An Exploratory Study of Neoadjuvant Cetuximab Followed by Cetuximab and Chemoradiotherapy in Women With Newly Diagnosed Locally Advanced Cervical Cancer

alexandrossfakianakis shared this article with you from Inoreader An Exploratory Study of Neoadjuvant Cetuximab Followed by Cetuximab and Chemoradiotherapy in Women With Newly Diagnosed Locally Advanced Cervical Cancer via American Journal of Clinical Oncology - Current Issue Objectives: This study explored the feasibility of cetuximab with chemoradiation in women with cervical carcinoma and evaluated fluorine-18 fluorodeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT) to assess early response to cetuximab (NCT00292955). Patients and Methods: Eligible patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB-IVB invasive carcinoma of the uterine cervix were treated on 1 of 3 dose levels (DL). DL1 consisted of neoadjuvant cetuximab, then concurrent radiotherapy with cetuximab 250 mg/m2/cisplatin 40 mg/m2, followed by weekly cetuximab. DL2 consisted of radiotherapy with cetuximab 200 mg/m2 and cisplatin 30 mg/m2. DL3 consisted of radiotherapy with cetuximab 250 mg/m2 and cisplatin 30 mg/m2. Patients underwent 18F-FDG-PET/CT before treatment, after neoadjuvant cetuximab, and at the end of treatment. Results: Of the 21 patients enrolled, 9, 3, and 9 were treated in DL1, DL2, and DL3, respectively. DL1 required dose reductions due to gastrointestinal toxicities. DL2 and 3 were tolerated with 1 dose-limiting toxicity (grade 4 renal failure) at DL3. Following 3 weekly treatments of neoadjuvant cetuximab in DL1, 7 patients had maximum standardized uptake value changes on 18F-FDG-PET/CT consistent with response to cetuximab. Of the 12 patients with locally advanced disease, eleven evaluable patients had no evidence of disease on 18F-FDG-PET/CT at treatment end. Five-year progression-free survival and overall survival rates for all patients were 57.5% and 58.5%, respectively. Conclusions: Cetuximab with cisplatin 30 mg/m2 and radiotherapy was tolerated. 18F-FDG-PET/CT demonstrated early evidence of response to neoadjuvant cetuximab. With advances in precision oncology and the recent approval of pembrolizumab in metastatic cervical cancer, dual-target inhibition with an epidermal growth factor receptor inhibitor may be a promising treatment in the future. View on Web

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Dose of deferasirox correlates with its effects, which differ between low‐risk myelodysplastic syndrome and aplastic anaemia

alexandrossfakianakis shared this article with you from Inoreader Dose of deferasirox correlates with its effects, which differ between low‐risk myelodysplastic syndrome and aplastic anaemia via Journal of Clinical Pharmacy and Therapeutics This study retrospectively evaluated the efficacy, safety and dose–effect relationships of deferasirox (DFX) in patients with low-risk myelodysplastic syndrome (MDS) and aplastic anaemia (AA) who were refractory to regular treatment in a real-world setting. We found that a significant decrease in serum ferritin (SF) and an improvement in haematologic parameters, organ function and even overall survival (OS) can be achieved if the accumulated DFX dose reaches a certain level. Patients with low-risk MDS need a higher dose than those with AA. Abstract What is known and objective Patients with low-risk myelodysplastic syndrome (MDS) and aplastic anaemia (AA) often need transfusions, which may accelerate iron overload. The aim of this study was to evaluate the efficacy, safety and dose–effect relationships of deferasirox (DFX) in patients with low-risk MDS and AA who were refractory to regular treatment in a real-world setting. Methods Patient data were recorded, and dose–effect relationships of DFX were calculated after the first 6 months. Total annual exposure to DFX was calculated after 12 months and expressed as the accumulated exposure time at a dosage of 20 mg/kg/day. Results and discussion Sixty-one patients with low-risk MDS and 51 with AA were enrolled. The minimum dosage of DFX needed for a significant serum ferritin (SF) decrease was 20 mg/kg/day at 6 months, and the minimum accumulation of DFX had to reach 9 months at 20 mg/kg/day by 12 months for patients with low-risk MDS. For patients with AA, the minimum dosage was 10 mg/kg/day at 6 months, and the minimum accumulation had to reach 3 months at 20 mg/kg/day by 12 months. With the same exposure, significant improvements in haematological parameters were also observed in AA. Lower liver enzymes compared with baseline were observed. Gastrointestinal disorders and elevated serum creatinine were the most common side effects. Higher exposure to DFX correlated with longer overall survival (OS). What is new and conclusion A significant decrease in SF and an improvement in haematologic parameters, organ function and even OS can be achieved if the accumulated DFX dose reaches a certain level. Patients with low-risk MDS need a higher dose than those with AA. View on Web

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Changes in Cough Airflow and Acoustics After Injection Laryngoplasty

alexandrossfakianakis shared this article with you from Inoreader Changes in Cough Airflow and Acoustics After Injection Laryngoplasty via The Laryngoscope We explored the following hypotheses in a cohort of patients undergoing injection laryngoplasty: (1) glottic insufficiency affects voluntary cough airflow dynamics and restoring glottic competence may improve parameters of cough strength, (2) cough strength can be inferred from cough acoustic signal, and (3) glottic competence changes cough sounds and correlates with spectrogram morphology. Our study thus indicates that injection laryngoplasty may help avert aspiration in patients with glottic insufficiency by improving cough effectiveness and that improved cough airflow measures may be tracked with cough sounds. Objective/Hypothesis We explored the following hypotheses in a cohort of patients undergoing injection laryngoplasty: (1) glottic insufficiency affects voluntary cough airflow dynamics and restoring glottic competence may improve parameters of cough strength, (2) cough strength can be inferred from cough acoustic signal, and (3) glottic competence changes cough sounds and correlates with spectrogram morphology. Study Type/Design Prospective interventional study. Methods Subjects with glottic insufficiency secondary to unilateral vocal fold paresis, paralysis, or atrophy, and scheduled for injection laryngoplasty completed an instrumental assessment of voluntary cough airflow using a pneumotachometer and a protocolized voluntary cough sound recording. A Wilcoxon signed-rank test was used to compare the differences between pre- and post-injection laryngoplasty in airflow and acoustic measures. A Spearman rank-order correlation was used to evaluate the association between airflow and acoustic cough measures. Results Twenty-five patients (13F:12M, mean age 68.8) completed voluntary cough airflow measurements and 22 completed cough sound recordings. Following injection laryngoplasty, patients had a statistically significant decreased peak expiratory flow rise time (PEFRT) (mean change: −0.03 s, SD: 0.06, p = 0.04) and increased cough volume acceleration (mean change: 13.1 L/s2, SD: 33.9, p = 0.03), suggesting improved cough effectiveness. Correlation of cough acoustic measures with airflow measures showed a weak relationship between PEFRT and acoustic energy (coefficient: −0.31, p = 0.04) and peak power density (coefficient: −0.35, p = 0.02). Conclusions Our study thus indicates that injection laryngoplasty may help avert aspiration in patients with glottic insufficiency by improving cough effectiveness and that improved cough airflow measures may be tracked with cough sounds. Level of Evidence 3 Laryngoscope, 2022 View on Web

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Bilateral upper extremity motor priming (BUMP) plus task-specific training for severe, chronic upper limb hemiparesis: study protocol for a randomized clinical trial

alexandrossfakianakis shared this article with you from Inoreader Bilateral upper extremity motor priming (BUMP) plus task-specific training for severe, chronic upper limb hemiparesis: study protocol for a randomized clinical trial via Trials - Latest Articles Various priming techniques to enhance neuroplasticity have been examined in stroke rehabilitation research. Most priming techniques are costly and approved only for research. Here, we describe a priming techni... View on Web

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Tailoring limb length based on total small bowel length in one anastomosis gastric bypass surgery (TAILOR study): study protocol for a randomized controlled trial

alexandrossfakianakis shared this article with you from Inoreader Tailoring limb length based on total small bowel length in one anastomosis gastric bypass surgery (TAILOR study): study protocol for a randomized controlled trial via Trials - Latest Articles The one anastomosis gastric bypass (OAGB) is being performed by an increasing number of bariatric centers over the world. However, the optimal length of the biliopancreatic (BP) limb remains a topic of discuss... View on Web

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Influence of cross‐sectional area and fat infiltration of paraspinal muscles on analgesic efficacy of epidural steroid injection in elderly patients

alexandrossfakianakis shared this article with you from Inoreader Influence of cross‐sectional area and fat infiltration of paraspinal muscles on analgesic efficacy of epidural steroid injection in elderly patients via Pain Practice Abstract Background An assessment of paraspinal muscle degeneration based on magnetic resonance imaging has been used to investigate both sarcopenia and myosteatosis. The morphologic changes in cross-sectional area and fat infiltration of the paraspinal muscles can affect pain outcomes after epidural steroid injection. Methods Patients ≥ 65 years of age who underwent fluoroscopy-guided lumbar epidural steroid injections were enrolled. Good analgesia was defined as ≥ 50% reduction in pain score at 4 weeks after injection. Cross-sectional area and grade of fat infiltration of the paraspinal muscles on magnetic resonance images at the level of L3-L4 disc were measured. Patient demographics, pain-related factors, clinical factors, and paraspinal muscle measurements were compared between good and poor analgesia groups. The factors associated with pain outcome after injection were identified using multivariate analysis. Results A total of 245 patients consisting of 149 and 96 patients in the good and poor analgesia groups, respectively, fully satisfied the study criteria for analysis. Patients of older age, opioid use, and high-grade foraminal stenosis were frequently observed in the poor analgesia group. The grade of fat infiltration of the paraspinal muscles was significantly higher in the poor analgesia group (Grade 2, 20.8 vs. 42.7%, P < 0.001), and this result was predominantly observed in female patients. However, there was no difference in muscle cross-sectional area between the two groups (18.29 ± 3.16 vs. 18.59 ± 3.03 cm2/m2, P = 0.460). The percentage of patients with good analgesia decreased as the grade of fat infiltration increased (Grade 0 = 75.0%, Grade 1 = 65.8%, Grade 2 = 43.0%, P < 0.001). Multivariate logistic regression analysis revealed that pre-injection opioid use [adjusted odds ratio (aOR) = 1.926, 95% confidence interval (CI) = 1.084–3.422, P = 0.025], moderate to severe foraminal stenosis (aOR = 2.859, 95% CI = 1.371–5.965, P = 0.005), and high-grade fat infiltration of the paraspinal muscles (aOR = 4.258, 95% CI = 1.805–10.043, P = 0.001) were significantly associated with poor analgesia after injection. Conclusion High fat infiltration of the paraspinal muscles at the mid-lumbar region appeared to be an independent factor associated with poor analgesia after epidural steroid injection in elderly patients with symptomatic degenerative lumbar spinal disease receiving conservative care. However, cross-sectional area of the paraspinal muscles was not associated with pain relief after injection. View on Web

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Novel cancer gene discovery using a forward genetic screen in RCAS-PDGFB-driven gliomas

alexandrossfakianakis shared this article with you from Inoreader Novel cancer gene discovery using a forward genetic screen in RCAS-PDGFB-driven gliomas via Neuro-Oncology Advance Access Abstract Background Malignant gliomas, the most common malignant brain tumors in adults, represent a heterogeneous group of diseases with poor prognosis. Retroviruses can cause permanent genetic alterations that modify genes close to the viral integration site. Methods Here we describe the use of a high-throughput pipeline coupled to the commonly used tissue-specific retroviral RCAS-TVA mouse tumor model system. Utilizing next generation sequencing, we show that retroviral integration sites can be reproducibly detected in malignant stem cell lines generated from RCAS-PDGFB-driven glioma biopsies. Results A large fraction of common integration sites contained genes that have been dysregulated or misexpressed in glioma. Others overlapped with loci identified in previous glioma-related forward genetic screens, but several novel putative cancer-causing genes were also found. Integrating retroviral tagging and clinical data, Ppfibp1 was highlighted as a frequently tagged novel glioma-causing gene. Retroviral integrations into the locus resulted in Ppfibp1 upregulation, and Ppfibp1-tagged cells generated tumors with shorter latency upon orthotopic transplantation. In human gliomas, increased PPFIBP1 expression was significantly linked to poor prognosis and PDGF treatment resistance. Conclusions Altogether, the current study has demonstrated a novel approach to tagging glioma genes via forward genetics, validating previous results, and identifying PPFIBP1 as a putative oncogene in gliomagenesis. View on Web

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