Adjuvant Therapy Research Articles

Thalidomide as an adjunctive therapy in complex childhood neuro-tuberculosis: a case report

BackgroundTuberculosis remains a global health challenge, with central nervous system tuberculosis (CNSTB) affecting 5–10% of extrapulmonary tuberculosis cases, leading to severe complications in children aged 2 to 4 years. Despite timely diagnosis and intervention, management of CNSTB is a challenge. Thalidomide, a TNF-α inhibitor, is a potential therapeutic option in cases resistant to adjuvant corticosteroid therapy. This case report describes the management of complicated CNSTB utilising thalidomide, a less commonly used drug, with a favourable outcome.Clinical presentationA 3-year-old boy diagnosed with CNSTB and having a ventriculoperitoneal shunt presented with left-sided hemiparesis. He was previously diagnosed with tubercular meningitis at 2.5 years of age. On anti-tubercular treatment and corticosteroid, he had a complicated course with drug-induced liver injury (DILI) and paradoxical reaction. Despite a year of anti-tubercular therapy, there was a deterioration in neurological symptoms, accompanied by an increase in the number of tuberculomas observed on MRI. Adjuvant treatment with thalidomide proved effective in suppressing immunological activation, leading to a reduction in tuberculomas.ConclusionThis case highlights the intricacies of CNSTB, including complications and refractory tuberculomas. Thalidomide was effective in managing these challenges, offering a potential therapeutic option in challenging CNSTB cases. Positive clinical and radiological responses underscore the need to further explore thalidomide as an adjunctive therapy in similar paediatric cases.

Longitudinal Trends in Patient-Reported Outcomes in the First Year After Lumpectomy Versus Mastectomy.

It is unclear how patient-reported outcomes (PROs) change longitudinally after breast cancer surgery. We sought to compare trends in PROs among patients who underwent lumpectomy versus mastectomy over the first year after surgery. Newly diagnosed stage 0-III female patients with breast cancer who underwent lumpectomy or mastectomy at an academic breast center between June 2019 and March 2023 were invited to participate in a longitudinal PRO study. Enrolled patients received the BREAST-Q™ module, a validated tool measuring domains, such as satisfaction with breasts, psychosocial well-being, physical well-being, and sexual well-being. Scores for each domain were compared between the lumpectomy and mastectomy groups over the first year after surgery. Linear mixed models were used to estimate the change in PRO scores over time. The cohort included 203 who underwent lumpectomy and 144 who underwent mastectomy. Patients who underwent lumpectomy were older, more likely to receive adjuvant radiation and endocrine therapy, and less likely to receive adjuvant chemotherapy. Patients who underwent lumpectomy demonstrated greater increases in scores over time for satisfaction with breasts, psychosocial well-being, and sexual well-being compared with patients who underwent mastectomy, after adjusting for the abovementioned covariates and receipt of reconstruction. The lumpectomy group had a larger decline in physical well-being over time compared with the mastectomy group. Patients who underwent lumpectomy demonstrated greater satisfaction with their breasts, psychosocial well-being, and sexual well-being but worse physical well-being over the first year after surgery compared with patients who underwent mastectomy. These results may help inform early-stage breast cancer patients making decisions about their surgical care.

Intraoperative Pathology Consultation in Patients With p16-Positive Unknown Primary Squamous Cell Carcinoma

Current guidelines recommend intraoperative frozen section(s) during diagnostic surgery for squamous cell carcinoma for unknown primary tumors (SCCUP). To determine the utility of intraoperative pathology consultation during transoral robotic surgery (TORS) in localizing primary tumors and influencing need for adjuvant therapy. A retrospective case series including 47 adult patients with human papillomavirus (HPV)-associated SCCUP who underwent TORS/oropharyngectomy between January 2016 and February 2023 was carried out at a single tertiary care hospital. The analysis took place on May 13, 2024. Nodal stage, tonsillectomy history, extranodal extension (ENE). Intraoperative pathology consultation and final pathology results were compared with surgical outcomes, including margin revision, need for second procedure and/or radiation with or without chemotherapy. This study included 47 adult patients. Mean (range) age was 61 (41-79) years; patients were mostly men (37 [79%]). Overall, primary tumors were identified in 37 patients (79%), including all cases with positive nodes involving more than 1 neck level. Patients whose primary tumor was not found tended to have tobacco use history (8/10 vs 13/37 [35%]; difference, 45%; 95% CI, 16%-74%) and absence of ENE (8/10 vs 15/37 [41%]; difference, 39%; 95% CI, 10%-68%). Primary tumor was identified intraoperatively in 18 of 37 patients (49%). SCCs identified intraoperatively were significantly larger than SCCs found on permanent sections only: mean (SE), 1.2 (0.13) cm vs 0.5 (0.1) cm (difference, 0.7 cm; 95% CI, 0.53-1.94). The sensitivity, specificity, positive predictive value, and negative predictive value of intraoperative consultation was 49% (95% CI, 33%-64%), 100% (95% CI, 100%-100%), 100%, and 34% (95% CI, 19%-53%), respectively. Margins were revised in 11 of 18 patients (61%) whose primary tumor was identified intraoperatively (during original procedure) and in 3 of 19 patients (16%) whose primary tumor was identified on permanent pathologic findings only (during a second procedure) (11/18 [61%] vs 3/19 [16%]; difference, 45%; 95% CI, 17%-73%). However, there was no significant difference in the use of adjuvant radiotherapy with or without chemotherapy or need for a second procedure based on intraoperative primary tumor localization. In this case series study, the sensitivity and negative predictive value of intraoperative pathology consultation among 47 patients was less than 50%. Given the lack of influence on the need for radiotherapy with or without chemotherapy or second procedure, the practical utility of routine intraoperative frozen section requires further scrutiny.

Effect of L-arginine on cystic fibrosis Pseudomonas aeruginosa biofilms.

Cystic fibrosis (CF) airways are L-arginine deficient which may affect susceptibility to infection with certain pathogens. The potential impact of L-arginine supplementation on Pseudomonas aeruginosa, a common CF airway pathogen, is unclear. This study investigated the effects of L-arginine on P. aeruginosa biofilm cultures, using the laboratory strain PAO1 and multi-drug resistant CF clinical isolates. P. aeruginosa biofilms were grown in a chambered cover-glass slide model for 24 h, then exposed to either L-arginine alone or combined with tobramycin for an additional 24 h. Biofilms were visualized using confocal microscopy, and viable cells were measured via plating for colony-forming units. Increasing concentrations of L-arginine in bacterial culture medium reduced the biovolume of P. aeruginosa in a dose-dependent manner. Notably, L-arginine concentrations within the physiological range (50 mM and 100 mM) in combination with tobramycin promoted biofilm growth, while higher concentrations (600 mM and 1200 mM) inhibited growth. These findings demonstrate the potential of L-arginine as an adjuvant therapy to inhaled tobramycin in treating P. aeruginosa infections in people with CF.

Efficacy and safety of postbiotic containing inactivated Lactobacillus reuteri (Limosilactobacillus reuteri) DSM 17648 as adjuvant therapy for Helicobacter pylori eradication in adults with functional dyspepsia: A randomized double-blind placebo-contolled trial.

Increasing the effectiveness of eradication therapy is an important task in gastroenterology. The aim was to evaluate the efficacy and safety of postbiotic containing inactivated (non-viable) Limosilactobacillus reuteri DSM17648 (Pylopass) as adjuvant treatment for Helicobacter pylori eradication in patients with functional dyspepsia (FD). This randomized, double-blind, placebo-controlled, multicenter, parallel study included Helicobacter pylori positive patients with FD. The postbiotic group received Pylopass 200 mg bid for 14 days in combination with eradication therapy (esomeprazole 20 mg bid + amoxicillin 1000 mg bid + clarithromycin 500 mg bid for 14 days) and another 14 days after completion of eradication therapy. The study was registered in the ISRCTN registry (ISRCTN20716052). Eradication efficiency was 96.7% for the postbiotic group versus 86.0% for the placebo group (P=0.039). Both groups showed significant improvements in quality of life and reduction of most gastrointestinal symptoms with no significant differences between groups. The overall number of digestive adverse effects in the postbiotic group was lower than in the placebo group. Serious adverse effects were not registered. The postbiotic containing inactivated L. reuteri DSM17648 significantly improves the effectiveness of H. pylori eradication therapy in FD and decreases overall number of digestive adverse effects of this therapy.

A 5-ALA mediated photodynamic therapy increases natural killer cytotoxicity against oral squamous cell carcinoma cell lines.

Oral squamous cell carcinoma (OSCC) constitutes over 90% of oral cancers, known for its aggressiveness and poor prognosis. Photodynamic therapy (PDT) has emerged as a promising adjuvant therapy and is linked to immunogenic cell death, activating innate and adaptive anti-tumor responses. Natural Killer (NK) cells, key players in malignant cell elimination, have not been extensively studied in PDT. This study evaluates whether PDT increases OSCC cell lines' susceptibility to NK cell cytotoxicity. PDT, using 5-aminolevulinic acid (5-ALA) and LED irradiation, was applied to Ca1 and Luc4 cell lines. Results showed a dose-dependent viability decrease post-PDT. Gene expression analysis revealed upregulation of NK cell-activating ligands (ULBP1-4, MICA/B) and decreased MHC class I expression in Ca1, suggesting increased NK cell susceptibility. Enhanced NK cell cytotoxicity was confirmed in Ca1 but not in Luc4 cells. These findings indicate that PDT may enhance NK cell-mediated cytotoxicity in OSCC, offering potential for improved treatment strategies.

Phytoconstituents with cardioprotective properties: A pharmacological overview on their efficacy against myocardial infarction.

Myocardial infarction (MI) is considered one of the most common cardiac diseases and major cause of death worldwide. The prevalence of MI and MI-associated mortality have been increasing in recent years due to poor lifestyle habits viz. residency, obesity, stress, and pollution. Synthetic drugs for the treatment of MI provide good chance of survival; however, the demand to search more safe, effective, and natural drugs is increasing. Plants provide fruitful sources for powerful antioxidant and anti-inflammatory agents for prevention and/or treatment of MI. However, many plant extracts lack exact information about their possible dosage, toxicity and drug interactions which may hinder their usefulness as potential treatment options. Phytoconstituents play cardioprotective role by either acting as a prophylactic or adjuvant therapy to the concurrently used synthetic drugs to decrease the dosage or relief the side effects of such drugs. This review highlights the role of different herbal formulations, examples of plant extracts and types of several isolated phytoconstituents (phenolic acids, flavonoids, stilbenes, alkaloids, phenyl propanoids) in the prevention of MI with reported activities. Moreover, their possible mechanisms of action are also discussed to guide future research for the development of safer substitutes to manage MI.

Differential effects of desvenlafaxine on hot flashes in women with breast cancer taking tamoxifen: a randomized controlled trial

Hot flashes (HF) are a common adverse event of prolonged tamoxifen use in women with estrogen receptor-positive breast cancer, impacting psychiatric health and quality of life. While desvenlafaxine does not interact with tamoxifen, its efficacy and safety in breast cancer patients remain unstudied. This phase 3, four-week, multi-center, three-arm, parallel-group, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of desvenlafaxine for treating HF in women with breast cancer taking tamoxifen, assessing potential differential effects in patients with psychiatric and inflammatory conditions. Between December 2017 and February 2019, 57 women aged 19 or older, regularly taking tamoxifen as adjuvant therapy, experiencing moderate-to-severe HFs for more than a month, were randomized to receive desvenlafaxine 50 mg/day (D-50), desvenlafaxine 100 mg/day (D-100), or placebo for four weeks. The primary endpoint was the change rate in HF scores over four weeks, with adverse events as a secondary endpoint. Both desvenlafaxine arms demonstrated greater HF score reductions compared to placebo: D-50 (2.20 points/week, 95% CI: 0.71, 3.68) and D-100 (2.34 points/week, 95% CI: 0.92, 3.76). Notably, D-50 arm showed significantly greater efficacy in patients with depression or elevated inflammation. Desvenlafaxine offers an effective and safe treatment regimen for HF in women with breast cancer taking tamoxifen. The presence of depression and inflammation may guide optimal desvenlafaxine dosing. (Trial Registration: ClinicalTrials.gov Identifier: NCT02819921)

Wound Healing Society 2023 update on guidelines for arterial ulcers.

The Wound Healing Society guidelines for the treatment of arterial insufficiency ulcers were originally published in 2006, with the last update in 2014. These guidelines provided recommendations, along with their respective levels of evidence, on seven categories: diagnosis, surgery, infection control, wound bed preparation, dressings, adjuvant therapy and long-term maintenance. Over the last 9 years, additional literature regarding these aspects of arterial ulcer management has been published. An advisory panel comprised of academicians, clinicians and researchers was chosen to update the 2014 guidelines. Members included vascular surgeons, internists, plastic surgeons, anaesthesiologists, emergency medicine physicians and dermatologists, all with expertise in wound healing. The goal of this article is to evaluate relevant new findings upon which an updated version of the guidelines will be based.

Upregulation of key factors of viral entry of corona- and influenza viruses upon TLR3-signaling in cells from the respiratory tract and clinical treatment options by 1,8-Cineol.

At the end of the 2019 coronavirus pandemic (COVID-19), highly contagious variants of coronaviruses had emerged. Together with influenza viruses, different variants of the coronavirus currently cause most colds and require appropriate drug treatment. We have investigated the expression of important factors for the replication of these viruses, namely transmembrane protease serine subtype 2 (TMPRSS2), neuropilin1 (NRP1), and angiotensin converting enzyme 2 (ACE2) or tumor necrosis factor-α (TNF-α) after toll like receptor-3 (TLR-3) stimulation using RT-qPCR and flow cytometry (FC) analysis. As model served primary fibroblasts derived from the lung and nasal cavity, as well as epidermal stem cells and fully matured respiratory epithelium. The stimulated cell cultures were treated with pharmaceuticals (Dexamethasone and Enzalutamide) and the outcome was compared with the phytomedicine 1,8-Cineol. The stimulation of TLR3 is sufficient to induce the expression of exactly those targets that were highly expressed in the corresponding culture type, specifically ACE2 and TMPRSS2 in respiratory epithelial stem cells and NRP1 in fibroblast cells. It seems this self-perpetuating cycle of infection-driven upregulation of key viral replication factors by the innate immune system represents an evolutionary advantage for viruses using these transcripts as viral replication factors. Likewise, to the standard pharmaceuticals with proven clinical efficiency, 1,8-Cineol was able to disrupt this self-perpetuating cycle. Considering the minor side effects and negligible pharmacological interactions with other drugs, it is conceivable that an adjuvant or combinatorial therapy with 1,8-Cineol for respiratory diseases caused by corona- or influenza viruses would be beneficial.

Cribriform morular thyroid carcinoma: Clinicopathological and molecular basis for both a preventive and therapeutic approach for a rare tumor (Review).

Cribriform morular thyroid carcinoma (CMTC) has been included within the group of thyroid tumors of uncertain histogenesis in the recent World Health Organization classification of endocrine tumors. Most CMTCs occur in young euthyroid women with multiple (and bilateral) thyroid nodules in cases associated with familial adenomatous polyposis (FAP) or as single nodules in sporadic cases. CMTC generally behaves indolently, while aggressiveness and mortality are associated with high‑grade CMTC. This tumor histologically displays a distinctive combination of growth patterns with morular structures. Strong diffuse nuclear and cytoplasmic immunostaining for β‑catenin is the hallmark of CMTC. Tumor cells are also positive for thyroid transcription factor‑1 and for estrogen and progesterone receptors, but negative for thyroglobulin and calcitonin. It is possible that the CMTC phenotype could result from blockage in the terminal/follicular differentiation of follicular cells (or their precursor cells) secondary to the permanent activation of the Wnt/β‑catenin pathway. In CMTC, the activation of the Wnt/β‑catenin pathway is the central pathogenetic event, which in FAP‑associated cases results from germline mutations of the APC regulator of WNT signaling pathway (APC) gene, and in sporadic cases from somatic inactivating mutations in the APC, AXIN1 and CTNNB1 genes. Estrogens appear to play a tumor‑promoting role by stimulating both the PI3K/AKT/mTOR and the RAS/RAF/MAPK signaling pathways. Additional somatic mutations (i.e. RET rearrangements, or KRAS, phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit α, telomerase reverse transcriptase or tumor protein 53 mutations) may further potentiate the development and progression of CMTC. While hemithyroidectomy would be the treatment of choice for sporadic cases without high‑risk data, total thyroidectomy would be indicated in FAP‑associated cases. There is insufficient clinical data to propose therapies targeting the Wnt/β‑catenin pathway, but multikinase or selective inhibitors could be used in a manner analogous to that of conventional thyroid tumors. It is also unknown whether adjuvant antiestrogenic therapy could be useful in the subgroup of women undergoing surgery with high‑risk CMTC, as well as when there is tumor recurrence and/or metastasis.

Disparities in the Occurrence of Long-Term Effects of Bone Marrow Suppression after Treatment in Adolescent Young Adult Breast Cancer Survivors.

Many adolescent and young adult (AYA) patients with breast cancer (BC) receive adjuvant therapy as initial treatment, with long-term bone marrow suppression as a potential complication, but no studies have evaluated the impact of race/ethnicity on the development of bone marrow suppression in AYA BC survivors. Female patients ages 15-39 years diagnosed with BC (2006-2018) and surviving ≥ 2 years were identified from the California Cancer Registry and linked to statewide hospitalization data. We estimated the cumulative incidence of developing late effects of bone marrow suppression, such as leukopenia, anemia, thrombocytopenia, bleeding, and infection/sepsis, during hospital discharge diagnoses present ≥ 2 years after diagnosis. We examined the impact of sociodemographic and clinical factors on late effects using multivariate Cox proportional hazards regression. Of 11,293 patients, 42.8% were non-Hispanic (nH) White, 28.8% Hispanic, 19.5% nHAsian/Pacific Islander, and 7.5% nH Black. In multivariable analyses, nH Blacks had the highest risk (versus nH Whites) of anemia [hazard ratio (HR) 1.72, 95% confidence interval (CI) 1.47-2.02], leukopenia (HR 1.56, CI 1.14-2.13), thrombocytopenia (HR 1.46, CI 1.08-1.99), major infection/sepsis (HR 1.64, CI 1.4-1.92), and bleeding (HR 1.89, CI 1.39-2.58). Hispanics had a higher risk of developing anemia (HR 1.17, CI 1.04-1.32), bleeding (HR 1.4, CI 1.12-1.76), and major infections/sepsis (HR 1.36, CI 1.21-1.52). Asian/Pacific Islanders had only a higher risk of developing bleeding (HR 1.33, CI 1.03-1.72). Patients from a low neighborhood socioeconomic status had a 20% higher risk of infection/sepsis (HR 1.21, CI 1.1-1.34), but there were no associations for the other late effects. We identified that AYAs of nH Black, Hispanic, and Asian/Pacific Islander race/ethnicity are at an increased risk of several late effects after adjuvant therapy compared with nH White patients. From these data, providers can implement early/frequent screening of hematologic late effects in these high-risk survivors.

Utility of Axillary Staging in Older Patients with HER2-Positive Breast Cancer.

The utility of sentinel lymph node biopsy (SLNB) in older patients remains controversial. Advancements in human epidermal growth factor receptor 2 (HER2)-directed therapy have revolutionized disease response rates and prognosis, supporting efforts to re-evaluate the utility of SLNB. We aimed to assess the differences in treatment and overall survival (OS) in older patients with HER2-positive breast cancer based on SLNB. Using the National Cancer Database (2010-2020), patients ≥ 70years of age diagnosed with cT1-2/cN0/M0, HER2-positive breast cancer were identified. Logistic regression assessed associations with SLNB, systemic therapy, and radiation. Cox proportional hazard models were used to identify factors associated with OS. Analyses were stratified by treatment sequence, i.e. upfront surgery or neoadjuvant therapy (NAT) followed by surgery. Of the 17,609 patients included, 94% underwent upfront surgery (n=16,492) and the remaining underwent NAT (n=1117). Those who underwent SLNB were more likely to receive adjuvant therapy, irrespective of nodal status {upfront surgery/systemic therapy (odds ratio [OR] 2.82, 95% confidence interval [CI] 2.17-3.67); upfront surgery/radiation (OR 3.97, 95% CI 3.03-5.21); NAT/radiation (OR 5.69, 95% CI 1.83-17.69)}. The breast pathologic complete response (pCR) rate was highest among the hormone receptor (HR)-negative/HER2-positive subtype (50.0%), of which none were found to be ypN+. Comorbidity burden was associated with significantly lower rates of adjuvant systemic therapy and worse OS. Patients who underwent SLNB, regardless of pN status, were more likely to receive adjuvant therapy. Nodal positivity is exceedingly rare for patients with a breast pCR following NAT, especially among the HR-negative/HER2-positive subtype. It is reasonable to consider omission of SLNB in select subgroups of older patients with HER2-positive breast cancer.

NTRK-fused central nervous system tumours: clinicopathological and genetic insights and response to TRK inhibitors

Background Neurotrophic tropomyosin receptor kinase (NTRK) gene fusions are found in 1% of gliomas across children and adults. TRK inhibitors are promising therapeutic agents for NTRK-fused gliomas because they are tissue agnostic and cross the blood–brain barrier (BBB). Methods We investigated twelve NGS-verified NTRK-fused gliomas from a single institute, Seoul National University Hospital. Results The patient cohort included six children (aged 1–15 years) and six adults (aged 27–72 years). NTRK2 fusions were found in ten cerebral diffuse low-grade and high-grade gliomas (DLGGs and DHGGs, respectively), and NTRK1 fusions were found in one cerebral desmoplastic infantile ganglioglioma and one spinal DHGG. In this series, the fusion partners of NTRK2 were HOOK3, KIF5A, GKAP1, LHFPL3, SLMAP, ZBTB43, SPECC1L, FKBP15, KANK1, and BCR, while the NTRK1 fusion partners were TPR and TPM3. DLGGs tended to harbour only an NTRK fusion, while DHGGs exhibited further genetic alterations, such as TERT promoter/TP53/PTEN mutation, CDKN2A/2B homozygous deletion, PDGFRA/KIT/MDM4/AKT3 amplification, or multiple chromosomal copy number aberrations. Four patients received adjuvant TRK inhibitor therapy (larotrectinib, repotrectinib, or entrectinib), among which three also received chemotherapy (n = 2) or proton therapy (n = 1). The treatment outcomes for patients receiving TRK inhibitors varied: one child who received larotrectinib for residual DLGG maintained stable disease. In contrast, another child with DHGG in the spinal cord experienced multiple instances of tumour recurrence. Despite treatment with larotrectinib, ultimately, the child died as a result of tumour progression. An adult patient with glioblastoma (GBM) treated with entrectinib also experienced tumour progression and eventually died. However, there was a successful outcome for a paediatric patient with DHGG who, after a second gross total tumour removal followed by repotrectinib treatment, showed no evidence of disease. This patient had previously experienced relapse after the initial surgery and underwent autologous peripheral blood stem cell therapy with carboplatin/thiotepa and proton therapy. Conclusions Our study clarifies the distinct differences in the pathology and TRK inhibitor response between LGG and HGG with NTRK fusions.

Effectiveness of food supplement on treatment outcomes and quality of life in pulmonary tuberculosis: Phased implementation approach.

By encouraging treatment adherence and lowering mortality, dietary supplements can serve as adjuvant therapy for the success of medical interventions. We determined the effect of locally accessible food supplements on treatment outcomes, and health-related quality of life in patients with pulmonary tuberculosis initiating anti-tuberculosis treatment (ATT) in Odisha, India. Between September 2017 and December 2018, implementation research in patients with newly diagnosed sputum smear-positive pulmonary tuberculosis initiating ATT in five districts of the tribal belt of Odisha, offered food supplements along with ATT in a phased manner. Clinical symptoms, anthropometry, sputum for M. tuberculosis (M. tb), health-related quality of life and return to normal function were assessed periodically, and favourable treatment outcome (cure or treatment completed) was measured at the end of treatment. The effect of the food supplement on unfavorable outcomes (treatment failure, death, or lost-to-follow-up) was modelled using mixed-effects Poisson regression to determine the risk factors. Among the 761 participants enrolled, 614 participants received the food supplement and 147 did not receive the food supplement. Among the 614 participants in the supplement group, 537 (87%) had a favorable outcome and among the 147 participants in the no-supplement group, 113 (77%) had a favorable outcome (p = 0.0017). Higher age (>55 years) [aRR = 2.1(95% CI: 1.1-3.8)], male gender [aRR = 1.7(95% CI: 1.2-2.9)], and smear grading ≥2+ [aRR = 1.5 (95% CI: 1.1-2.2)] were associated with unfavorable treatment outcomes. Nutritional status, quality of life and lung health showed significant improvement from baseline in the supplement group. Improvement in the nutritional status of the patient can be considered a predictor of treatment success rates. Early food supplementation has a positive impact on the nutritional status.

Prevention of Sarcopenia and Maintenance of Exercise Tolerance by Individualized Prehabilitation in a Patient With Esophageal Cancer During Preoperative Adjuvant Therapy: A Case Report

Prevention of Sarcopenia and Maintenance of Exercise Tolerance by Individualized Prehabilitation in a Patient With Esophageal Cancer During Preoperative Adjuvant Therapy: A Case Report

Real-world use and outcomes of targeted therapy and immunotherapy for adjuvant treatment of BRAF-mutated melanoma patients in the United States.

Using a customized, harmonized US electronic health record database, real-world prescription patterns of first-line adjuvant immunotherapy and targeted therapy were retrospectively assessed for BRAFV600-mutated melanoma. Adults with BRAFV600 mutation-positive stage IIIA-D cutaneous melanoma who received first-line adjuvant immunotherapy (nivolumab or pembrolizumab) or targeted therapy (dabrafenib plus trametinib) between 1 January 2014 and 30 August 2020 in the NOBLE database were included. Patients were followed from first-line adjuvant therapy initiation for at least 6 months, until death, progression, follow-up loss, or data cutoff. Primary endpoints were proportion of patients receiving either therapy in first-line and second-line, treatment switching, treatment timing, and status at the end of first-line therapy. Secondary endpoints included discontinuation rates, recurrence-free survival (RFS), and overall survival (OS). Of 318 patients evaluated, 67.6% received nivolumab, 14.2% pembrolizumab, and 18.2% targeted therapy as first-line adjuvant therapy. Median treatment duration was longest for nivolumab (292 days) and shortest for targeted therapy (115 days). Reason for discontinuation was recorded for 195 of 274 patients who discontinued first-line therapy; most common reasons were treatment completion and treatment-related toxicity [87/158 (55.0%) and 29/158 (18.4%), respectively, in immunotherapy-treated patients; 9/37 (24.3%) and 21/37 (56.8%) in targeted therapy-treated patients]. Median RFS and OS for targeted therapy and nivolumab were not reached and were 34.6 and 38.1 months, respectively, for pembrolizumab. These results inform on prescription preferences and clinical outcomes for BRAFV600-mutated melanoma patients in the first-line adjuvant setting.

Levator Labii Superioris Alaeque Nasi Targeted Botulinum Toxin Injection for Treatment of Perinasal Facial Discomfort and Snarling.

Botulinum toxin has been increasingly studied and used for varying conditions, most notably, cosmetics. However, it has been shown that botulinum toxin demonstrates a high efficacy in treating spasticity disorders throughout the body, including the face. Facial spasms vary in pathophysiology, region, and severity. Some can be so severe that they can cause discomfort and emotional distress due to the involuntary facial expressions caused by the spasms. Most spasticity conditions are often treated with adjuvant therapy of oral muscle relaxants and analgesics depending on severity. However, these treatments impose risks of varying adverse effects from sedation, hypotension, and if chronic use, more severe effects such as central nervous system complications or QT prolongation. In addition, if spasms are localized, the muscle relaxant's mechanism is not targeted, leading to unnecessary systemic use. That being said, a more targeted and manageable treatment such as botulinum toxin presents itself as a potential option for patient's physical condition and everyday life quality. Our case presents a 62-year-old male, with a chronic history of localized, idiopathic spasms and discomfort within the Levator Labii Superioris Aqulae Nasi region. The patient had no history of previous neurological disorders, and imaging was unremarkable. The patient had been treated over the past 13 years with varying oral therapeutics including Cymbalta, Ibuprofen, and cyclobenzaprine with limited improvement, but presented to the clinic seeking a different treatment plan, as the adverse effects from the muscle relaxants were impeding his everyday activities. The patient was also experiencing significant pain and emotional stress due to the spasms. The risk and benefits of treatment options were discussed and the patient decided to move forward with botulinum injections. After the first injection, the patient reported his pain had significantly improved and was relieved to be off of chronic pain medications. Our case demonstrates, what increasing literature further also supports: botulinum toxin is becoming a potential effective treatment for a breadth of spasticity disorders with a more targeted mechanism, and more manageable treatment plan, while simultaneously improving the patient's quality of life.

DRD2 activation inhibits choroidal neovascularization in patients with Parkinson's disease and age-related macular degeneration.

Neovascular age-related macular degeneration (nAMD) remains a major cause of visual impairment and puts considerable burden on patients and health care systems. L-DOPA-treated Parkinson Disease (PD) patients have been shown to be partially protected from nAMD, but the mechanism remains unknown. Using murine models, combining 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and laser-induced nAMD, standard PD treatment of L-DOPA/DOPA-decarboxylase inhibitor, or specific dopamine receptor inhibitors, we here demonstrate that L-DOPA treatment-induced increase of dopamine mediated dopamine receptor D2 (DRD2) signaling inhibits choroidal neovascularization independently of MPTP-associated nigrostriatal pathway lesion. Analyzing a retrospective cohort of more than two hundred thousand nAMD patients receiving anti-VEGF treatment from the French nationwide insurance database, we show that DRD2-agonist treated (PD) patients have a significantly delayed age of onset for nAMD (81.4 (±7.0) vs 79.4 (±8.1) years old, respectively, p<0.0001) and reduced need for anti-VEGF therapies (-0.6 injections per 100 mg/day daily dose of DRD2 agonists the second year of treatment), similar to the L-DOPA treatment. While providing a mechanistic explanation for an intriguing epidemiological observation, our findings suggest that systemic DRD2 agonists might constitute an adjuvant therapy to delay and reduce the need for anti-VEGF therapy in nAMD patients.

From Adenoma to Carcinoma: the Unexpected Evolution of an Apparently Stable Adrenal Lesion.

There is a lack of solid long-term evidence with respect to the management over time of adrenal incidentalomas that miss clearly benign radiological features. We present the case of a 75-year-old man with a non-secreting adrenal mass, apparently stable in size (14 mm) and unchanged in features for 2 years, but subsequently diagnosed as adrenal carcinoma. The patient was referred to Grande Ospedale Metropolitano Niguarda in August 2022 due to the presence of a large lesion in the left adrenal site. In 2017, a 14 mm, 20 HU, round, regular-edged lesion was detected at a CT scan without contrast medium. Over the next two years, the patient was re-evaluated every 6 months with follow-up CT scans with no apparent densitometric or dimensional changes in the known lesion. In September 2022, 3 years after the last CT scan, the patient was hospitalised for pneumonia. An abdominal CT scan acquired during the hospitalisation showed an increase of the lesion to 14.5x10x12 cm. The patient subsequently underwent open nephrosurrenectomy, and histological examination confirmed the presence of an adrenal carcinoma (proliferation index 5%, Weiss score 7). No adjuvant therapy was administered, and the last CT scan in December 2022 was negative for the recurrence of the disease. Adrenal carcinoma usually presents as a clearly malignant lesion with rapid growth and a marked tendency to metastasise. This case highlights how an adrenal adenoma with indeterminate features is worthy of follow-up over time despite its apparent dimensional and radiological stability [1].