Post-initial Treatment Research Articles

Early recurrence as a pivotal event in nasopharyngeal carcinoma: identifying predictors and key molecular signals for survivors

PurposeThe duration of response to treatment is a significant prognostic indicator, with early recurrence (ER) often predicting poorer survival outcomes in nasopharyngeal carcinoma (NPC) survivors. This study seeks to elucidate the factors contributing to the onset of ER following radiotherapy in NPC survivors.MethodsThis investigation encompassed 2,789 newly diagnosed NPC patients who underwent radical intensity-modulated radiotherapy. Ordinal logistic regression analysis was employed to evaluate the independent predictors of earlier recurrence. A machine learning-based prediction model of NPC recurrence patterns was developed. Tumorous RNA-sequencing (in-house cohort: N = 192) and biological tipping point analysis were utilized to infer potential molecular mechanisms associated with ER.ResultsOur results demonstrated that ER within 24 months post-initial treatment was the optimal time frame for identifying early malignant progression in NPC survivors. The ER cohort (150 of 2,789, 5.38%) exhibited a notably short median overall survival of 48.6 months. Multivariate analyses revealed that male gender, T4 stage, local or regional residual disease, detectable pre- and post-radiotherapy EBV DNA, and the absence of induction chemotherapy were significant predictors of earlier recurrence. The machine learning-based predictive model further underscored the importance of tumor-related factors in NPC recurrence. Moreover, ER emerged as a pivotal stage in NPC progression, with 15 critical transition signals identified potentially associated with the negative modulation of the immune response.ConclusionsOur comprehensive analysis of NPC recurrence patterns has unveiled insights into the key factors driving ER and provided novel insights into potential early warning biomarkers and the mechanisms underlying NPC progression.

Comparative analysis among therapeutic modalities in ruptured hepatocellular carcinoma and identification of imaging predictors for survival

BackgroundSpontaneous rupture of hepatocellular carcinoma (rHCC) poses a life-threatening complication with a mortality rate of 25–75%. Treatment aims at achieving hemostasis and includes options such as trans-arterial embolization, perihepatic packing, and hepatic resection. The optimal treatment remains a subject of debate. Our retrospective review evaluates these treatments and investigates imaging’s role in prognosis for rHCC patients.PurposeWe aimed to compare survival outcomes among rHCC patients who received transarterial embolization (TAE), surgery (perihepatic packing, hepatectomy), or best supportive care (BSC), while also identifying predictive imaging factors in these patients.Materials and methodsAll patients diagnosed with rHCC and admitted to Maharaj Nakorn Chiangmai Hospital between January 2012 and December 2021 were included. We reviewed clinical features, imaging results, treatment modalities, and outcomes. In order to balance pretreatment confounders, inverse probability treatment weighting (IPTW) was employed. Flexible parametric survival regression was utilized to compare survival outcomes and identify imaging factors predicting the survival of rHCC patients. Hazard ratios (HR) and the difference in restricted mean survival time (RMST) were reported.ResultAmong the 186 rHCC patients included, we observed 90-day and 1-year mortality rates of 64% and 84%, respectively. Both the TAE and surgery groups exhibited significantly lower 1-year mortality rates compared to BSC. The HR were 0.56 (95% CI 0.33–0.96) for TAE and 0.52 (95% CI 0.28–0.95) for surgery compared to BSC. Both the TAE and surgery also significantly extended the 1-yeaar life expectancy post-initial treatment when compared to BSC, with an RMST difference of + 55.40 days (95% CI 30.18–80.63) for TAE vs. BSC and + 68.43 days (95% CI 38.77–98.09) for surgery vs. BSC. The presence of active contrast extravasation and bleeding in both lobes were independent prognostic factors for 1-year survival.ConclusionsTAE and surgical treatments provide comparable survival benefits for rHCC patients, extending survival time by approximately 2 months compared to best supportive care. We strongly recommend active management for all rHCC patients whenever possible.

Efecto de bioestimulantes sobre la calidad del fruto de manzana Golden Glory en Chihuahua, México

The cultivation of apple (Malus domestica (Borkh.) Borkh.) holds significant global importance due to their flavor and nutritional value. In Mexico, Chihuahua leads in production, yet the response of the Golden Glory variety to biostimulants remains unstudied. This study aimed to evaluate the effect of biostimulants on fruit quality in Golden Glory apple. Conducted in Namiquipa, Chihuahua, during the 2023 season, the study employed randomized experimental design with treatments (amino acids, algae, fulvic acids, and a control) spraying weekly from flowering to near harvest. Fruit characteristics were evaluated 90 days post-initial treatment. Amino acids significantly improve fruit weight (27.98 %), diameters (8.41 % polar and 9.28 % equatorial), color (178.8 %), and total soluble solids (TSS;5.72 %), while reducing malic acid content and enhancing TSS/AT ratio by 23.21 %, with no impact firmness. Fruit quality met marketing standards. Seaweed and fulvic acids treatment showed no significant improvement parameters. These results underscore amino acids ‘efficacy in enhancing 'Golden Glory' apples quality. Keywords: amino acids, seaweed, fulvic acids, Malus domestica Borkh

Clinical Presentation and Treatment Strategies for Laryngeal Neuroendocrine Carcinoma: Insights from a Rare Case

Intriduction -Neuroendocrine neoplasms (NEN) of the larynx are very rare, accounting for <1% of all laryngeal carcinomas. Based on the 2022 IARCH/WHO classification, NENs are characterised as well-differentiated neuroendocrine tumours (NET), which can further be divided into grades 1-3 based on Ki-67 levels and mitotic count, or poorly differentiated neuroendocrine carcinomas (NEC) consisting of small cell carcinoma and large cell carcinoma. In this case report, we describe a rare presentation of NEC of the larynx encountered in a 54-year-old man and how diagnostic and therapeutic dilemmas unfolded. Case description: A 6-month history of breathing and swallowing difficulties led to a tracheostomy due to stridor, in the emergency department. Imaging revealed a soft tissue mass involving the supraglottic larynx but no significant associated cervical lymphadenopathy. The biopsy from the growth was suggestive of poorly differentiated NEC as an AJCC stage cT3N0M0. However, there was local progression post-initial treatment with vincristine, doxorubicin and cyclophosphamide (VAC). The chemotherapy regimen was switched to carboplatin and etoposide. The patient received definitive radiation therapy and completed the planned dose of radiation.After 10 months of disease-free interval, there was local recurrence with lung nodules that prompted rechallenge with platinum and etoposide. The patient is doing well and remains clinically and radiologically stable to maintenance therapy with carboplatin & etoposide. Conclusion: NENs of the larynx and especially NECs, are difficult to diagnose as they are rare and have varied molecular profiles. Its management frequently calls for multimodal approaches with chemotherapy and radiation therapy. Due to the developments in diagnostic and therapeutic modalities, our knowledge of NENs has been enhanced which contributed to better practice standards. Nevertheless, standardized treatment strategies remain to be determined by large cohort studies and comprehensive molecular profiling that can determine improved clinical outcomes.

Rare Case of Testicular Metastasis of Prostate Carcinoma after 13 Years of Prostatectomy: A Case Report and Review of the Literature

Metastasis of prostate cancer to the testes is a rare phenomenon, often indicating advanced-stage disease. This case report details a 79-year-old man with a history of prostate cancer, who underwent endoscopic-extraperitoneal radical prostatectomy and bilateral pelvic lymph node dissection. The patient subsequently received radiation therapy for local recurrences. Thirteen years post-surgery, a testicular ultrasound revealed a cystic mass in the left testis, initially suspected to be a primary neoplasm. However, pathology with immunohistochemical analyses confirmed metastasis from prostate adenocarcinoma. Testicular metastasis of prostate cancer is uncommon, underscoring the aggressiveness and potential spread of the tumor. Clinically evident testicular metastases develop in only a small percentage of prostate cancer patients. This case report highlights the importance of considering metastatic disease in the differential diagnosis of testicular masses and the necessity of clinicopathologic correlation in such evaluations. Early detection and accurate diagnosis are crucial for managing testicular metastasis and improving patient outcomes. The case also emphasizes the significance of long-term follow-up in prostate cancer patients, as metastasis can occur many years post-initial treatment. Furthermore, it illustrates the critical role of advanced imaging techniques and thorough pathological assessments in identifying and managing metastatic spread. This report contributes to the limited but growing body of literature on testicular metastasis from prostate cancer, providing insights for clinicians in recognizing and managing this rare but serious complication. It underscores the need for ongoing research to better understand the mechanisms of metastatic spread and develop targeted therapeutic strategies.

The Rate of Re-treatment in Patients Treated with Teprotumumab: A Multicenter Study of 119 Patients with 1 Year of Follow-up

Objective or PurposeTo determine the rate of retreatment in patients who receive a full course of teprotumumab therapy for Thyroid Eye Disease (TED) and drivers of retreatment. DesignMulti center, retrospective study SubjectsAll patients who received a full course of treatment and had available data at 1 year post initial treatment were included. MethodsCharts were reviewed for the following information: age, gender, months since diagnosis of TED, smoking status, prior treatments. Further, the clinical activity score (CAS), proptosis and the Gorman diplopia score were reviewed at baseline, at the end of the first course and at baseline for the second course in those who received it. A logistic regression model was created to review the drivers of retreatment. Main Outcome MeasuresRate of retreatment and the drivers of retreatment. Results119 patients were included from 3 centers across the US. The overall retreatment rate was 24% (29/119). There was no difference between the 3 sites (p = 0.6). In univariate analyses, at baseline, there was no difference in proptosis (p = 0.07), diplopia score (p = 0.4) or duration of TED (p = 0.4), between retreated and non-retreated patients. From the retreated group, 82% had a significant proptosis response (≥ 2 mms reduction from baseline) following their initial course, while 68% of patients had a clinically significant proptosis response in the non-retreated group (p = 0.16). The use of other treatments prior to the first infusion of teprotumumab and baseline thyroid dysfunction, were not significantly different between the retreated and non-retreated groups (p = 0.06 and 0.09, respectively). The mean (SD) difference between the end of first treatment and at baseline prior to second treatment (in those who received it) was 2 (2) for CAS, 2 mms (4) for proptosis and 1 (1) for diplopia. Age as the only significant driver of retreatment (p < 0.05). Retreated patients were 7 years older than their non retreated counterparts (age 60 vs 53 (p < 0.05). ConclusionsIn patients receiving a full course of teprotumumab therapy, the rate of retreatment is 24%. Age is the only driver of retreatment.

Intracranial management of HER-2 overexpression breast cancer with extensive volume or symptomatic brain metastases.

This study aimed to evaluate the impact of high intracranial burden and symptomatic presentation of brain metastases on treatment outcomes in patients with HER-2 positive breast cancer. Through a retrospective analysis, we explored the intracranial responses following the application of HER-2 targeted therapy alone or in combination with other modalities and further elucidated the relationship between treatment efficacy, intracranial progression-free survival (PFS), overall survival (OS), and the burden of intracranial lesions and symptomatic presentations. A retrospective analysis was conducted on cases of HER-2 overexpressing breast cancer patients with brain metastases. Clinical records were reviewed to extract patient demographics, treatment modalities, and intracranial disease characteristics. Intracranial tumor burden was quantified at diagnosis and post-initial treatment. High intracranial tumor burden was defined as either total metastatic volume >15 cc, or the largest lesion >3 cm. Responses were assessed using established criteria. The correlation between intracranial disease parameters and intracranial progression-free survival (PFS) and overall survival (OS) was determined. The study comprised 65 patients with HER-2 overexpression breast cancer and brain metastases. Symptomatic presentation was observed in 69.2% of patients at the diagnosis of brain metastases. Treatment with HER-2 target therapy alone or in combination with other modalities resulted in substantial intracranial responses, with 81.5% achieving at least a partial response at 3 months from therapy initiation. Median intracranial PFS and OS for patients with high intracranial burden were 9 and 22 months, respectively. Patients with high intracranial burden and symptomatic presentation at diagnosis demonstrated worse PFS and OS to those with lower burden and absence of symptoms (p < 0.05 for each). Her-2 overexpressing breast cancer and brain metastases face significant challenges, particularly those with high intracranial tumor burden, which correlates with poorer outcomes and higher incidence of leptomeningeal metastasis. Most patients responded positively to initial therapies, especially anti-HER-2 treatments combined with radiotherapy. Larger tumors necessitated more comprehensive treatment approaches, such as WBRT and SRS. Key factors influencing intracranial tumor control included the Ki-67 index, intracranial tumor burden, and continuous use of HER-2 targeted therapy post-diagnosis.

Enhancing Therapeutic Efficacy and Safety of Immune Checkpoint Inhibition for Bladder Cancer: A Comparative Analysis of Injectable vs. Intravesical Administration.

Bladder cancer (BC) presents a significant global health burden, characterized by high recurrence rates post-initial treatment. Gender differences in BC prevalence and response to therapy emphasize the importance of personalized treatment strategies. While Bacillus Calmette-Guérin (BCG) remains a cornerstone of BC therapy, resistance poses a challenge, necessitating alternative strategies. Immune checkpoint inhibitors (ICIs) have shown promise, yet systemic toxicity raises concern. Intravesical administration of ICIs offers a potential solution, with recent studies demonstrating the feasibility and efficacy of intravesical pembrolizumab. Although systemic toxicity remains a concern, its localized administration may mitigate adverse events. Additionally, liposomal delivery of ICIs exhibits promises in enhancing drug penetration and reducing toxicity. Novel imaging modalities compatible with Vesical Imaging-Reporting and Data System (VI-RADS) and capable of predicting high-grade bladder cancer can aid the pre-operative shared decision making of patient and surgeon. Future research should focus on refining treatment approaches, optimizing dosing regimens, and leveraging advanced imaging techniques to improve patient outcomes. In conclusion, intravesical immunotherapy presents a promising avenue for BC treatment, offering enhanced therapeutic effectiveness while minimizing systemic toxicity. Continued research efforts are essential to validate these findings and optimize intravesical immunotherapy's role in BC management, ultimately improving patient outcomes.

The complex dynamics of therapeutic leave in Psychiatry

IntroductionTherapeutic leave, the temporary and authorized absence of a patient from a psychiatric inpatient facility, is a practice rooted in the shift of mental illness towards more humane and recovery oriented care. This shift began to gain momentum in the mid-20th century, with the deinstitutionalization movement, which sought to treat psychiatric patients in less restrictive environments and facilitate their integration into the community. Today, therapeutic leave remains relevant in general psychiatry inpatient treatment facilities, and on an international level. It’s additionally used as a way to assess the progress and the stability of the patient outside the controlled environment that is the hospital, and to provide a gradual transition back into independent living and potential stressors of the outside world. But it is administered more on tradition and perceived benefits than on solid scientific grounding, reflecting a practice guided by clinical experience rather than empirical data or guidelines.ObjectivesOur review aims to evaluate the existing body of research on therapeutic leave in general psychiatry inpatient units. We intend to identify the outcomes that have been studied, and assess the extent and nature of their impact.MethodsThis scoping review was conducted through a comprehensive search of academic databases, including Google Scholar, PubMed, Embase, Cochrane Library, and PsycINFO. Search terms were carefully selected to capture relevant publications, and the results were screened for their pertinence to the review’s aims. Studies focused on forensic settings were excluded.ResultsThe literature on therapeutic leave is notably limited, and the prevalence of its utilization in clinical practice remains unclear. Scientific publications primarily address readmission rates, with two indicating an increased risk in patients granted leave during their inpatient treatment. However, one report suggested a potential reduction. Length of stay (LOS) was negatively impacted, with prolonged hospitalization in these patients shown in one report. Post-discharge emergency room visits seem unaffected. A rise in readmission rates and LOS typically suggests higher subsequent healthcare costs. However, findings from another study contradict this expectation, with reduction of costs post-initial inpatient treatment. The literature also explores the hazards linked to therapeutic leave, highlighting that a significant portion, between 30 to 80%, of inpatient suicides transpire during such leave. Additional concerns extend to non-fatal self-harm, as well as the possibility of patients causing harm to others or to property.Conclusions Our review reveals a significant research gap in therapeutic leave’s effects, with a reduced number of outcomes studied and inconclusive findings. Future studies should aim to clarify these outcomes and eventually define therapeutic leave protocols.Disclosure of InterestNone Declared

Non-Invasive MRD Monitoring in Multiple Myeloma Patients By Heavy/Light Chain Analysis

Introduction The majority of multiple myeloma (MM) patients are now achieving very deep responses. The most sensitive disease detection techniques are currently bone marrow assays. However, as bone marrow sampling is invasive and unpleasant for patients it is important to investigate whether blood-based assays could be equally or more informative of disease status. The heavy/light chain assay (Hevylite TM, The Binding Site, UK) evaluates serum heavy/light chains (HLC) for IgG, IgA and IgM M-proteins. This study assessed whether the HLC assay could act as an effective marker for disease in the bone marrow of treated MM patients and evaluated the prognostic utility of HLC measurements at best response and relapse time points. Methods 104 IgG and IgA MM patients were recruited either prior to transplant or during chemotherapy. Median follow up was 18 months. Routine M-protein tests were performed alongside HLC testing with parameters including involved HLC (iHLC), uninvolved HLC (uHLC) and kappa/lambda HLC ratio (HLCr). A bone marrow flow cytometry (NGF) assay was performed up to a sensitivity of 10 -6 and was considered to be the gold standard assay. Disease response was determined according to the IMWG criteria. Results and Discussion At pre- and post-transplant time points there was significant agreement between HLC measurements and NGF, with uHLC being the most sensitive measurement (86%) and HLCr the most specific (100%). Both uHLC and HLCr show substantial agreement with the bone marrow NGF method whilst iHLC cannot be used to indicate bone marrow status. Survival analysis showed significantly inferior progression free survival (PFS) in patients with an abnormal uHLC (p=0.01) (Figure A) or HLCr (p=0.02) result post-transplant but no survival difference based on iHLC status (p=0.78) (Figure B). Interestingly, performing survival analysis on these same samples using serum immunofixation (IFE) status (positive or negative) did not produce a significant PFS difference between participants (p=0.21). During long term follow up, HLC values showed a correlation with depth of response, with uHLC being abnormal in 60% of complete response (CR) patients. This suggests that those participants currently grouped as CR may be able to be further subdivided according to uHLC level and this could have a prognostic value in the monitoring and treatment of these patients. At best response uHLC was the only HLC or free light chain (FLC) measurement which gave a significant difference in PFS for all patients in partial response (PR) or better (p=0.005), remaining true when analysing patients in ≥CR only (p=0.002). The addition of free light chain measurements into the HLC analysis did not improve the significance of these survival differences. In relapsed patients, paired comparisons of M-protein and disease activity markers at best response vs. prior to clinical relapse were performed. uHLC was the only marker which was significantly different between the two time points in IgG and IgA patients. The significance of this was confirmed by showing that those patients in stable disease did not experience a significant change in uHLC levels. For other M-protein variables such as total immunoglobulin, IFE status and FLC values there was an increase in levels or abnormality between best response and pre-relapse but these were not significant. The paired comparison suggests that monitoring an individual using HLC could help to detect relapse earlier than conventional methods. In all analyses performed the HLC assay showed increased sensitivity and utility over the IFE technique. Conclusion This study suggests that the HLC assay can be used prior to bone marrow analysis to help influence decisions and improve the patient and laboratory experience. These results can be put into practice during patient follow up post initial treatment in the following ways: At deepest response an abnormal uHLC or HLCr suggests a positive MRD status, meaning a possible reduction or delay in the requirement for bone marrow assessment.All patients in ≥VGPR should have HLC performed alongside conventional assays during follow up.If uHLC values become abnormal during follow up then it should be assumed that the patient is about to undergo relapse. The measurement of HLC values have been shown to be a significant marker in this study, for sensitively detecting the M-protein, giving further clarification of response status and predicting early relapse.

Change in resilience among spousal caregivers of patients with newly-diagnosed advanced cancer over the first six months posttreatment in China

ObjectiveA longitudinal observational study was conducted and aimed to examine the change in resilience among spousal caregivers of newly-diagnosed advanced cancer patients over the first six months after initial treatment. MethodsIn total, 312 Chinese spousal caregivers who were taking care of their patients with newly-diagnosed advanced cancer were recruited. The level of resilience was measured using the Connor–Davidson Resilience Scale at the first month post-initial treatment (T1), three-month post-initial treatment (T2), and six-month post-initial treatment (T3). Latent growth modeling analyses were performed to examine changes in resilience using Mplus 8.3. ResultsThe mean scores of resilience in spousal caregivers were 54.01 ± 7.68 at T1, 56.20 ± 6.38 at T2, and 57.97 ± 6.70 at T3, respectively. Results of latent growth modeling indicated that spousal caregivers showed a significant increase in their resilience scores over the first six months post-treatment (Mean slope = 1.98, p < 0.001). Furthermore, a significant individual variation in the rate of changes in resilience scores allowed spouses to be categorized into two groups: 42.9% participants with fast growth and 57.1% participants with slight growth. ConclusionOur findings highlight the importance that new knowledge about change patterns of resilience in the nursing field is beneficial to reveal different psychosomatic health. Acknowledging that resilience is a dynamic process that changes over time, it is crucial for healthcare providers to monitor the psychological adjustment and focus of vulnerable caregivers, particularly spouses.

Application of a revised model for coping with advanced cancer to qualitatively explore lung cancer survivors’ experiences of ongoing physical effects, novel treatments, uncertainty, and coping

PurposeLung cancer remains underrepresented in cancer survivorship research. This study aimed to understand survivors’ physical/psychological challenges, experiences of immunotherapy (IO) and targeted therapy (TT), and psychological adjustment through application of the Roberts et al. (2017) advanced cancer adaptation of Folkman and Greer’s appraisal and coping model.MethodsAdults 6–24 months post-initial treatment completion were recruited via an Australian cohort study. Participant demographic, clinical, quality of life, and distress data were obtained through the cohort database. Qualitative interviews were conducted and analyzed using Framework methods. Roberts et al. (2017)’s model informed data interpretation and presentation.ResultsTwenty interviews were conducted (10 females; average age 69 years). Participants’ diagnostic stages varied (stage I = 2, stage II = 4, stage III = 8, stage IV = 6); most had received IO/TT (n = 14) and were on average 17 months (range 10–24) post-diagnosis. Three themes were identified and mapped to the Roberts’ framework: (1) Ongoing illness events: most participants reported functioning well despite ongoing physical effects. Those on IO/TT reported side effects; some were unexpected/serious. (2) Adjusting to life with lung cancer: most expressed hope for the future while simultaneously preparing for disease progression. Those receiving IO/TT experienced uncertainty given limited survival information. (3) Learning to live with lung cancer: participants described emotion, problem, and meaning based on coping strategies.ConclusionsFindings may guide development of supportive care resources/interventions focused on uncertainty, IO/TT communication and decision-making, and coping.Implications for Cancer SurvivorsMany people with lung cancer are living well with their ongoing illness. Despite challenges, many survivors are adapting to issues as they arise and are maintaining a sense of hope and optimism.

Outcomes of ATA Low-Risk Pediatric Thyroid Cancer Patients Not Treated With Radioactive Iodine Therapy.

The American Thyroid Association (ATA) Pediatric Guidelines recommend patients not receive radioactive iodine therapy (RAIT) for differentiated thyroid cancer (DTC) confined to the thyroid. Since publication, there is ongoing concern whether withholding RAIT will result in a lower rate of remission. This study explores whether ATA low-risk patients treated with and without RAIT achieved similar remission rates. Medical records of patients <19 years old diagnosed with DTC and treated with total thyroidectomy between 2010 and 2020 were reviewed. Multivariate logistic regression was performed to evaluate factors influencing RAIT administration and remission rate. Ninety-five patients with ATA low-risk DTC were analyzed: 53% (50/95) and 47% (45/95) were treated with and without RAIT, respectively. RAIT was used to treat 82% of patients before 2015 compared with 33% of patients after 2015 (P < .01). No significant difference in 1-year remission rate was found between patients treated with and without RAIT, 70% (35/50) vs 69% (31/45), respectively. With longer surveillance, remission rates increased to 82% and 76% for patients treated with and without RAIT, respectively. Median follow-up was 5.8 years (IQR 4.3-7.9, range 0.9-10.9) and 3.6 years (IQR 2.7-6.6; range 0.9-9.3) for both cohorts. No risk factors for persistent or indeterminate disease status were found, including RAIT administration, N1a disease, and surgery after 2015. Withholding RAIT for pediatric patients with ATA low-risk DTC avoids exposure to radiation and does not have a negative impact on remission rates. Dynamic risk stratification at 1-year after initial treatment is a suitable time point to assess the impact of withholding RAIT for these patients.

Longitudinal differences in iron deposition in periaqueductal gray matter and anterior cingulate cortex are associated with response to erenumab in migraine.

The objective of this longitudinal study was to determine whether brain iron accumulation, measured using magnetic resonance imaging magnetic transverse relaxation rates (T2*), is associated with response to erenumab for the treatment of migraine. Participants (n = 28) with migraine, diagnosed using international classification of headache disorders 3rd edition criteria, were eligible if they had six to 25 migraine days during a four-week headache diary run-in phase. Participants received two treatments with 140 mg erenumab, one immediately following the pre-treatment run-in phase and a second treatment four weeks later. T2* data were collected immediately following the pre-treatment phase, and at two weeks and eight weeks following the first erenumab treatment. Patients were classified as erenumab responders if their migraine-day frequency at five-to-eight weeks post-initial treatment was reduced by at least 50% compared to the pre-treatment run-in phase. A longitudinal Sandwich estimator approach was used to compare longitudinal group differences (responders vs non-responders) in T2* values, associated with iron accumulation. Group visit effects were calculated with a significance threshold of p = 0.005 and cluster forming threshold of 250 voxels. T2* values of 19 healthy controls were used for a reference. The average of each significant region was compared between groups and visits with Bonferroni corrections for multiple comparisons with significance defined as p < 0.05. Pre- and post-treatment longitudinal imaging data were available from 28 participants with migraine for a total of 79 quantitative T2* images. Average subject age was 42 ± 13 years (25 female, three male). Of the 28 subjects studied, 53.6% were erenumab responders. Comparing longitudinal T2* between erenumab responders vs non-responders yielded two comparisons which survived the significance threshold of p < 0.05 after correction for multiple comparisons: the difference at eight weeks between the erenumab-responders and non-responders in the periaqueductal gray (mean ± standard error; responders 43 ± 1 ms vs non-responders 32.5 ± 1 ms, p = 0.002) and the anterior cingulate cortex (mean ± standard error; responders 50 ± 1 ms vs non-responders 40 ± 1 ms, p = 0.01). Erenumab response is associated with higher T2* in the periaqueductal gray and anterior cingulate cortex, regions that participate in pain processing and modulation. T2* differences between erenumab responders vs non-responders, a measure of brain iron accumulation, are seen at eight weeks post-treatment. Less iron accumulation in the periaqueductal gray and anterior cingulate cortex might play a role in the therapeutic mechanisms of migraine reduction associated with erenumab.

Macrophage activation syndrome in adults: Characteristics, outcomes, and therapeutic effectiveness of etoposide-based regimen.

ObjectivesTo describe the clinical characteristics and outcomes of adult macrophage activation syndrome (MAS) patients and to provide experience for the treatment.MethodsAdult patients with MAS admitted to Beijing Friendship Hospital from December 2014 to September 2021 were enrolled in this study. Clinical data of patients were collected and analyzed.ResultsA total of 118 adult MAS patients entered this study. MAS was the first manifestation in 43 (36.4%) patients, while 75 (63.6%) developed MAS after the diagnosis of autoimmune disease (AID) with a median diagnostic interval of 2 (0.5–359) months. Eighty-two patients were initially treated with glucocorticoid-based regimen; the overall response (OR) rate at the 2-week posttreatment was 37.8%. Forty-five patients switched to etoposide-based regimen, and the OR rate was 84.4%. Thirty-six patients were initially treated with etoposide-based regimen, and the OR rate at the 2-week posttreatment was 80.6%. Serum IL-18 (P = 0.021), IFN-γ (P = 0.013), IP-10 (P = 0.001), IL-10 (P = 0.041), IL-1RA (P < 0.001), and TNF-α (P = 0.020) levels of patients were significantly decreased in the remission phase than in the active phase. Levels of SDF-1α (P = 0.018) and IL-7 (P = 0.022) were higher in refractory patients, while the GRO-α level had a strong tendency toward statistical significance (P = 0.050). The probability of overall survival (OS) at 3, 6, and 36 months after HLH diagnosis were 89.8%, 89.0%, and 87.9%, retrospectively. The active MAS status at the 2-week post initial treatment [P = 0.009, HR = 15.281, 95% CI, (0.1.972, 118.430)] and baseline neutrophil count (Neu) <1.5 × 109/l [P = 0.017, HR = 3.678, 95% CI, (1.267, 10.672)] were negative prognostic factors.ConclusionMAS typically occurs within 2 months after the onset of autoimmune disease in adults. SDF-1α, IL-7, and GRO-α could be used to predict refractory MAS. The etoposide-based regimen is effective and tolerable for adult MAS.

Impacts of oak-focused silvicultural treatments on the regeneration layer nine years posttreatment in a productive mixed-oak southern Appalachian forest

Oaks (Quercus spp.) are foundational species in forests and woodlands in the eastern USA. An oak regeneration bottleneck has occurred throughout its range in recent decades, and refining silvicultural treatments to localized conditions has become a focus in addressing this problem. This study was developed to determine species regeneration dynamics among oak and oak competitors on productive sites in response to silvicultural treatments in oak-dominated southern Appalachian mountain forests. The treatments were: an oak shelterwood treatment (25–30% basal area [BA]) reduction through midstory removal with herbicides); a prescribed fire treatment (two, late-dormant season prescribed fires occurring over a 9-yr period); a shelterwood and burn treatment (one, late-dormant season prescribed fire 3–5 yr following 30–40% BA removal); and an unmanaged control. To determine treatment impacts on the regeneration layer, changes in relative and absolute importance values and stems ha-1 (germinants up to stems ≤ 4.9 cm diameter at breast height [DBH]) were calculated at the species group and individual species level 0 and 9 yr postinitial treatment. The greatest relative increases in importance values were 1,401% and 2,995% for the red oak group and yellow-poplar (Liriodendron tulipifera), respectively, in the shelterwood and burn (SWB). Changes in all species groups were predominantly influenced by the smallest size-class (< 0.6 m tall), with the exception of northern red oak (Q. rubra) and yellow-poplar in the SWB. The SWB significantly reduced importance values of all shade-tolerant species groups and was the only treatment to decrease red maple (Acer rubrum) importance value and density over the study duration. The prescribed fire (RXF) treatment increased the red oak group importance value, while simultaneously decreasing yellow-poplar's importance value and increasing red maple's importance value. Changes in the red oak group in the SWB and the RXF were driven by northern red oak. Treatments did not significantly change the importance value of the white oak group. The SWB was the only treatment to significantly decrease overstory BA. The RXF and SWB treatments improved the competitive status of only some oak species, but modifications to these treatments might result in better control of yellow-poplar and red maple competition, further improving oak's competitive status. Although the SWB resulted in modest recruitment of northern red oak saplings, all treatments appear in need of additional follow-up vegetation control to further improve the competitiveness and recruitment of oak into large size-classes.

Effect of application time of 38% silver diamine fluoride solution on arresting early childhood caries in preschool children: a randomised double-blinded controlled trial protocol

BackgroundTo study the caries lesion activity response to topical 38% silver diamine fluoride (SDF) therapy with increasing treatment application time.Methods/designThe design is a stratified-randomised, double-blind, active-controlled, parallel-group clinical trial with nine treatment arms. The trial will involve recruiting at least 414 3- to 5-year-old kindergarten children with caries, who will receive approximately 0.004 mL of 38% SDF (the typical amount applied per the manufacturer’s instructions) to treat each caries lesion. The children will be stratified by caries status, randomised by blocks, and allocated to nine groups of SDF application times: 3, 5, 10, 15, 30, 45, 60, 120, and 180 s. The outcome measure is caries lesion activity (active/arrest) at the tooth-surface level at 6 months post-initial treatment. A calibrated dentist will conduct the blinded clinical examinations at baseline and at the 6-month follow-up. In addition, the parents will be surveyed to examine the effects of the moderating variables, such as oral hygiene, on caries lesion activity. The hypothesis is that a monotonically increasing trend can be found between the SDF application time and the proportion of caries lesions that are arrested. The Cochran-Armitage test for trends in proportions, corrected for clustering within children, will be used to determine the relationship between the exposure to SDF (the SDF application time) and the response (proportion of lesions arrested) in children, taking into consideration the effect of the moderating variables as well as the nesting of multiple caries lesions within an individual child. An EC 80 analysis (an 80% maximal concentration) will be used to determine the exposure (the SDF application time) for 80% caries lesion arrest. Bootstrap methods will be used for clustered data and will be resampled by clustering to determine the 95% confidence interval.DiscussionThis study will help with determining the optimal application time for SDF treatment. It will provide an evidence-based protocol for the use of SDF to arrest tooth decay in the primary teeth of young children. The results will inform an evidence-based SDF protocol to arrest caries, which affects 573 million children with tooth decay worldwide.Trial registrationClinicalTrials.gov NCT04655430. Registered on 7th December 2020.

Clinical Outcomes of a Novel Cranial Movement Therapy (CMT) in Post-Traumatic Brain Injury: A Case Report

<h3>Research Objectives</h3> To describe potential effects of a novel Cranial Movement Therapy (CMT) on long-lasting post-Traumatic Brain Injury (TBI) symptoms. <h3>Design</h3> Case report. <h3>Setting</h3> Specialized private practice on concussion and TBI. <h3>Participants</h3> A 57-year-old female with sustaining post-TBI symptoms for 2 years, with a new incident 2 weeks prior to initial visit. <h3>Interventions</h3> A novel technique of CMT was originally developed to improve post-TBI symptoms by potential restoration of the cranial bones' position and optimization of CSF and blood flow. This approach consists of a detailed history of the mechanism of injury, systematic evaluation including palpation, assessment, and manipulation of the cranial bones, cervical spine and surrounding musculature. Each session, symmetry, mobility, and tonicity of cranial structures and soft tissues were assessed. Treatment protocol consisted of 5 consecutive sets of proposed CMT technique on the palate and other osseous cranial structures found with deficits, of 1 session every 20 minutes, over the course of 4 days with added home-based cognitive training program. Follow-up was repeated for 2 months post-initial treatment. <h3>Main Outcome Measures</h3> Primary outcomes were severity of headache and cognitive dysfunction on a 0-10 scale and frequency of occurrence. <h3>Results</h3> Following receiving CMT, the participant reported 80% decrease in headache severity (5/10 to 1/10) and complete resolution (100% decrease) of cognitive dysfunction (6/10 to 0/10) at the conclusion of treatment on day 4 with no recurrence after 2 months of follow up. <h3>Conclusions</h3> This case report successfully documented a significant reduction in severity and frequency of headaches, complete elimination of cognitive difficulties following application of this novel CMT technique in a patient experiencing long-lasting post-TBI symptoms. Findings warrant future randomized controlled investigation of this approach in the treatment of patients with post-TBI symptoms. <h3>Author(s) Disclosures</h3> Primary authors (CS) who has originally developed this novel technique foresees potential financial conflict of interest since he is the CEO/owner of the facility this case is treated. All other authors declare that they have no relevant financial or non-financial competing interests to report.

Comparative efficacy and safety of interventions for treating head lice: a protocol for systematic review and network meta-analysis

BackgroundHead lice infestation is a major public health problem around the globe. Its treatment is challenging due to product failures resulting from rapidly emerging resistance to existing treatments, incorrect treatment...

The role of Ureaplasma parvum serovar-3 or serovar-14 infection in female patients with chronic micturition urethral pain and recurrent microscopic hematuria.

BackgroundUreaplasma parvum (UP) is commonly isolated in the genitor-urinary tract and may cause various clinical features, including microscopic hematuria (MH). Some UP serovars are more commonly related with specific urogenital disease, but the evidences have been conflicting. This study primarily aimed to research the possible associations between specific UP serotypes and genito-urinary pathogenicity in female patients showing MH with/without chronic micturition urethral pain (CMP).MethodsThis study retrospectively reviewed 276 female patients having MH with/without CMP, who visited health screening center or female infertility clinic. All patients underwent multiplex polymerase chain reaction (PCR) tests with vaginal and urine samples to evaluate the infection rate and serotypes of UP. The antimicrobial susceptibility of UP and the predictors of CMP among UP infected patients were also analyzed. All patients were followed up at least for 6-months.ResultsForty-nine patients (17.8%) showed urinary UP infection. Urinary UP serotyping showed the prevalence of seorvar-1, -3, -6 and -14 were 24.5%, 30.6%, 18.4% and 26.5%, respectively. 79.6% of the urinary UP positive patients accompanied vaginal UP infection. 22 patients of the cohort (8.0%) had CMP whereas serovars-3 and -14 accompanied CMP in 54.5% and 41.0% cases, respectively. No serovars-6 infection case had CMP. 26.4% of the cohort were infertile whereas 10.9% of these infertile patients were positive for urinary tract infection with UP serotype-3 or -14. Doxycycline, josamycin and pristinamycin were the most active antibiotics with the lowest rate of resistance (0.0%) for treating UP. At 1-month post-initial treatment with doxycycline, all UP serotypes were eradicated and no patient complained of urethral discomfort. However, simultaneous urinary and vaginal reinfection of serovar-3 (5 cases) and serovar-5 (1 case) were confirmed at 3-months post-initial doxycycline therapy. The logistic regression analyses revealed that serovars-3 [hazard ratio (HR) 1.354, P value 0.018] and -14 (HR 1.103, P value 0.046) were significantly associated with CMP in female patients having MH.ConclusionsUP serovars-3 and -14 infections could be associated with CMP in female patients having MH. Doxycycline, josamycin and pristinamycin were effective for treating UP. Serovar-3 showed higher reinfection rate than other serotypes after antibiotics treatment.