Initial Treatment Research Articles

Appearance of New Lesions Associate With Poor Prognosis in Pembrolizumab-Treated Urothelial Carcinoma

ObjectivesThis study investigated the variations in response patterns, including target lesion enlargement and the emergence of new lesions, in patients with urothelial carcinoma receiving pembrolizumab therapy and assessed the impact of new lesions on patient outcomes. MethodsThis retrospective analysis included patients with urothelial carcinoma treated with pembrolizumab following platinum failure. Response Evaluation Criteria in Solid Tumors criteria were used to assess the target lesion size and appearance of new lesions. Patients were categorized into 2 groups: the primary progressive disease (PD) group, consisting of patients who progressed within 28 to 84 days of treatment initiation, and the secondary PD group, consisting of patients who progressed more than 84 days after treatment initiation. Survival analyses were performed to evaluate the impact of new lesions on patient outcomes. ResultsIn this study, 42 patients experienced primary PD, and 37 experienced secondary PD. Among patients with primary PD, 64.3%, 73.8%, 45.2% had an increase of 20% or more in target lesion size, newly emerged lesions, and both an increase in target lesion size and new lesions, respectively. Kaplan–Meier analysis revealed that patients with primary PD and new lesions had significantly shorter overall survival after PD than those with only target lesion growth and those with secondary PD (both P < .001). ConclusionThis study revealed the heterogeneity of response patterns during pembrolizumab therapy in patients with urothelial carcinoma and primary pembrolizumab resistance and the presence of new lesions early in treatment. Earlier imaging evaluation should be performed to assess for the appearance of new lesions, leading to sequential treatment.

Racial Disparities in Receipt of Guideline-Concordant Care in Older Adults With Early Breast Cancer

Racial disparities in receipt of guideline-concordant care (GCC) among older patients with potentially curable breast cancer are understudied. To determine whether rates of GCC, time to treatment initiation, and all-cause mortality in stage I to III breast cancer differ by race among older adults. This cohort study used data from the National Cancer Database and included patients aged 65 years and older with stage I to III breast cancer, diagnosed between 2010 and 2019. Data analysis was conducted between July 2022 to July 2023. Race, defined as non-Hispanic Black or non-Hispanic White. The primary outcome was nonreceipt of GCC, defined using the National Comprehensive Cancer Network guidelines, and all-cause mortality. The secondary outcome was time to treatment initiation. Univariate and multivariate regression analysis were used to determine association between exposure and outcomes. Models for GCC and all-cause mortality included age, stage, receptor status, year of diagnosis, Charlson-Deyo comorbidity index, insurance, health care setting, and neighborhood-level educational attainment and median income. The analytic cohort included 258 531 participants (mean [SD] age, 72.5 [6.0] years), with 25 174 participants who identified as non-Hispanic Black (9.7%) and 233 357 participants who identified as non-Hispanic White (90.3%), diagnosed between 2010 and 2017. A total of 4563 non-Hispanic Black participants (18.1%) and 35 374 non-Hispanic White participants (15.2%) did not receive GCC. Non-Hispanic Black race, compared with non-Hispanic White race, was associated with increased odds of not receiving GCC in the multivariate analysis (adjusted odds ratio [aOR], 1.13; 95% CI, 1.08-1.17; P < .001). Non-Hispanic Black race was associated with 26.1% increased risk of all-cause mortality in the univariate analysis, which decreased to 4.7%, after adjusting for GCC and clinical and sociodemographic factors (adjusted hazard ratio, 1.05; 95% CI, 1.01-1.08; P = .006). Non-Hispanic White race, compared with non-Hispanic Black race, was associated with increased odds of initiating treatment within 30 (OR, 1.65; 95% CI, 1.6-1.69), 60 (OR, 2.11; 95% CI, 2.04-2.18), and 90 (OR, 2.39; 95% CI, 2.27-2.51) days of diagnosis. In this cohort study, non-Hispanic Black race was associated with increased odds of not receiving GCC and less timely treatment initiation. Non-Hispanic Black race was associated with increased all-cause mortality, which was reduced after adjusting for GCC and clinical and sociodemographic factors. These findings suggest that optimizing timely receipt of GCC may represent a modifiable pathway to improving inferior survival outcomes among older non-Hispanic Black patients with breast cancer.

Effects of Progesterone on Vasomotor Symptoms in Postmenopausal Women (PROGEST) - a Prospective Multi-Center Randomized Double-Blind Placebo-Controlled Trial (RDPCT).

Introduction Monotherapy with progesterone for treatment of vasomotor symptoms (VMS) was more effective than placebo treatment of postmenopausal healthy women in a Canadian trial. The PROGEST-trial was initiated to fulfill FDA-approval criteria for the indication of treatment of postmenopausal VMS. Methods This prospective randomized, double-blind placebo-controlled clinical trial studied three doses of oral micronized progesterone (200 mg, 300 mg, 400 mg) and placebo for 12 weeks. Postmenopausal women with moderate to severe VMS (> 50 per week) were screened for one week for VMS frequency, then randomized to 200, 300 or 400 mg progesterone daily or placebo for a double-blinded trial of 12 weeks duration. Results 74 women were recruited in 12 study centers. 44 terminated the study as per protocol (PP). Moderate to severe hot flushes decreased by 7.4/d in the placebo arm, 7.7 VMS/d with 200 mg/d progesterone (P4), 8.3 VMS/d on 300 mg/d and 9.0 VMS/d on 400 mg/d P4, respectively by week 12. 32treatment emergent adverse events were documented in 18 participants, mostly minor AEs. The only SAE was a syncope requiring hospitalization on the day after treatment initiation, leading to discontinuation of the drug. Discussion Baseline VMS frequency was much higher in the German than in the Canadian study and the course of the placebo group had a markedly stronger decrease in VMS-frequency during the PROGEST study (-7.4/d) than in the Canadian trial (-1.4/d). Trial populations differed by age, BMI, the number of women with natural menopause, and comorbidities, mainly hypertension. Conclusion Premature discontinuation of the trial due to insufficient subject accrual rate led to only 55 randomized participants for analysis, therefore the study results lack statistical power. Still, a slight dose-dependent improvement in VMS was seen for all doses, while AE frequency did not increase with progesterone dose.

Accelerating access: The power of gold carding in reducing treatment delays.

114 Background: Delays in time to treatment initiation (TTI) for cancer patients have been shown to impact survival/mortality/outcomes, and cause patient distress. The process of obtaining prior authorizations (PA) often leads to significant treatment delays, affecting patient outcomes and posing administrative challenges for healthcare providers. PAs have become a ubiquitous part of modern healthcare, aimed at ensuring appropriate utilization of medical treatments and reducing costs. In recent years, the concept of gold carding (GC), a practice where payers waive PA on services and prescription drugs ordered by providers with a proven track record of PA approvals based on guideline concordance or pathway adherence, has gained attention as a potential solution to provide administrative relief to all stakeholders affected by the PA process. This abstract seeks to explore the impact of GC on TTI for a large multi-site community-based oncology practice in The US Oncology Network having a GC contract with a regional payer. Methods: Using administrative claims data from 2021 to 2023, we derived a population of cancer patients who initiated chemotherapy as their first treatment, calculated the TTI (time from the date of first consultation to the date of treatment initiation), and compared TTI between GC and non-GC patients. Results: The average TTI for 4,836 patients that met the inclusion criteria was 26.3 days. Patients initiating therapy under a GC eligible payer coverage started therapy 4.5 days earlier (22.13 days vs 26.68 days, p&lt;0.00001, Kruskal–Wallis test). 80% of GC eligible patients started their treatment within 30 days of their initial consultation. Conclusions: The findings indicate that gold carding has the potential to expedite the time to treatment initiation for cancer patients. Further research is needed to quantify the cost savings, patient and provider satisfaction, and other intangible benefits from GC. Gold carding offers a viable approach to balance guideline concordant care with lowering administrative burden. We enthusiastically support legislative reforms that encourage gold carding and selectively implement prior authorization requirements based on stratification of health care providers’ performance and adherence to evidence-based medicine. Patient Count Average TTI (days) GC 401 22.13 Commercial 217 21.13 Managed Medicare 184 23.32 Non-GC 4435 26.68 Commercial 1610 25.41 Managed Medicare 1405 27.37 Medicare 959 26.48 Managed Medicaid 254 29.06 Medicaid 112 29.54 All Other 95 30.15

9-HODE associates with thalamic atrophy and predicts white matter damage in multiple sclerosis

BackgroundMultiple sclerosis (MS) is characterized by extensive tissue damage leading to a range of complex symptoms, including physical disability and cognitive dysfunction. Recent work has indicated the clinical relevance of bioactive lipid mediators (LMs), which are known to orchestrate inflammation and its resolution and are deregulated in MS. However, it is unknown whether LM profiles relate to white matter (WM) damage. ObjectivesTo investigate the potential association between plasma-derived LMs and MRI-quantified WM damage using fractional anisotropy (FA) and grey matter (GM) atrophy in dimethyl fumarate-treated relapsing remitting MS (RRMS) patients. MethodsSeverity of FA-based WM damage and GM atrophy was determined in RRMS patients (n=28) compared to age- and sex-matched controls (n=31) at treatment initiation (baseline) and after 6 months. Plasma LMs were assessed using HPLC-MS/MS and baseline LMs were correlated to changes in FA and brain volumes. ResultsWe observed significant WM damage in RRMS patients (mean age 41.4 [SD 9.1]) at baseline and follow-up (z-score=-0.33 and 0.31, respectively) compared to controls (mean age 41.9 [SD 9.5]; p<0.001 for both comparisons). Patients with severe WM damage showed a decline of thalamic volume (p=0.02), and this decline correlated (r=0.51, p<0.001) with lower baseline levels of 9-HODE. This LM also predicted FA worsening (beta=0.14, p<0.001) over time at 6 months. ConclusionDespite the relatively small sample size, lower baseline levels of the LM 9-HODE correlated with more thalamic atrophy and predicted subsequent worsening of WM damage in RRMS patients.

Predicting Pathologic Complete Response in Locally Advanced Rectal Cancer with [68Ga]Ga-FAPI-04 PET, [18F]FDG PET, and Contrast-Enhanced MRI: Lesion-to-Lesion Comparison with Pathology.

Neoadjuvant therapy in patients with locally advanced rectal cancer (LARC) has achieved good pathologic complete response (pCR) rates, potentially eliminating the need for surgical intervention. This study investigated preoperative methods for predicting pCR after neoadjuvant short-course radiotherapy (SCRT) combined with immunochemotherapy. Methods: Treatment-naïve patients with histologically confirmed LARC were enrolled from February 2023 to July 2023. Before surgery, the patients received neoadjuvant SCRT followed by 2 cycles of capecitabine and oxaliplatin plus camrelizumab. 68Ga-labeled fibroblast activation protein inhibitor ([68Ga]Ga-FAPI-04) PET/MRI, [18F]FDG PET/CT, and contrast-enhanced MRI were performed before treatment initiation and before surgery in each patient. PET and MRI features and the size and number of lesions were also collected from each scan. Each parameter's sensitivity, specificity, and diagnostic cutoff were derived via receiver-operating-characteristic curve analysis. Results: Twenty eligible patients (13 men, 7 women; mean age, 60.2 y) were enrolled and completed the entire trial, and all patients had proficient mismatch repair or microsatellite-stable LARC. A postoperative pCR was achieved in 9 patients (45.0%). In the visual evaluation, both [68Ga]Ga-FAPI-04 PET/MRI and [18F]FDG PET/CT were limited to forecasting pCR. Contrast-enhanced MRI had a low sensitivity of 55.56% to predict pCR. In the quantitative evaluation, [68Ga]Ga-FAPI-04 change in SULpeak percentage, where SULpeak is SUVpeak standardized by lean body mass, had the largest area under the curve (0.929) with high specificity (sensitivity, 77.78%; specificity, 100.0%; cutoff, 63.92%). Conclusion: [68Ga]Ga-FAPI-04 PET/MRI is a promising imaging modality for predicting pCR after SCRT combined with immunochemotherapy. The SULpeak decrease exceeding 63.92% may provide valuable guidance in selecting patients who can forgo surgery after neoadjuvant therapy.

Effect of telemonitoring and as-needed patient support on positive airway pressure therapy adherence.

Obstructive sleep apnea (OSA) affects patient health and public welfare. Positive airway pressure (PAP) therapy is the preferred treatment of OSA, but therapy adherence rates remain suboptimal. Current literature demonstrates telemonitoring interventions to support improved PAP therapy adherence. To evaluate the effect of interval telemonitoring of PAP therapy data at 2 and 4 weeks after treatment initiation in patients with moderate-to-severe obstructive sleep apnea with as-needed patient support and troubleshooting by telephone consultation. Ninety-nine participants were enrolled in this study, 50 in the control group and 49 in the intervention group. Data were analyzed using descriptive and inferential statistics using SPSS 28.0 software. The primary outcome of interest was 90-day PAP adherence. Mean PAP adherence scores diverged at 90 days after PAP initiation, with the intervention group having a significantly higher mean score (M = 49.24, SD = 38.18) relative to the control group (M = 36.38, SD = 37.69). Likewise, continued PAP usage at 90 days after therapy initiation diverged between participant groups, with the intervention group having a significantly higher mean score (M = 89.80, SD = 30.58) relative to the control group (M = 72.00, SD = 45.36). The intervention resulted in significantly higher mean PAP adherence and a greater percentage of participants demonstrating continued PAP usage at 90 days after therapy initiation but did not result in a statistically significant increase in what is considered and defined as "good PAP adherence" (adherence of ≥70%). Data-triggered telemonitoring protocols offer supplementary support to patients in need and improve PAP adherence.

Addressing gaps in the diagnosis of TB in children

Since 2000, efforts to develop new treatments for TB have been promising, but diagnosing TB, especially in children, remains a challenge. This issue of the Journal includes the first in a series of articles related to TB in children, highlighting new diagnostic tests that do not rely on sputum, and have great potential for improving diagnosis and treatment initiation. Key to a reduction in TB prevalence, experts are engaging with communities to find undiagnosed cases and combat the stigma of TB. International collaborations are also central to integrating novel diagnostics and providing support for these vulnerable populations.

PREVALENCE OF DIDANOSINE-RELATED RETINAL TOXICITY AT AN URBAN ACADEMIC CENTER AS DIAGNOSED WITH ULTRA-WIDEFIELD IMAGING.

Antiretroviral therapy has revolutionized HIV treatment with didanosine (DDI) as a pioneering drug. However, DDI has been associated with retinal toxicity, characterized by peripheral chorioretinal degeneration with macular sparing. Despite its clinical recognition, the prevalence and risk factors for didanosine-induced retinopathy are not well described. This retrospective case series analyzed 127 DDI-treated patients at Weill Cornell Medicine Department of Ophthalmology. Inclusion criteria included at least 6 months of DDI use and available ultra-widefield imaging. Patients were categorized as affected or unaffected based on retinal imaging assessed by two reviewers. The affected group was further divided into "probable" or "possible" retinopathy. Patient demographics, DDI usage characteristics, and imaging findings were analyzed with statistical comparisons drawn between affected and unaffected cohorts. Of the 127 patients, 9 (7%) showed signs of didanosine-induced retinal toxicity. On average, the affected group was older compared with the unaffected group (65.1 vs. 56.5 years, P = 0.025), with lower BMI (23.2 vs. 27.4, P = 0.04), and older at the start of the treatment (51.6 vs. 40.8 years, P = 0.026). Mild phenotypes with peripheral pigmentary changes were also identified using ultra-widefield imaging. This pioneering academic study highlighted a notable prevalence of DDI-induced retinal toxicity. Statistical analysis demonstrated age, BMI, and age at treatment initiation as potential risk factors. Ultra-widefield autofluorescence emerged as a valuable tool in detecting and delineating findings. Follow-up studies are needed to determine the necessity of regular screening for individuals on or with a history of didanosine use.

Impact of respiratory tract infections on spinal muscular atrophy with focus on respiratory syncytial virus infections: a single-centre cohort study.

Spinal muscular atrophy (SMA) is a degenerative neuromuscular disorder leading to muscle hypotonia, weakness, and respiratory and bulbar impairment. Infants with SMA have an increased risk of respiratory tract infections (RTI) including severe respiratory syncytial virus (RSV) infections. Therefore, guidelines for the treatment of SMA recommend RSV prophylaxis with palivizumab for patients aged below two years who have compromised motor functions ("non-sitters"). Since palivizumab is not approved for RSV prophylaxis in SMA patients in Switzerland, payers usually do not grant cost approvals for this indication. Therefore, this study aimed to investigate the frequency of severe RTI among SMA patients focusing on RSV infections requiring hospital treatment and to determine the long-term impact of RSV infections on the natural history of SMA. A single-centre cohort study at the tertiary paediatric Neuromuscular Centre Zurich, Switzerland, including data of SMA patients with a genetic-based therapy initiated below two years of age between May 2019 and December 2022. All hospitalisations were analysed with a focus on severe RTI and especially RSV infections, and their impact on nutritional and respiratory function. The costs of inpatient treatment of RSV infections were determined and compared with estimated expenses for RSV prophylaxis with palivizumab. 12 SMA patients (median age at treatment initiation: 3.5 months, range: 0-17 months) were followed for a cumulative period of 25.75 years (7 SMA type 1; 5 SMA type 2 including one presymptomatic individual). With an incidence rate of 2.34 per patient-year, the risk of severe RTI was especially high in SMA type 1 (versus 0.1 in SMA type 2, p = 0.044). A total of 37 hospitalisations (279 hospital days) was necessary for the treatment of RTI in general; 9 of them were attributed to RSV infections (in 5 SMA type 1 patients; 84 hospital days). Only 3/12 SMA patients had received seasonal RSV prophylaxis with palivizumab. No RSV infections requiring hospital treatment occurred in patients while receiving seasonal RSV prophylaxis. During RTI, nutritional support had to be commonly initiated and continued after discharge. In 3/7 SMA type 1 patients, non-invasive ventilation was started during acute treatment for RTI and continued to the end of follow-up. We observed a high risk of RTI, especially RSV infections, among young SMA patients. Failure to adhere to established care protocols, for example by omitting RSV prophylaxis, may be linked to a heightened risk of morbidity in these children.

Mapping the patient journey and treatment patterns in early-stage (stage I-III) non-small cell lung cancer

IntroductionWe map the patient journey from symptom onset to intervention and describe primary treatment in a retrospective population-based cohort study of patients in a large healthcare-provider. MethodsNewly diagnosed adult patients diagnosed with stages I-III non-small cell lung cancer (NSCLC) between 2016 and 2019 were identified from the Israel National Cancer Registry and chart review was performed to extract de-identified data. The following timelines were constructed: from symptom onset to imaging, imaging to biopsy, and biopsy to primary treatment initiation. Cutoff: 31st December 2021. The initial symptom was captured up to one year prior to biopsy. ResultsAmong 302 patients (41 % female, 70 % >=65 years, 79 % former or current smoking, 62 % adenocarcinoma), 34.1 % stage I, 10.3 % stage II, 42.1 % stage III and 13.6 % unknown (AJCC ver. 8). In the baseline year, 80.5 % of patients reported at least one symptom to their physician, and 12.3 % reported four or more symptoms. The most common symptoms reported were cough (29.8 %), pneumonia (24.2 %), chest pain (18.5 %), bronchitis (17.5 %) and wheezing (17.2 %). For patients with an initial symptom (n=243) median time from symptom onset to imaging was 5.5 months (95% CI:4.8–6.3), and time from imaging to primary treatment initiation was 2.6 (2.3–2.9) months in all patients. Total duration from symptom to intervention was 8.5 months (7.6–9.3). Over 93 % of stage I patients underwent surgery and 4.9 % received definitive radiation. Over 83 % of stage II patients underwent surgery; of these, 54.8 % received adjuvant/neoadjuvant chemotherapy. Of stage III patients, 68.5 % received definitive chemoradiation (half received durvalumab), and the remaining underwent surgery with adjuvant/neoadjuvant treatment. ConclusionA total of 80.5 % of patients were symptomatic and the median duration from symptom onset to treatment initiation was 8.5 month long. Improving patient and physician awareness to lung cancer symptoms, and the introduction of screening programs are essential for reducing those delays.

Development of a novel cancer diagnostic center to facilitate care coordination for patients with new or suspected diagnoses of cancer.

81 Background: Navigating a cancer diagnosis is a multifaceted challenge, characterized by intricate care coordination that creates potential for workup and treatment delays, lapses in care, and potentially negatively affecting clinical outcomes. We have developed a novel physician and advanced practitioner-led cancer diagnostic program (CDP) to help navigate patients with a suspected cancer through the diagnostic and staging workup, discussion of results, and linkage to oncologic care. Patients are referred to the CDP, an administrative intake coordinator creates a medical chart, verifies insurance, gathers records, and schedules appointments. An intake nurse reaches out within 24 hours to obtain clinical information and review of systems. Patients are offered an in-person or video visit with the advanced practitioner for history and physical, labs, and further coordination of testing. Here, we aim to describe the demographic and clinical patterns of referral and clinical outcomes of patients who were referred to a CDP over one calendar year. Methods: We retrospectively analyzed 154 patients with a new cancer diagnosis to have at least 1 encounter at the Johns Hopkins CDP between January 1, 2022, and December 31, 2022. Data were retrospectively collected from medical records and stored within Johns Hopkins REDCap. Descriptive analyses were used to describe the data. Results: Among the 154 total patients included in this analysis, 65.6% were White, 24.7% were Black, 3.2% were Asian, and 1.9% were of Hispanic, Latino, or Spanish origin. Insurance coverage was most frequently (46.8%), Medicare (40.3%), and Medicaid (8.4%). Referral distribution shows 50 inpatient and 104 outpatient referrals. Primary cancer diagnoses were most often gastrointestinal (39.6%), upper airway and lung (26.6%), and genitourinary (9.1%). Conclusions: The Johns Hopkins CDP exemplifies the potential for dedicated diagnostic and treatment initiation programs to improve oncologic care, particularly for vulnerable populations. The center facilitates expedited diagnostic resolution, to increased ease of workup for patients and providers, and potentially improve clinical outcomes such as linkage to care and time to treatment. Accepting referrals from inpatient and outpatient settings captures a broad patient pool, including those who may otherwise experience lapses in care owing to complex care navigation needs. In conclusion, we describe a novel care delivery model to potentially optimize healthcare delivery in oncologic care. Inpatient Referral Outpatient Referral Percent minority populations 34% 23.1% Stage 4 at diagnosis 74% 52.9% Patients initiating treatment with curative intent 42.3% 30% Median length of hospitalization 7 days N/A Median time from pathology results to discharge -2.5 days N/A Median time from pathology results to treatment initiation 20 days 16.5 days

Comparing Glucagon-like peptide-1 receptor agonists versus metformin in drug-naive patients: A nationwide cohort study.

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are increasingly being prescribed in drug-naive patients. We aimed to contrast add-on therapy, adherence, and changes in biomarkers, 1 year after treatment initiation with GLP-1 RA or metformin. Using Danish nationwide registers, we included incident GLP-1 RA or metformin users from 2018 to 2021 with glycated hemoglobin (HbA1c) ≥ 42 mmol/mol. GLP-1 RA initiators were matched to metformin initiators in a ratio of 1:1 to assess outcomes in prediabetes and diabetes. Main outcomes analyzed were 1-year risk of add-on glucose-lowering medication and 1-year risk of nonadherence. One-year risks were estimated with multiple logistic regression and standardized. Multiple linear regression was used to estimate the average differences in biomarker changes. In total, 1778 individuals initiating GLP-1 RA and metformin were included. After standardizing for various factors, GLP-1 RA compared with metformin was associated with reduced 1-year risk of add-on glucose-lowering treatment in patients with prediabetes (1-year risk ratio [RR]: 0.27, 95% confidence interval [CI]: 0.10-0.44) and diabetes (RR: 0.67, 95% CI: 0.37-0.98). GLP-1 RA was associated with higher 1-year risk of nonadherence among patients with prediabetes (RR: 1.60, 95% CI: 1.45-1.75), but no difference in patients with diabetes (RR: 0.88, 95% CI: 0.70-1.06). Compared to metformin, GLP-1 RA was associated with greater HbA1c reduction (prediabetes: -2.59 mmol/mol 95% CI: -3.10 to -2.09, diabetes: -3.79 mmol/mol, 95% CI: -5.28 to -2.30). GLP-1 RA was associated with a reduced risk of additional glucose-lowering medication, achieving better glycated hemoglobin control overall. However, among patients with prediabetes, metformin was associated with better adherence.

Outcomes with initiation of inpatient immunotherapy.

7 Background: Immune checkpoint inhibitors (ICIs) have transformed cancer care; however, studies establishing their benefit have been primarily conducted in robust patients (pts) with good performance status. Administration of ICI to hospitalized pts remains a subject of debate. While there is often a desire to reverse clinical course in patients who are acutely ill, previous studies show minimal benefit from anticancer therapy near the end of life with the potential for toxicity. While ICI are generally better tolerated than traditional cancer therapies, the median time to response ranges from 2-6 months and pts with a poor PS may not derive benefit. ICIs also bring significant financial burdens to pts and healthcare systems. The role of ICIs in the inpatient setting remains unclear. Methods: This study retrospectively examined pts who received PD-(L)1 inhibitors while IP between 2016 and 2023 at MedStar Georgetown University Hospital. Data were collected manually from institutional EMR. Descriptive statistics were used to depict the pt population and show their outcomes. The Kaplan-Meier method estimated survival probabilities from treatment initiation to follow-up or death, with 95% confidence intervals (α = 0.05). The Log rank non-parametric test compared survival distributions among ICIs. Results: Of the 38 pts who initiated ICI as an inpatient, 16 were male (42.1%) and 22 were female (57.9%). The median age was 60 years (31–88 years). Gastrointestinal malignancies were most common indication (31.6%), followed by thoracic/head and neck (21.1%) and hematologic (18.4%) cancers. Among the cohort, 26.3% received nivolumab, 68.4% received pembrolizumab, and 5.3% received a combination of nivolumab and ipilimumab. PD-L1 status was unknown for the majority (79.0%) of pts at time of ICI; 15.8 % were known to be PD-L1 high. Only 14 of 35 (40.0%) patients went on to receive any additional immunotherapy after discharge. The median days to death after discharge was 16 days (0-376 days), with a mean of 36.4 days. The median overall survival was 137 days from IP treatment initiation. The survival probability at 91 days was 65.5% (95% CI: 45.4-79.7) and 31.0% (95% CI: 15.6-47.9) at 182 days. No significant differences were observed between the survival distributions by ICI type (p=0.966) or primary malignancy (p=0.488). Conclusions: Our findings underscore the complexities of initiating inpatient ICI treatment and question its appropriateness. Delaying ICI to outpatient settings may enhance pt tolerance, optimize outcomes, and potentially mitigate unnecessary costs. This approach may allow thorough consideration of performance status outside the hospital, possibly improving treatment effectiveness while reducing futile acute care costs.

Single-inhaler triple versus LABA-ICS therapy for COPD: Comparative safety in real-world clinical practice

Recent treatment guidelines for chronic obstructive pulmonary disease (COPD) have replaced the long-acting beta2-agonist and inhaled corticosteroid (LABA-ICS) combination with single-inhaler triple therapy that adds a long-acting muscarinic antagonist (LAMA-LABA-ICS). Yet, the corresponding trials reported numerically higher incidences of cardiovascular adverse events with triple therapy compared with LABA-ICS. Does single-inhaler triple therapy increase the incidence of major adverse cardiovascular events, compared with LABA-ICS, in a real-world clinical practice setting? We identified a cohort of COPD patients, 40 years or older, treated during 2017-2021, from the United Kingdom's Clinical Practice Research Datalink. Among LAMA-naïve patients, initiators of single-inhaler triple therapy were matched 1:1 to LABA-ICS users on time-conditional propensity scores. They were compared on the incidence of major adverse cardiovascular events (MACE), defined as hospitalization for myocardial infarction or stroke, or all-cause-mortality, over one year. The cohort included 10,255 initiators of triple therapy and 10,255 matched users of LABA-ICS. The incidence rate of MACE was 11.3 per 100 per year with triple therapy compared with 8.7 per 100 per year for LABA-ICS. The corresponding adjusted hazard ratio (HR) of MACE with triple therapy was 1.28 (95% CI: 1.05-1.55), relative to LABA-ICS, though the increase was mainly in the first four months (HR 1.41; 95%CI: 1.14-1.74). The HR of all-cause death was 1.31 (95% CI: 1.06-1.62), while for acute myocardial infarction and stroke hospitalization it was 1.00 (95% CI: 0.56-1.79) and 1.06 (95% CI: 0.48-2.36), respectively, with triple therapy, relative to LABA-ICS. In a real-world setting of COPD treatment, patients who initiated single-inhaler triple therapy had an increased incidence of MACE compared with similar patients treated with a LABA-ICS inhaler. This small increase was due to the all-cause mortality component, occurring mainly in the first four months after treatment initiation.

Fièvre Q chronique. Revue de la littérature à propos d’un cas de spondylodicite à hémocultures négatives

IntroductionFever is a cosmopolit zoonosis due to Coxiella burnetii. The diagnosis of chronic Q fever can be really misleading. The growth of this bacterium is difficult and blood cultures are often negatives. Case presentationWe rapport here the case of a 69-year-old man presenting with an alteration of his general condition and low back pain. He suffered from a well-controlled HIV infection and lower limb arteriopathy treated with a cross-femoral bypass. A computed tomography scan revealed a L3–L4 abscessed spondylodiscitis but multiple blood cultures remained sterile, and the transthoracic echocardiography was normal. PET scan showed a hypermetabolism on L3–L4 vertebrae but also indicated an intense uptake of the cross-femoral bypass. C. burnetii serology was in favour of a chronic Q fever. The management of this chronic Q fever needed a multidisciplinary discussion. Three months after the treatment initiation, C. burnetii serology was reduced by a titer and has stabilized 6months to a year. ConclusionChronic Q fever and mostly osteoarticular diseases are difficult to diagnose. We have to evoke the diagnosis of osteoarticular chronic Q fever in case of insidious inflammatory syndrome, negatives blood cultures spondylodiscitis especially when associated to endocarditis or vascular infection, and in case of spondylodiscitis with a granulomatous histology without Mycobacterium tuberculosis. Although there are many complementary tests (PET scanner, PCR), serology remains the cornerstone of diagnosis.

Planned Dental Extractions After Radiation Therapy.

Nonrestorable teeth are recommended to be extracted prior to radiation therapy (RT). Occasionally, preradiation extractions introduce unacceptable delays in treatment initiation. Planned dental extractions immediately postradiation presents an alternative strategy, though outcomes are uncertain. To evaluate the feasibility and safety of dental extractions immediately postradiation. A prospective cohort study including patients planned for curative-intent RT but unable or unwilling to proceed with 1 or more extractions recommended pretreatment was carried out. From January 2020 to September 2022, 58 patients were screened and 50 enrolled. The dental care was performed at a single academic department and the cancer care at regional centers. Analysis took place between September 22, 2023, and June 10, 2024. On completion of RT, patients were recommended to complete extractions as soon as feasible, and ideally within 4 months. The primary end point was the actuarial cumulative incidence of exposed alveolar bone noted by any practitioner at any time after extraction, calculated using Gray method with death as a competing risk. As a pilot study, no formal power calculation was performed; resources allowed for 50 evaluable patients. Among the 50 participants enrolled, RT was nonoperative for 32 patients (64%) and postoperative for 18 patients (36%). Intensity-modulated RT (IMRT) was delivered in all patients. Of the 50 patients, 20 (40%) declined dental extractions immediately postradiation and the remaining 30 (60%) underwent a median (range) of 8.5 (1-28) extractions at a median (range) of 64.5 (13-152) days after RT. The median (IQR) follow-up for survivors without exposed bone was 26 (17-35) months from the end of RT. The 2-year cumulative incidence of any exposed bone was 27% (95% CI, 14%-40%). The 2-year incidence of exposed bone for those who underwent dental extractions immediately postradiation was 40% (95% CI, 22%-58%) and 7% (95% CI, 0%-22%) for those who did not. Of the 13 who developed exposed bone: 4 resolved, 1 was lost to follow-up, and 8 were confirmed as osteoradionecrosis. This cohort study found that postradiation dental extractions incur considerable risk, even if performed within a 4-month window.

Therapeutic hypothermia: A descriptive, cohort study conducted over 10 years at a tertiary care public hospital.

Introduction. Therapeutic hypothermia (TH) reduces the risk of death or disability in children with moderate to severe hypoxic ischemic encephalopathy (HIE). Objective. To describe a population of patients with HIE that required TH and their course until discharge. Population and methods. Retrospective, descriptive, cohort study. All patients admitted to TH between 2013 and 2022 were studied. Epidemiological, clinical, monitoring, and treatment data were assessed, together with supplementary tests and condition at discharge. Risk factors were compared between deceased patients and survivors; and, among the latter, those requiring special healthcare needs (SHCN) at discharge. Results. A total of 247 patients were included. Mortality: 11%. Most common sentinel event: prolonged second stage of labor (39%). Treatment initiation: median of 5 hours of life. Seizures: 57%. Intravenous erythropoietin: 66.7%. Abnormal pattern in brain function monitoring: 52%. Normalization of monitoring: median of 24 hours. Pathological magnetic resonance imaging: 42%. Predictor variables of mortality: severe Sarnat and Sarnat staging and pathological ultrasound upon admission. Conclusion. The overall mortality rate was 11%. Referrals increased more markedly since 2018. The time of TH initiation was later than in previous reports. Severe neurological signs as per the Sarnat and Sarnat staging and a pathological baseline cranial ultrasound were independent predictors of mortality at discharge. Patients with SHCN at discharge showed a normalized tracing in the amplitude-integrated electroencephalography performed later. The most common finding in the magnetic resonance imaging was basal ganglia involvement. No statistically significant differences were observed in terms of clinical characteristics or complications among patients who received erythropoietin.

Topical Application of 0.05% Cyclosporine for the Treatment of Neurotrophic Keratopathy Secondary to Herpes Simplex Keratitis

The purpose of this study was to assess the effectiveness and tolerability of 0.05% cyclosporine A (CsA) eye drops for neurotrophic keratopathy (NK) secondary to herpes simplex keratitis (HSK). Fifteen patients (15 eyes) with prior HSK and secondary NK, classified as stage 2 or 3 on the basis of the Mackie classification, were enrolled. All patients received a combined treatment regimen of 0.05% CsA eye drops (1 drop 4 times daily), a silicone hydrogel bandage contact lens, and 0.15% ganciclovir ophthalmic gel (1 drop 3 times daily). For patients achieving corneal healing, CsA was continued at a reduced dosage of twice daily for an additional 2 months and other treatments were discontinued. Follow-ups were scheduled at weeks 1, 2, 3, and 4 and at months 2 and 3 after treatment initiation, followed by a 3-month follow-up period. Key outcomes, including best-corrected visual acuity, Schirmer I test, and corneal sensitivity, were assessed at each visit before and after treatment. Significant reductions were observed in the area of corneal defects, expressed as proportion of total corneal area, throughout follow-up period. Complete corneal healing was achieved by 13.3% of patients by week 2, 60.0% by week 3, 86.7% by week 4, and 100.0% by week 8, with the mean (SD) time to healing being 3.8 (1.8) weeks (range, 2-8 weeks). Additionally, significant improvements were noted in diseased eyes for best-corrected visual acuity, tear secretion (Schirmer I test values), and corneal sensitivity after treatment. CsA eye drops, with bandage lenses and ganciclovir, effectively resolve NK from HSK, without adverse effects. This combination therapy shows promise for future clinical use and research. Our study is a retrospective observational study because it involves the analysis of previously collected data, so the study was not registered prior to its commencement. However, if it is necessary for publication, we are willing to proceed with retrospective registration.

Pathological response following neoadjuvant immune checkpoint inhibitors in patients with hepatocellular carcinoma: a cross-trial, patient-level analysis

Neoadjuvant use of immune checkpoint inhibitors (ICIs) before liver resection results in pathological tumour regression in patients with hepatocellular carcinoma. We aimed to describe the characteristics of pathological responses after preoperative ICI therapy for hepatocellular carcinoma and to evaluate the association between the depth of tumour regression and relapse-free survival. In this cross-trial, patient-level analysis, we performed a pooled analysis of data from patients with hepatocellular carcinoma receiving ICI therapy before liver resection as part of a global collaborative consortium (NeoHCC) of five phase 1 and 2 clinical trials and standardised observational protocols conducted in 12 tertiary referral centres across the USA, UK, and Taiwan. Eligible patients were adults (aged ≥18 years) diagnosed with hepatocellular carcinoma by tissue core biopsy before treatment initiation, a Liver Imaging Reporting and Data System score of 5 on imaging, or both, with an Eastern Cooperative Oncology Group performance status score of 0-1, and no extrahepatic spread or previous ICI treatment. Pathological response was measured as the percentage of non-viable tumour in the resected surgical specimen, with major pathological response corresponding to at least 70% tumour regression and pathological complete response corresponding to 100% tumour regression. We correlated pathological response with radiological overall response using RECIST criteria (version 1.1) and relapse-free survival, and evaluated the threshold of tumour regression that could be optimally associated with relapse-free survival. At data cutoff on Jan 31, 2024, 111 patients were included in the study, of whom data on pathological response were available for 104 (94%) patients. Patients received treatment from Oct 5, 2017, to Nov 15, 2023, mostly ICI combinations (76 [69%]), for a median of 1·4 months (IQR 0·7-2·9). 87 (78%) patients were men and 24 (22%) were women. Most patients had underlying viral chronic liver disease (73 [66%]) and Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma (61 [55%]), without portal vein thrombosis (87 [78%]). We observed major pathological response in 33 (32%) patients and pathological complete response in 19 (18%) patients. Radiological overall response was associated with major pathological response, with 23 (74%) of 31 patients with radiological response showing major pathological response compared with ten (14%) of 73 patients without radiological response (p<0·0001). However, ten (30%) of 33 major pathological responses were not predicted by radiological response. After a median follow-up of 27·2 months (95% CI 22·3-32·1), median relapse-free survival for the whole cohort was 43·6 months (95% CI 28·3-not evaluable). Relapse-free survival was significantly longer in patients with major pathological response than in those who did not have a major pathological response (not reached [95% CI not evaluable-not evaluable] vs 28·3 months [12·8-43·8]; hazard ratio 0·26 [0·10-0·66]; p=0·0024) and in patients with pathological complete response than in those who did not have a pathological complete response (NR [95% CI not evaluable-not evaluable] vs 32·8 months [15·0-50·5]; 0·19 [0·05-0·78]; p=0·010). Unbiased recursive partitioning of the cohort for the risk of relapse, death, or both identified a threshold of 90% as the optimal cutoff of pathological tumour regression to predict improved relapse-free survival. The extent of tumour regression following neoadjuvant ICI therapy could identify patients with improved relapse-free survival following liver resection. The threshold of at least 90% tumour regression should be validated for its surrogate role for relapse-free survival in phase 3 randomised controlled trials. None.