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  • Netanyahu nominates Trump for Nobel Peace Prize – World

    Netanyahu nominates Trump for Nobel Peace Prize – World

    Israeli Prime Minister Benjamin Netanyahu said on Monday he has nominated Donald Trump for the Nobel Peace Prize, presenting the US president with a letter he sent to the prize committee.

    The move comes as Israel continues its onslaught on Gaza, which has so far killed 57,523 Palestinians. Last year, the UN-backed International Criminal Court (ICC) issued arrest warrants for Netanyahu, citing allegations of war crimes and crimes against humanity. The court said he, along with ex-defence minister Yoav Gallant, “intentionally and knowingly deprived the civilian population in Gaza of objects indispensable to their survival”, including food, water, medicine, fuel, and electricity.

    “He’s forging peace as we speak, in one country, in one region after the other,” Netanyahu said at a dinner with Trump at the White House.

    Trump has received multiple Nobel Peace Prize nominations from supporters and loyal lawmakers over the years and has made no secret of his irritation at missing out on the prestigious award.

    The Republican has complained that he had been overlooked by the Norwegian Nobel Committee for his mediating role in conflicts between India and Pakistan, as well as Serbia and Kosovo.

    In 2024, he insisted that he was more deserving of a Nobel than ex-president Barack Obama, and complained how it was unfair that “anybody else” but him would have been honoured with one.

    In June, Pakistan had also decided to formally recommend Trump for the coveted prize, given his role in de-escalating the India-Pakistan conflict when both neighbours stepped back from the brink of war after US mediation.

    However, as the US joined Israel’s war with Iran and launched attacks on three Iranian nuclear facilities, Pakistani lawmakers, activists, authors and ex-diplomats criticised the move. A resolution was also submitted in the Senate by the Jamiat Ulema-i-Islam-Fazl to rescind the decision but led to no tangible outcome as Pakistan had not officially submitted the nomination.

    Trump has also demanded credit for “keeping peace” between Egypt and Ethiopia and brokering the Abraham Accords, a series of agreements aiming to normalise relations between Israel and several Arab nations.

    He campaigned for office as a “peacemaker” who would use his negotiating skills to quickly end conflicts in Ukraine and Gaza, although both conflicts are still raging more than five months into his presidency.

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  • How the U.S.-Israeli Strikes Empowered the Iranian Regime

    How the U.S.-Israeli Strikes Empowered the Iranian Regime

    Israel’s June 13 assault on Iran, designed to decapitate Tehran’s military and nuclear program, is one of the worst setbacks the Islamic Republic has ever experienced. In less than two weeks, the Israel Defense Forces managed to assassinate dozens of senior Iranian commanders and nuclear scientists. The IDF destroyed many of Iran’s air defense systems and damaged its nuclear facilities. Israel bombed Iran’s energy infrastructure, military bases, and various missile production sites. The strikes were precise, indicating that Israeli intelligence had penetrated the highest levels of Iran’s armed forces and government. And toward the end of the attacks, the United States joined in. As a result, the Iranian military is weaker now than it was just a month earlier.

    But instead of collapsing under the shock, the Islamic Republic appears to have gained a new lease on life. The strikes caused a rally-around-the-flag effect as Iranians condemned them and celebrated the government’s response. The Iranian regime mourned its lost officials but swiftly replaced them. The operations thus made the Iranian nation more cohesive and strengthened the hand of the Islamic Revolutionary Guard Corps (IRGC).

    Iranian society is unlikely to become more rigidly Islamist in response to the strikes. To maintain internal stability, the government might even tolerate more social freedoms. But the regime will probably become more repressive, arresting anyone it sees as a traitor. And critically, Iranians may be more willing to accept the state as it is. The country could now have a new social contract, one that prioritizes national security above everything else.

    Iran’s national security strategy, however, remains broadly unchanged. The Islamic Republic may be weaker in some ways, but its leaders are proud of having withstood the Israeli and American assaults. They see the substantial damage they inflicted on Israel’s cities as a major achievement. And they continue to believe that demonstrating resolve in the face of aggression is the only way to deter their opponents. Iranian leaders will thus set out to rebuild the country’s network of proxies: the so-called axis of resistance. They will trust diplomacy even less than before. Instead, they will lay the groundwork for a long war of attrition with Israel—and a potential nuclear breakout.

    UNITE AND FIGHT

    In the weeks before Israel attacked Iran, it seemed as if Tehran and Washington might peacefully resolve their dispute over Iran’s nuclear program. For the first time since abandoning the Joint Comprehensive Plan of Action in 2018, the nuclear deal that Iran had reached with the United States and other major countries three years earlier, U.S. President Donald Trump’s team indicated it was willing to accept an arrangement in which Iran would be able to enrich uranium up to 3.67 percent—the level the United States agreed to under the JCPOA—rather than no enrichment at all. Tehran, for its part, was once again open to speaking directly to American officials rather than exclusively through mediators. Some analysts believed a new nuclear agreement could be near.

    But as negotiations progressed, the Trump administration began walking back its initial flexibility, oscillating between demanding zero enrichment and the full dismantlement of Iran’s nuclear infrastructure. Israel, meanwhile, steadily degraded Tehran’s position by picking apart Hezbollah (Tehran’s most powerful partner), tearing through Hamas, and taking out some of Iran’s air defenses. The Islamic Republic grew even weaker in December, when rebels toppled Syrian President Bashar al-Assad, another faithful Iranian ally. Eventually, a sense of resignation took hold in Tehran: many officials and analysts alike came to believe that—deal or no deal—Israel, the United States, or both would attack.

    Tehran still proceeded with caution. It knew that its people were seething after decades of repression and that it risked even more domestic anger if it provoked a direct confrontation with Washington. Iranian officials thus stayed at the negotiating table, hoping to avoid an assault while trying to shore up their domestic backing—for instance, by suspending enforcement of the unpopular law mandating that women fully cover their hair in public and easing other restrictions on freedom of expression.

    The Israeli and U.S. attacks led to an outburst of Iranian nationalism.

    It is unclear how much these steps helped the government when the first Israeli bombs fell. At first, many ordinary Iranians assumed the conflict would be a short confrontation between two governments that was unlikely to affect them. But as the strikes intensified, targeting infrastructure and killing ordinary citizens, many Iranians began to conclude that the attacks were not merely a war against the regime but a war against the nation itself. These sentiments swelled after Trump and Israeli officials urged Tehran’s residents to evacuate their homes. “I’m no fan of the Islamic Republic, but it’s now time to show solidarity for Iran,” one Tehran resident told the Financial Times. “Trump and Netanyahu say ‘evacuate’ as if they care about our health. How can a city of 10 million evacuate? My husband and I are not going to pave the ground for them. Let them kill us.”

    Rather than prompting popular outrage at the Iranian state, the attacks led to an outburst of nationalism. As the Islamic Republic weathered Israel’s assault and retaliated with ballistic missiles of its own, the regime’s response was cheered on by Iranian writers, artists, and singers, many of whom are typically apolitical or in opposition to the government. Iranian commentators across the political spectrum likened the Israeli assault to Nazi Germany’s 1941 invasion of the Soviet Union, casting the conflict as Iran’s own patriotic war: a national struggle that transcends politics. Even some longtime dissidents and former political prisoners joined in. For instance, hundreds of political and civil rights activists—many of whom have been previously imprisoned—condemned Israel’s attacks in a joint statement. “In defense of our homeland’s territorial integrity, independence, national defense capabilities, … we stand united and resolute,” it declared. These actors carefully kept some distance from the regime. But their emphasis on solidarity aligned with the government’s message. Israel’s strikes thus relieved some of the internal pressure on the Islamic Republic.

    The Iranian government is likely to use this respite to accelerate its militarization in preparation for sustained conflict. Less constrained by domestic pressure, it will channel resources into the IRGC and other armed forces and security agencies, especially since many in Tehran expect the fragile cease-fire to collapse at any moment. But it will struggle to prove that it can handle another war, especially given the extent to which its ranks have been penetrated by Israeli intelligence operatives. Critics have accused the regime of prioritizing ideological loyalty over competence, allowing individuals who simply mouthed hard-line slogans to rise through the ranks while concealing their true allegiances. Others point out the irony that, as the government fixated on enforcing the veiling law and cracking down on political dissidents under the pretext of fighting foreign subversion, its actual adversaries were quietly infiltrating its most sensitive institutions.

    The resulting fallout has triggered calls for investigations, accountability, and even the resignation of the senior officials accused of overseeing such a catastrophic intelligence failure. Whether any top official will actually face consequences remains to be seen. But one response already appears certain: Tehran is likely to launch internal purges, expand its surveillance apparatus, and rely on ordinary citizens to participate in monitoring and reporting suspicious activities.

    Iran has been summarily executing those it accuses of collaborating with Israel.

    Still, the country’s leaders are trying to keep the country’s society unified. Pro-government preachers across the country have suddenly begun blending iconic, pre-revolutionary patriotic songs into Shiite religious rituals—a mix of nationalism and Islamism that the regime historically avoided but now appears eager to embrace. Similarly, state-controlled media and municipal officials are now invoking pre-Islamic Persian mythology in their messaging, linking legendary figures to slain IRGC commanders. This cocktail has drawn mixed reactions, with many skeptical Iranians arguing that the gestures are merely opportunistic. Yet other citizens are joining in, having concluded that they must confront these external threats with the government they have, not the one they want.

    Some Iranians believe that to make sure today’s social cohesion lasts into the future, senior officials will take steps to moderate. The government, after all, has acknowledged the support of Iranians who have historically opposed the regime and, implicitly conceding past mistakes, promised better treatment of the population. It might release political prisoners and repair relations with sidelined moderate figures, including former presidents Mohammad Khatami and Hassan Rouhani, to project national unity. It could also continue to let women go unveiled and allow for more free expression. It has already marginalized some hard-liners, who had pushed for Iran to attack Israel before June 13. (Some of these figures and analysts had argued that the country was already at war and thus needed to strike, even though doing so risked further upsetting an already fractured populace.)

    But whether the government’s promise of moderation signals a genuine opening remains unclear. Many Iranians believe the government will instead double down on its hard-line stance, viewing reconciliation as too risky in wartime and expecting that the wave of nationalist solidarity will allow them to be more repressive while limiting blowback. The state, for example, has been summarily executing those it accuses of collaborating with Israel. It has established checkpoints across major cities to arrest suspected collaborators, as it did during the 1980s—the last time Iran was subjected to similar kinds of attacks. The regime could also mix and match, liberalizing in some respects while growing more restrictive in others. Iranians, after all, are ambivalent about the state’s reaction. “It’s unsettling, but also somewhat reassuring to see them near my house,” a different Tehran resident told the Financial Times, referring to the IRGC paramilitary volunteers. “I could never imagine seeing Basijis and feeling happy.”

    STAY THE COURSE

    Israeli and U.S. officials are, of course, focused more on whether Tehran is a threat to them than whether it is a threat to its people. And after a year and a half of indirect and direct conflict, many of them believe the regime is nowhere near as menacing as it was before. According to these commentators, Iran’s aggressive Middle East strategy has been a failure, given the collapse of Hezbollah in Lebanon, Assad in Syria, and Hamas in Gaza—plus the damage to Iran’s own military.

    The IRGC, however, sees the situation differently. Its leaders believe the country’s forward defense strategy—fighting adversaries by conducting asymmetric warfare near or within their borders rather than on Iranian soil—has been vindicated. This approach successfully deterred Israel and the United States from attacking for years and thus bought Tehran critical time to build up the industrial infrastructure, technical expertise, and institutional resilience it can now use to rapidly rebuild its nuclear and ballistic missile programs, even after the devastating bombings.

    IRGC leaders had argued for years that they needed to take the fight abroad to protect the nation—claiming, for example, that failing to shore up Assad in Damascus would lead to strikes in Tehran. In a sense, they have now been proved correct. Iran had designed its regional posture to create layers of defense in the form of its various partners, believing that this network would force adversaries to penetrate multiple fronts before striking the homeland. That, of course, is exactly what Israel did. In other words, the way the war has played out allows the IRGC and its hard-line allies in the regime to assert that their strategy worked as intended. This argument is easy to rebut: the layered defense delayed, but did not prevent. attacks on Iranian soil. But for Tehran, that delay is precisely the point: it bought the government time to prepare, learn from Israel’s tactics, and cast the war as an existential national struggle.

    Iran is therefore unlikely to behave much differently after this attack, although it will make some adjustments to reflect the realities that have emerged in the past year and a half. The regime could look to reconstitute the axis of resistance by rebuilding Hezbollah as a more agile, small force closer to its original form rather than as the quasi army it had become. (It would still equip the group with advanced missile capabilities.) In Syria, Tehran will try to take advantage of the current power vacuum by empowering grassroots militant groups. Neither of these steps will be easy: Hezbollah is under pressure from Lebanese officials and continues to suffer Israeli bombardment, and the new Syrian government, which is consolidating control over its territory, is hostile to Iran and has begun moving closer to Israel. Still, Tehran sees openings. The war in Gaza has fueled widespread anger toward Israel across the region, driving bottom-up demand for renewed resistance to the Islamic Republic’s enemy. In fact, Iran’s survival and its missile strikes on Israeli territory have also earned it admiration among many Arab populations.

    Tehran will likely continue to pursue nuclear ambiguity.

    Tehran, meanwhile, is more skeptical of diplomacy than ever. The shock of the attacks—which included the assassination of senior IRGC commanders and a failed attempt to kill a key nuclear negotiator, Ali Shamkhani—has drained away whatever credibility American assurances might once have had. In the past, Iran distrusted Washington but saw talks as a potential avenue for sanctions relief and de-escalation. Now, Iranian officials will not only assume that the United States will violate any agreement but also that negotiations are a cover for coercion or military action, given that Israel’s attack occurred just two days before scheduled talks between Tehran and Washington. Nevertheless, Iran is likely to remain engaged, combining maximum resistance to the regional order with maximum diplomacy, in order to communicate its redlines and further expose what it views as the West’s bad faith. By doing so, Tehran can justify its behavior to both internal and external audiences and put pressure on Israel and the United States.

    Still, Iran does not appear to be rushing toward the bomb. By crossing the nuclear threshold, Tehran would validate the very accusations it has long denied and risk triggering a larger conflict with U.S. forces. Iran also does not see nuclear weapons as a substitute for a strong conventional military. It is a large country that has porous borders with multiple unstable neighbors. It is involved in overlapping territorial disputes about oil fields, water resources, and maritime boundaries. These external challenges are compounded by Iran’s internal vulnerabilities, including chronic ethnic tensions along its periphery. And it has a long history of enduring foreign invasions and meddling. There is a reason why generations of Iranian leaders have invested extensively in building a conventional military, regardless of the type of regime.

    Instead of rushing for a bomb, Tehran will likely continue to pursue nuclear ambiguity, suspending cooperation with the International Atomic Energy Agency. Doing so will also pressure the IAEA to lobby against future attacks on Iran, since the agency can resume inspections only if Iran’s nuclear sites are no longer under threat. Tehran believes this approach, which conceals its enrichment activity, will also provide it with greater flexibility to advance its program without notice. And it sees the suspension as a just comeuppance for the IAEA: Iranian officials are incensed that the agency has not condemned the Israeli and American attacks even though Iran is a signatory of the Nuclear Nonproliferation Treaty (from which it has threatened to withdraw), which guarantees members the peaceful use of nuclear energy. In fact, Iranian officials believe the IAEA gave Israel and the United States useful intelligence and was exploited to justify the attacks. As Tehran pointed out, the agency released a report just a few days before the attack, declaring that Iran’s cooperation with IAEA inspectors was “less than satisfactory.”

    That doesn’t mean Iran will eventually build a nuclear weapon. Whether or when the country will obtain the ultimate deterrent remains an open question. But what is clear is this: Iran is unbowed and unlikely to behave differently than it did before. That means Israel may decide to strike again. Iran could swiftly retaliate. The conflict between these parties is far from over, and the Middle East should expect more turbulence ahead.

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  • Multidisciplinary Management of Paraneoplastic pemphigus associated wi

    Multidisciplinary Management of Paraneoplastic pemphigus associated wi

    Introduction

    Paraneoplastic syndrome encompasses diverse disorders that arise as a result of cancer. These conditions are characterized by systemic effects that do not stem directly from tumor invasion, size, or metastasis, but rather from the distant impacts of malignancy.1 Such syndromes can affect multiple organ systems, including the endocrine, neurological, hematological, dermatological, rheumatological, musculoskeletal, gastrointestinal, renal, soft tissue, skeletal, and metabolic systems. The diagnosis of paraneoplastic syndrome can be particularly challenging, as its symptoms may resemble those of other medical conditions, highlighting the complex interplay between immune response and cancer development.1 Mucocutaneous lesions showed variabilities and may appear as pemphigus vulgaris, pemphigus foliaceous, bullous pemphigoid, erythema multiforme and lichen planus.2

    Paraneoplastic pemphigus (PNP) is a rare life-threatening mucocutaneous autoimmune disease.3 It is characterized by blistering, Intractable mucositis, and benign and malignant neoplasms.3 Pathogenesis though not fully understood, however autoimmunity and cell mediated immunity have been proposed mainly against plakin family.4 The development of paraneoplastic effects is closely tied to the interactions between tumors and the host immune system. Tumors can release onconeural antigens that provoke immune responses, inadvertently targeting nerve tissues due to shared epitopes. This can lead to paraneoplastic neurological syndromes (PNS), where neurological symptoms arise without direct tumor invasion. Research indicates that cytotoxic T lymphocytes (CTLs) are predominantly activated in response to these antigens, reflecting a strong immune mechanism aimed at tumor destruction that paradoxically damages the nervous system. Additionally, immune checkpoint inhibitors may reveal PNS, highlighting the breakdown of immune tolerance and suggesting potential therapeutic pathways. Overall, tumors orchestrate immune-mediated responses that result in PNS, illustrating the complex relationship between malignancy and neurological effects. The emergence of paraneoplastic effects is intricately linked to the interactions between tumors and the host’s immune system. Tumors can secrete onconeural antigens that elicit immune responses, which may inadvertently target nerve tissues due to the presence of shared epitopes. This phenomenon can result in paraneoplastic neurological syndromes (PNS), characterized by neurological symptoms that occur without direct invasion by the tumor. Studies have shown that cytotoxic T lymphocytes (CTLs) are primarily activated in response to these antigens, indicating a robust immune response aimed at tumor elimination that, paradoxically, harms the nervous system. Furthermore, the use of immune checkpoint inhibitors may unmask PNS, underscoring the disruption of immune tolerance and suggesting new therapeutic avenues.1,5,6 Clinical characteristics are very variable. The head and neck region, trunk and proximal extremities are most affected.4 We report a case of PNP that was successfully treated using a multi-disciplinary approach.

    Case Presentation

    Chief Complaints

    Sixty-one years old male patient presented to the ER department with severe inflammation of the left eye and scaly erythematous skin eruptions affecting the hands, trunk, and feet.

    History of Present Illness

    The patient lesions started to develop a month before presentation to ER.

    History of Past Illness, Personal and Family History

    The patient history was insignificant.

    Physical Examination

    Twenty nail dystrophies with multiple violaceous to brownish edematous plaques and hemorrhagic crusts over the proximal nail folds were observed (Figure 1). Multiple superficial skin erosions with erythematous bases over the trunk (Figure 2). He also had extensive oral ulceration involving the dorsum and ventral surfaces of the tongue, buccal mucosa, labial mucosa, erythematous bleeding areas and encrustation of the lips (Figure 3). These lesions were associated with significant unintentional weight loss and loss of appetite. The patient was admitted to the hospital for a full workup including screening for malignancy.

    Figure 1 Oral ulceration in the dorsum surface of the tongue, erythematous papules on the lip.

    Figure 2 Onychodystrophy with multiple violaceous to brownish edematous plaques and hemorrhagic crusts over the proximal nail folds.

    Figure 3 Multiple superficial skin erosion with erythematous bases over the trunk.

    Laboratory Examinations

    Histopathological examination of the skin lesions confirmed a diagnosis of paraneoplastic pemphigus (Figure 4).7 After screening for malignancy, the patient was found to have a large retroperitoneal mass. CT tomography-guided biopsy of the tumor confirmed the diagnosis of low-grade B cell non-Hodgkin.

    Figure 4 Histopathological examination of skin lesions was consistent with paraneoplastic pemphigus showing (A) suprabasilar acantholysis with “tombstoning” of the basilar keratinocytes and (B, B-1) band-like lymphocytic infiltrate in the dermis with some eosinophils, and full thickness epidermal necrosis. (hematoxylin and eosin stain, x 40) (hematoxylin and eosin stain, x 10).

    Final Diagnosis

    This patient was diagnosed with paraneoplastic pemphigus associated with B-Cell lymphoma.

    Treatment

    The patient was referred to a hematology-oncology team. During his hospital admission, he was treated with cyclophosphamide 600 mg for six cycles and 60 mg/day prednisone orally for five days, but the oral lesions were resistant. Therefore, an oral medicine team was consulted for further management. Oral lesions were managed with: Prednisolone 10 mg tablets use fresh mixture twice daily morning and before bedtime dissolve in 10 mL of water, gargle and hold in the mouth for 5 to 10 minutes, do not swallow. Tetracycline 250-mg mouthwash four times daily was used to hold the fresh solution and spit out. A thin film of betamethasone dipropionate topical ointment 0.05% bid and fucidic acid cream 2% qid were applied to the lips. This resulted in a better lesion response and improved oral intake by the patient (Figure 5), which has a significant positive impact on patient’s satisfaction and quality of life. Consent was obtained from the patient for the publication of the case report including pictures.

    Figure 5 Oral ulceration on the 5th day post therapy.

    Outcome and Follow-Up

    Follow-up for 2 years, the patient has fully recovered.

    Discussion

    Paraneoplastic pemphigus (PNP) is a rare autoimmune skin condition classified among blistering diseases and is consistently linked to neoplasms.8 The concept of paraneoplastic autoimmune multiorgan syndrome (PAMS) was introduced by Nguyen et al in 2011, emphasizing on the systemic nature of PNP9 which is seen as multiorgan involvement in these patients a variety of subsets of auto-antibodies to several tissues.3,10,11

    Mucosal involvement is considered a characteristic of PNP. In the case presented, the entire oral cavity, including the tongue and lips, was affected. The lesions presented as painful ulcers, erosions, and crusting of the lips, which showed minimal response to treatment. Early mucosal involvement is recognized as a key indicator of PNP, affecting the entire oral cavity, tongue, lips, or other mucosal areas.12 These lesions typically manifest as painful erosions that do not respond well to treatment.12 Conversely, skin lesions exhibit a broader and more diverse range of appearances, primarily located on the torso, head, and proximal extremities.12

    As Regard to the diagnosis and management of such a case, include a high clinical suspicion, early diagnosis, complete tumor resection, and intravenous immunoglobulin (IVIG) administration.12 As in the current case, one of the associated tumors with PNP includes non-Hodgkin’s lymphoma.3,13 Additionally, as observed in this instance, the most consistent clinical manifestation is the persistent stomatitis, which is recognized as an early indicator due to its intensity and resistance to treatment.14

    Erosions and ulcerations can impact all areas of the oropharynx, with a significant extension onto the vermillion border of the lip.14 Mucosal lesions often persist, and recovery may take several months.12 A single patient may exhibit various types of lesions, which can transition from one form to another.15,16 This variability may be attributed to the dominance of either cell-mediated or humoral-mediated pathogenic mechanisms.17 Diagnosing such cases is complex and should adhere to the diagnostic criteria initially established by Anhalt et al, which have recently been updated by Mimouni et al.18 Differential diagnosis, may include Pemphigus vulgaris, Bullous pemphigoid and Erythema multiforme.19

    PNP therapy presents significant challenges due to the infrequency of the condition.19 To address this, it may be beneficial to adhere to the six steps outlined by Frew et al, which encompass the stabilization of vital signs, assessment for any underlying malignancies, precise diagnosis of PNP, removal and medical management of the triggering tumor, and the treatment of PNP through immunosuppression, immunomodulation, or plasmapheresis.20 Moreover, High-dose corticosteroids can be used as first line therapy such as high-dose prednisolone.20–22 Additionally, high-dose corticosteroids, such as high-dose prednisolone, can serve as a primary treatment option. Mucosal lesions tend to respond poorly to treatment, thus multidisciplinary approach may facilitate healing and improve overall prognosis.16

    Conclusion

    Paraneoplastic pemphigus (PP) is a rare and fatal autoimmune disease associated with an underlying malignancy. Management of PNP is challenging and involves several therapeutic modalities. This report highlights the importance of a collaborative holistic approach, especially for serious conditions that affect well-being. A multidisciplinary approach to achieve early diagnosis, prevention and better management is essential to improve the quality of life of such patients despite the possible poor prognosis.

    Institutional Review Board Statement

    Ethical review and approval were not required for this case study due to the specific policies of King Saud University. The institution does not provide an institutional review board (IRB) for case reports, as these typically involve the retrospective analysis of a single patient’s medical history. Such reports are generally considered to have a lower level of ethical concern compared to other research methodologies that involve multiple participants or interventional procedures. This approach is based on the understanding that case reports primarily focus on documenting and sharing unique or noteworthy clinical observations, which can contribute to medical knowledge without posing significant ethical risks. However, it is important to note that patient confidentiality, agreement and privacy were still maintained throughout the reporting process, adhering to standard ethical practices in medical publishing.

    Disclosure

    The authors report no conflicts of interest in this work.

    References

    1. Vogrig A, Muñiz-Castrillo S, Desestret V, Joubert B, Honnorat J. Pathophysiology of paraneoplastic and autoimmune encephalitis: genes, infections, and checkpoint inhibitors. Ther Adv Neurol Disord. 2020;13. doi:10.1177/1756286420932797

    2. Balighi K, Azizpour A, Sadeghinia A, Saeidi V. A case report of paraneoplastic pemphigus associated with retroperitoneal inflammatory myofibroblastic tumor. Acta Med Iran. 2017;55(5):340–343.

    3. Anhalt G, Kim S, Stanley J, et al. Paraneoplastic pemphigus. An autoimmune mucocutaneous disease associated with neoplasia. Int J Gynecol Obstet. 1991;36(3):264. doi:10.1016/0020-7292(91)90751-p

    4. Paolino G, Didona D, Magliulo G, et al. Paraneoplastic pemphigus: insight into the autoimmune pathogenesis, clinical features and therapy. Int J Mol Sci. 2017;18(12):2532. doi:10.3390/ijms18122532

    5. Zaborowski MP, Michalak S. Cell-mediated immune responses in paraneoplastic neurological syndromes. Clin Dev Immunol. 2013;2013:1–11. doi:10.1155/2013/630602

    6. Firsty NN. RS3PE as paraneoplastic rheumatic syndrome. SCRIPTA SCORE Sci Med J. 2021;2(2):123–132. doi:10.32734/scripta.v2i2.4387

    7. Svoboda SA, Huang S, Liu X, Hsu S, Motaparthi K. Paraneoplastic pemphigus: revised diagnostic criteria based on literature analysis. J Cutan Pathol. 2021;48(9):1133–1138. doi:10.1111/cup.14004

    8. Kelly S, Schifter M, Fulcher DA, Lin MW. Paraneoplastic pemphigus: two cases of intra-abdominal malignancy presenting solely as treatment refractory oral ulceration. J Dermatol. 2015;42(3):300–304. doi:10.1111/1346-8138.12753

    9. Nguyen VT, Ndoye A, Bassler KD, et al. Classification, clinical manifestations, and immunopathological mechanisms of the epithelial variant of paraneoplastic autoimmune multiorgan syndrome: a reappraisal of paraneoplastic pemphigus. Arch Dermatol. 2001;137(2):193–206.

    10. Sinha A. Paraneoplastic pemphigus: autoimmune-cancer nexus in the skin. Anticancer Agents Med Chem. 2015;15(10):1215–1223. doi:10.2174/1871520615666150716105425

    11. Amber KT, Valdebran M, Grando SA. Paraneoplastic autoimmune multiorgan syndrome (PAMS): beyond the single phenotype of paraneoplastic pemphigus. Autoimmun Rev. 2018;17(10):1002–1010. doi:10.1016/j.autrev.2018.04.008

    12. Hayanga AJ, Lee TM, Pannucci CJ, et al. Paraneoplastic pemphigus in a burn intensive care unit: case report and review of the literature. J Burn Care Res. 2010;31(5):826–829. doi:10.1097/bcr.0b013e3181eed4b4

    13. Nousari HC, Deterding R, Wojtczack H, et al. The mechanism of respiratory failure in paraneoplastic pemphigus. N Engl J Med. 1999;340(18):1406–1410. doi:10.1056/nejm199905063401805

    14. Amagai M. Autoimmune and infectious skin diseases that target desmogleins. Proc Jpn Acad Ser B Phys Biol Sci. 2010;86(5):524–537. doi:10.2183/pjab.86.524

    15. Vassileva S, Drenovska K, Manuelyan K. Autoimmune blistering dermatoses as systemic diseases. Clin Dermatol. 2014;32(3):364–375. doi:10.1016/j.clindermatol.2013.11.003

    16. Zhu X, Zhang B. Paraneoplastic pemphigus. J Dermatol. 2007;34(8):503–511. doi:10.1111/j.1346-8138.2007.00322.x

    17. Wade MS, Black MM. Paraneoplastic pemphigus: a brief update. Australas J Dermatol. 2005;46(1):1–8. doi:10.1111/j.1440-0960.2005.126_1.x

    18. Mimouni D, Anhalt GJ, Lazarova Z, et al. Paraneoplastic pemphigus in children and adolescents. Br J Dermatol. 2002;147(4):725–732. doi:10.1046/j.1365-2133.2002.04992.x

    19. Paolino G, Garelli V, Didona D, et al. Melanosis of the lower lip subverted by filler injection: a simulator of early mucosal melanoma. Australas J Dermatol. 2017;58(1):71–72. doi:10.1111/ajd.12475

    20. Frew JW, Murrell DF. Current management strategies in paraneoplastic pemphigus (Paraneoplastic autoimmune multiorgan syndrome). Dermatol Clin. 2011;29(4). doi:10.1016/j.det.2011.06.016

    21. Gergely L, Váróczy L, Vadász G, Remenyik É, Illés Á. Successful treatment of B cell chronic lymphocytic leukemia-associated severe paraneoplastic pemphigus with cyclosporin A. Acta Haematol. 2003;109(4):202–205. doi:10.1159/000070972

    22. Martínez-Peinado C, Galán-Gutiérrez M, Ruiz-Villaverde R, Solorzano-Mariscal R. Adalimumab-induced pityriasis lichenoides chronica that responded well to methotrexate in a patient with psoriasis. Actas Dermosifiliogr. 2016;107(2). doi:10.1016/j.ad.2015.07.011

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  • e4mXplains: Google’s Veo 3 could help cut ad costs—but blur the line between real & fake – Exchange4media

    1. e4mXplains: Google’s Veo 3 could help cut ad costs—but blur the line between real & fake  Exchange4media
    2. Google rolls out its new Veo 3 video-generation model globally  TechCrunch
    3. This $12.99/month hack gives you access to Google’s Veo 3 AI video tool — here’s how  inkl
    4. This simple trick gets you 3 months of Google Gemini Veo 3 for free – here’s how you can create the best AI videos without dropping a dime  TechRadar
    5. I used Gemini Veo to recreate core memories and my wife will never forgive me  TechRadar

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  • Clinical insights on transforaminal lumbar interbody fusion (TLIF) imp

    Clinical insights on transforaminal lumbar interbody fusion (TLIF) imp

    Introduction

    Spinal degenerative diseases, such as degenerative disc disease and spondylolisthesis, are significant causes of chronic back pain and functional disability.1–4 Transforaminal lumbar interbody fusion (TLIF) has emerged as a widely adopted surgical procedure to treat these conditions, aiming to restore spinal stability through vertebral fusion.5 TLIF involves the placement of an interbody cage into the disc space after the removal of the damaged disc, which promotes fusion between adjacent vertebrae.6,7 Compared to other lumbar fusion techniques, TLIF allows for a minimally invasive approach that reduces tissue disruption and postoperative recovery time.8

    One of the key factors influencing the success of TLIF is bone health, particularly bone mineral density (BMD). Patients with osteopenia or osteoporosis are at an increased risk for complications such as cage subsidence, pedicle screw loosening, and pseudarthrosis—conditions that hinder successful fusion and may require revision surgery.9–12 Therefore, understanding and optimizing bone health is crucial for improving surgical outcomes in TLIF.13 Recent advancements in bone health assessment technologies, including high-resolution imaging techniques and novel biomarkers, have improved our ability to evaluate BMD more accurately and predict outcomes in spinal fusion surgeries.

    This systematic review seeks to provide clinical insights into TLIF procedures by examining key factors that enhance and monitor bone health following spinal fusion surgery. Specifically, we will explore the predictive value of BMD assessments, the role of bone graft materials in promoting fusion, and methods for monitoring postoperative bone health to prevent complications.

    Materials and Methods

    This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines,14 as shown in Figure 1. The primary objective is to evaluate the impact of bone health on TLIF outcomes, focusing on BMD, cage subsidence, pseudarthrosis rates, and fusion success. A comprehensive literature search was conducted across PubMed, Scopus and Cochrane databases to identify relevant studies published between 2010 and 2024. The search terms included combinations of “transforaminal lumbar interbody fusion”, “TLIF”, “bone mineral density”, “cage subsidence”, “osteoporosis”, “pseudarthrosis”, “bone graft”, and “fusion monitoring”. Studies were included if they provided clinical or radiographic outcomes related to TLIF and bone health.

    Figure 1 Selection criteria flow chart.

    Notes: PRISMA figure adapted from Liberati A, Altman D, Tetzlaff J et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Journal of clinical epidemiology. 2009;62(10). Creative Commons.14.

    In this review, the studies considered for inclusion were carefully selected based on several well-defined criteria an they are shown in Table 1.9,15–23 Primarily, we focused on studies that investigated patients who had undergone transforaminal lumbar interbody fusion (TLIF) surgery to address degenerative lumbar conditions. Our aim was to gather comprehensive insights into the role of bone mineral density (BMD), the materials used for bone grafting, the occurrence of cage subsidence, and the issue of pseudarthrosis—key factors that directly influence the success of TLIF procedures. The types of studies included varied, encompassing clinical trials, cohort studies, retrospective reviews, and systematic reviews, provided they were conducted on human subjects. To ensure relevance and consistency, only studies published in English between 2010 and 2024 were included in our analysis.

    Table 1 Studies Included in This Systematic Review

    Conversely, we excluded certain types of studies that did not meet our review’s objectives. Case reports and conference abstracts were omitted, as they often lack the depth of data required for a systematic analysis of TLIF outcomes. Similarly, studies focusing on other spinal fusion techniques that did not provide specific insights into TLIF were excluded to maintain a clear focus. Animal studies and preclinical trials were also not considered, as our review concentrated on clinical outcomes in human populations.

    For each included study, a structured approach was used to extract the necessary data. Key information collected included the study design and sample size, offering insight into the robustness and scope of each study. We also examined patient demographics, such as age, sex, and the presence of comorbidities, which are known to influence the outcomes of spinal fusion surgeries. Preoperative BMD assessments, including tools like DEXA scans and MRI-based vertebral bone quality (VBQ) scores, were recorded to assess the correlation between bone health and postoperative complications.

    Furthermore, details about the surgical techniques used, such as standard TLIF or minimally invasive TLIF (MIS-TLIF), were documented to explore any potential differences in outcomes between these approaches. Postoperative outcomes, such as the incidence of cage subsidence, pseudarthrosis, fusion rates, and screw loosening, were also critical elements of our data extraction process. Additionally, we paid close attention to the types of bone graft materials employed—whether autografts, allografts, or bone morphogenetic proteins (BMP)—as these materials significantly affect the fusion process. Lastly, the methods used to monitor bone health postoperatively, including radiography and CT scans, were collected to provide insights into the effectiveness of these techniques in detecting complications early.

    Quality Assessment

    The methodological quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS) for observational studies and the Cochrane Risk of Bias tool for randomized controlled trials.24 Studies with a score of 6 or above on the NOS or low risk of bias were considered of high quality as shown in Table 2.

    Table 2 Risk of Bias Assessment

    Results

    For this study, a total of 207 articles were initially identified. After removing all duplicates, a set of 94 articles remained for screening. Following the screening process and the application of inclusion and exclusion criteria, ten articles were selected (Table 1).

    Bone Mineral Density and TLIF Outcomes

    Several studies emphasized the importance of preoperative BMD assessment in predicting TLIF outcomes. Low BMD, particularly in osteopenic and osteoporotic patients, was consistently associated with higher rates of complications, such as cage subsidence and screw loosening.25–28 For instance, Ai et al (2024)15 demonstrated that MRI-based vertebral bone quality (VBQ) and endplate bone quality (EBQ) scores were strong predictors of cage subsidence. Higher VBQ and EBQ scores correlated with an increased risk of subsidence, with a cut-off VBQ score of 3.4 predicting subsidence with high sensitivity and specificity.

    Similarly, Bekas et al (2024) highlighted that lower BMD significantly affects the success of lumbar interbody fusion, including TLIF, and increases the likelihood of implant failure. The review of these studies suggests that patients with osteoporosis or osteopenia should undergo thorough BMD evaluations prior to surgery, as these assessments can inform surgical planning and the choice of implants and bone grafts.16

    Cage Subsidence and Predictive Factors

    Cage subsidence is a critical complication following TLIF that can result in loss of intervertebral height and revision surgery.29 Studies have explored various methods for predicting subsidence risk preoperatively. Khoylyan et al (2024) demonstrated the clinical utility of MRI-based VBQ scores in predicting subsidence in patients undergoing TLIF and posterior lumbar interbody fusion (PLIF). A VBQ score of 2.70 was found to have 100% sensitivity in predicting subsidence based on segmental lordosis changes.17

    The study by Chang et al (2024) found that patients with osteopenia had a significantly higher rate of screw loosening and cage subsidence following minimally invasive TLIF (MIS-TLIF). The research highlighted that the risk of complications is significantly greater in osteopenic patients compared to those with normal BMD, underscoring the need for more cautious surgical planning in these populations.9

    Graft Materials and Fusion Success

    A critical factor in the success of TLIF is the choice of bone graft material, which influences the rate of spinal fusion. Kim et al (2023) provided a comprehensive comparison of different graft materials, including autografts, allografts, and bone morphogenetic proteins (BMP). Autologous bone grafts, particularly iliac crest bone grafts (ICBG), remain the gold standard for TLIF due to their osteogenic, osteoconductive, and osteoinductive properties. However, the use of BMP has gained popularity due to its ability to promote bone growth without the morbidity associated with iliac crest harvesting.18

    Despite the promising results with BMP, Zhong et al (2024) found no significant reduction in the rate of pseudarthrosis when BMP was used in TLIF procedures compared to other graft materials. The study concluded that while BMP may enhance fusion rates, it does not significantly decrease the likelihood of revision surgery due to pseudarthrosis, particularly in patients with underlying comorbidities such as diabetes.19

    Pseudarthrosis and Radiographic Monitoring

    Pseudarthrosis, or nonunion of the vertebrae after fusion surgery, is a significant complication that affects patient outcomes and often necessitates revision surgery. Issa et al (2024) conducted a study on the use of computed tomography (CT) scans for assessing pseudarthrosis after lumbar fusion surgeries. Their findings demonstrated that CT scans remain the gold standard for detecting pseudarthrosis, especially when evaluating interbody fusion and facet joint fusion.20

    The study by Chen et al (2024) further examined the role of modic changes in influencing fusion rates. The meta-analysis revealed that patients with modic changes had a lower fusion rate at 3- and 6-month follow-ups compared to those without such changes. This finding highlights the importance of considering modic changes when assessing fusion progress postoperatively.21

    Surgical Techniques and Complications

    The comparison between different surgical techniques for TLIF, particularly MIS-TLIF versus traditional open TLIF, revealed notable differences in complication rates. Formby et al (2016) found that patients with osteoporosis who underwent TLIF had significantly higher rates of cage subsidence and iatrogenic fractures compared to non-osteoporotic patients. However, the radiographic complications did not translate into worse clinical outcomes, suggesting that careful patient selection and monitoring can mitigate the risks associated with osteoporosis in spinal fusion surgeries.22

    In terms of minimally invasive approaches, Chang et al (2024) reported a higher rate of screw loosening in osteopenic patients undergoing MIS-TLIF compared to those receiving dynamic stabilization. This suggests that while MIS-TLIF offers benefits such as smaller incision size and faster recovery, it may not be the optimal choice for patients with compromised bone quality.21

    Discussion

    The findings of this systematic review highlight the critical role of bone health in the success of transforaminal lumbar interbody fusion (TLIF) surgeries, particularly in patients with low bone mineral density (BMD). TLIF remains a preferred surgical approach for treating degenerative lumbar conditions, yet its success largely depends on patient-specific factors such as bone quality, preoperative preparation, and the choice of graft material.

    Several studies emphasized that low BMD, including osteopenia and osteoporosis, significantly increases the risk of complications such as cage subsidence, screw loosening, and pseudarthrosis.9,15,22 In particular, Ai et al (2024) demonstrated that both vertebral bone quality (VBQ) and endplate bone quality (EBQ) scores, derived from MRI assessments, were predictive of postoperative cage subsidence in TLIF patients.15 These findings suggest that preoperative BMD assessment, through techniques like dual-energy X-ray absorptiometry (DEXA) or MRI-based VBQ, should be integral to surgical planning for patients undergoing TLIF. Patients with lower BMD scores could benefit from alternative or enhanced surgical strategies, such as the use of stronger interbody cages or biological enhancements to mitigate the risks of implant failure.

    Cage subsidence is a well-documented complication that can compromise the stability of the interbody fusion and lead to further surgical intervention.30,31 The studies reviewed showed a clear association between BMD and the likelihood of subsidence,32 with Khoylyan et al (2024) suggesting that MRI-based VBQ scores may offer a clinically sensitive threshold for predicting subsidence risk.17 This finding is particularly important for surgeons aiming to prevent postoperative complications by adjusting surgical techniques or choosing more robust cage materials based on preoperative imaging.

    The utility of MRI-based assessments provides a radiation-free alternative to conventional BMD assessment methods, offering a convenient and reliable tool for preoperative risk stratification. By integrating these scoring systems into routine pre-surgical evaluations, surgeons can make informed decisions that improve patient outcomes, particularly for those at higher risk for cage subsidence.

    One of the key variables affecting fusion success in TLIF is the type of bone graft used. Kim et al (2023)9 provided a detailed comparison of autografts, allografts, and bone morphogenetic proteins (BMP), highlighting that autologous bone grafts, particularly iliac crest bone grafts (ICBG), remain the gold standard for promoting fusion due to their osteogenic properties. However, the morbidity associated with harvesting autografts has led to increased interest in alternative materials, such as BMP.

    Despite BMP’s promise in enhancing fusion rates, Zhong et al (2024)19 found no significant reduction in pseudarthrosis or reoperation rates when BMP was used compared to other graft materials. This suggests that while BMP may aid in achieving fusion, it may not offer significant advantages in preventing pseudarthrosis in the context of single-level TLIF procedures. The use of BMP may still be warranted in cases where autografts are not feasible, but careful consideration should be given to the patient’s overall health and potential risk factors such as diabetes, which can increase the likelihood of pseudarthrosis.

    Monitoring bone health and fusion success postoperatively is crucial to preventing complications such as pseudarthrosis. Several studies in this review support the use of computed tomography (CT) as the gold standard for assessing bone fusion, particularly in detecting pseudarthrosis.19,20 Issa et al (2024) emphasized that CT scans provide a reliable method for evaluating fusion in the posterolateral gutters, facet joints, and interbody spaces, which are critical areas for determining the success of TLIF.20

    In contrast, Chen et al (2024)9 suggested that the presence of modic changes can negatively impact the fusion rate, particularly in the early postoperative period. This highlights the need for regular and comprehensive radiographic monitoring, particularly in patients with modic changes or low BMD. Early detection of potential issues through CT or MRI can guide timely interventions, such as pharmacological support with agents that promote bone healing or revision surgery.

    Given the critical influence of bone health on TLIF outcomes, optimizing bone quality preoperatively is crucial, especially for patients with osteopenia or osteoporosis. Notably, strategies to improve bone health include pharmacological interventions such as bisphosphonates, selective estrogen receptor modulators (SERMs)33 and the use of bone-anabolic agents.34 While the studies reviewed provide valuable insights into enhancing and monitoring bone health in TLIF, several limitations remain. Many studies lacked long-term follow-up, which is critical for understanding the durability of fusion and the impact of BMD on outcomes over time. Additionally, there is limited consensus on the exact BMD threshold that significantly increases the risk of complications such as subsidence or pseudarthrosis, suggesting a need for future research to define these parameters more clearly.

    Moreover, while BMP and other graft materials have been extensively studied, there remains a lack of uniformity in the metrics used to evaluate their effectiveness. Standardized measures of fusion success, particularly in patients with low BMD, would allow for more robust comparisons across studies and help refine clinical guidelines.

    Future research should focus on longitudinal studies that track the long-term outcomes of TLIF in osteopenic and osteoporotic patients, as well as the development of novel biomaterials or pharmacological agents that specifically target bone health in the spinal fusion context. Additionally, the integration of advanced imaging techniques, such as MRI-based scoring systems, into routine clinical practice could be further explored to improve preoperative risk assessments and postoperative monitoring.

    Conclusion

    In conclusion, this systematic review underscores the importance of enhancing and monitoring bone health in patients undergoing TLIF. Preoperative BMD assessments, such as MRI-based VBQ scores, provide valuable insights into the risk of complications like cage subsidence and pseudarthrosis, enabling more tailored surgical strategies. While autografts remain the gold standard for bone grafting in TLIF, BMP and other alternative materials offer viable options for patients in whom autograft harvesting is not feasible. Postoperative monitoring with CT scans remains crucial for detecting complications early, particularly in high-risk patients with low BMD or modic changes.

    Further research is needed to establish clear BMD thresholds for surgical planning and to evaluate the long-term effectiveness of different graft materials in improving fusion success. By addressing these gaps, future studies can contribute to more personalized and effective treatment strategies for patients undergoing TLIF.

    Data Sharing Statement

    The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

    Author Contributions

    All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

    Disclosure

    The authors declare that they have no conflict of interest to disclose.

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    26. Jones C, Okano I, Salzmann SN, et al. Endplate volumetric bone mineral density is a predictor for cage subsidence following lateral lumbar interbody fusion: a risk factor analysis. Spine J. 2021;21(10):1729–1737. doi:10.1016/j.spinee.2021.02.021

    27. Bocahut N, Audureau E, Poignard A, et al. Incidence and impact of implant subsidence after stand-alone lateral lumbar interbody fusion. Orthop Traumatol Surg Res. 2018;104(3):405–410. doi:10.1016/j.otsr.2017.11.018

    28. Okano I, Jones C, Salzmann SN, et al. Endplate volumetric bone mineral density measured by quantitative computed tomography as a novel predictive measure of severe cage subsidence after standalone lateral lumbar fusion. Eur Spine J. 2020;29(5):1131–1140. doi:10.1007/s00586-020-06348-0

    29. Hu F, Xue L, Zhao D, Chen C, Jing F, Yang Q. Magnetic resonance imaging-based vertebral bone quality score for prediction of cage subsidence and screw loosening in patients undergoing degenerative lumbar surgery: a meta-analysis. Neurospine. 2024;21(3):913–924. doi:10.14245/ns.2448496.248

    30. Ushirozako H, Hasegawa T, Ebata S, et al. Impact of sufficient contact between the autograft and endplate soon after surgery to prevent nonunion at 12 months following posterior lumbar interbody fusion. J Neurosurg Spine. 2020:1–10. doi:10.3171/2020.5

    31. Xi Z, Mummaneni PV, Wang M, et al. The association between lower Hounsfield units on computed tomography and cage subsidence after lateral lumbar interbody fusion. Neurosurg Focus. 2020;49(2):E8. doi:10.3171/2020.5.FOCUS20169

    32. Kim MC, Chung HT, Cho JL, Kim DJ, Chung NS. Subsidence of polyetheretherketone cage after minimally invasive transforaminal lumbar interbody fusion. J Spinal Disord Tech. 2013;26(2):87–92. doi:10.1097/BSD.0b013e318237b9b1

    33. Al-Najjar YA, Quraishi DA, Kumar N, Hussain I. Bone health optimization in adult spinal deformity patients: a narrative review. J Clin Med. 2024;13(16):4891. doi:10.3390/jcm13164891

    34. Hong N, Shin S, Lee S, Rhee Y. Romosozumab is associated with greater trabecular bone score improvement compared to denosumab in postmenopausal osteoporosis. Osteoporos Int. 2023;34(12):2059–2067. doi:10.1007/s00198-023-06889-2

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  • Trends in Diabetic Medication Use and Hypoglycemia Incidence Among Older Adults in Japan: A Retrospective Observational Study and a 10-Year Analysis Based on Level of Care Need Using Linked Medical and Long-Term Care Data

    Trends in Diabetic Medication Use and Hypoglycemia Incidence Among Older Adults in Japan: A Retrospective Observational Study and a 10-Year Analysis Based on Level of Care Need Using Linked Medical and Long-Term Care Data


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  • Following hiccup, macOS 26 beta 3 now available for Apple Silicon

    Following hiccup, macOS 26 beta 3 now available for Apple Silicon

    Earlier today, Apple released its new set of developer betas, but a distribution issue affected the Apple Silicon version of macOS Tahoe 26 developer beta 3. Now, the issue seems to have been resolved, and the update is now available for all compatible Macs.

    What happened?

    Users on X claimed that the hiccup involved Rosetta 26 beta 3, a required component for running Intel apps on Apple Silicon. Apple didn’t confirm the issue, but whatever the problem might have been, it seems to have been solved.

    This means that macOS Tahoe 26 beta 3 is now available for all compatible Macs, including those powered by M1, M2, and M3 chips.

    Here’s how to install the macOS Tahoe 26 developer beta 3:

    1. Backup your Mac
    2. Open System Settings
    3. Go to General ⇾ Software Update
    4. Click the ‘i’ icon next to Beta Updates
    5. From the dropdown menu in the top-right, select the macOS Developer Tahoe Beta
    6. Hit ‘Done’

    Any sign of the public beta?

    As Apple said during the WWDC25 keynote, public betas are expected to drop this month. Public betas typically arrive alongside developer beta 3 or 4, so the wait is almost over.

    As for developer beta 3, Apple hasn’t detailed what, if any, new features or changes made their way into the system beyond the usual under-the-hood improvements and bug fixes. But we’re already digging in to see what’s changed and will keep you posted, so be sure to check back soon.

    As always, if you spot any changes in today’s macOS Tahoe 26 beta 3, let us know in the comments.

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  • MicroStrategy didn’t buy more bitcoin – for the first time in three months

    MicroStrategy didn’t buy more bitcoin – for the first time in three months

    By Tomi Kilgore

    MicroStrategy has acquired more than 69,000 bitcoins since it last took a pause, to bring its total holdings to nearly 600,000 bitcoins

    It is now bigger news when MicroStrategy Inc. doesn’t buy any bitcoin than when it does.

    The self-proclaimed largest bitcoin treasury company, which is technically still a software company (MSTR), disclosed Monday that it didn’t acquire any bitcoin during the week of June 30 to July 6.

    That’s the first week MicroStrategy, which is doing business as Strategy, didn’t acquire any bitcoin since the week of March 31 to April 6.

    The stock slipped 2% on Monday, as the price of bitcoin (BTCUSD) declined about 1.5% over the past 24 hours.

    From April 7 through June 29, MicroStrategy spent $6.77 billion to buy 69,140 bitcoins, at an average price of about $97,906 per bitcoin. At current prices, the value of those purchases has increased by 10.4% to $7.49 billion.

    The company currently owns 597,325 bitcoins, which it purchased for $42.4 billion at an average price of $70,982 per bitcoin. That holding is currently worth $64.71 billion.

    MicroStrategy also didn’t issue any common or preferred shares in the latest week to raise money for bitcoin purchases. But it did announce a sales agreement in which it may issue and sell shares of 10% preferred stock with a total offering price of up to $4.2 billion.

    The company said it plans to use proceeds from the sales agreement for general corporate purposes, including bitcoin purchases.

    MicroStrategy’s stock has soared 38.5% in 2025, while bitcoin has rallied 16.1% and the S&P 500 index SPX has tacked on 6.1%.

    Separately, in the world of bitcoin treasury companies, Singapore-based developer of artificial-intelligence education Genius Group Ltd. (GNS) said it has increased its bitcoin treasury target by 10 times, to 10,000 bitcoins.

    The company said it plans to use debt financing, issue convertible bonds and preferred shares, and use money made from its business to raise money for the bitcoin purchases.

    Genius’s stock dropped about 7% on Monday. It has lost 6.5% so far this month after rocketing 331.8% in June.

    -Tomi Kilgore

    This content was created by MarketWatch, which is operated by Dow Jones & Co. MarketWatch is published independently from Dow Jones Newswires and The Wall Street Journal. 

    
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  • AI-enabled piezoelectric wearable device offers accurate and low-cost joint health tracking

    AI-enabled piezoelectric wearable device offers accurate and low-cost joint health tracking

    In the pursuit of more effective and accessible solutions for joint health monitoring, researchers are constantly seeking innovative ways to enhance the capabilities of wearable devices. A recent article published in Nano-Micro Letters, authored by Professor Jin-Chong Tan and Professor Hubin Zhao from the University of Oxford and University College London, presents a groundbreaking AI-enabled piezoelectric wearable device for accurate joint torque sensing, leveraging the unique properties of boron nitride nanotubes (BNNTs).

    Why this research matters

    • Enhanced joint health monitoring: Traditional methods for assessing joint torque are often confined to laboratory settings or require complex setups, limiting their feasibility for real-world applications. This new wearable device offers a portable, non-invasive solution for continuous joint torque monitoring, crucial for evaluating joint health, guiding interventions, and monitoring rehabilitation progress.

    • High sensitivity and accuracy: The device’s high-sensitivity BNNTs/polydimethylsiloxane composite enables precise and dynamic knee motion signal detection, while the lightweight neural network processes complex signals for accurate torque, angle, and load estimation, providing reliable data for joint health assessment.

    • Low-cost and accessible solution: The compatibility of the materials and design with low-power, resource-limited settings makes this wearable device a cost-effective and accessible solution for diverse populations across regions with varying levels of development, potentially revolutionizing joint health monitoring on a global scale.

    Innovative design and mechanisms

    • Boron nitride nanotubes and polydimethylsiloxane: BNNTs are highlighted as ideal materials for constructing high-performance piezoelectric sensors due to their exceptional mechanical strength, thermal stability, and intrinsic piezoelectric properties. The uniform dispersion of BNNTs in a PDMS matrix results in a highly sensitive piezoelectric film capable of capturing complex knee motion signals.

    • Inverse design structure: The wearable device employs an inverse-designed structure with a negative Poisson’s ratio, precisely matched to the biomechanics of the knee joint. This unique design ensures optimal biomechanical compatibility, enhancing motion tracking fidelity and enabling detailed sensing of complex loading conditions during knee movements.

    • Artificial intelligence integration: The integration of a lightweight on-device artificial neural network allows for real-time processing and analysis of the complex piezoelectric signals generated during movement. The AI algorithm accurately extracts targeted signals and maps them to corresponding physical characteristics, such as torque, angle, and loading, providing valuable insights into joint health.

    Applications and future outlook

    • Joint health monitoring: This wearable device can continuously monitor joint torque, offering valuable data for the evaluation of joint health and early detection of potential issues. It can be particularly beneficial for individuals with musculoskeletal conditions, the elderly, and athletes, enabling timely interventions and personalized rehabilitation plans.

    • Rehabilitation and injury prevention: By providing real-time torque assessment and risk assessment of joint injury, the device can play a crucial role in rehabilitation programs, ensuring safe and effective recovery. It can also help in preventing injuries by alerting users to potentially harmful joint movements or excessive torque.

    • Future research directions: Future research should focus on further optimizing the sensing materials, device design, and AI algorithms to enhance the performance, accuracy, and adaptability of the wearable device. Exploring additional complementary modalities and integrating the device with wearable robotics or exoskeletons could further expand its applications and utility in various fields.

    This innovative AI-enabled piezoelectric wearable device represents a significant step forward in joint health monitoring, offering a low-cost, high-sensitivity solution with broad potential applications. Stay tuned for more groundbreaking research from Professor Jin-Chong Tan and Professor Hubin Zhao’s team as they continue to push the boundaries of wearable technology and contribute to improved joint health and rehabilitation outcomes.

    Source:

    Shanghai Jiao Tong University

    Journal reference:

    Chang, J., et al. (2025). AI-Enabled Piezoelectric Wearable for Joint Torque Monitoring. Nano-Micro Letters. doi.org/10.1007/s40820-025-01753-w.

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  • Cardiologists share 10 daily habits that hurt your heart: Too much salt to lack of sleep

    Cardiologists share 10 daily habits that hurt your heart: Too much salt to lack of sleep

    When we think of heart disease, we often imagine it as a jolt — a heart attack, a stroke, or a medical emergency that arrives without warning. But according to cardiologists, the real danger to your heart could be hiding in the patterns of your everyday life. From late-night snacking to endless screen time, skipped meals to excess salt, it’s our daily routines that may be damaging our cardiovascular health, regardless of age, gender, or body size.

    “It is commonly believed that heart disease occurs only in older or obviously unfit individuals. Actually, cardiovascular disease can accumulate over years, maybe in young, thin, or ‘healthy-looking’ people. Heritability, stress, and lifestyle are factors, and prevention is the way to go,” Dr Vikrant Khese, Cardiologist, Apollo Clinic, Kharadi, tells Health Shots.

    In recent years, the incidence of heart-related conditions in individuals below 50 years of age, has seen a rise. This busts the myth that heart disease is only for older people or men, says Dr Nitin Bote, Interventional Cardiologist, K.J. Somaiya Hospital and Research Centre.

    “We are actually seeing an increasing number of young patients, including women, presenting with early symptoms of heart disease, caused by stress, lifestyle, and hormonal changes. Another myth is that if you take medication, lifestyle modifications are not required. This is very much not the case. Medication controls risk but long-term cardiac health relies on habit changes,” adds Dr Bote.

    Daily habits that affect heart health

    Here are some of the daily lifestyle habits that may silently raise cardiovascular risk:

    1. Chronic sleep deprivation

    Inadequate rest increases stress hormone levels and blood pressure, straining the heart. According to a 2010 study about sleep duration as a risk factor for cardiovascular disease, there was an increased risk of Congenital Heart Disease in subjects with sustained 5 or fewer, 6, 7, and 9 hours or more, compared with those with 8 hours of sleep.

    2. Excess screen time

    If you spend hours on phones or in front of the TV, be mindful. Studies have found a correlation between excessive use of mobile phones and TV screens, and an increased risk of coronary artery disease, heart failure, and ischaemic heart disease. This is because these activities promote a sedentary lifestyle, affecting circulation and movement, and thereby raising the risk of obesity, which is not good for the heart.

    3. Constant late-night snacking

    Making a habit of late-night snacking can disrupt metabolism, impact insulin levels, and even add to weight and cholesterol issues.

    4. Skipping meals or eating irregularly

    According to Dr Bote, missing meals or consuming huge, irregular portions, can raise insulin levels and disrupt metabolic balance, indirectly impact cardiovascular health.

    5. Excess salt intake

    One of the most overlooked threats for your heart? Salt. Both Dr Khese and Dr Bote, agree that excessive salt is one of the biggest risks for heart damage. “Through processed snack foods, restaurant meals, or what may be perceived as benign condiments, most individuals take in twice the daily recommended amount of sodium,” says Dr Bote. Explaining the risks, Dr Khese adds, “Consuming salt in excess on a regular basis increases blood sodium concentrations that attract fluid into the blood vessels, causing them to swell. This is what increases blood pressure and causes the heart to work more forcefully, which can lead to hypertension, left ventricular hypertrophy (thickening of heart muscle), and eventually heart failure. Too much salt consumption also hardens arteries in the long term.”

    Also read: 6 signs you’re eating too much salt

    6. High sugar and trans-fat consumption

    Want to take care of your heart? Give up or reduce sugary drinks, packaged snacks, and fried foods, which tend to increase inflammation and unhealthy cholesterol.

    7. Low intake of fibre, fruits, and vegetables

    A lack of nutrient-dense foods means the body misses out on key antioxidants and heart-protective fibre. Your diet plays a key role in protecting your heart, so if you consume a high-trans fat diet with added sugar and red meat, with low fibre, fruit, and vegetable consumption, you may be inviting a cardiovascular risk, says Dr Khese.

    8. Physical inactivity

    Even normal-weight individuals are at risk for unfavourable lipid profiles, hypertension, and insulin resistance if they are sedentary. Sedentary life affects circulation, causes inflammation, and promotes the development of plaque in the arteries, independent of body size. “Everyday physical movement, even just walking, can dramatically lower cardiovascular risk,” asserts Dr Bote.

    9. Unmanaged chronic stress

    Long-term emotional stress can elevate blood pressure and contribute to hormonal imbalances that affect heart health.

    10. Skipping routine medical check-ups

    Missing preventive screenings can delay diagnosis of high blood pressure, cholesterol, or early-stage heart disease.

    How to improve your heart health

    Prevention is the best cure! So, making simple, sustainable shifts like eating more fibre, avoiding sugary beverages, sleeping well, managing stress, and even simply walking for 30 minutes daily — can dramatically reduce long-term heart disease risk.

    Regular health check-ups, especially after the age of 30, are crucial to catch warning signs before they turn critical.

    “Heart disease is preventable in most cases. By being mindful of what we eat, staying physically active, managing stress, and getting enough sleep, we can protect our hearts from damage that builds silently over time,” says Dr Bote.

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