Health Rounds: Experimental antibiotic kills drug-resistant fungi
A experimental antibiotic can kill dangerous drug-resistant fungi that are spreading around the world, Chinese researchers reported in Nature, opens new tab.
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Antibiotics are usually ineffective against fungal infections. Unlike conventional antibiotics, the new drug, mandimycin, targets the lipid membrane that encases the fungus, disrupting its physiological processes and circumventing resistance mechanisms.
Mandimycin belongs to a class of drugs known as glycosylated polyene macrolides, which also includes the last-resort antifungal amphotericin B.
In test tubes, mandimycin killed multiple types of drug-resistant fungi including species of Candida, Cryptococcus neoformans and Aspergillus fumigatus, researchers from China Pharmaceutical University reported.
All of the tested fungi were resistant to at least two existing drugs, and all are on the World Health Organization's fungal priority pathogens list, which includes infectious fungi with significant unmet need and public health importance, the researchers noted.
In mice, mandimycin was effective against a strain of Candida auris that is resistant to all major types of antifungals, the researchers said.
A commentary, opens new tab published with the report called mandimycin 'a probable treasure trove of actionable intelligence in the battle against drug-resistant fungal infections.'
The new antifungal molecule is so radically different from existing drugs that it 'breaks the mold,' the commentary authors said.
EARLY BREAST CANCER MIGHT NOT WARRANT LYMPH NODE SURGERY
The practice of removing armpit lymph nodes in patients with early breast cancer may not be necessary or particularly beneficial, a new study in The New England Journal of Medicine, opens new tab suggests.
Early-stage breast cancer has traditionally been treated with removal of the primary tumor and nearby lymph nodes. Pathologists then examine the nodes that were closest to the tumor for evidence that cancer cells have started to spread to other parts of the body.
So-called axillary nodal status has long been regarded as one of the most important prognostic factors in breast cancer and is used to guide therapy.
But lymph node removal often comes with pain, swelling, numbness, and risks of infection and fluid buildup. As medical therapies for breast cancer have improved, the need for lymph node removal is being questioned.
To learn more, researchers recruited 5,502 patients with breast tumors no greater than 5 centimeters and normal-appearing lymph nodes and randomly assigned half of them to skip armpit lymph node removal.
At five years, 91.7% of the retained-lymph node group and 91.9% of the removed-lymph node group were still free of invasive disease, and 98.2% and 96.9%, respectively, were still alive.
Patients whose lymph nodes were removed were less likely to eventually have a recurrence found in a lymph node, but that did not afford them any benefit in terms of survival without invasive disease, or overall survival.
An editorial, opens new tab published with the study notes that the findings are in line with those of a similar trial reported in 2023.
While noting that more study is needed, Dr. Eric Rubin, Editor-in-Chief of the journal, said in a statement, "We are beginning to see a future where many women with early-stage breast cancer are going to be able to avoid axillary-node dissection and its attendant complications.'
OVARIAN CANCER SCREENING MISSES CASES IN MINORITY GROUPS
Current blood test thresholds for patients with possible ovarian cancers are likely contributing to underdiagnosis in U.S. minority groups, according to a new study.
International guidelines use blood levels of a protein produced by ovarian cancer cells, called cancer antigen 125, to recommend which patients with pelvic masses should undergo evaluation for ovarian cancer. The thresholds were developed from studies in white patients, according to a report in JAMA Network Open, opens new tab.
When researchers reviewed data on 212,477 U.S. patients with ovarian cancer diagnosed from 2004 through 2020, they found that Black patients and Native American patients had significantly lower odds of having an elevated CA-125 level when their ovarian cancer was diagnosed.
After accounting for individual risk factors, Native American and Black patients were 23% less likely to have an elevated CA-125 level at diagnosis.
Ovarian cancer patients with misleadingly low CA-125 levels started chemotherapy an average of nine days later than patients with elevated CA-125 levels, the researchers also found.
Earlier studies found that Black patients are more likely to be diagnosed with late-stage ovarian cancer than white patients, the authors noted.
'Current CA-125 thresholds may miss racially and ethnically diverse patients with ovarian cancer,' they said.
'With 19,000 new ovarian cancer diagnoses annually in the U.S. and 314,000 worldwide, if the CA-125 thresholds were updated to have similar sensitivity for Black patients as White patients, we estimate that at least 60 patients each year would be diagnosed at an earlier stage in the U.S. and 1,500 worldwide.'
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Helm by Sarah Hall review – a mighty epic of climate change in slow motion
Even if Sarah Hall did not begin her acknowledgments by saying that it's taken her 20 years to write Helm it would be evident. Not from a cursory glance at her bibliography, perhaps: in that time Hall has published six other novels and three volumes of extraordinary short stories. But in every other way, and the moment you begin reading. There's the subject, for starters. Ever since the first paragraph of her first novel, Haweswater, in which an early 20th-century man drives his horse and cart through the waters of a Cumbrian valley recently drowned by a dam, Hall has been concerned with landscape, with weather, with nature in all its forms, with the ways in which we affect each other. In The Carhullan Army, climate change has already happened. Cumbria is semi-tropical, temperate England a folk memory; a dystopian vision that feels, this baked summer, uncomfortably close to reality. The Wolf Border, published in 2015, was, among many other things, about the ethics and unpredictabilities of rewilding an apex predator, while Hall's last novel, Burntcoat, written in the first lockdown, was set in and after a pandemic. Her story Later, His Ghost is set in a perpetual windstorm of total climate breakdown; in One in Four, a virologist writes to his wife, apologising for getting things wrong. In this new novel, weather and climate are not just potent settings but the main event. The central character in Helm is the Helm, Britain's only named wind. This wind, which is local to Cumbria, occurs when air sweeping down Cross Fell, above the Eden valley, creates both a crest and a low bar of cloud. 'Tricky to explain/visualise', admits Helm. 'For now, imagine a skater launching off a quarter pipe two thousand feet high, then somersaulting. Again. And again and again.' As the book begins, Helm witnesses its own arrival. An ice age, sun flares, ash cloud; and, relatively insignificant in the context of such deep time, the evolution of humanity. Because there are many people in the novel, too, which is structured by braiding their stories with Helm's, but also with lists: the forces of Helm, for instance, which range from '0. Zero Helm (complete calm). Mean wind speed < 1mph. Weathervanes and trees unmoving, grass still, water as mirror, smoke rising vertically from roundhouses/cottages/plague pyres' to '12. Hurricane Helm (Hand of God). Wind speed 73-83mph, phenomenal damage and widescale loss of life, Eden reconfigured biblically, Carlisle-Settle train lifted off the tracks, history made, FIN.' Other lists include names for Helm and the damage Helm can wreak; or the trinkets Helm collects, often after that damage (Howdah pistol, iron skullcap, Apple iPhone 11 64GB, Tornado F3 series, eject pin). The pictures humans make, trying to understand, locate, corral Helm. Helm finds people amusing, and watches as they succeed each other; Hall's ambition may be bounded by one valley, but it reaches through thousands of years. Her subjects range from a neolithic tribe to a medieval exorcist; from an isolated 18th-century wife to a quixotic Victorian meteorologist; from a wind-touched, lonely mid-20th-century child to a present-day academic counting plastic particles in the air. From stone tools to the Industrial Revolution to the advent of AI, each era has its own existential encounters with Helm: as deity or devil, as a psychological or a scientific mystery. Both sides are made complacent by Helm's longevity, size and power, by human smallness and briefness, neither realising, until perhaps too late, that these little beings threaten Helm's own existence. A project of this scope, which requires a range of research and imagination that could have produced several historical novels, not to mention an entire other volume of meteorological expertise, holds so much in suspension around its whirling, windy core that it could easily blow apart. But, despite the occasional threat or lull, Helm doesn't. Partly, I would argue, this is because of Hall's development as a consummate short story writer. Her novels are never less than hugely accomplished, but the narrative demands of the longer form, especially in more conventional earlier work, can sometimes dissipate the blaze of which she is capable. Hall is freed by the constraints of the short story – like the female sculptor in her last novel, Burntcoat, she burns away everything extraneous – and her work only gains in concentrated, suggestive power. Each strand of Helm has this concentration; the characters and voices could stand alone, but they flow together into something deep and rich, held together by the Eden valley, and its Helm. And by the writing. Hall's work on place, and especially this corner of England, has always been virtuosic, a tough and supple poetry anchored in decades of attention to Cumbrian land and plants and skies. In her first novels it sometimes threatened to submerge everything else, but in Helm is so embedded on the page that it's easy to take for granted, until you pause and back up to really look at the 'dirty, clay-slipped sky', or a gaggle of Victorian children, born into the shantytown that grows up around the railway, collecting on a hillside to eat magic mushrooms and stare at the 'silly jinking stars'. Every era in Helm has its own seeing; the same land, the same wind filtered through time-specific fears and hopes and work, time-specific knowings, from a neolithic world interpreted through animal behaviour to the bathos of 21st-century cycling waterproofs, pub menus, emails. Hall has a thrilling command of vocabulary, with the concurrent deployment of etymologies and the hinterlands they bring; words often work not as single notes, but as chords, big ideas slipping in on the wakes of concrete specificities. So NaNay, a neolithic girl, watches as the wind approaches: 'In the centre it was blue-grey, like bull-hide, with the dull pearl-shine of scales at its edges. It was faceless and its body was its only government.' The 'spectral gap' is a technical term of modern mathematics and quantum mechanics as well as meteorology. But what heft and metaphorical possibility such a gap has, when a retired policeman in a glider is required to fly into it. Above all it is the wind itself that holds this vastly ambitious, serious – but also often playful and ironic – book together. Some might find Helm's voice initially a little arch, a little unplaced relative to the human voices, but it grows on you. Antic, needy, angry, curious, millennia-old Helm, who gives and takes, fascinates and awes, is feared and loved, and loves in return; who absorbs violences, propitiations, yearnings, and who is now beginning to feel 'a bit wrong'. There has been so much change, over so many millennia, but this is different. 'It's complicated. Hard to put Helm's fingers on it.' It isn't that Helm is old, more that 'Whatever is wrong … feels insidious, sneaky, infectious. The surprise disease on the routine tests. Some kind of weird intimate growth you find accidentally and go, Jesus, how long has that been there? A toxic waft when you're asleep. Lights out.' Sign up to Inside Saturday The only way to get a look behind the scenes of the Saturday magazine. Sign up to get the inside story from our top writers as well as all the must-read articles and columns, delivered to your inbox every weekend. after newsletter promotion The neolithic tribe listens to Helm in its prime, 'splintering and shredding the valley, its voice mourning its own violence'. In the mid-20th century Helm searches for a young girl, his friend, who has been locked in an asylum, and, trying to look beyond the valley, 'rises, higher, until being is difficult'. At the 21st-century meteorological observation post, 2,000ft up, Helm whips and churns and 'calls to awful prayer'. A prayer for itself, perhaps, because whatever Hall's intentions – an urgent rallying, a tribute, a warning – this novel reads like nothing so much as an elegy. Helm by Sarah Hall is published by Faber (£20). To support the Guardian order your copy at Delivery charges may apply.
