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Background and Purpose: Prior studies reported conflicting findings regarding the association of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis with measures of brain health. We examined whether NAFLD and liver fibrosis are associated with structural brain imaging measures in middle- and old-age adults., Methods: In this cross-sectional study among dementia- and stroke-free individuals, data were pooled from the Offspring and Third Generation cohorts of the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Study of Health in Pomerania. NAFLD was assessed through abdominal imaging. Transient hepatic elastography (FibroScan) was used to assess liver fibrosis in FHS and RS. Linear regression models were used to explore the relation of NAFLD and liver fibrosis with brain volumes, including total brain, gray matter, hippocampus, and white matter hyperintensities, adjusting for potential confounders. Results were combined using fixed effects meta-analysis., Results: In total, 5660 and 3022 individuals were included for NAFLD and liver fibrosis analyses, respectively. NAFLD was associated with smaller volumes of total brain (β = -3.5, 95% confidence interval [CI] = -5.4 to -1.7), total gray matter (β = -1.9, 95% CI = -3.4 to -0.3), and total cortical gray matter (β = -1.9, 95% CI = -3.7 to -0.01). In addition, liver fibrosis (defined as liver stiffness measure ≥8.2 kPa) was related to smaller total brain volumes (β = -7.3, 95% CI = -11.1 to -3.5). Heterogeneity between studies was low., Conclusions: NAFLD and liver fibrosis may be directly related to brain aging. Larger and prospective studies are warranted to validate these findings and identify liver-related preventive strategies for neurodegeneration., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: This retrospective study evaluated the efficacy of gabapentin for the treatment of pain syndromes related to radiation-induced mucositis in patients with head and neck cancers treated with concurrent chemoradiation., Methods: Data from 42 patients with head and neck malignancies treated with concurrent chemoradiotherapy using an intensity-modulated radiotherapy technique were analyzed. Gabapentin was initiated in the second week of radiotherapy. Opiates were prescribed in addition to gabapentin as clinically indicated to obtain adequate pain control., Results: At a median dose of 2700 mg/day of gabapentin, only 33% and 55% of patients required additional low-dose narcotic medications for pain control during the third and fourth week of treatment, respectively, despite exhibiting a grade 2 or higher mucositis in 71% and 86% of the patients, respectively. Furthermore, during the last weeks of treatment, 71% of the patients required additional low-dose opiates for adequate pain control, despite the presence of grade 2 or higher mucositis in 95% and 100% of patients at Weeks 5 and 6, respectively. Only 1 patient had a treatment-related interruption of >3 days during chemoradiotherapy., Conclusions: Gabapentin appears to be promising in reducing the need for high total doses of opioids and avoiding unplanned treatment interruptions for patients with head and neck malignancies treated with concurrent chemoradiotherapy and should be further evaluated prospectively in controlled clinical trials.

Objectives: The elective dissection of cervical lymph nodes from patients with early oral tongue cancer and a clinically negative neck (T1/T2N0), remains an unsettled issue that continues to be investigated. This study examines clinical and histopathologic factors through univariate and multivariate analysis to correlate the risk of neck micrometastasis in patients with T1/T2N0 squamous cell carcinoma of the oral tongue., Study Design and Methods: The clinical files and histologic sections of tumor from 45 clinically determined N0 patients were retrospectively analyzed. The factors examined include degree of tumor cell differentiation, T1/T2 staging, presence of perineural invasion, presence of angiolymphatic invasion, type of invasion front, depth of muscle invasion, and tumor thickness., Results: Independent correlates of positive occult neck metastasis included greater tumor thickness ( P = 0.01), greater depth of muscle invasion ( P = 0.01), T2 stage ( P = 0.01), poorly differentiated tumors ( P = 0.007), infiltrating-type invasion front ( P = 0.03), presence of perineural invasion ( P = 0.001), and presence of angiolymphatic invasion ( P = 0.005). The final multivariate model for estimation of an increased probability of occult neck disease included greater tumor thickness, presence of perineural invasion, infiltrating-type invasion front, poorly differentiated tumors, and T2 stage., Conclusions: The clinical and histopathologic factors studied herein permit greater selectivity and more informed decision-making than does presurgical evaluation, when addressing elective neck treatment for early N0 oral tongue cancer. The multivariate model derived from this study appears to be a more reliable method for determining the patients most likely to benefit from elective neck dissection.

Various non-invasive techniques for prenatal diagnosis have been under investigation. We evaluated the success of fetal sexing using a non-invasive technique for obtaining fetal cells, uterine cervix brushing, in combination with FISH. Thirty pregnant women who completed between 6 and 10 weeks of gestation and who were scheduled to undergo pregnancy termination were included in the study. A Pap smear cytobrush was inserted through the external os to a maximum depth of 2 cm and removed while rotating it a full turn. The material that was caught on the brush was spread on four microscope slides. Two-color FISH was used for fetal sexing. Following pregnancy termination, a placental sample was used for full karyotyping. In 29/30 cases FISH diagnosis was confirmed by chromosomal analysis. The only male case in which a Y chromosome was not seen was from a pregnancy of 6 weeks 6 days gestational age. One case was mosaic of 46,XY/47,XXY (25%). In most cases (7/13) the Y chromosome was already identified in the first analyzed slide. With the use of a cytobrush fetal cells can be easily obtained for the purpose of prenatal diagnosis of chromosomal disorders., (Copyright 2001 John Wiley & Sons, Ltd.)

In this era of decreasing reimbursement, health systems have been forced to become more efficient and decrease resource utilization to remain financially viable. One of the methods of internal cost control has been the use of clinical pathways. Given the complexity of treatment of head and neck cancer patients, clinical pathways can help to standardize decision making and introduce uniformity in resource utilization. The objective of this study is to compare resource utilization and outcomes before and after implementation of a clinical pathway for head and neck surgical patients. We observed significant decreases in hospital costs as well as shorter lengths of stay after pathway implementation. It is our belief that a uniform management tool is beneficial in this complex disease.

We present a review of the postoperative course, complications, and functional outcome of 190 patients consecutively treated with supracricoid partial laryngectomy with cricohyoidoepiglottopexy. The average times until removal of the tracheostomy and nasogastric feeding tubes were 9 and 16 days, respectively. The postoperative mortality rate was 1%. Major complications included pneumonia from aspiration, cervical wound infection, symptomatic laryngocele, ruptured pexis, laryngeal chondroradionecrosis, and laryngeal stenosis in 8.5%, 4.2%, 3.1%, 1%, 0.5%, and 0.5% of the patients, respectively. Completion total laryngectomy, permanent gastrostomy, and permanent tracheostomy were requested in 0.5% of the patients. Normal swallowing without gastrostomy and respiration without tracheostomy was achieved by the first postoperative year in 98.4% (187/190) of the patients. This article presents a univariate analysis of the potential correlation between various variables and the duration of tracheostomy and the length of time the nasogastric feeding tubes were inserted, the mortality incidence and causes, the incidence and type of the various complications, and the duration of hospitalization. Comparison of our data with the reported functional results after vertical partial laryngectomy suggested that supracricoid partial laryngectomy with cricohyoidoepiglottopexy does not result in an increased rate of postoperative complications.

Background: Gastroesophageal reflux disease occasionally presents with laryngeal symptoms. Such patients are often referred for a gastroenterology evaluation. This study was designed to determine whether an empiric trial of high-dose omeprazole therapy could reliably identify patients with reflux laryngitis and thus obviate the need for a gastroenterology workup., Methods: Patients were evaluated with a history, physical examination, esophageal manometry, upper endoscopy, and 24-hour pH-metry for determination of the presence of absence of underlying gastroesophageal reflux disease and then received an empiric trial of oral omeprazole therapy (20 mg twice daily for 1 month). A positive omeprazole test result was defined as resolution of all laryngeal symptoms on completion of the empiric trial of therapy., Results: Two patients were classified as having no reflux, and eight were classified as having reflux. Omeprazole test results were positive in six patients. Five of six had reflux, but one patient had no evidence for reflux. Omeprazole test results were negative in four patients. Three of four had reflux, and one did not. Despite the absence of antisecretory therapy, laryngeal symptoms did not recur in either patient without reflux during follow-up. Laryngeal symptoms were managed in two of the three patients with reflux who had negative omeprazole test results and who were using inhalers in combination with histamine H2 receptor antagonist therapy for their reflux disease. One patient with reflux who had a negative omeprazole test result responded to higher doses of omeprazole, and the five patients with reflux who had positive omeprazole test results all responded to continuation of omeprazole., Conclusions: The omeprazole test may be useful in confirming the suspicion of reflux laryngitis in patients suspected of having this disease after an otolaryngology evaluation. However, there is a potential for false-positive and false-negative test results. A gastroenterology evaluation may aid in the identification of false-positive test results by documenting the absence of reflux in certain responders.

Twenty patients with glottic squamous cell carcinoma and a fixed true vocal cord underwent neoadjuvant chemotherapy followed by supracricoid partial laryngectomy with cricohyoidoepiglottopexy. Phonation, respiration, and deglutition were preserved. Local control was better than has been previously reported for either extended vertical partial laryngectomy or radiation therapy. All patients were monitored for at least 3 years or until death. The Kaplan-Meier 3-year survival, local recurrence, nodal recurrence, distant metastasis, and second primary rates were 75%, 10.8%, 5%, 10.8%, and 10.8%, respectively. Overall local control was achieved in all cases, and laryngeal preservation in 90%. Our experience suggested that neoadjuvant chemotherapy with supracricoid partial laryngectomy with cricohyoidoepiglottopexy deserves further consideration in the treatment of glottic tumors with a fixed true vocal cord.

Background: Vertical partial laryngectomy (VPL) and radiation therapy (RT) are the recommended conventional conservative options for glottic carcinoma classified as T2. In series presenting more than 100 patients with a minimum 3-year follow-up, however, local recurrence rates were reported as 22-43.5%. The authors' experience with a new strategy based on continuous cisplatin-fluorouracil induction chemotherapy (IC) and supracricoid partial laryngectomy with cricohyoepiglottopexy (CHEP) is presented., Methods: A retrospective analysis of 67 patients who presented with untreated moderately to well differentiated invasive glottic carcinoma classified as T2, managed from 1983 to 1991 with IC and CHEP, was conducted. Statistical analysis of survival, local control, nodal control, distant metastasis, and metachronous second primary tumor incidence was based on the Kaplan-Meier actuarial method. Univariate analysis was performed to analyze the relationships between various factors and survival, local recurrence, and nodal recurrence. Clinical response, histologic response, IC toxicity and postoperative course were reported., Results: The Kaplan-Meier 5-year survival, local recurrence, nodal recurrence, distant metastasis, and metachronous second primary tumor estimate were 92.3%, 5.6%, 1.5%, 1.8%, and 5.6%, respectively. Overall laryngeal preservation was achieved in 65 patients (97%). Ultimate local control was achieved in all patients but one. Nodal recurrence was statistically more likely in patients presenting with a local recurrence. Analysis of the specimens demonstrated complete histologic response to IC in 25 (37.3%) patients. A strong statistical relation (P < 0.0001) was noted between complete clinical response after IC and complete histologic response., Conclusions: The change from the prevailing treatment modalities of RT and VPL to a new multimodal strategy (IC+CHEP) did not decrease survival and allowed for an increase in laryngeal preservation rate. The high rate (37.3%) of complete histologic response suggests that IC deserves further consideration in the management of patients with glottic carcinoma classified as T2. The favorable results achieved in this series, when compared with historic controls, should stimulate prospective clinical trials comparing the two surgical procedures (CHEP vs. VPL with or without IC) for resection of Stage II glottic carcinoma.

Cell kinetics were studied, in vivo, in 19 patients with metastatic melanoma by autoradiographic technics. Multiple tumor labeling indices (L.I.) were determined with intralesional H3-TdR in 19 patients and were correlated with the presence of melanin. Serial biopsies were obtained to derive percent labeled mitoses (PLM) curves for 9 individual patients. Duration of the S and G2 phases were calculated using 50 and 37% intercepts from the PLM curves, as well as by two computerized cell-cycle analysis programs, and the results were compared. Tumor L.I.s were found to be reproducible for distant metastases of similar size in the same patient. Tumor L.I.s had a bimodal distribution for the 19 patients examined. The two significantly distinct subgroups had L.I.s of 18.2 +/- 3.4% and 6.7 +/- 2.1%. The presence of melanin correlated with the higher L.I. subgroup. The difference in L.I. may reflect a higher growth fraction or a shorter germinative cycle in melanotic tumors. However, the presence of melanin did not correlate with a change in the duration of S or G2 phases. The sum of Ts and Tg2 was approximately 24 hours, regardless of the analytic method. These kinetic parameters are being monitored during chemotherapy for prognostic indicators.

Deferoxamine, a free radical scavenger and iron chelator, has been shown to improve skin flap survival in ischemic flap surgery in rats. The present study investigates the value of deferoxamine in ischemic flap surgery in the porcine model. Four 4 x 12 cm flaps, 3 cm apart and 3 cm from the dorsal midline, were elevated on each of six female pigs, weighing 50 to 60 pounds each. The animals were divided into two test groups. Group 1 received six 1 gm doses of deferoxamine in 4 ml of sterile water intramuscularly every 6 hours preoperatively for five doses, followed by the administration of 1 g every 6 hours for the first 6 days postoperatively. Group 2 received 4 ml of normal saline administered intramuscularly as above. The percentage of flap necrosis was assessed on postoperative day 7 by the weighing paper technique. Group 1 had 17.1% necrosis and group 2 had 33% necrosis (p less than 0.005). Deferoxamine has decreased flap necrosis in the porcine model and may be of use in augmenting the surviving length of flaps in human beings.