evaluation. 88 newborns were treated with ibuprofen for HsPDA; after treatment 60 patients had a closed ductus (responders) while 28 were non-responders. A lower PLTc was observed in infants with HsPDA but difference was not statistically significant. Among treated infants, non-responders had a lower GA, were more likely mechanically ventilated and had a PLT significantly lower than responders (111.000/μl vs. 184.000/μl, p=0,001). In the multivariate analysis only invasive ventilation and low PLTc were independent factors for treatment failure.

Conclusion: A low PLTc increases the risk of treatment failure of PDA. Further studies are needed to evaluate the prognostic and therapeutic implications of this observation.

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