Category: 3. Business

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The UK’s third-largest steelworks has been placed under government control, creating an uncertain future for nearly 1,500 workers in Rotherham and Sheffield.

Insolvency courts granted a compulsory winding up order sought by creditors owed hundreds of millions of pounds by Speciality Steels UK (SSUK) – part of the Liberty Steel metals empire of controversial tycoon Sanjeev Gupta.

The company will now be placed in the hands of the Official Receiver and special managers from consultancy firm Teneo, which has been appointed to run it on behalf of the liquidator.

The government has agreed to cover the ongoing wages and costs of the plant while a buyer for is sought.

Liberty Steel said the decision to put the firm into compulsory liquidation was “irrational”.

Chief transformation officer Jeffrey Kabel said the move would “impose prolonged uncertainty and significant costs on UK taxpayers for settlements and related expenses, despite the availability of a commercial solution”.

Lawyers for Mr Gupta had applied for a four-week adjournment to allow time to place the company in a “pre-pack administration”, which allows an insolvent company to sell its assets to a bidder.

He wanted funding from investment giant BlackRock and Fidera, which invests in distressed companies, to buy back the business.

Winding up the company, his lawyers argued, could place the business in “free fall” and incur significant disruption, cost and risk to a nationally important steel company and its 1,500 workers.

The judge found the company was “hopelessly insolvent” with £600,000 in the bank, a monthly wage bill of £3.7m, supported by a parent group that has 15 entities in insolvency proceedings across nine jurisdictions.

Introduction

Glaucoma is a leading cause of irreversible blindness worldwide, and is characterized by optic neuropathy with associated visual field damage.^1,2 Intraocular pressure (IOP) control is the gold-standard method of slowing the progression of glaucoma, which can be achieved through various means, including pharmacotherapy, laser, and surgery.³ Transscleral cyclophotocoagulation (TCP) and endoscopic cyclophotocoagulation (ECP) are two laser-based cycloablative techniques that are commonly used to treat mild to end-stage glaucomatous disease.^4–7

TCP is a laser-based procedure designed to reduce IOP by indirectly targeting the ciliary processes.⁴ Accurate targeting in TCP is critical, as deviations can lead to suboptimal results and damage to surrounding ocular tissues. Complications of TCP include prolonged inflammation, pain, hyphema, and hypotony.⁵ While evolutions in TCP have led to improved safety, this technique still lacks the ability to treat with a targeted approach. ECP is a relatively newer technique, offering a more targeted and controlled method of cycloablation.⁶ Previous literature has demonstrated that ECP effectively reduces IOP with lower risk of collateral damage to surrounding tissue.^7,8 Unlike TCP, ECP involves direct visualization of the ciliary processes via an endoscope.

Previous histological and acute structural analyses have demonstrated clear differences in tissue effects between TCP and ECP.^7,9 TCP induces widespread disruption of the ciliary body, including coagulative necrosis of the stroma often with extension into adjacent structures like the pars plana. In contrast, ECP produces more localized alterations, primarily affecting the ciliary epithelium. These differences can be observed under both light and scanning electron microscopy (SEM), further validating that ECP is a more tissue-sparing approach.

A newly developed ECP system (Leos™ BVI Medical Waltham, MA, USA) features enhanced imaging capabilities through a high-resolution camera and customized LED illumination, offering over twice the pixel density of traditional systems (40,000 vs 17,000 pixels). Using a single-use 19-gauge endoscope, laser delivery is integrated with real-time projections of intraocular images onto a large display allowing for a more detailed view. During treatment, a red aiming beam ensures precise targeting of the ciliary processes, much like standard ECP. Unlike standard ECP setups that require manual adjustment by an assistant, the Leos system automates parameters such as image focus, illumination, and orientation. The introduction of this system—with enhanced resolution and automated imaging capabilities—may further refine the precision of ECP.

This study aims to extend prior findings by comparing the acute structural changes induced by standard ECP, Leos ECP, and TCP on the ciliary body and surrounding structures in human cadaveric eyes.

Materials and Methods

No living human subjects or identifiable private information were involved in this study. As such, this study was exempted for IRB review by the Colorado Multiple Institutional Review Board under institutional policy.

This study was designed to compare acute structural changes induced by standard ECP, the investigational Leos ECP system, and TCP using SEM on three human cadaveric eyes. Human eyes were obtained within 24 hours of death from the Lions World Vision Institute (Tampa, Florida). Eyes had no prior history of glaucoma, intraocular surgery (excluding lens implantation), or laser intervention. Institutional review board waiver was obtained for this tissue-based laboratory analysis, and this study was performed in accordance with the latest declaration of Helsinki.

Each globe was inflated to physiologic intraocular pressure using balanced salt solution injected via a 25-gauge needle through the optic nerve. This facilitated optimal internal tension and consistent external placement of the TCP probe. Two eyes were divided into three 120° sections—one untreated segment served as a control, while the remaining two-thirds received Leos ECP (0.25W) and either the standard ECP (0.25W) or TCP (2.5W, 2–4 seconds), respectively. In a third eye, the globe was hemisected; one half was treated with Leos ECP (0.25W) and the other half with TCP (2.5W, 2–4 seconds). Treated areas were demarcated with permanent ink to help with subsequent sectioning and orientation.

A 2.4 mm corneal incision was made and the anterior chamber and ciliary sulcus were deepened with viscoelastic (Healon, Advanced Medical Optics, Santa Ana, CA, USA) to visualize the ciliary processes. Endoscopic treatments were delivered using either a reusable 19-gauge laser microendoscope (EndoOptiks^®, BVI Medical Waltham, MA) or a single-use 19-gauge Leos ECP device (BVI Medical, Waltham, MA), both of which delivered continuous-wave 810 nm diode laser energy with a 640 nm red aiming beam. ECP was applied until visible whitening and shrinkage of the processes was observed.

For TCP, a G-probe was connected to an Iridex 810nm diode laser (Mountain Vew, CA, SLx diode laser photocoagulation system). The probe was positioned 1.2 mm posterior to the limbus and aligned perpendicularly to the limbus externally on the sclera. Energy was delivered in pulses of ~2.5W for 2 to 4-second duration, targeting the pars plicata region. Laser treatment was titrated as needed to minimize audible “pops” which indicated tissue over-treatment.

Following treatment, all eyes were sectioned at the level of the pars plana and divided into control and treatment segments. Each section was fixed in 10% Neutral buffered formalin (Sigma-Aldrich, St. Louis, MO, USA) and stored on wet ice for transfer to the electron microscopy facility.

The tissues designated for acute structural evaluation were initially fixed in 2.5% glutaraldehyde at 4°C for 24 hours. The samples were then rinsed in 0.1 M phosphate-buffered saline, followed by secondary soaking in 1% osmium tetroxide. Subsequently, the specimens underwent graded ethanol dehydration and were kept in acetone. They were then critical point dried, ion coated, and then imaged using SEM to assess microarchitectural changes in the ciliary body and adjacent ocular structures.

All SEM images were analyzed by a single observer with extensive experience (MYK). Particular focus was paid to the ciliary processes and changes to the ciliary epithelium after treatment. Further observations were made on any tissue disorganization and extension of damage into the pars plana and iris stroma. The observer was not masked to the treatment modality. Statistical methods were not applicable due to the qualitative nature of SEM image comparisons.

Results

Electron microscopic analysis revealed distinct acute structural alterations among the different treatment modalities. In untreated control samples, the ciliary processes exhibited well-preserved architecture with intact epithelial surfaces and regularly arranged longitudinal ridges (Figure 1A). Tissues treated with the standard ECP and Leos ECP method demonstrated moderate ciliary epithelial disruption, including blunting and partial flattening of the ciliary processes (Figure 1B and C). There was minimal damage to the pars plana. TCP treated tissues displayed extensive tissue disorganization, including destruction of ciliary processes that extended into the iris and pars plana (Figure 1D). These acute structural patterns were consistently observed across all treated sections from each eye. None of the laser treatment modalities resulted in detectable damage to the adjacent scleral tissue in any of the specimens.

Figure 1 (A) Scanning electron microscopy of normal ciliary processes (arrows) with adjacent pars plana (asterisk) and iris stroma (I). (B) Scanning electron microscopy of standard endoscopic cyclophotocoagulation-treated ciliary processes showing shrinking of the processes with blunting of their tips (arrows). The adjacent pars plana (asterisk) and iris stroma (I) are unaffected. (C) Scanning electron microscopy of the LEOS endoscopic cyclophotocoagulation-treated ciliary processes showing shrinking of the processes with blunting of their tips (arrows). The adjacent pars plana (asterisk) and iris stroma (I) are unaffected. (D) Scanning electron microscopy of transscleral cyclophotocoagulation-treated ciliary processes showing extensive architectural destruction (straight arrows).

Discussion

This study provides new insights into the acute structural impact of different cyclophotocoagulation modalities on the ciliary processes. Both the novel Leos ECP and standard ECP demonstrated more targeted tissue destruction without the collateral tissue damage seen with TCP. These findings further validate results from previous literature by confirming SEM patterns and by introducing comparable histologic outcomes with a novel ECP platform.^7–11

The significance of minimizing collateral damage during cyclophotocoagulation rests in its clinical implications. Namely, excessive destruction of the ciliary body, stroma, and adjacent iris tissue has been associated with complications such as phthisis, hypotony, and prolonged inflammation.⁵

SEM has been used in prior studies to assess structural changes^7,8,10,12 and laser-induced injury patterns¹³ with exquisite resolution, making it a valuable tool for evaluating the effects of glaucoma and laser treatment. These views offer insights into laser-induced cellular disruption, stromal damage, and epithelial integrity beyond what is visible with light microscopy. Incorporation of electron microscopic analysis in the current study allows for a more refined analysis of tissue alterations across different cycloablation modalities.

Cyclophotocoagulation is the only surgical modality that targets aqueous production; ECP is the only micro-invasive surgery to do so.^14–16 Therefore, both surgical techniques are important parts of a glaucoma surgeon’s armamentarium. Compared to TCP, the safety profile of ECP has been demonstrated to be more favorable in both prospective and retrospective studies.^16,17 Though conventional ECP outcomes are good, improvements in device design may further reduce clinical variability and ensure safety. Importantly, the consistency in histologic findings between the two ECP modalities evaluated here suggest the Leos system is similar in tissue impact. However, the Leos system may offer the additional benefit of simpler and more consistent operation through its enhanced imaging capabilities, more detailed view, its larger, more ergonomic screen and standardized settings, which limit risk of human error in manual setting adjustments.

Attempts have also been made to modify TCP to mitigate complications with MicroPulse CPC, which cycles laser energy off/on to allow cooling of tissue during transscleral laser therapy.^18,19 With MicroPulse there is still extensive histological and structural damage, through a recent meta-analysis found a more favorable side-effect profile versus traditional TCP.²⁰ MicroPulse, like TCP, lacks direct visualization of ciliary tissue and variations in anatomy.²¹

Limitations

Despite these promising results, there are limitations inherent to this study. First, the analysis was performed by a single, unmasked observer, which introduces the potential for interpretation bias. Human cadaveric eyes cannot replicate the dynamic biological processes of live tissue, such as inflammation, wound healing, and aqueous humor flow. Thus, it is unclear how these findings will translate into clinical outcomes. Additionally, the number of eyes studied was small with only three cadaveric globes evaluated. This limited size restricts generalizability. As such, findings should be interpreted as preliminary rather than conclusive. Further research could be aimed at correlating these structural findings with functional data such as aqueous production rates. Future studies are also needed to validate these results using multiple, masked observers, a rigorous quantitative scoring system, and a larger sample size. It would also be valuable to investigate whether the other advances in the Leos ECP system lead to improved surgeon and surgical staff satisfaction, ergonomics, shortened learning curve for new surgeons and improved operative efficiency all of which are incredibly important in our current climate.

Conclusions

In this study, we demonstrate that both standard ECP and the novel Leos ECP produce significantly less acute structural disruption to the ciliary body compared to TCP. While the Leos ECP system yielded tissue effects similar to standard ECP, its enhanced imaging and automated features may translate into greater clinical consistency and usability across operators. However, this remains a hypothesis and requires confirmation through clinical trials. These findings also further validate the more targeted approach that ECP offers compared to TCP.

Acknowledgment

BVI sponsored the study through an unrestricted research grant.

Disclosure

Malik Y. Kahook: Consultant to FCI, New World Medical, and SpyGlass Pharma, Ownership of SpyGlass Pharma, Patent Royalties from Alcon, New World Medical, FCI, and SpyGlass Pharma. Leonard Seibold: Consultant to New World Medical, Thea, and Abbvie/Allergan. The authors report no other conflicts of interest in this work.

References

1. Jonas JB, Aung T, Bourne RR, Bron AM, Ritch R, Panda-Jonas S. Glaucoma. Lancet. 2017;390(10108):2183–2193. doi:10.1016/S0140-6736(17)31469-1

2. Zhang N, Wang J, Li Y, Jiang B. Prevalence of primary open angle glaucoma in the last 20 years: a meta-analysis and systematic review. Sci Rep. 2021;11(1):13762. doi:10.1038/s41598-021-92971-w

3. Schwartz K, Budenz D. Current management of glaucoma. Curr Opin Ophthalmol. 2004;15(2):119–126. doi:10.1097/00055735-200404000-00011

4. Brancato R, Giovanni L, Trabucchi G, Pietroni C. Contact transscleral cyclophotocoagulation with Nd:YAG laser in uncontrolled glaucoma. Ophthalmic Surg. 1989;20(8):547–551.

5. Sheheitli H, Persad PJ, Feuer WJ, Sayed MS, Lee RK. Treatment outcomes of primary transscleral cyclophotocoagulation. Ophthalmol Glaucoma. 2021;4(5):472–481. doi:10.1016/j.ogla.2020.12.014

6. Pastor SA, Singh K, Lee DA, et al. Cyclophotocoagulation: a report by the American academy of ophthalmology. Ophthalmology. 2001;108(11):2130–2138. doi:10.1016/s0161-6420(01)00889-2

7. Pantcheva MB, Kahook MY, Schuman JS, Noecker RJ. Comparison of acute structural and histopathological changes in human autopsy eyes after endoscopic cyclophotocoagulation and trans-scleral cyclophotocoagulation. Br J Ophthalmol. 2007;91(2):248–252. doi:10.1136/bjo.2006.103580

8. Pantcheva MB, Kahook MY, Schuman JS, Rubin MW, Noecker RJ. Comparison of acute structural and histopathological changes of the porcine ciliary processes after endoscopic cyclophotocoagulation and transscleral cyclophotocoagulation. Clin Exp Ophthalmol. 2007;35(3):270–274. doi:10.1111/j.1442-9071.2006.01415.x

9. Beardsley R, Law SK, Caprioli J, et al. Comparison of outcomes between endoscopic and transcleral cyclophotocoagulation. Vision. 2017;1(4). doi:10.3390/vision1040024

10. Smith RS, Boyle E, Rudt LA. Cyclocryotherapy: a light and electron microscopic study. Arch Ophthalmol. 1977;95(2):285–288. doi:10.1001/archopht.1977.04450020085015

11. Lanzagorta-Aresti A, Montolío-Marzo S, Davó-Cabrera JM, Piá-Ludeña JV. Transscleral versus endoscopic cyclophotocoagulation outcomes for refractory glaucoma. Eur J Ophthalmol. 2021;31(3):1107–1112. doi:10.1177/1120672120914230

12. Sihota R, Goyal A, Kaur J, Gupta V, Nag TC. Scanning electron microscopy of the trabecular meshwork: understanding the pathogenesis of primary angle closure glaucoma. Indian J Ophthalmol. 2012;60(3):183–188. doi:10.4103/0301-4738.95868

13. Basu PK. Application of the scanning electron microscopy in ophthalmic research. Indian J Ophthalmol. 1983;31(5):476–485.

14. Kirk S, Kirk C, Barnes R, Kirk T. Minimally invasive glaucoma surgeries, is two better than one? Invest Ophthalmol Visual Sci. 2020;61(7):976.

15. Klug E, Chachanidze M, Nirappel A, et al. Outcomes of phacoemulsification and endoscopic cyclophotocoagulation performed with dual blade ab interno trabeculectomy or trabecular micro-bypass stent insertion. Eye. 2022;36(2):424–432. doi:10.1038/s41433-021-01475-4

16. Francis BA, Flowers B, Dastiridou A, Yelenskiy A, Chopra V, Alvarado JA. Endoscopic cyclophotocoagulation and other cyclodestructive methods: histopathologic comparison of in vivo treatment in humans and monkeys. Ophthalmol Glaucoma. 2019;2(6):413–421. doi:10.1016/j.ogla.2019.08.008

17. Francis BA, Berke SJ, Dustin L, Noecker R. Endoscopic cyclophotocoagulation combined with phacoemulsification versus phacoemulsification alone in medically controlled glaucoma. J Cataract Refract Surg. 2014;40(8):1313–1321. doi:10.1016/j.jcrs.2014.06.021

18. Moussa K, Feinstein M, Pekmezci M, et al. Histologic changes following continuous wave and micropulse transscleral cyclophotocoagulation: a randomized comparative study. Trans Vision Sci Technol. 2020;9(5):22. doi:10.1167/tvst.9.5.22

19. Hwang YH, Lee S, Kim M, Choi J. Comparison of treatment outcomes between slow coagulation transscleral cyclophotocoagulation and micropulse transscleral laser treatment. Sci Rep. 2024;14(1):23944. doi:10.1038/s41598-024-75246-y

20. Chavez MP, Guedes GB, Pasqualotto E, et al. Micropulse transscleral laser treatment vs. continuous wave transscleral cyclophotocoagulation for the treatment of glaucoma or ocular hypertension: a meta-analysis. J Glaucoma. 2025;34(8):575–584. doi:10.1097/ijg.0000000000002583

21. Feldman RM, el-Harazi SM, LoRusso FJ, McCash C, Lloyd WC, Warner PA. Histopathologic findings following contact transscleral semiconductor diode laser cyclophotocoagulation in a human eye. J Glaucoma. 1997;6(2):139–140. doi:10.1097/00061198-199704000-00011

The delay in Pakistan’s 5G spectrum auction has cost the exchequer billions in potential revenue. An Auditor General audit flagged indecision and weak coordination between PTA and MoITT.

The main reason for the delay is uncertainty over the proposed PTCL–Telenor Pakistan merger. The Competition Commission of Pakistan (CCP) is yet to decide, citing incomplete documentation from PTCL.

Minister for IT and Telecommunication Shaza Fatima Khawaja said the ministry cannot influence the CCP. She stressed that the body is independent and must complete its review.

The 5G Spectrum Auction Advisory Committee, led by the finance minister, will act only after the CCP delivers its verdict.

A senior IT Ministry official said the auction design depends on the number of operators post-merger. He explained that the terms vary if there are four or three players.

Pakistan currently has four telecom operators. Jazz holds a 37% share, Zong 26%, Telenor 22%, and Ufone—PTCL’s subsidiary—13%.

Officials added that PTCL’s submissions were unclear and required further clarification. This has further prolonged the CCP’s decision-making process.

Concerns remain due to Ufone’s consistent financial losses, unlike the profitable performance of Jazz, Zong, and Telenor.

A PTCL-Ufone spokesperson did not respond to media queries despite repeated requests.

 

Today’s world runs on critical minerals. The elements are the building blocks of batteries, electronics, and a slew of other technologies and are often key to the economic and national security of a nation. In the US, most of these elements are imported, and researchers have been working for years to find domestic sources of these minerals to avoid supply chain disruptions.

At the American Chemical Society Fall 2025 meeting, Pacific Northwest National Laboratory (PNNL) scientist Chinmayee Subban explained how she and her team extract critical minerals using the waste from a technology capable of tweaking ocean chemistry, to lower the costs of both processes.

Critical mineral recovery processes almost always use acid-base chemistry; it’s precipitation chemistry at scale, Subban said. But industrial acids and bases can be expensive to manufacture and store, so “it’s always valuable if you can find low-grade waste chemicals that you could use for the extraction,” she said.

Electrochemical ocean alkalinity enhancement, or OAE—a process wherein scientists increase the pH of seawater to draw carbon dioxide from the air and counter ocean acidification—offers one such source of acid. Through a public-private partnership with Ebb Carbon, PNNL scientists have deployed an OAE system developed by the company. The system uses electricity and a specialized membrane to separate ocean water into streams of acidic, basic (alkaline), and partially deionized water. But “the benefits of the ocean alkalinity are limited to the alkaline stream,” Subban said. “There’s a lot of acid that’s generated.”

That waste acid can be used to extract minerals from another waste stream: the salty brine left over from desalination, which is the first step of the electrochemical OAE system. “Think of it as Lego blocks,” Subban said. If the steps are in the correct order, scientists can generate a couple of mineral coproducts depending on the starting feed water and local industrial ecology, she explained.

So far, Subban’s team has demonstrated that waste acid can pull lithium from the salty brine produced during desalination. Her team has also pulled uranium from the water, and her future work will focus on extracting strontium, she said.

They’ve also shown that waste acid can extract nickel from locally sourced olivine minerals, flipping the economics of domestic nickel extraction. The scientists showed that, even without accounting for any revenue from CO₂ removal credits, “we were able to get sufficient net positive benefits” on the dollar per ton, she said. In fact, the waste acid digests the olivine faster than a commercial equivalent, Subban said, likely because the low grade acid contains a small amount of salt.

To “take something that is a waste and [use it] to improve aspects of the lithium and nickel extraction will be incredibly beneficial down the road,” said Tyler Bridges, a graduate researcher at Virginia Tech and attendee of the presentation. “There’s a lot of exciting work that’s being done in that field right now,” he added.

AI-driven scribes that record patient visits and draft clinical notes for physician review led to significant reductions in physician burnout and improvements in well-being, according to a Mass General Brigham study of two large healthcare systems.

The findings, published in JAMA Network Open, draw on surveys of more than 1,400 physicians and advanced practice providers at both Harvard-affiliated Mass General Brigham and Atlanta’s Emory Healthcare.

At MGB, use of ambient documentation technologies was associated with a 21.2 percent absolute reduction in burnout prevalence at 84 days, while Emory Healthcare saw a 30.7 percent absolute increase in documentation-related well-being at 60 days.

“Ambient documentation technology has been truly transformative in freeing up physicians from their keyboards to have more face-to-face interaction with their patients,” said study co-senior author Rebecca Mishuris, chief medical information officer at MGB, a faculty member at Harvard Medical School, and a primary care physician in the healthcare system. “Our physicians tell us that they have their nights and weekends back and have rediscovered their joy of practicing medicine. There is literally no other intervention in our field that impacts burnout to this extent.”

Physician burnout affects more than 50 percent of U.S. doctors and has been linked to time spent in electronic health records, particularly after hours. There is additional evidence that the burden and anticipation of needing to complete their appointment notes also contributes significantly to physician burnout.

“Burnout adversely impacts both providers and their patients who face greater risks to their safety and access to care,” said Lisa Rotenstein, a co-senior study author and director of The Center for Physician Experience and Practice Excellence at Brigham and Women’s Hospital. She is also an assistant clinical professor of medicine at the UCSF School of Medicine. “This is an issue that hospitals nationwide are looking to tackle, and ambient documentation provides a scalable technology worth further study.”

“Our physicians tell us that they have their nights and weekends back and have rediscovered their joy of practicing medicine.”

Rebecca Mishuris, Mass General Brigham
 

Qualitative feedback from users touted that ambient documentation enabled more “contact with patients and families,” improvements in their “joy in practice,” while recognizing its potential to “fundamentally [change] the experience of being a physician.” However, some users felt it added time to their note-writing or had less utility for certain visit types or medical specialties. Since the pilot studies began, the AI technologies have evolved as the vendors make changes based on user feedback and the large language models that power the technologies improve themselves through additional training, warranting continued study.

The researchers analyzed survey data from pilot users of ambient documentation technologies at two large health systems. At Mass General Brigham, 873 physicians and advanced practice providers were given surveys before enrolling, then after 42 and 84 days. About 30 percent of users responded to the surveys at 42 days, and 22 percent at 84 days. All 557 Emory pilot users were surveyed before the pilots and then at 60 days of use, with an 11 percent response rate. Researchers analyzed the survey results quantifying different measures of burnout at Mass General Brigham and physician well-being at Emory Healthcare.

The study authors added that given that these were pilot users and there were limited survey response rates, the findings likely represent the experience of more enthusiastic users, and more research is needed to track clinical use of ambient documentation across a broader group of providers.

Mass General Brigham’s ambient documentation program launched in July 2023 as a proof-of-concept pilot study involving 18 physicians. By July 2024, the pilot, which tested two different ambient documentation technologies, expanded to more than 800 providers. As of April 2025, the technologies have been made available to all Mass General Brigham physicians, with more than 3,000 providers routinely using the tools. Later this year, the program will look to expand to other healthcare professionals such as nurses, physical and occupational therapists, and speech-language pathologists.  

“Ambient documentation technology offers a step forward in healthcare and new tools that may positively impact our clinical teams,” said Jacqueline You, lead study author and a digital clinical lead and primary care associate physician at Mass General Brigham. “While stories of providers being able to call more patients or go home and play with their kids without having to worry about notes are powerful, we feel the burnout data speak similar volumes of the promise of these technologies, and importance of continuing to study them.”

Ambient documentation’s use will continue to be studied with surveys and other measures tracking burnout rates and time spent on clinical notes inside and outside of working hours. Researchers will evaluate whether burnout rates improve over time as the AI evolves, or if these burnout gains plateau or are reversed.

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This project received financial support from the Physician’s Foundation and the National Library of Medicine of the National Institutes of Health.

A phase 2 study (NCT03560479) evaluating Alpha1H for the treatment of patients with non–muscle-invasive bladder cancer (NMIBC) met its primary and secondary end points, according to an announcement from Hamlet BioPharma.¹

Final findings from the study revealed that approximately 80% of patients treated with Alpha1H experienced a response, with an average tumor size reduction in the high-dose group of 59%. Additionally, clinical benefit was observed in patients who received a second installation.

The study also demonstrated that Alpha1H reached tumor tissue, triggered tumor cell apoptosis, and led to rapid shedding of tumor cells into the urine. Additionally, Alpha1H led to the downregulation of more than 700 of approximately 800 cancer-related genes, per RNA analysis. Investigators also noted a broad immune response with Alpha1H overlapping with BCG, except responses occurred more rapidly and without lasting adverse effects (AEs) compared with what is historically observed with BCG.

Regarding safety, no serious treatment-related AEs were reported, including at higher dose levels or with repeat dosing. The incidence of mild, local AEs was similar between the Alpha1H and placebo arms. No systemic AEs were observed with Alpha1H, which is consistent with its local mechanism of action.

Data from the final analysis of the study have been submitted to the FDA, and Hamlet BioPharma is coordinating with the regulatory agency on the design of a phase 3 study.

“The final clinical report’s consistent efficacy outcomes and favorable safety profile are highly encouraging. The strength of the data provides compelling evidence of Alpha1H’s potential to become a much-needed proactive treatment option, and we look forward to advancing it in our regulatory discussions,” Catharina Svanborg, MD, PhD, chief executive officer of Hamlet BioPharma, stated in a news release. “We are committed to bringing this innovative therapy to patients as quickly and safely as possible. These results mark a major milestone for Hamlet BioPharma and for people with cancer in the urinary bladder. The study was made possible through close collaboration with leading universities and medical centers, including Lund University, Sweden, Motol University Hospital, Czechia and Linnane Pharma AB, whose combined expertise ensured robust design, execution, and analysis.”

Alpha1H Background and Phase 2 Study Design

Alpha1H is designed to form the Alpha1H complex by binding to oleic acid; in preclinical and animal models, the agent has demonstrated the ability to kill a various cancer cells, including the inhibition of tumor development in a bladder cancer model.²

In the phase 2 study, investigators enrolled patients at least 18 years of age with non-muscle invasive papillary bladder cancer per cystoscopy appearance and were slated to undergo transurethral resection of bladder tumor (TURBT).³ Patients needed retain bladder content for at least 1 hour.

Key exclusion criteria comprised a history of muscle-invasive bladder cancer; a history of NMIBC with an interval shorter than 6 months after previous TURBT; treatment with intravesical BCG or chemotherapy within 12 months of enrollment; any other cancer diagnosis within the last 5 years; acute urinary tract infection; and prior radiotherapy or systemic chemotherapy.

In the main part of the study, patients were randomly assigned to received Alpha1H at 7.4 mg/mL or placebo on days 1, 3, 5, 8, 15 and 22 of a single cycle. During an open-label dose-escalation portion, Alpha1H was also given at daily doses of 37 mg/mL and 74 mg/mL.

Safety, efficacy of cell shedding, and changes in papillary characteristics. Secondary end points included induction of apoptosis, histopathology scoring, and tumor response to Alpha1H by gene expression analysis.¹

References

1. Hamlet BioPharma announces the completion of the Alpha1H phase II study in non-muscle invasive bladder cancer. News release. Hamlet BioPharma. August 21, 2025. Accessed August 21, 2025. https://hamletbiopharma.com/hamlet-biopharma-announces-the-completion-of-the-alpha1h-phase-ii-study-in-non-muscle-invasive-bladder-cancer/
2. Alpha1H. Hamlet BioPharma. Accessed August 21, 2025. https://hamletbiopharma.com/cancer/alpha1h-2/
3. A first-in-human study of alpha1H in patients with non-muscle invasive bladder cancer. ClinicalTrials.gov. Updated August 19, 2020. Accessed August 21, 2025. https://clinicaltrials.gov/study/NCT03560479

The European Commission has approved a tablet formulation of zanubrutinib (Brukinsa) for use in all previously authorized indications of the capsule formulation.¹

This follows the FDA’s approval of the tablet formulation in June 2025.²

Zanubrutinib is approved in the European Union in the following indications:³

• as monotherapy for the treatment of adult patients with Waldenström macroglobulinemia who have received at least 1 prior therapy, or in first-line treatment for patients unsuitable for chemoimmunotherapy.
• as monotherapy for the treatment of adult patients with marginal zone lymphoma who have received at least 1 prior anti-CD20-based therapy.
• as monotherapy for the treatment of adult patients with chronic lymphocytic leukemia
• in combination with obinutuzumab (Gazyva) for the treatment of adult patients with refractory or relapsed follicular lymphoma who have received at least 2 prior systemic therapies

Notably, in the United States, zanubrutinib is also approved for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy; however, zanubrutinib does not hold any MCL indications in the European Union (EU).^3,4

The recommended dose of the tablet formulation reflects that of the capsule formulation at 320 mg per day.¹ Each tablet is 160 mg, allowing patients to take 2 tablets daily instead of 4 80-mg capsules.

“Developed to meet the real-world needs of patients, the new [zanubrutinib] tablet formulation aims to simplify treatment, reduce pill burden, and enhance ease of administration, reflecting our continuous focus on patient-centered innovation,” Giancarlo Benelli, senior vice president and head of Europe at BeOne Medicines, stated in a news release. “With more than 200,000 patients treated globally and the broadest label of any BTK inhibitor in Europe, zanubrutinib’s differentiated clinical profile continues to make an impact for people facing certain B-cell cancers.”

Safety Overview

Compiled safety data in the zanubrutinib European Union prescribing information show that most common occurring adverse effects reported in at least 20% of patients treated with zanubrutinib monotherapy (n = 1550) included upper respiratory tract infection(36%), bruising (32%), hemorrhage/hematoma(30%), neutropenia(30%), musculoskeletal pain(27%), rash(25%), pneumonia(24%), diarrhea (21%), and cough(21%).³

The most common grade 3 or higher AEs that occurred in at least 3% of patients comprised neutropenia (21%), pneumonia (14%), hypertension (8%), thrombocytopenia (6%), anemia (6%), and hemorrhage/hematoma (4%). AEs led to treatment discontinuation of zanubrutinib monotherapy in 4.8% of patients, with the most common being pneumonia(2.6%). AEs led to dose reductions in 5.0% of patients.

In the phase 2 ROSEWOOD trial (NCT03332017), among patients with relapsed/refractory follicular lymphoma treated with zanubrutinib in combination with obinutuzumab (n = 143), the most common AEs reported in at least 20% of patients included thrombocytopenia(37%), neutropenia(31%), and fatigue(27%). Grade 3 or higher AEs reported in more than 3% of patients included neutropenia^§ (25%), thrombocytopenia(16%), pneumonia(15%), and anemia (5%). AEs led to treatment discontinuation in 4.9% of patients, with the most common being pneumonia (4.2%). AEs led to dose reduction in 7.0% of patients.

References

1. The European Commission has approved a tablet formulation of BeOne Medicines’ Brukinsa for use across all of its previously authorized indications. News release. BeOne Medicines. August 21, 2025. Accessed August 21, 2025. https://ir.beonemedicines.com/news/european-commission-approves-tablet-formulation-of-beone-medicines-brukinsar-for-all-approved-indications/60a73cd1-3e95-46b4-b377-578f401440b9
2. U.S. FDA approves tablet formulation of BeOne’s Brukinsa for all approved indications. News release. BeOne. June 11, 2025. Accessed August 21, 2025. https://www.businesswire.com/news/home/20250611860939/en/U.S.-FDA-Approves-Tablet-Formulation-of-BeOnes-BRUKINSA-for-All-Approved-Indications
3. Brukinsa. European Medicines Agency. Accessed August 21, 2025. https://www.ema.europa.eu/en/medicines/human/EPAR/brukinsa
4. Brukinsa. Prescribing information. BeOne. Updated June 2025. Accessed August 21, 2025. https://beonemedicines.us/PDF/BRUKINSAUSPI.pdf