Citations

A male patient in his 70s with a history of tobacco use, organising pneumonia and rheumatoid arthritis that had been treated for several years with rituximab currently being treated with tocilizumab, presented with progressively worsening shortness of breath, increasing oxygen requirements and weakness. He had a history of COVID-19 infection 6 months prior to presentation. Initial COVID-19 PCR testing at presentation was negative. Bronchoalveolar lavage was positive for COVID-19 but negative for spike antibodies. It was thought that he did not clear his prior COVID-19 infection due to his immunocompromised state while taking rituximab. On recommendation of infectious disease, he was treated with a prolonged course of nirmatrelvir/ritonavir, remdesivir and corticosteroids with significant symptom improvement.

Background Acute ischemic stroke arising from medium vessel occlusions (MeVO) poses substantial challenges in treatment and management. This study aims to elucidate the outcomes and factors contributing to achieving excellent recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3) versus successful recanalization (mTICI 2b) in patients with MeVO stroke undergoing mechanical thrombectomy (MT). Methods We conducted a multinational study analyzing data from the MAD‐MT (Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy) registry, encompassing 37 centers across North America, Asia, and Europe, collected between September 2017 and July 2023. The study included acute ischemic stroke patients with MeVO treated with MT, with or without intravenous thrombolysis, who achieved mTICI 2b–3 post‐MT. Results Among 1463 patients with successful recanalization (mTICI 2b–3), 523 achieved mTICI 2b recanalization, and 940 achieved mTICI 2c–3. Distal occlusions exhibited higher odds of excellent recanalization compared with proximal MeVO vessel occlusions (odds ratio, 1.58; 95% CI, 1.17–2.15; P = 0.003). Cardioembolic stroke pathogenesis was associated with a higher likelihood of excellent recanalization (1.67; 95% CI, 1.07–2.59; P = 0.018). Patients achieving mTICI 2c–3 recanalization demonstrated lower initial National Institutes of Health Stroke Scale scores, significant improvements in postprocedural National Institutes of Health Stroke Scale shift, and a higher percentage of favorable 90‐day outcomes compared with those with mTICI 2b. However, no significant difference in 90‐day mortality rates was observed. Conclusion This study underscores that among patients with MeVO stroke with successful recanalization (mTICI 2b–3) there is higher likelihood of achieving excellent recanalization (mTICI 2c–3) in distal occlusions and cardioembolic pathogenesis. mTICI 2c–3 scores post‐MT correlate with improved clinical outcomes compared with mTICI 2b, affirming the superiority of excellent recanalization over successful recanalization in patients with MeVO stroke. Further prospective studies and randomized controlled trials are warranted for validation.

ABSTRACT During virus replication in cultured cells, copy-back defective viral genomes (cbDVGs) can arise. CbDVGs are powerful inducers of innate immune responses in vitro , but their occurrence and impact on natural infections of human hosts remain poorly defined. We asked whether cbDVGs were generated in the brain of a patient who succumbed to subacute sclerosing panencephalitis (SSPE) about 20 years after acute measles virus (MeV) infection. Previous analyses of 13 brain specimens of this patient indicated that a collective infectious unit (CIU) drove lethal MeV spread. In this study, we identified 276 replication-competent cbDVG species, each present in over 100 copies in the brain. Six species were detected in multiple forebrain locations, implying that they travelled long-distance with the CIU. The cbDVG to full-length genomes ratio was often close to 1 (0.6–1.74). Most cbDVGs were 324–2,000 bases in length, corresponding to 2%–12% of the full-length genome; all are predicted to have complementary terminal sequences. If improperly encapsidated, these sequences have the potential to form double-stranded structures that can induce innate immune responses. To assess this, we examined the transcriptome of all brain specimens. Several interferon and inflammatory response genes were upregulated, but upregulation levels did not correlate with cbDVG levels in the specimens. Thus, the CIU that drove MeV pathogenesis in this brain includes, in addition to two complementary full-length genome populations, many locally restricted and few widespread cbDVG species. The widespread cbDVG species may have been positively selected but how they impacted pathogenesis remains to be determined. IMPORTANCE Copy-back defective viral genomes (cbDVGs) can drive virus–host interactions. They can suppress virus replication directly, by competing with full-length genomes, or indirectly by stimulating antiviral immunity. In vitro , cbDVG can slow down infections and promote persistence, but there is limited documentation of their presence in human hosts or of their impact on disease. We had the unique opportunity to analyze the brain of a patient who succumbed to subacute sclerosing panencephalitis, a rare but lethal consequence of measles. We detected more than 270 distinct cbDVG species; most were restricted to one specimen, but several reached all lobes of the forebrain, suggesting positive selection. Our analyses provide the missing knowledge of the diversity of cbDVG in a natural infection of a human host. They also reveal that a collective infectious unit that caused lethal human brain disease includes few widespread cbDVG, in addition to two ubiquitous complementary full-length genome populations.

Abstract Background: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo. Methods: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. We included iPCAo patients treated with either EVT or MM. The primary outcome was the modified Rankin Scale (mRS) at 90 days, with secondary outcomes including functional independence, mortality, and safety profiles such as hemorrhagic complications. Results: A total of 177 patients were analyzed (88 MM and 89 EVT). EVT showed a statistically significant improvement in 90-day mRS scores (OR = 0.55, 95% CI = 0.30–1.00, p = 0.048), functional independence (OR = 2.52, 95% CI = 1.02–6.20, p = 0.045), and a reduction in 90-day mortality (OR = 0.12, 95% CI = 0.03–0.54, p = 0.006) compared to MM. Hemorrhagic complications were not significantly different between the groups. Conclusion: EVT for iPCAo is associated with better neurological outcomes and lower mortality compared to MM, without an increased risk of hemorrhagic complications. Nevertheless, these results should be interpreted with caution due to the study’s observational design. The findings are hypothesis-generating and highlight the need for future randomized controlled trials to confirm these observations and establish definitive treatment guidelines for this patient population.

Abstract Background Radiotherapy of breast cancer can be associated with dermatitis. Grade ≥ 2 radiation dermatitis can be painful and impair the patients’ quality of life. To reduce the risk of this complication, patients have to perform skin care several times each day. This may require a considerable level of compliance. This randomized DAI-BREAC trial investigates whether a mobile application reminding the patients four times per day to perform skin care (reminder app) will contribute to reduction of grade ≥ 2 radiation dermatitis. Methods This multinational, randomized, active-controlled, parallel-group, multicenter trial compares standard skin care supported by a reminder app (Arm A) versus standard skin care alone (Arm B) regarding grade ≥ 2 radiation dermatitis in patients receiving adjuvant radiotherapy for breast cancer. The effect of the app will be considered clinically relevant, if the rate of grade ≥ 2 radiation dermatitis is reduced from 25.4% (rate identified in a preceding study) to 15%. A total of 134 patients per arm including drop-outs are required. Secondary aims include pain (visual analogue scale), patient satisfaction with the app (questionnaire), impact of the app on the use of health technology (questionnaire), and benefit from support (coaching) by staff members regarding the use of the app (questionnaire). Discussion If reminder app contributes to a decrease of grade ≥ 2 radiation dermatitis in patients irradiated for breast cancer, it will likely become a useful instrument for these patients. Trial registration: clinicaltrials.gov (NCT06483477; URL: https://clinicaltrials.gov/show/NCT06483477). Registered on 1st of July, 2024. First patient is planned to be included in September 2024.

Background: Video capsule retention is a complication that can have serious consequences in patients with Crohn’s disease (CD). The patency capsule was developed to detect small bowel strictures. The usefulness of patency capsules in patients who do not have evidence of small bowel disease on imaging is uncertain. Study: This is a multicenter retrospective study of patients with suspected or confirmed CD who underwent a patency capsule study between January 2017 and February 2023. We excluded patients who were lost to follow-up or did not have computerized tomography or magnetic resonance imaging of the abdomen within 180 days before or after the patency capsule study. Results: A total of 105 patients met the inclusion criteria with 69% having a confirmed CD diagnosis. The majority of patients (95/105; 90.5%) passed their patency capsule. A total of 91 patients had their subsequent video capsule endoscopy (VCE), with 96.7% (88/91) successfully passing the capsule. Out of those who passed the VCE, 2 patients had patency capsule retention. Both had normal small bowel imaging. Meanwhile, the 3 patients who had VCE retention had evidence of small bowel disease in their imaging scans. The presence of abnormal small bowel wall thickening or stricture on imaging had a statistically significant association with VCE retention (P=0.02). Conclusion: Our study demonstrated a statistically significant association between small bowel disease on imaging and retention of both patency capsules and VCE. Small bowel imaging in patients with suspected or documented CD had a negative predictive value of 100% for VCE retention.

AbstractBackgroundThe clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS).MethodsPatients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis.ResultsOut of 2′938 patients, 222 (7.6%) patients died during 1‐year follow‐up. A more than 28.8‐fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18–2.12, p =.002). Clinically relevant myocardial injury was related to an increased 5‐year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21–2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22–2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17–1.89, p =.001).ConclusionThis study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow‐up.