Treatment Characteristics Research Articles

Clinical profiling, treatment characteristics and outcome in Behcet's Disease (BD)-A retrospective cohort study from Karnataka Rheumatology Association (KRA).

Behcet's disease (BD) has a heterogeneous and unpredictable phenotype that differs in various geographical areas. To describe the clinical phenotype & outcome of Behcet's disease(BD) from Karnataka, India and compare them with large cohorts from endemic regions. Databases of practising rheumatologists from Karnataka were reviewed to retrieve clinical characteristics, course of illness, prescribing information and outcome at last follow-up of patients clinically diagnosed as BD. The classification criteria, namely revised International criteria for Behcet's disease (rICBD) and International study group (ISG) criteria were applied. Outcome was defined as complete or partial remission, persistent disease or relapse. We included 72 patients, equal gender distribution and mean age 37.4 ± 12.8years from 8 rheumatology centres. Commonest presentations were recurrent oral aphthosis 58(80.6%), genital ulcers 36(50%) and ocular manifestations 40(55.6%). Three-quarters [51/72(70.8%)] fulfilled rICBD criteria whereas only half [36/72(50%)] fulfilled ISG criteria. Apart from glucocorticoids [53/72(73.6%)], frequently prescribed therapies were colchicine 39(54.2%) and azathioprine 35(48.6%). Eleven-patients received biologics(anti-TNF-α) and JAK inhibitors to treat severe organ involvement. HLA-B*51 and pathergy tests were positive in 27/45(60%) and 12/34(35.3%) patients respectively. Outcomes were documented in 94.4%(68/72) patients at median follow-up of 24 (12;36) months. Majority [46/68(67.6%)] had complete remission, 17/68(25%) had partial remission, 4/68(5.9%) had persistent while 1/68(1.5%) had relapsing course. Majority of BD patients had orogenital aphthosis and ocular manifestations and an excellent response to treatment. Key Points • In our region, Behçet's Disease primarily manifests with recurrent oral aphthae and ocular involvement, with comparatively lower incidence of severe genital ulcers and neurological involvement than in endemic regions. • Apart from glucocorticoids, colchicine and azathioprine are the most commonly used agents. Biologics and JAK inhibitors are prescribed infrequently, primarily in cases of severe organ involvement. • A significant proportion of patients achieved either complete or partial remission during follow-up, with no observed mortality suggesting a milder disease course and better outcome compared to endemic regions. • Gender, HLA-B*51 status, and pathergy response did not exert any significant influence on the clinical profile or outcome in BD patients in Karnataka.

Methodological Considerations in Evaluating Breast Cancer Screening Studies.

In evidence-based medicine frameworks, the highest level of evidence is derived from quantitative synthesis of double-masked, high-quality, randomly assigned controlled trials. Meta-analyses of randomly assigned controlled trials have demonstrated that screening mammography reduces breast cancer deaths. In the United States, every major guideline-producing organization has recommended screening mammography in average-risk women; however, there are controversies about age and frequency. Carefully controlled observational research studies and statistical modeling studies can address evidence gaps and inform evidence-based, contemporary screening practices. As breast imaging radiologists develop and evaluate existing and new screening tests and technologies, they will need to understand the key methodological considerations and scientific criteria used by policy makers and health service researchers to support dissemination and implementation of evidence-based screening tests. The Wilson and Jungner principles and the U.S. Preventive Services Task Force general analytic framework provide structured evaluations of the effectiveness of screening tests. Key considerations in both frameworks include public health significance, natural history of disease, cost-effectiveness, and characteristics of screening tests and treatments. Rigorous evaluation of screening tests using analytic frameworks can maximize the benefits of screening tests while reducing potential harms. The purpose of this article is to review key methodological considerations and analytic frameworks used to evaluate screening studies and develop evidence-based recommendations.

Keratinocyte carcinomas in survivors of childhood cancer: A report from the childhood cancer survivor study

BackgroundChildhood cancer survivors (CCS) are at increased risk for keratinocyte carcinomas (KC) however, the long-term incidence of single and multiple KC is not well established. ObjectiveIdentify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS. MethodsKC were identified among Childhood Cancer Survivor Study participants, a cohort of five-year cancer survivors diagnosed <21 years of age between 1970-1999 in North America. Cumulative incidence was estimated, and multivariable models assessed relative rates of KC associated with survivor and treatment characteristics. ResultsAmong 25,658 participants, 1,446 developed 5,363 KC (93.5% basal cell carcinoma, 6.7% squamous cell carcinoma; mean age 37.0 years (range 7.3-67.4), mean latency 25.7 years; 95.3% White and 88.4% with radiotherapy [RT]). Mean lesion count was 3.7 with 26.1% experiencing ≥4. RT imparted a 4.5-fold increase in the rate of any KC and 9.4-fold increase in the rate of ≥4 KC. Allogeneic and autologous hematopoietic cell transplant were associated with a 3.4- and 2.3-fold increased rate of KC, respectively. LimitationsParticipant self-reporting of some data including race without skin phototype and past medical history may have impacted analysis. ConclusionsThe burden of KC in CCS remains high, but predictable risk factors should guide screening

Impact of proton versus photon adjuvant radiotherapy on overall survival in the management of skull base and spinal chordomas: a National Cancer Database analysis.

Chordomas are rare tumors that originate from undifferentiated remnants of the notochord. Currently, there are no established guidelines regarding the choice of adjuvant radiation modality for patients surgically treated for chordomas. Using a nationwide, multicenter database, the authors aimed to compare long-term survival outcomes associated with the use of proton or photon adjuvant therapy for the management of chordomas of skull base and spine. The National Cancer Database (NCDB) was queried for chordoma cases from 2004 to 2017. Patient, tumor, and treatment characteristics were extracted from the database. The primary outcome was overall survival (OS). Kaplan-Meier survival analyses were conducted to investigate differences in outcome on propensity score-matched cohorts of patients treated with proton or photon adjuvant radiotherapy. Of the 3490 patients available, 424 met the inclusion criteria for this study. In the prematching analysis, patients receiving adjuvant photon therapy were significantly older (median age 57.0 vs 45.0 years, p < 0.001) and were more commonly male (61% vs 43%, p < 0.001) compared with those receiving proton therapy. Races were equally distributed among radiotherapy modalities (p = 0.64). Patients with chordomas of the mobile spine or sacrum were less likely to receive proton compared with photon therapy (37% vs 58%). Patients receiving proton therapy were more often represented among private insurance holders (69% vs 52%, p < 0.001) as well as in the highest income quartile (52% vs 40%, p = 0.008). Patients traveled farther to receive proton, as opposed to photon, therapy (median 59.0 vs 34.9 miles, p < 0.001). On postmatching Kaplan-Meier analysis encompassing all chordoma cases, no difference in OS between photon and proton therapy was revealed (HR 0.75, 95% CI 0.39-1.44; p = 0.39). A Kaplan-Meier analysis only including patients with skull base chordomas reached similar results (HR 0.83, 95% CI 0.31-2.22; p = 0.71). In patients with spine chordomas, however, a significant difference was found, as proton therapy exhibited a superior OS over photon therapy (HR 0.28, 95% CI 0.09-0.81; p = 0.012). Based on this nationwide analysis, patients with private insurance and higher income were more likely to receive proton adjuvant radiotherapy, while those with spinal or sacral chordomas were less likely to receive this modality. Despite this disparity, an OS benefit was observed in patients with chordomas of the spine and sacrum who received adjuvant proton therapy, in comparison with a matched cohort of patients treated with photon therapy. Conversely, this advantageous outcome was not evident in cases of chordomas located at the skull base.

Placebo Effect in the Treatment of Patellar Tendinopathy and Its Influencing Factors: Systematic Review With Meta-analysis and Meta Regression of Randomized Controlled Trials.

The effectiveness of nonsurgical treatment of patellar tendinopathy is questioned due to the conflicting results of placebo-controlled randomized controlled trials (RCTs) in which placebo arms often show impressive results. To quantify the magnitude of placebo effect of the different nonsurgical treatments of patellar tendinopathy. We also evaluated the influence of patients and treatments characteristics on the response to the placebo. Systematic review; Level of evidence, 1. We searched PubMed, Web of Science, Embase, Scopus, Cochrane Library, and gray literature databases on May 10, 2023, with no time limitation. RCTs on nonoperative treatment of patellar tendinopathy, including a placebo control arm reporting the evolution of symptoms after placebo administration, were included. A single-arm meta-analysis was performed with the Victorian Institute of Sport Assessment-Patella (VISA-P) at mid-term follow-up (3-6 months) as the primary outcome. The VISA-P score at short-term (1-3 months) and long-term (6-12 months) follow-ups, as well as visual analog scale (VAS) for pain at all 3 time points were also analyzed. A subanalysis based on the type of placebo and a meta-regression were conducted to look for potential determinants of the placebo effect. Risk of bias and level of evidence were also analyzed using the revised tool for risk of bias in randomized trials and Grading of Recommendations Assessment, Development and Evaluation. In total, 14 studies (251 patients) were included. VISA-P score at mid-term follow-up (3-6 months) showed statistically significant improvements of 13 of 100 points (P = .001). The change at short-term follow-up (1-3 months) was not statistically significant, whereas at long-term follow-up (6-12 months) it was 27 of 100 points (P < .001). Regarding VAS, results were statistically significant only at mid-term (MD = -1.5/10; P = .02) and long-term (MD = -3.2/10; P < .001) follow-ups. The meta-regression showed positive correlations between the response to placebo and the follow-up length (P < .001) and the effect size in the experimental group (P = .006). The level of evidence was moderate for mid- and long-term results and low for short-term results. The placebo effect for nonsurgical treatments of patellar tendinopathy is long-lasting (up to 12 months) and statistically and clinically significant. It has a perceived and true component and differs among treatments. The duration of follow-up and the effect size of experimental groups correlate with the magnitude of the placebo component, underlining the importance of RCTs to determine the effectiveness of new treatments of patellar tendinopathy.

Examining inequities associated with incarceration among breast cancer patients.

Breast cancer treatment patterns and quality of care among patients experiencing incarceration are underexplored. This study examined associations between incarceration and breast cancer disease and treatment characteristics. This retrospective analysis was conducted at a tertiary center in the Southeastern United States that serves as the state's safety-net hospital and primary referral site for the state's prisons. All patients ≥18 years diagnosed with breast cancer between 4/14/2014-12/30/2020 were included. Incarceration status was determined through electronic health record review. Linear regression was used to estimate the association of incarceration with time to treatment. Unadjusted overall survival (OS) was estimated using the Kaplan-Meier method with log-rank tests to compare groups. Of the 4329 patients included, 30 (0.7%) were incarcerated at the time of diagnosis or treatment (DI) and 4299 (99.3%) had no incarceration history (NI). Compared to patients who were NI, patients who were DI were younger (p < 0.001), more likely to be unmarried (p < 0.001), and more likely to have family history of breast cancer (p = 0.02). Patients who were DI had an increased time from diagnosis to neoadjuvant chemotherapy (+47.2 days on average, 95% CI 3.9-90.5, p = 0.03) and from diagnosis to surgery (+20 days on average, 95% CI 6.5-33.5, p = 0.02) compared to NI patients. No difference in OS was observed (log-rank p = 0.70). Patients who are incarcerated experienced significant delays in breast cancer care. While no differences in mortality were appreciated, these findings are concerning, as they indicate poorer care coordination for patients who are incarcerated. Further research is necessary to understand the full scope of these disparities and elucidate factors that contribute to them.

Trends in Presentation, Management, and Survival of Women With Breast Cancer in a Multiethnic, Middle-Income Asian Setting.

Granular data on breast cancer (BC) are pertinent for surveillance, planning, and monitoring of cancer care delivery. We determined the trends in clinical presentation, management, and survival of women with BC in a multiethnic middle-income Asian setting over 15 years. Data of 7,478 Malaysian women newly diagnosed with invasive BC between 2005 and 2019 from three hospital-based cancer registries were included. Trends in demographic, tumor, and treatment characteristics were compared across period 1 (P1): 2005-2009, period 2 (P2): 2010-2014, and period 3 (P3): 2015-2019. Overall survival and net survival were determined. More women in P3 than P1 were older than 60 years at diagnosis. Only a marginal increase in proportion of women with stage I disease was observed (23.7% v 27.2% in P1 and P3, respectively, P = .004). Nonetheless, patients were increasingly presenting with smaller tumors, fewer axillary node involvement, well-differentiated tumors, and hormone receptor expression in recent times. Proportion of women with human epidermal growth factor receptor 2 (HER2)-overexpressed tumors significantly decreased. Among indicated patients, receipt of anticancer therapies was somewhat similar over the calendar periods, except for neoadjuvant chemotherapy and anti-HER2 therapy, where increases in administration were noted. Significant improvements in survival were observed over the 15 years, particularly for HER2-overexpressed BCs. Although the improvements in BC survival that we have observed validate ongoing cancer control efforts and treatment advances, study findings suggest that more could be done for earlier detection and improved access to effective therapies in our settings.

Treatment of Esophageal Atresia in Germany: Analysis of National Hospital Discharge Data From 2016 to 2022

BackgroundEsophageal atresia (EA) is a complex malformation. Multidisciplinary management is necessary, with the operative repair being the most challenging step in the treatment algorithm. The complete care structure for children with EA in Germany has not been analyzed yet. MethodsIn the observed period 2016–2022, inpatient EA cases were analyzed 1) during the hospital stay of birth, and 2) during the hospital stay of corrective surgery in patients aged up to 365 days, both based on national hospital discharge data. Patients’ comorbidities, hospital caseload, treatment characteristics (e.g. surgical approach) and outcome parameters were analyzed. Results1) 1190 newborn EA cases were treated in 260 hospitals during the perinatal period. 54% had at least one additional malformation, and 16% had a birthweight below 1500 g. In-hospital mortality was 8.4%.2) 1475 corrective operations for EA were performed in 111 hospitals with a consistent median annual caseload of 2 (P25–P95 1–8) per hospital. At least one indicator for a complicated perioperative course was documented in 63.7% of cases. The use of bronchoscopy was coded in 50% of cases. Median ventilation time during the entire hospital stay was 176 h (P25–P95: 95–1759 h). ConclusionsNewborns with EA are complex and early postoperative complications are common. The care structure is decentralized, and there was no trend towards centralization in the observed period. The low documented use of bronchoscopy is noteworthy. Centralization of the highly complex and schedulable corrective surgery for EA is necessary to evaluate outcomes and might improve the quality of care and resource utilization. Category of the manuscript and type of studyoriginal article, observational cross-sectional study, secondary data analysis.

Recovery of cranial nerve neuropathies after LINAC-based stereotactic radiosurgery for benign cavernous sinus meningioma

PurposeCranial Nerve Neuropathies (CNNs) often accompany Cavernous Sinus Meningioma (CSM), for which Stereotactic Radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSR) are established treatments. This study assesses CNNs recovery in CSM patients treated with LINAC, offering insight into treatment effectiveness.MethodsThis study was conducted on 128 patients with CSM treated with LINAC-based SRS/FSR between 2005 and 2020 at a single institution. 46 patients presented with CNNs. The study analyzed patients’ demographics, clinical parameters, SRS/FSR treatment characteristics, post-treatment CNNs recovery duration, status, and radiological control on their last follow-up.ResultsThe median follow-up duration was 53.4 months. Patients were treated with SRS (n = 25) or FSR (n = 21). The mean pretreatment tumor volume was 9.5 cc decreasing to a mean end-of-follow-up tumor volume was 5.1 cc. Radiological tumor control was achieved in all cases. CNN recovery was observed in 80.4% of patients, with specific nerve recoveries documented as follows: extra-ocular nerves (43.2%), trigeminal nerve (32.4%), and optic nerve (10.8%). A higher CNNs recovery rate was associated with a smaller pre-treatment tumor volume (p < 0.001), and the median time-to-improvement was 3.7 months. Patients with tumor volumes exceeding 6.8 cc and those treated with FSR exhibited prolonged time-to-improvement (P < 0.03 and P < 0.04 respectively).ConclusionsThis study suggests that SRS/FSR for CSM provides good and sustainable CNNs recovery outcomes with excellent long-term radiological control. A higher CNNs recovery rate was associated with a smaller pre-treatment tumor volume. while shorter time-to-improvement was identified in patients treated with SRS compared to FSR, particularly in those with small pre-treatment tumor volume.

Suicide in individuals with eating disorders who had sought mental health treatment in England: a national retrospective cohort study

Although studies have suggested a high risk of suicide in people with eating disorders, most studies have focused on suicidal ideation and attempts. There is little research on the characteristics of people with eating disorders who died by suicide, nor investigation of trends over time. We aimed to compare the characteristics of patients with eating disorders who died by suicide versus patients with other mental health diagnoses who died by suicide in England and to examine the trends in rates. In this national retrospective cohort study, data on all people (aged ≥10 years) who died by suicide in England, UK, between Jan 1, 1997, and Dec 31, 2021, while under the care (within the previous 12 months) of mental health services were obtained from the National Confidential Inquiry into Suicide and Safety in Mental Health (NCISH), in which clinical information is collected via a questionnaire completed by the mental health professional responsible for the patient's care. Incidence of suicide in, and demographic, clinical, and treatment characteristics of, patients with a diagnosis of eating disorder (as recorded by the treating clinician) who died by suicide were compared with patients with other mental health diagnoses who died by suicide within the same timeframe using univariable logistic regression analysis. People with related lived experience were involved in the study design, implementation, interpretation, and writing of the manuscript. Of 119 446 people for whom NCISH were notified of dying by suicide in England, 30 795 were under the recent care of mental health services, of whom 30 246 had known diagnoses and were included in analyses. Of these individuals, 10 373 (34%) were female and 19 873 (66%) were male; 2236 (8%) were of minority ethnicity; 382 (1%) had a diagnosis of eating disorder and 29 864 (99%) had another mental health diagnosis. Compared with patients with other mental health diagnoses who died by suicide, patients with eating disorders were younger (median age 33 years [range 15-90] vs 45 years [10-100]), more often female (343 [90%] female and 39 [10%] male in the eating disorders group; 10 030 [34%] female and 19 834 [66%] male in the other diagnoses group), and less likely to have evidence of conventional risk factors for suicide such as living alone (odds ratio [OR] 0·68, 95% CI 0·55-0·84). 22 (6%) of 382 were from a minority ethnic group. Patients with an eating disorder were characterised by a greater clinical complexity (eg, self-harm [OR 2·31, 95% CI 1·78-3·00], comorbidity [9·79, 6·81-14·1], and longer duration of illness [1·95, 1·56-2·43]), and were more likely to have died following overdoses (2·00, 1·62-2·45) than patients with other diagnoses. Childhood abuse (52 [37%] of 140) and domestic violence (18 [20%] of 91) were common in patients with eating disorders. Similar to patients with other diagnoses, most (244 [75%] of 326) of those with eating disorders who died by suicide were rated as low risk by clinicians at last contact. The number of suicide deaths in patients with eating disorders rose between 1997 and 2021 (incidence rate ratio [IRR] 1·03, 95% CI 1·02-1·05; p<0·0001), but rates fell when accounting for the greater number of patients entering mental health services (IRR 0·97, 0·95-1·00; p=0·033). This study was focused on people who sought help from mental health services. It did not consider subtypes of eating disorders or include a control group, but it does highlight possible areas for intervention. The comprehensive provision of evidence-based treatment for eating disorders and underlying conditions to address the clinical complexity in these patients might help to reduce suicide. Recognising limitations in clinical risk assessment, addressing early life experiences and current adversities, and appropriate prescribing might also be of benefit. Suicide prevention must remain a priority for eating disorder services and mental health care more widely. The Healthcare Quality Improvement Partnership.

Effect of Statins on Patients With Osteoradionecrosis of the Jaw

BackgroundOsteoradionecrosis of the jaw (ORN) is a refractory late complication of radiation therapy. Radiation-induced fibrosis (RIF) is the most likely mechanism for developing ORN, and statins are effective against RIF. However, no reports have indicated the direct effectiveness of statins in treating ORN. PurposeThis study aimed to measure the association between statin exposure and ORN disease resolution. Study design, setting, sampleThis retrospective cohort study included patients with ORN diagnosed between January 2008 and December 2020 at the Hospital’s Department of Oral and Maxillofacial Surgery. Patients who were immunocompromised or followed up for < 6 months were excluded. Predictor variableThe predictor variable was statin exposure, which was defined as the use of statins for dyslipidemia by coincidence. Main outcome variableThe main outcome variable was ORN disease progression status (good prognosis). Patients who showed full recovery and improvement were included in the good prognosis group, and those who showed invariance and deterioration were included in the poor prognosis group. CovariatesWe analyzed the clinicodemographic including the age of onset, sex, history of smoking, alcohol consumption, history of chemotherapy, tumor site, association with dental treatment, location (maxilla or mandible), the time to ORN onset from radiation therapy, and stage of ORN, and treatment characteristics including hyperbaric oxygen therapy, long-term macrolide administration, and sequestrectomy. AnalysesWe analyzed the association between statin exposure/covariates and time to ORN improvement using bivariate and multivariate Cox regression. The significance level was set at p = 0.05. ResultsWe analyzed 102 patients, and the improvement rate was 32.4%. The favorable prognostic factors were statin exposure (adjusted hazard ratio [HR], 3.71; 95% confidence interval [CI], 1.62–8.50; p = 0.002), onset in the maxilla (HR, 2.15; 95% CI, 1.02–4.55; p = 0.045), and stage 1 of ORN (HR, 2.65; 95% CI, 1.20–5.83; p = 0.016). Conclusions and RelevanceIn this study, statin exposure, onset in the maxilla, and stage 1 of Lyons’s classification were favorable prognostic factors for ORN. Statins may be a novel and effective treatment for ORN.

Mexican Registry of Cardiomyopathies: baseline data, diagnostic strategies, and treatment approaches in Mexico.

The study aimed to know the clinical, demographic, diagnostic, and treatments characteristics in patients with cardiomyopathies in Mexico. The Mexican Registry of Cardiomyopathies (REMEMI) is an observational, prospective and national study of patients with cardiomyopathies, which includes: Dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM) and arrhythmogenic cardiomyopathy of the right ventricle (ARVC). A total of 1026 patients from most states of the Mexican Republic (19) were included, with 494 corresponding to DCM, 490 to HCM, 35 to RCM, and seven to ARVC. We found significant differences between the various cardiomyopathy phenotypes (p < 0.05) in the coexistence with diabetes, use of implantable defibrillator, presence of ventricular tachycardia, and NYHA functional class ≥ 1. There were no significant differences in age and predominant gender between each one. When analyzing by phenotype, we found that patients with HCM have limited use of diagnostic methods considered indispensable, such as cardiac magnetic resonance, Holter monitoring, and genetic testing in patients and their relatives. Seeking contemporary information through observational registries in Mexico is a valuable opportunity to understand the characteristics of the methods used in the study and treatment of diseases such as cardiomyopathies by Mexican physicians. It can provide information for the implementation of management guidelines and strategies to disseminate findings to improve healthcare in our country.

Epidemiological, clinical, biochemical, and treatment characteristics of brucellosis cases in Turkey.

In our study, we aimed to evaluate the epidemiological features of brucellosis and the efficacy of different treatment options in patients with various organ involvements. Patients diagnosed with brucellosis and treated in two different centers between 2009 and 2019 were retrospectively screened and evaluated regarding epidemiological and clinical features, laboratory findings, and treatment responses. The study included 297 complete-data patients (76% of rural patients were farmers). Farming (76%) and raw dairy (69%) were the main transmission methods. Most patients (98.6%) had positive tube agglutination tests. Ninety-two patients' blood and bodily fluid cultures grew Brucella spp. The incidence of leukopenia was 18.8%, thrombocytopenia 10.7%, anemia 34.3%, and pancytopenia 4.3%. Doxycycline and rifampicin were the major treatments, with streptomycin utilized in osteoarticular patients. Pregnant women with neurobrucellosis took ceftriaxone and trimethoprim-sulfamethoxazole. After one year, 7.1% of patients relapsed. Doxycycline + streptomycin and doxycycline + rifampicin had similar relapse rates (p = 0.799). The double- and triple-antibiotic groups had identical recurrence rates (p = 0.252). In uncomplicated brucellosis cases doxycycline + streptomycin and doxycycline + rifampicin treatments were equally effective. Again, there is no statistical difference in relapse development rates between double and triple combination treatments in uncomplicated brucellosis cases. Relapsed patients generally miss follow-ups, interrupt therapy, have osteoarticular involvement, and get short-term treatment. Patients with focused participation should be thoroughly checked at diagnosis and medicine, and treatment should be lengthy to prevent relapses.

Real-World Experience With Cemiplimab in Advanced Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most common nonmelanoma skin cancer in Canada. However, few real-world reports exist on the treatment of refractory locally advanced (LA) and metastatic cSCC with cemiplimab to date. The objective of this study was to characterize the demographic and clinical outcomes of advanced cSCC patients on cemiplimab in a real-world setting. Retrospective analysis of adult patients with refractory LA and metastatic cSCC treated with cemiplimab at the London Regional Cancer Program in Canada. Patient demographics and treatment characteristics were reported, as well as Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS). Forty patients were included in this study. Sixteen (40%) had LA disease and 24 (60%) had metastatic disease. Median treatment duration was 3.5 months (range: 0.6-29.4 months). Kaplan-Meier analyses of the entire study population revealed that the median OS was not reached [NR; 95% confidence interval (CI) 9.1 months-NR], but median PFS was 11.5 months (95% CI 7.0 months-NR). A total of 25% of patients experienced at least one adverse event from cemiplimab. Reasons for treatment discontinuation were death from any cause (25%), disease progression (15%), cemiplimab adverse events (5%), and other causes (15%). The 12 month estimates of OS and PFS were lower than pivotal phase I and II clinical trials. However, toxicity was tolerable. Cemiplimab remains a safe and effective therapy in patients with refractory LA and metastatic cSCC disease.

Signaling dynamics in coexisting monoclonal cell subpopulations unveil mechanisms of resistance to anti-cancer compounds

BackgroundTumor heterogeneity is a main contributor of resistance to anti-cancer targeted agents though it has proven difficult to study. Unfortunately, model systems to functionally characterize and mechanistically study dynamic responses to treatment across coexisting subpopulations of cancer cells remain a missing need in oncology.MethodsUsing single cell cloning and expansion techniques, we established monoclonal cell subpopulations (MCPs) from a commercially available epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer cell line. We then used this model sensitivity to the EGFR inhibitor osimertinib across coexisting cell populations within the same tumor. Pathway-centered signaling dynamics associated with response to treatment and morphological characteristics of the MCPs were assessed using Reverse Phase Protein Microarray. Signaling nodes differentially activated in MCPs less sensitive to treatment were then pharmacologically inhibited to identify target signaling proteins putatively implicated in promoting drug resistance.ResultsMCPs demonstrated highly heterogeneous sensitivities to osimertinib. Cell viability after treatment increased > 20% compared to the parental line in selected MCPs, whereas viability decreased by 75% in other MCPs. Reduced treatment response was detected in MCPs with higher proliferation rates, EGFR L858R expression, activation of EGFR binding partners and downstream signaling molecules, and expression of epithelial-to-mesenchymal transition markers. Levels of activation of EGFR binding partners and MCPs’ proliferation rates were also associated with response to c-MET and IGFR inhibitors.ConclusionsMCPs represent a suitable model system to characterize heterogeneous biomolecular behaviors in preclinical studies and identify and functionally test biological mechanisms associated with resistance to targeted therapeutics.

Uptake of ultra-hypofractionated radiation therapy following breast-conserving surgery among patients with early-stage breast cancer: a multi-institutional questionnaire survey.

In patients with early-stage breast cancer following breast surgery, ultra-hypofractionated (UHF) breast/chest wall radiation therapy (RT) has been shown to be non-inferior to a moderate-hypofractionated (MHF) regimen, with a minimal risk of breast induration, in the FAST-Forward trial, and UHF is now becoming the standard regimen in Europe. Herein, we aimed to investigate Japanese patients' attitudes toward the UHF regimen. A questionnaire-based survey was conducted at 13 RT centers in nine prefectures across Japan. All patients underwent breast-conserving surgery, followed by either conventional fractionation (2Gy/fr) or MHF (2.66Gy/fr) whole-breast irradiation (WBI) with or without a tumor bed boost. The questionnaire consisted of 13 questions mainly addressing quality-of-life during RT. Key questions included an 11-point scale (0-10) for rating the patients' enthusiasm for the UHF regimen and prioritization of the following treatment-related effects: treatment efficacy, acute/late adverse effects, physical/emotional/financial burden, and breast cosmesis. The patient and treatment characteristics were assessed by a physician. In total, 247 questionnaires were administered between November 2022 and June 2023. The age distribution was as follows: < 50:50s:60s: ≥ 70 = 59 (24%):76 (30%):63 (26%):49 (20%). Sixty-nine percent of patients rated their enthusiasm for the UHF regimen at ≥ 6 out of 10 points (45% rated 10/10). Treatment efficacy was the highest priority for most patients (89%), whereas breast cosmesis the lowest priority (53%). Patients' enthusiasm for UHF-WBI was observed across the cohort. These results could motivate researchers and clinicians to introduce UHF regimens in clinical practice.

Frequency of and risk factors associated with local recurrence after spinal stereotactic body radiation therapy without surgery.

This study aimed to identify factors associated with local recurrence after spinal stereotactic body radiation therapy (SBRT), focusing on patient movement during treatment and tumor characteristics. A total of 48 patients who underwent spinal SBRT alone without surgery from August 2017 to October 2022 were evaluated. Logistic regression analysis was conducted to identify factors associated with local recurrence, including patient movement and tumor characteristics such as soft tissue involvement and tumor volume. Patient movement during treatment was measured using cone beam computed tomography before and after irradiation. Among the included cases, 68.7% and 42.6% had soft tissue involvement and movement exceeding 1mm, respectively. The median follow-up duration for local recurrence was 11.6 (range: 0.7-44.9) months, whereas the median duration to local recurrence was 6.3 months. Within 12 months, 29.3% of the patients experienced local recurrence, among whom 43.9% moved ≥ 1mm during treatment, whereas 15.8% did not move. Univariable analysis found that both soft tissue involvement (OR = 10.3, 1.21-87.9; p = 0.033) and patient movement ≥ 1mm (OR = 5.75, 1.45-22.8; p = 0.013) were associated with local recurrence. Multivariable analysis identified patient movement as an independent prognostic factor for local recurrence (OR = 5.15, 1.06-25.0; p = 0.042). Our results suggest that patient movement during spinal SBRT was associated with local recurrence, emphasizing the need for better immobilization techniques and shorter delivery times to improve tumor control.

Endoscopic approach for biliopancreatic disease after pancreaticoduodenectomy: a 10-year single-center experience.

In surgically altered anatomy (SAA), endoscopic retrograde cholangiopancreatography (ERCP) can be challenging, and it remains debatable the choice of the optimal endoscopic approach within this context. We aim to show our experience and evaluate the technical and clinical success of endoscopic treatment performed in the setting of adverse events (AE) after pancreaticoduodenectomy (PD). This study was conducted on a retrospective cohort of patients presenting biliopancreatic complications after PD from 01/01/2012 to 31/12/2022. All patients underwent ERCP at our Endoscopy Unit. Clinical, instrumental data, and characteristics of endoscopic treatments were collected. 133 patients were included (80M, mean age = 65 y.o.) with a total of 296 endoscopic procedures (median = 2 procedures/treatment). The indications for ERCP were mainly biliary AE (76 cases, 57.1%). Technical success was obtained in 121 patients of 133 (90.9%). 112 out of 133 (84.2%) obtained clinical success. Nine patients out of 112 (8%) experienced AEs. Clinical success rates were statistically different between patients with biliary or pancreatic disease (93.4% vs 73.6%, p < 0.0001). Septic patients were 38 (28.6%) and showed a worse prognosis than non-septic ones (clinical success: 65.7% vs 91.5%, p = 0.0001). During follow-up, 9 patients (8%), experienced recurrence of the index biliopancreatic disease with a median onset at 20months (IQR 6-40.1). Our case series demonstrated that the use of a pediatric colonoscope in ERCP procedures for patients with AEs after PD is both safe and effective in treating the condition, even in a long-term follow-up.

Childhood-onset systemic lupus erythematosus: A descriptive and comparative study of clinical, laboratory, and treatment characteristics in two populations.

The aim of this study was to characterize childhood-onset systemic lupus erythematosus (SLE) in two large cohorts from Turkey and the United States. Patients diagnosed with childhood-onset SLE who fulfilled the 1997 American College of Rheumatology classification criteria for SLE from four reference centers in Turkey and the University of Pittsburgh School of Medicine in the United States were included in this study. A comparative analysis was conducted to evaluate the similarities and differences in clinical and laboratory features, damage accrual, and treatment experiences between the two populations. A total of 174 patients with childhood-onset SLE were included in this study (108 patients from Turkey and 66 patients from the United States). The female-to-male ratio was similar between the two cohorts (∼3:1, p = .73). The median age at diagnosis was 11.67years (2.19-17.93) in the Turkish cohort and 13.68years (2.74-17.93) in the U.S. cohort (p < .001). Photosensitivity (45.4% and 21.2%; p = .007) and renal involvement (41.7% and 36.4%; p = .045) were higher in the Turkish cohort. Anti-Ro/SSA (34.8% and 15.7%; p < .001), anti-Sm (59.1% and 19.4%; p < .001), and anti-RNP (47.0% and 14.8%; p < .001) positivity was more frequent in the U.S. cohort. Current use of rituximab (37.9% and 1.9%; p < .001) and belimumab (19.7% and 0%; p < .001) was more prevalent in the U.S. cohort, while the use of cyclophosphamide (often according to the low dose Euro-Lupus protocol) throughout the disease course (24.1% and 4.5%; p < .001) was more frequent in the Turkish cohort. SLICC/ACR Damage Index scores were not different between the two cohorts. This study provides detailed clinical and laboratory features of childhood-onset SLE in two independent and geographically divergent cohorts. Our findings suggest an earlier age of disease onset and a higher prevalence of kidney involvement in Turkish patients. Differences in treatment approaches were also noted. However, damage accrual related to SLE does not appear to be different between the two patient populations.

Characteristics of depression treatment in men with testosterone deficiency

BACKGROUND: Treatment of depression in men with testosterone deficiency is particularly challenging because of the overlap between the symptoms of depression itself and those associated with testosterone deficiency, which requires the development of additional diagnostic and therapeutic approaches. AIM: To enhance the effectiveness of comprehensive treatment of depression in men with testosterone deficiency. MATERIALS AND METHODS: The study involved 140 male participants (aged 18–65 years) diagnosed with depressive episodes and recurrent depressive disorder according to the International Classification of Diseases, 10th revision. Patients were divided into the main group (testosterone levels below 12.1 nmol/l) and the control group (normal testosterone levels). The main group (n=90) was further divided into three therapeutic subgroups of 30 patients each: receiving sertraline monotherapy, testosterone monotherapy, and combined sertraline and testosterone treatment. The control group included men with depression and normal testosterone levels (n=50), who received sertraline only. RESULTS: Depression in men in the context of testosterone deficiency has distinct clinical features, both phenomenologically and syndromally. The severity of the depressive syndrome in men with testosterone deficiency is lower (17.0 [16.0; 18.75] points on the HDRS scale) than in patients with normal testosterone levels (19.0 [18.0; 22.0] points on the HDRS scale), and the depressive episode tends to occur later in life (47.0 [42.0; 55.0] years) compared to those with normal levels of testosterone (29.5 [24.25; 40.0] years) and is less likely to be recurrent than in those with normal testosterone levels (29.5 [24.25; 40.0] years). The study of the efficacy and safety of depression therapy in the context of testosterone deficiency shows that a combined approach to the treatment of depression in men with testosterone deficiency has both advantages (considering the specifics of patients by normalizing testosterone levels and erectile function) and disadvantages (relatively higher risk of adverse events) compared to sertraline monotherapy. CONCLUSION: The identified characteristics of the course and treatment of depression in the context of reduced testosterone levels allowed for the development of a more effective therapeutic and diagnostic algorithm.