Does paired genetic testing improve targeted therapy choices and screening recommendations for patients with upper gastrointestinal cancers and their families? A prospective cohort of 42 patients

Objectives
Our study was designed to assess whether paired normal-tumour testing increased access to targeted therapy, clinical trials and influenced cancer screening recommendations given to patients and their families.

Design
Prospective cohort study.

Setting
Academic cancer centre in the Pacific Northwest region of the USA.

Participants
Patients newly diagnosed between 01 January 2021 and 31 December 2022 with cancers of the oesophagus, gastro-oesophageal junction and stomach (CEGEJS) were included. All other cancer diagnoses such as head and neck, duodenal and lower gastrointestinal tract cancers were excluded.

Intervention
Paired germline and tumour genetic test within 90 days of new patient visit.

Primary outcome measures
Number of targeted therapies received (or not) when eligible, follow-up treatment data and number of inherited predispositions to cancers identified. No secondary outcome measures.

Results
Of 42 patients, 32 (76.2%) were eligible for at least one targeted therapy. 19 patients received immunotherapy, when 16 had a biomarker predicting immunotherapy benefit, and benefit of immunotherapy was unclear for 3. Another 11 did not have this biomarker, and 6 of them received immunotherapy. Six pathogenic variants were identified in four high-risk genes. By 01 January 2024, 18 patients (42.9%) had died of complications of cancer.

Conclusion
More than 75% of patients who received tumour testing were eligible for a targeted therapy regardless of their stage at diagnosis, emphasising the need to expand access to testing with staging workup to improve survival outcomes. Six families received personalised screening recommendations, thanks to this study.

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Intravenous Lidocaine for Gut Function Recovery

To the Editor Dr Paterson and colleagues conducted a randomized clinical trial to evaluate the effect of perioperative IV lidocaine on return of gut function after elective minimally invasive colon resection. I was surprised by the lack of discussion regarding the observed difference in postoperative opioid consumption between the lidocaine and placebo groups and its potential impact on the study’s findings.

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Inhibition of Ipsilesional M1 β Oscillations by Contralesional M1 Following Acute Ischemic Stroke: A TMS-EEG Study

Stroke, Ahead of Print. BACKGROUND:This study aimed to investigate neurophysiological mechanisms underlying functional impairment and recovery after acute ischemic stroke using transcranial magnetic stimulation combined with electroencephalography, focusing on interhemispheric interactions and oscillatory dynamics.METHODS:This single-center case-control study (December 2022 to May 2024) included 19 ischemic stroke patients within 14 days of symptom onset (mean age, 47.95±12.41 years; 15 [79%] males) with 3-month poststroke follow-up. Sixteen age-matched healthy controls (53.56±9.83 years; 12 [80%] males) were included. Transcranial magnetic stimulation-evoked electroencephalography potentials, local mean field power during 25 ms and 35 ms (local mean field power25–35 ms), and power spectral density of the ipsilesional primary motor cortex (ilM1) were calculated when single-pulse transcranial magnetic stimulation was sequentially applied to the contralesional M1 (clM1) and ilM1. Spearman correlation analysis evaluated associations between transcranial magnetic stimulation combined with electroencephalography parameters and clinical outcomes: Fugl-Meyer assessment, Fugl-Meyer assessment-upper extremity subscale, National Institutes of Health Stroke Scale, and National Institutes of Health Stroke Scale changes from baseline to 3 months poststroke.RESULTS:Stroke patients exhibited simplified transcranial magnetic stimulation-evoked electroencephalography potential waveforms with reduced amplitudes compared with healthy controls. The contralesional resting motor threshold of stroke patients was significantly lower compared with healthy controls (t=−2.79;P=0.009). The contralesional resting motor threshold was positively associated with the local mean field power25–35 msof ilM1 with stimulation on ilM1 (r=0.482;P=0.018). The power and power spectral density of β oscillations were negatively associated with the Fugl-Meyer assessment (r=−0.557,P=0.014;r=−0.417,P=0.038, respectively) and Fugl-Meyer assessment-upper extremity (r=−0.503,P=0.014;r=−0.389,P=0.05, respectively), but the power of β oscillations was positively associated with changes in the National Institutes of Health Stroke Scale (r=0.507;P=0.027) with stimulation on clM1.CONCLUSIONS:Increased excitability of the clM1 is associated with decreased excitability of the ilM1. The inhibition of β oscillations in the ilM1 by the clM1 serves as a biomarker for poststroke functional impairment and recovery. Neuromodulation of the clM1 to enhance the β oscillations of ilM1 may be a promising treatment strategy.

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Diagnostic value of BNLF2b antibody, dual-antibody testing and Epstein-Barr virus DNA in nasopharyngeal carcinoma: a prospective cohort study in Hunan Province, China

Objectives
This study evaluates the diagnostic value of the BNLF2b antibody, dual antibody testing and Epstein-Barr virus DNA (EBV-DNA) individually and in combination for nasopharyngeal carcinoma (NPC) detection.

Design
A prospective cohort study.

Setting
The study was conducted at Hunan Cancer Hospital, in a region in China with a high incidence of NPC, between January 2024 and June 2024.

Participants
A total of 350 patients with suspected NPC were enrolled based on clinical suspicion (eg, metastatic cervical lymph nodes or nasopharyngeal abnormalities with non-specific symptoms). The inclusion criteria included age ≥18 years, residency in Hunan Province, and provision of informed consent. The exclusion criteria included prior history of NPC or other head and neck malignancies, severe immunological/systemic diseases and inability to complete diagnostic evaluations.

Primary and secondary outcome measures
Demographic, clinical and biomarker data were collected, including BNLF2b antibody, EBV-DNA and dual antibody testing. Diagnostic performance metrics were calculated against histopathological confirmation as the gold standard. Follow-up assessments were conducted for non-NPC cases.

Results
Among 350 suspected NPC participants, 74 were diagnosed with NPC through biopsy. BNLF2b antibody exhibited the highest sensitivity (83.78%) and specificity (95.65%) among single biomarkers in NPC diagnosis, outperforming dual-antibody testing and EBV-DNA. Combining BNLF2b with dual-antibody testing improved specificity to 99.64%, although with reduced sensitivity (67.57%). NPC-diagnosed participants and those testing positive for BNLF2b or dual antibody biomarkers had a significantly higher prevalence of family history of NPC (p

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Are Procalcitonin Measures a Reliable Predictor of Stopping Antibiotics Among Patients With Sepsis?

To the Editor The Biomarker-Guided Duration of Antibiotic Treatment in Hospitalised Patients With Suspected Sepsis (ADAPT-Sepsis) trial, which compared biomarker-guided antibiotic duration vs standard care in critically ill patients with sepsis, found that a procalcitonin (PCT) protocol decreased antibiotic duration (mean difference, 0.88 days; 95% CI, 0.19 to 1.58) but increased mortality (absolute difference, 1.57; 95% CI, −2.18 to 5.32). The authors, likely relying on the 95% CI for mortality being less than their 5.4% noninferiority margin, concluded, “Care guided by measurement of PCT reduces antibiotic duration safely compared with standard care.”

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Minimum clinically important difference in Quantitative Lung Fibrosis score associated with all-cause mortality in idiopathic pulmonary fibrosis: subanalysis from two phase II trials of pamrevlumab

Objectives
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease. Chest high-resolution CT (HRCT) is instrumental in IPF management, and the Quantitative Lung Fibrosis (QLF) score is a computer-assisted metric for quantifying lung disease using HRCT. This study aimed to assess the change in QLF score associated with a minimum clinically important difference (MCID) of IPF symptoms and physiological lung function, and also determine the MCID of QLF change associated with all-cause mortality to serve as an imaging biomarker to confirm disease progression and response to therapy.

Design and study setting
We conducted post hoc analyses of prospective data from two IPF phase II studies of pamrevlumab, a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity.

Participants
Overall, 152 patients with follow-up visits after week 24.

Methods
We used the anchor-based Jaeschke’s method to estimate the MCID of the QLF score that corresponded with the already established MCID of St. George’s Respiratory Questionnaire (SGRQ) and percent-predicted forced vital capacity (ppFVC). We also conducted a Cox regression analysis to establish a sensitive and robust MCID of the QLF score in predicting all-cause mortality.

Results
QLF changes of 4.4% and 3.6% corresponded to the established MCID of a 5-point increase in SGRQ and a 3.4% reduction in ppFVC, respectively. QLF changes of 1% (HR=4.98, p=0.05), 2% (HR=4.04, p=0.041), 20 mL (HR=6.37, p=0.024) and 22 mL (HR=6.38, p=0.024) predicted mortality.

Conclusion
A conservative metric of 2% can be used as the MCID of QLF for predicting all-cause mortality. This may be considered in IPF trials in which the degree of structural fibrosis assessed via HRCT is an endpoint. The MCID of SGRQ and FVC corresponds with a greater amount of QLF and may reflect that a greater amount of change in fibrosis is required before there is functional change.

Trial registration number
NCT01262001, NCT01890265.

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Minimum clinically important difference in Quantitative Lung Fibrosis score associated with all-cause mortality in idiopathic pulmonary fibrosis: subanalysis from two phase II trials of pamrevlumab

Objectives
Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease. Chest high-resolution CT (HRCT) is instrumental in IPF management, and the Quantitative Lung Fibrosis (QLF) score is a computer-assisted metric for quantifying lung disease using HRCT. This study aimed to assess the change in QLF score associated with a minimum clinically important difference (MCID) of IPF symptoms and physiological lung function, and also determine the MCID of QLF change associated with all-cause mortality to serve as an imaging biomarker to confirm disease progression and response to therapy.

Design and study setting
We conducted post hoc analyses of prospective data from two IPF phase II studies of pamrevlumab, a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity.

Participants
Overall, 152 patients with follow-up visits after week 24.

Methods
We used the anchor-based Jaeschke’s method to estimate the MCID of the QLF score that corresponded with the already established MCID of St. George’s Respiratory Questionnaire (SGRQ) and percent-predicted forced vital capacity (ppFVC). We also conducted a Cox regression analysis to establish a sensitive and robust MCID of the QLF score in predicting all-cause mortality.

Results
QLF changes of 4.4% and 3.6% corresponded to the established MCID of a 5-point increase in SGRQ and a 3.4% reduction in ppFVC, respectively. QLF changes of 1% (HR=4.98, p=0.05), 2% (HR=4.04, p=0.041), 20 mL (HR=6.37, p=0.024) and 22 mL (HR=6.38, p=0.024) predicted mortality.

Conclusion
A conservative metric of 2% can be used as the MCID of QLF for predicting all-cause mortality. This may be considered in IPF trials in which the degree of structural fibrosis assessed via HRCT is an endpoint. The MCID of SGRQ and FVC corresponds with a greater amount of QLF and may reflect that a greater amount of change in fibrosis is required before there is functional change.

Trial registration number
NCT01262001, NCT01890265.

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