NEJM This Week — May 28, 2026

Ultrasound facilitated catheter directed fibrinolysis for acute pulmonary embolism by Kenneth Rosenfield from Massachusetts General Hospital, Boston and co authors. Acute pulmonary embolism encompasses a broad spectrum of clinical severity, a fact that emphasizes the need for risk informed therapy.

For patients who present with hemodynamic instability, the consensus is that early thrombus removal by means of systemically administered fibrinolysis is On the other hand, The appropriate treatment strategy for patients whose condition appears to be stable, but who have evidence of right ventricular dysfunction, and clinical or laboratory signs that suggest a risk In this study.

Five hundred forty-four patients with intermediate risk pulmonary embolism were randomly assigned to undergo ultrasound facilitated catheter directed fibrinolysis with altoplase Plus anticoagulation, the intervention group, or anticoagulation alone, the control group, according to pre specified treatment protocols.

The primary outcome of a composite of pulmonary embolism related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of pulmonary embolism within seven days. Occurred in 4% of patients in the intervention group and in 10.3% of those in the control group. The effect was driven primarily by a lower risk of cardiorespiratory decompensation or collapse in the intervention group.

Alex Spyropolis from Hofstra Northwell, Hemstead, New York, and Suresh Vidantham from Washington University School of Medicine, St. Louis. Write in an editorial that the findings of the study by Rosenfield and co authors represent a major advance in the foundation of evidence for thrombolytic approaches.

The findings support a lower threshold for the use of ultrasound facilitated catheter directed thrombolysis in patients with pulmonary embolism who would have been characterized as having intermediate high risk or the equivalent according to recent guidelines. However, the wisdom of applying this approach to patients with less severe intermediate risk pulmonary embolism remains unclear and will benefit from additional studies, including those assessing long term functional outcomes.

applying mechanical thrombectomy and potentially using safer background anticoagulants, such as factor eleven or factor eleven A inhibitors.

Stem Cell Derived Biologic Ventricular Assist Tissue in Heart Failure by Wolfram Hubertus Zimmermann from the University Medical Center Göttingen, Germany, and co-authors. The most prevalent pathologic feature of heart failure with a reduced ejection fraction is a loss of cardiomyocite. It is estimated that approximately one billion cardiomyocytes are lost in each patient with symptomatic heart failure with a reduced ejection fraction.

Would cardiac re muscularization by cardiomyocyte transplantation be a viable measure to address this underlying condition? Biologic ventricular assist tissue biovac. health is formulated from engineered heart muscle composed of cardiomyocytes and stromal cells derived from allogenaic induced pluripotent stem cells for cardiac remuscularization.

In this phase 1-2 study of tissue-engineered heart repair by means of biovat transplantation, patients with heart failure and a reduced ejection fraction were treated with biovat allograph. Which consisted of five, ten, or twenty engineered heart muscle units. All the patients received immunosuppression. Twelve patients completed the pre specified three month interim follow up. In this interim analysis at three months.

Cardiac remuscularization with biovat was associated with an increase in the target heart wall thickness, left ventricular ejection fraction, and Kansas City Cardiomyopathy Questionnaire Overall Summary Score. All the patients had at least one adverse event. Longer-term follow-up and further clinical investigation seem warranted.

In an editorial, Kenneth Margules from the University of Pennsylvania, Philadelphia, writes that like any novel and well executed study, this one poses some new questions. To what extent is the engineered heart muscle mechanically integrated with the native myocardium, and could such integration be improved?

What is the basis for the changes in function between three months and one year or more after the implantation of engineered heart muscle? Are such changes caused by improved maturation, vascularization, or mechanical conditioning? Why is there less arrhythmia with the implantation of engineered heart muscle than with alternative approaches that use cell injection? Can autologous recipient derived engineered heart muscle be generated to avoid the need for lifelong immunosuppression?

As this trial and subsequent inquiries involving applications of engineered heart muscle proceed, we look forward to answers to these questions and clarification of the role of engineered heart muscle in the treatment of patients with advanced heart failure. In a science behind the study article, Deepak Shrivistaba from the Gladstone Institute's San Francisco writes that the study by Zimmerman and co authors extends a translational arc that spans two decades.

From the derivation of human induced pluripotent stem cells to directed differentiation into cardiomyocytes, to the engineering of contractile myocardial tissue to implantation in a patient with advanced heart failure. The scientific importance of this work lies in its demonstration of feasibility. The authors have shown that large scale stem cell derived myocardial tissue can be manufactured under clinical grade conditions.

Surgically transplanted and monitored with multimodal imaging and electrophysiological studies in patients with advanced heart failure. This notable feat sets the stage for further study of treatment efficacy of this product and other forms of cardiac cell transplantation. For decades, cardiac regeneration has oscillated between exuberant promise and sobering reality. Zimmerman and colleagues bring the field one step closer to a tangible goal.

replacing lost myocardium with living contractile tissue. Whether Biovat will ultimately transform the care of advanced heart failure remains uncertain. What is clear is that the science underpinning this effort has matured from aspiration to clinical experimentation.

Xanodatimab with and without tis Lelisumab in her two positive gastrosophageal cancer by Kohe Shitara from the National Cancer Center Hospital East, Kashiwa, Japan and co authors. Xanidatamab, a dual HER two targeted bi specific antibody, plus chemotherapy, both with and without the program death one PD one inhibitor TIS Lelisumab.

Showed encouraging efficacy and safety as first line therapy in phase two studies involving patients with HER2 positive gastroesophageal adenocarcinoma. In this phase two Adenocarcinoma were randomly assigned to receive xanidatomab and tisla lisumab plus chemotherapy. Xanodatimab plus chemotherapy or trastusiumab plus chemotherapy at a median follow up of twenty five point nine months.

once progression free survival was longer with xanidatomab plus chemotherapy, both with and without tisleab twelve point four months in each than with trestumab chemotherapy eight point one month. At the time of this interim analysis, overall survival was longer with xanodatimab tis lelisumab chemotherapy than with trastusiumab chemotherapy.

Further analyses are planned to assess xanidatomab chemotherapy. Diarrhea was the most common adverse event of grade three or higher in all three treatment groups. Decompression with or without Duroplasty for Chiari one and Syringomyelia by David Limbrick Jr. from the Virginia Commonwealth University School of Medicine Richmond and co authors. In children with Chiari type I malformation and syringomyelia, neurosurgical posterior fossa decompression provides clinical improvement.

but whether juroplasty in sizing the jura and placing a jural graft improves outcomes, is unclear. This trial compared neurosurgical posterior fossa decompression with duroplasty With decompression alone, in 162 persons 21 years of age or younger with cerebellar tonsillar ectopia of at least. at least five millimeters and a maximum search diameter of three to nine point nine millimeters. The trial showed no significant difference with respect to the primary outcome of surgical complications.

Because of the small trial size, the results do not rule out the possibility of a smaller difference in the incidence of complications. Larger trials are needed to determine the relative benefits and risks of these two procedures.

Visceral leishmaniasis is a potentially life-threatening form that results from bloodborne dissemination of the parasite. The number of cases of cutaneous leishmaniasis is increasing, particularly in the eastern Mediterranean region, but the prevalence of visceral leishmaniasis is decreasing globally. Laboratory diagnosis of the Leishmaniaces has shifted to the use of molecular methods to test tissue samples such as skin or bone marrow, which can be used to identify infecting species.

Treatment is challenged by limited drug choices. A recent advance is the use of combination therapies for visceral leishmaniasis. Two human leishmaniasis vaccines are undergoing preclinical testing or are ready for human testing. A sixty four year old woman with fatigue, memory changes, and falls. A case record of the Massachusetts General Hospital by Shamik Bhadacharya and colleagues.

A sixty four year old woman was admitted with three weeks of worsening fatigue, followed by memory changes, poor concentration, and unsteady gait that led to falls. Her symptoms began during a summer trip to Maine, where she spent time outdoors and initially were attributed to poor sleep or anxiety.

As her condition progressed, she developed difficulty with routine tasks, word finding and balance, prompting repeated emergency visits. Neurologic examination revealed mild inattention, slowed cognition, and subtle weakness. MRI of the brain showed numerous bilateral white matter lesions with ring like enhancement, raising concern for infection, inflammation, or malignancy.

On the basis of cerebrospinal fluid analysis and imaging, an inflammatory or demyelinating process was considered most likely. Without a definitive diagnosis, a brain biopsy was performed and revealed tumefactive demyelination. The patient's symptoms improved with glucocorticoid therapy. A diagnosis of multiple sclerosis was then established using the 2024 McDonald criteria, which focus on the location, size, and type of central nervous system lesions.

And long term disease modifying therapy was initiated.

The twenty twenty five to two thousand thirty Dietary Guidelines for Americans Progress, Pitfalls, and the Path Forward A Perspective by Deirdre Tobias and Frank Hugh from Brigham and Women's Hospital, Boston. The twenty twenty five to two thousand thirty Dietary Guidelines for Americans were introduced in january twenty twenty six as the most significant reset of federal nutrition policy to date.

These guidelines represent progress in some areas, but raise concerns about transparency, internal consistency, practical implementation, and ignoring of key scientific evidence. Only fourteen of its fifty-six specific recommendations were implemented, and this departure from established procedures raises questions about how evidence was weighted and synthesized.

And amplifies concerns about procedural transparency. The new dietary guidelines increase recommended protein intake as high as double the adult recommended dietary allowance. However, there is little evidence that substantially increasing population protein intake confers additional health benefits. The guidelines retain longstanding guidance to limit saturated fats.

But concurrent messaging that encourages increasing intake of meat, full fat dairy products, butter, and beef tallow makes it difficult to translate guidance into practice. The guidelines embrace concise, consumer oriented messaging, including advice to eat real food and eat less highly processed food, but its lack of specificity limits its policy relevance.

Areas of confusion and contradiction remain. Restoring confidence in the dietary guidelines will require stronger scientific grounding and greater transparency in their development. Getting serious about tick-borne diseases, shifting research priorities, a perspective by Derland Fish from Yale School of Public Health, New Haven, Connecticut. The incidence of Lyme disease has steadily increased since the discovery of the causative agent, Borrelia Bergdorferi, in nineteen eighty two.

In recent years, an estimated five hundred thousand cases have been diagnosed each year in the United States. Cases of other tick borne diseases, including anaplasmosis, babesiosis, and poasin virus infection, have also increased. Despite forty years of research aimed at controlling Lyme disease, there are currently no available prevention methods that substantially reduce disease incidence in humans.

Failure to address this epidemic is in part a result of the misdirection of research efforts, which have emphasized clinical disease and pathogen microbiology rather than the root cause of Lyme disease. The infected tick vectors in the environment, which remain uncontrolled. In the United States, Lyme disease, anaplasmosis, babesiosis, and Poassin virus infections are all transmitted by only two tick species.

states the deer or black legged tick Exodes scapularis in the upper midwest and northeast, and the western black legged tick in the westernmost state. With the former accounting for more than ninety eight percent of human cases. Both these species are dependent on deer for reproduction, since adult ticks feed and mate on deer. These tick populations cannot be sustained in the absence of deer.

Research programs involving vaccines designed to prevent ticks from feeding on humans could be refocused to investigate vaccine use in deer. Pursuing vaccines for deer could eliminate the time and expense millions of dollars required for human clinical trials and product review by the U.S. Food and Drug Administration.

A eulogy for structural competence? A perspective by Jeremy Green from the Johns Hopkins University School of Medicine, Baltimore, and co authors. Structural Competence died a quiet death in march two thousand twenty six when the Liaison Committee on Medical Education ruled that medical schools in the United States are folks no longer need to teach either structural competence or health equity to receive accreditation.

The teaching of health equity in medical schools had already been targeted by anti woke activists, whereas structural competence, a wonkier term, had not previously elicited backlash. Structural competence was a more recent concept defined in twenty twelve and combined aspects of two older ideas structural violence and cultural competence. Medical educators could use the concept to highlight the crucial role of social factors in the causation, diagnosis, treatment, and prevention of disease.

The concept had quickly earned acceptance in medical curricula, and as it gained traction, accreditation bodies took note. In october twenty twenty three, the LCME's function and structure of a medical school introduced a new standard seven point six structural competence, cultural competence, and health inequities.

The standard defined structural competence as the capacity for health professionals to recognize and respond to the role that social, economic, and political structural factors play in patient and community health. At the same time, however, several state legislatures were pressuring public universities to restrict discussions of racism, gender, and health equity.

In March, the LCME released an expansive overhaul that will govern accreditation reviews starting in twenty twenty seven to twenty twenty eight. The entire twenty twenty three text of standard seven point six had been purged. Structural competence as a regulatory standard has met an untimely demise.

When Closure Finds You, a perspective by James Feinstein from the University of Colorado School of Medicine, Aurora. It was the first and only time doctor Feinstein pronounced a child dead over the phone. Lucy had just celebrated her fifteenth birthday. As doctor Feinstein sat in his sunlit living room, he saw Lucy's mother's number flash across his phone. He had expected to sing happy birthday to Lucy.

Instead he heard the trembling voice of a mother trying to navigate the worst moment of her life. Doctor Feinstein, she's not acting herself, her mother said. I need you to tell me what to do. I think she is dying. doctor Feinstein forced his mind to the stillness and clarity required at the edge of life. Where are you? She's on our couch at home, her mom said. nine hundred one one is coming. Do you want the paramedics to perform CPR?

They had rehearsed this dialogue many times before. Lucy had a progressive neurologic disease that stole her strength. Over time Lucy's muscles withered, and the simple acts of moving, eating, and breathing became monumental. But her mind remained untouched. As she grew older, Lucy had developed an ability to ask hard questions and to hear hard answers, a type of courage that doctor Feinstein had often seen in other children with life limiting illnesses.

Both Lucy and her parents had always been clear and resolute when they reviewed her do not resuscitate DNR orders. No chest compressions, no breathing tubes, no prolonging of suffering. At doctor Feinstein's recommendation, Lucy's DNR was taped up in a few spots in their home.

A new voice entered the call, gravely and steadily. I'm the paramedic on scene. I'm her doctor, doctor Feinstein said. They have a DNR order in place, if you think that's where we are headed. That's where we are headed, he confirmed. They don't want any invasive life saving measures, doctor Feinstein said. Her DNR should be in the kitchen cabinet.

At her funeral the following week, doctor Feinstein hovered at the edge of the room. He wanted to put his arms around Lucy's parents and hug them tightly, but they avoided talking to him. He understood that grief took different forms, But he couldn't help but wonder if they somehow blamed him. Did her mother wish doctor Feinstein had never picked up the phone? Would they have made different decisions in those final moments?

In the months that followed, doctor Feinstein's mind often returned to those unanswered questions. Then, after more than a decade, Lucy's parents called him. They told a few stories. I hope you know, her mom said, how much she trusted you. doctor Feinstein's lower lip quivered. This was not a direct answer to the questions that had lingered in his thoughts for years, but it was more than enough.

He felt the unexpected arrival of peace, on its own timeline and its own terms, and certainly nothing he could have ever willed to fruition himself.

In our images in clinical medicine, bronchoscopy in a seventy seven year old man with suspected lung cancer showed black patches on the bronchial mucosa. Biopsy revealed ciliated epithelium with sub epithelial accumulation of macrophages containing black pigments. A diagnosis of bronchial anthracosis, a benign, often incidental finding indicating carbon pigment deposition in the mucosa, was made. Bronchial anthrocosis is associated with prolonged exposure to biomass smoke or environmental dust.

On further history taking, the patient reported having socialized around open fires for decades of his life in the Middle East, as well as having been exposed to substantial amounts of dust while incarcerated for ten years. In another image, a fifty seven year old woman presented with left wrist pain after slipping on ice and falling on her palm.

On examination, there was dorsal angulation of the distal forearm proximal to the wrist, a finding known as a dinner fork deformity, owing to its contour, which is similar to that of an upside down fork. An X ray of the left wrist showed a collie's fracture. A collie's fracture is a fragility fracture that indicates a diagnosis of osteoporosis in postmenopausal women, regardless of results of bone mineral density testing.

In a third image, a fifty-one year old man presented with a two-hour history of coffee ground emesis and difficulty swallowing. Operendoscopy showed black discoloration and friability of the mucosa from the mid esophagus to the gastroesophageal junction. See images from this case of acute esophageal necrosis at NEJM dot org Read more from our issue at NEJM.org Let us know what you think about our podcast. Any comments or suggestions may be sent to audio at NEJM dot org. Thank you for listening.