Search

Background: Exercise-associated secondary amenorrhea results in estrogen deficiency, which may lead to dysfunction in estrogen's normal cardioprotective pathways. Estrogen may be essential in a woman's endothelial adaptations to exercise. The objective of this review was to assess the association between secondary amenorrhea in physically active women and cardiovascular disease (CVD) risk., Methods and Results: A literature search was performed in January 2023 and updated in August 2023 of the Cumulative Index to Nursing and Allied Health Literature (EBSCOhost), Cochrane Library, Embase (Ovid), MEDLINE (Ovid), SPORTDiscus (EBSCOhost), and Scopus from inception to present with no date or language limitations. Citation chaining was done to screen for additional studies. Eight sources were searched for gray literature. Studies that compared physically active women with amenorrhea to physically active women with eumenorrhea aged 18 to 35 years with evidence of CVD, alterations to cardiovascular physiology, or CVD risks were included. Eighteen observational studies from 3 countries were included. Overall, the quality of evidence was good. A meta-analysis was performed. Physically active women with secondary amenorrhea had significantly lower estradiol, flow-mediated dilation, resting heart rate, systolic blood pressure, and diastolic blood pressure and higher total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol., Conclusions: Estrogen deficiency resulting from exercise-associated secondary amenorrhea in physically active women may impact cardiovascular physiology and certain CVD risk factors. The research in this area is observational; therefore, findings should be interpreted cautiously. However, as exercise-associated secondary amenorrhea is reversible and the primary prevention of CVD is important for public health, it may be important to treat secondary amenorrhea and restore estrogen levels.

Background Gender-related factors are psycho-socio-cultural characteristics and are associated with adverse clinical outcomes in acute myocardial infarction, independent of sex. Whether sex- and gender-related factors contribute to the substantial heterogeneity in hospital length of stay (LOS) among patients with non-ST-segment-elevation myocardial infarction remains unknown. Methods and Results This observational cohort study combined and analyzed data from the GENESIS-PRAXY (Gender and Sex Determinants of Cardiovascular Disease: From Bench to Beyond Premature Acute Coronary Syndrome study), EVA (Endocrine Vascular Disease Approach study), and VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI [Acute Myocardial Infarction] Patients study) cohorts of adults hospitalized across Canada, the United States, Switzerland, Italy, Spain, and Australia for non-ST-segment-elevation myocardial infarction. In total, 5219 participants were assessed for eligibility. Sixty-three patients were excluded for missing LOS, and 2938 were excluded because of no non-ST-segment-elevation myocardial infarction diagnosis. In total, 2218 participants were analyzed (66% women; mean±SD age, 48.5±7.9 years; 67.8% in the United States). Individuals with longer LOS (51%) were more likely to be White race, were more likely to have diabetes, hypertension, and a lower income, and were less likely to be employed and have completed secondary education. No univariate association between sex and LOS was observed. In the adjusted multivariable model, age (0.62 d/10 y; P <0.001), unemployment (0.63 days; P =0.01), and some of countries included relative to Canada (Italy, 4.1 days; Spain, 1.7 days; and the United States, -1.0 days; all P <0.001) were independently associated with longer LOS. Medical history mediated the effect of employment on LOS. No interaction between sex and employment was observed. Longer LOS was associated with increased 12-month all-cause mortality. Conclusions Older age, unemployment, and country of hospitalization were independent predictors of LOS, regardless of sex. Individuals employed with non-ST-segment-elevation myocardial infarction were more likely to experience shorter LOS. Sociocultural factors represent a potential target for improvement in health care expenditure and resource allocation.

Inhibition of the protein phosphatase calcineurin (CN) ameliorates pathophysiologic and cognitive changes in aging rodents and mice with aging-related Alzheimer's disease (AD)-like pathology. However, concerns over adverse effects have slowed the transition of common CN-inhibiting drugs to the clinic for the treatment of AD and AD-related disorders. Targeting substrates of CN, like the nuclear factor of activated T cells (NFATs), has been suggested as an alternative, safer approach to CN inhibitors. However, small chemical inhibitors of NFATs have only rarely been described. Here, we investigate a newly developed neuroprotective hydroxyquinoline derivative (Q134R) that suppresses NFAT signaling, without inhibiting CN activity. Q134R partially inhibited NFAT activity in primary rat astrocytes, but did not prevent CN-mediated dephosphorylation of a non-NFAT target, either in vivo, or in vitro. Acute (≤1 week) oral delivery of Q134R to APP/PS1 (12 months old) or wild-type mice (3-4 months old) infused with oligomeric Aβ peptides led to improved Y maze performance. Chronic (≥3 months) oral delivery of Q134R appeared to be safe, and, in fact, promoted survival in wild-type (WT) mice when given for many months beyond middle age. Finally, chronic delivery of Q134R to APP/PS1 mice during the early stages of amyloid pathology (i.e., between 6 and 9 months) tended to reduce signs of glial reactivity, prevented the upregulation of astrocytic NFAT4, and ameliorated deficits in synaptic strength and plasticity, without noticeably altering parenchymal Aβ plaque pathology. The results suggest that Q134R is a promising drug for treating AD and aging-related disorders., (© 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

As demonstrated by increased hippocampal insulin receptor density following learning in animal models and decreased insulin signaling, receptor density, and memory decline in aging and Alzheimer's diseases, numerous studies have emphasized the importance of insulin in learning and memory processes. This has been further supported by work showing that intranasal delivery of insulin can enhance insulin receptor signaling, alter cerebral blood flow, and improve memory recall. Additionally, inhibition of insulin receptor function or expression using molecular techniques has been associated with reduced learning. Here, we sought a different approach to increase insulin receptor activity without the need for administering the ligand. A constitutively active, modified human insulin receptor (IRβ) was delivered to the hippocampus of young (2 months) and aged (18 months) male Fischer 344 rats in vivo. The impact of increasing hippocampal insulin receptor expression was investigated using several outcome measures, including Morris water maze and ambulatory gait performance, immunofluorescence, immunohistochemistry, and Western immunoblotting. In aged animals, the IRβ construct was associated with enhanced performance on the Morris water maze task, suggesting that this receptor was able to improve memory recall. Additionally, in both age-groups, a reduced stride length was noted in IRβ-treated animals along with elevated hippocampal insulin receptor levels. These results provide new insights into the potential impact of increasing neuronal insulin signaling in the hippocampus of aged animals and support the efficacy of molecularly elevating insulin receptor activity in vivo in the absence of the ligand to directly study this process., (© 2020 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Background Clinical practice guideline ( CPG ) developers have yet to endorse a consistent and systematic approach for considering sex-specific cardiovascular information in CPG s. This article describes an initiative led by the Canadian Cardiovascular Society to determine the feasibility and outcomes of a structured process for considering sex in a CPG for the management of ST-segment-elevation myocardial infarction. Methods and Results A sex and gender champion was appointed to the guideline development committee. The feasibility of tailoring the CPG to sex was ascertained by recording (1) the male-female distribution of the study population, (2) the adequacy of sex-specific representation in each study using the participation/prevalence ratio, and (3) whether data were disaggregated by sex. The outcome was to determine whether recommendations for CPG s based on an assessment of the evidence should differ by sex. In total, 175 studies were included. The mean percentage of female participants reported in the studies was 24.5% ( SD : 6.6%; minimum: 0%; maximum: 51%). The mean participation/prevalence ratio was 0.62 ( SD : 0.16; minimum: 0.00; maximum: 1.19). Eighteen (10.2%) studies disaggregated the data by sex. Based on the participation/prevalence ratio and the sex-specific analyses presented, only 1 study provided adequate evidence to confidently inform the applicability of the CPG recommendations to male and female patients. Conclusions Implementing a systematic process for critically appraising sex-specific evidence for CPG s was straightforward and feasible. Inadequate enrollment and reporting by sex hindered comprehensive sex-specific assessment of the quality of evidence and strength of recommendations for a CPG on the management of ST-segment-elevation myocardial infarction.

Background Postoperative clinical outcomes associated with the preoperative continuation or discontinuation of angiotensin-converting enzyme inhibitors ( ACEIs ) or angiotensin receptor blockers ( ARBs ) before cardiac surgery remain unclear. Methods and Results In a single-center, open-label, randomized, registry-based clinical trial, patients undergoing nonemergent cardiac surgery were assigned to ACEI / ARB continuation or discontinuation 2 days before surgery. Among the 584 patients screened, 261 met study criteria and 126 (48.3%) patients were enrolled. In total,121 patients (96% adherence; 60 to continuation and 61 to ACEI / ARB discontinuation) underwent surgery and completed the study protocol, and follow-up was 100% complete. Postoperative intravenous vasopressor use (78.3% versus 75.4%, P=0.703), vasodilator use (71.7% versus 80.3%, P=0.265), vasoplegic shock (31.7% versus 27.9%, P=0.648), median duration of vasopressor (10 versus 5 hours, P=0.494), and vasodilator requirements (10 versus 9 hours, P=0.469) were not significantly different between the continuation and discontinuation arms. No differences were observed in the incidence of acute kidney injury (1.7% versus 1.6%, P=0.991), stroke (no events, mortality (1.7% versus 1.6%, P=0.991), median duration of mechanical ventilation (6 versus 6 hours, P=0.680), and median intensive care unit length of stay (43 versus 27 hours, P=0.420) between the treatment arms. Conclusions A randomized study evaluating the routine continuation or discontinuation of ACEIs or ARB s before cardiac surgery was feasible, and treatment assignment was not associated with differences in postoperative physiological or clinical outcomes. These preliminary findings suggest that preoperative ACEI / ARB management strategies did not affect the postoperative course of patients undergoing cardiac surgery. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifier: NCT 02096406.

Background: The association between obesity and mortality risks following coronary revascularization is not clear. We examined the associations of BMI (kg/m 2 ) with short-, intermediate-, and long-term mortality following coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) in patients with different coronary anatomy risks and diabetes mellitus status., Methods and Results: Data from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) registry were analyzed. Using normal BMI (18.5-24.9) as a reference, multivariable-adjusted hazard ratios for all-cause mortality within 6 months, 1 year, 5 years, and 10 years were individually calculated for CABG and PCI with 4 prespecified BMI categories: overweight (25.0-29.9), obese class I (30.0-34.9), obese class II (35.0-39.9), and obese class III (≥40.0). The analyses were repeated after stratifying for coronary risks and diabetes mellitus status. The cohorts included 7560 and 30 258 patients for CABG and PCI, respectively. Following PCI, overall mortality was lower in patients with overweight and obese class I compared to those with normal BMI; however, 5- and 10-year mortality rates were significantly higher in patients with obese class III with high-risk coronary anatomy, which was primarily driven by higher mortality rates in patients without diabetes mellitus (5-year adjusted hazard ratio, 1.78 [95% CI, 1.11-2.85] and 10-year adjusted hazard ratio, 1.57 [95% CI, 1.02-2.43]). Following CABG, overweight was associated with lower mortality risks compared with normal BMI., Conclusions: Overweight was associated with lower mortality following CABG and PCI. Greater long-term mortality in patients with obese class III following PCI, especially in those with high-risk coronary anatomy without diabetes mellitus, warrants further investigation., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Although patients with kidney disease have potential to benefit from revascularization, they are also at higher risk of complications, which may affect quality of life., Methods and Results: We studied a cohort of 8198 adults who underwent coronary angiography in Alberta, between 2004 and 2008, and completed health-related quality-of-life (HR-QOL) surveys. Changes in HR-QOL measures were most favorable among patients who received coronary artery bypass graft (CABG), but did not significantly differ by kidney function within groups of patients who received CABG, percutaneous coronary intervention (PCI), or medical therapy (P value for interaction between estimated glomerular filtration rate [eGFR] and revascularization status >0.10 for all outcomes). Among those who received CABG, the adjusted mean EuroQol 5 dimensions (EQ-5D) utility score for those with eGFR >90 mL/min per 1.73 m(2) increased by 0.11 (95% CI, 0.09-0.14) and for those with eGFR <30 mL/min per 1.73m(2) by 0.13 (95% CI, 0.05-0.21). The adjusted mean EQ-5D utility score also increased similarly at all levels of eGFR for those who received PCI and for those who received medical management. Mean changes in Seattle Angina Questionnaire (SAQ) scores were also similar across all levels of eGFR within each treatment group for the quality of life, angina frequency, angina stability, physical limitations, and treatment satisfaction domains of the SAQ. Among those who received CABG, the adjusted mean SAQ quality of life score for those with eGFR >90 mL/min per 1.73m(2) increased by 22.1 (95% CI, 18.5-25.7) and for those with eGFR <30 mL/min per 1.73m(2) by 14.0 (95% CI, 2.31-25.63)., Conclusions: Changes in HR-QOL do not vary by kidney function among patients selected for CABG, PCI, or medical management of coronary disease., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Limited data exist as to the relative contribution of sex and gender on health-related quality of life (HRQL) among patients with acute coronary syndrome (ACS). This study aims to evaluate the effect of sex and gender-related variables on long-term HRQL among young adults with ACS., Methods and Results: GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary SYndrome) is a multicenter, prospective cohort study (January 2009 to August 2013) of adults aged 18 to 55 years, hospitalized with ACS. HRQL was measured at baseline, 1, 6, and 12 months using the Short Form-12 and Seattle Angina Questionnaire (SAQ) among 1213 patients. Median age was 49 years. Women reported worse HRQL than men over time post-ACS, both in terms of physical and mental functioning. Gender-related factors were more likely to be predictors of HRQL than sex. Femininity score, social support, and housework responsibility were the most common gender-related predictors of HRQL at 12 months. We observed an interaction between female sex and social support (β=0.44 [95% confidence interval, 0.01, 0.88]; P=0.047) for the physical limitation subscale of the SAQ., Conclusions: Young women with ACS report significantly poorer HRQL than young men. Gender appears to be more important than sex in predicting long-term HRQL post-ACS. Specific gender-related factors, such as social support, may be amenable to interventions and could improve the HRQL of patients with premature ACS., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Study Objective: To determine the rate of secondary prevention cardiovascular drug utilization in a cohort of patients who underwent coronary artery bypass graft (CABG) surgery—including specific drugs and their dosages, drug adherence, and assessment of targeted therapy--from admission to 1 year after CABG surgery., Design: Retrospective analysis., Setting: Cardiovascular quaternary care medical center in Edmonton, Canada., Patients: The entire cohort consisted of 1031 adults who underwent CABG surgery between January 2009 and March 2010; a randomly selected subset of 151 patients was used to evaluate medication use and target-directed therapy at 1 year after CABG surgery., Measurements and Main Results: Utilization rates of aspirin, β-blockers, statins, and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEIs/ARBs) on admission and at discharge were determined for the entire cohort by using data from a large clinical patient registry. The proportion of patients discharged receiving all four classes of medications was 35%. Individual utilization rates for aspirin, β-blockers, and statins were 96%, 94%, and 95%, respectively; use of ACEIs/ARBs was lowest at 42%. In the 1-year post-CABG surgery substudy, medication use and target-directed therapy at 1 year after CABG surgery were evaluated by using community pharmacy and electronic health records. The proportion of patients receiving all four classes of medications at 1 year was 48%. Individual utilization rates for aspirin, β-blockers, statins, and ACEIs/ARBs were 95%, 84%, 84%, and 65%, respectively. Medication adherence, assessed by the medication possession ratio, for β-blockers, statins, and angiotensin-modulating agents at 1 year exceeded 0.85, thereby demonstrating high adherence. Evaluation of target-directed treatment of dyslipidemia and diabetes mellitus demonstrated suboptimal control, with only 66% and 54% of patients, respectively, achieving the recommended therapeutic targets., Conclusion: The utilization rate for patients receiving all four classes of secondary prevention cardiovascular medications was 35% at discharge and 48% at 1 year after CABG surgery. These rates were primarily limited by the low utilization of angiotensin-modulating agents, although their rate improved by 22% from discharge. Utilization rates, however, were high for aspirin, β-blockers, and statins both at discharge and 1 year after surgery. Opportunities remain to further optimize secondary prevention cardiovascular pharmacotherapy in patients who undergo CABG surgery, either while in the hospital or immediately subsequent to discharge.

Recent reports demonstrate that the activation and interaction of the protease calpain (CP) and the protein phosphatase calcineurin (CN) are elevated in the late stages of Alzheimer's disease (AD). However, the extent to which CPs and CN interact during earlier stages of disease progression remains unknown. Here, we investigated CP and CN protein levels in cytosolic, nuclear, and membrane fractions prepared from human postmortem hippocampal tissue from aged non-demented subjects, and subjects diagnosed with mild cognitive impairment (MCI). The results revealed a parallel increase in CP I and the 48 kDa CN-Aα (ΔCN-Aα48) proteolytic fragment in cytosolic fractions during MCI. In primary rat hippocampal cultures, CP-dependent proteolysis and activation of CN was stimulated by application of oligomeric Aβ((1-42)) peptides. Deleterious effects of Aβ on neuronal morphology were reduced by blockade of either CP or CN. NMDA-type glutamate receptors, which help regulate cognition and neuronal viability, and are modulated by CPs and CN, were also investigated in human hippocampus. Relative to controls, MCI subjects showed significantly greater proteolytic levels of the NR2B subunit. Within subjects, the extent of NR2B proteolysis was strongly correlated with the generation of ΔCN-Aα48 in the cytosol. A similar proteolytic pattern for NR2B was also observed in primary rat hippocampal cultures treated with oligomeric Aβ and prevented by inhibition of CP or CN. Together, the results demonstrate that the activation and interaction of CPs and CN are increased early in cognitive decline associated with AD and may help drive other pathologic processes during disease progression., (.)

Objectives/hypothesis: Assess the safety and efficacy of combined antegrade and retrograde esophageal dilation (CARD) for complete esophageal stenosis following head and neck cancer (HNC) treatment. Review HNC dysphagia management., Study Design: Retrospective review of all patients undergoing CARD following HNC treatment between May 2001 and September 2008., Methods: Forty-five patients were identified for review. Parameters assessed included: ability to obtain intraoperative esophageal patency, complications, number of dilations required, diet, and gastric tube (GT) status. Factors associated with dilation failure were analyzed., Results: Intraoperative esophageal patency was obtained in 91% of patients. Median number of all dilations per patient was three. Median number of CARDs per patient was one. Resumption of oral intake occurred in 36/45 (80%). Diet results included: regular or soft diet 32/45 (71%), GT removal 27/45 (60%), and GT dependence with nothing by mouth 9/45 (20%). Laryngeal and pharyngeal stenosis, radionecrosis, tracheotomy dependence, and elongated stenosis were associated with dilation failure. Complications occurred in 18/63 (29%) CARD procedures: eight pneumomediastinum, seven GT site problems, two esophageal perforations, and one pharyngeal infection. All complications resolved spontaneously or with minimal interventions., Conclusions: CARD was safe and effective. Intraoperative patency was achieved in 91% of patients. Eighty percent resumed oral intake. The majority of patients had their GTs removed and resumed a soft or regular diet. Dilation failure was associated with laryngeal, pharyngeal, and excessively long esophageal stenosis, often resulting from radionecrosis. Complications were minor. CARD should be considered before relegating patients with complete esophageal stenosis to chronic GT dependence or subjecting them to laryngopharyngo esophagectomy.

Background and Aim: Accepting donors of advanced age may increase the number of hearts available for transplantation. Objectives were to review the outcomes of using cardiac donors 50 years of age and older and to identify predictors of outcome at a single institution., Methods: A retrospective analysis of all adult cardiac transplants (n = 338) performed at our institution between 1988 and 2002 was conducted., Results: Of these, 284 patients received hearts from donors <50 years old and 54 received hearts from donors > or =50 years old. Recipients of hearts from older donors had a greater frequency of pretransplant diabetes (19% vs 33%), renal failure (16% vs 30%), and dialysis (3% vs 9%). There were no differences in ICU or postoperative length of stay, days ventilated, or early rejection episodes. Recipients of older donor hearts, however, had increased perioperative mortality (7% vs 17%; p = 0.03). Multivariate analysis identified older donors (OR 2.599; p = 0.03) and donor ischemia time (OR 1.006; p = 0.002) as significant predictors of perioperative mortality. Actuarial survival at 1 (87% vs 74%), 5 (76% vs 69%), and 10 (59% vs 58%) years was similar (p = 0.08) for the two groups. Separate multivariate analyses identified pretransplant diabetes as the sole predictor of long-term survival (HR 1.659; p = 0.02) and transplant coronary disease (HR 2.486; p = 0.003)., Conclusions: Despite increased perioperative mortality, donors > or =50 years old may be used with long-term outcomes similar to those of younger donor hearts. This has potential to expand the donor pool. Pretransplant diabetes has a significant impact on long-term outcomes in cardiac transplantation and requires further investigation.

Objectives: The objective of this study was to describe and evaluate the efficacy of an endoscopic technique for the management of postchemoradiation hypopharyngeal stenosis in head and neck cancer patients., Study Design: Retrospective review., Methods: Patients with postchemoradiation hypopharyngeal stenoses were identified from the Dana Farber Cancer Institute head and neck database. Patients who had undergone extirpative surgery and reconstruction were excluded. All patients underwent either anterograde dilatation (AD) by the lead author (C.A.S.) or transgastric retrograde esophagoscopy with anterograde dilatation (TREAD) (C.A.S., M.T.J.). Chemoradiation records, clinic notes, operative reports, and swallowing test data were reviewed. Removal of the gastric feeding tube was considered the endpoint of rehabilitation., Results: Seventeen patients had postcricoid stenoses identified by modified barium swallow. Endoscopy confirmed 15 postcricoid stenoses and 2 proximal esophageal stenoses. Nine (53%) patients had partial stenoses, and eight (47%) had complete stenoses. Eight partial stenosis patients underwent 10 AD procedures and 3 TREAD procedures. Eight complete stenosis patients underwent 9 TREAD procedures and 26 subsequent AD procedures. Fifteen of 16 (93%) patients resumed swallowing after dilatation. Thirteen (81%) patients maintained their weight on an oral diet and had their gastric feeding tubes removed. Complications included hypopharyngeal perforation (13%), abdominal wall infection (6%), stomach wall dehiscence (6%), and chondroradionecrosis of the cricoid cartilage (6%)., Conclusions: Postcricoid hypopharyngeal stenosis may be partial or complete after organ sparing chemoradiation for head and neck cancer. Using the TREAD technique, successful rehabilitation of swallowing can be achieved with a low incidence of complications.

At the Dana-Farber Cancer Institute Head and Neck Cancer Clinic, 114 previously untreated patients with advanced squamous cell carcinoma of the head and neck (17% stage III; 83% stage IV) were managed with induction chemotherapy using cis-platinum, bleomycin, and methotrexate, followed by definitive extirpative surgery and/or radiation therapy. The present report evaluates this group from a surgical and surgical pathology standpoint. The following aspects are evaluated: predictability of, and conversion to, resectability during induction chemotherapy; ease of surgical technique and intraoperative assessment; patterns of pre-op and post-op risks and complications; gross and histopathologic observations of the extent and character of residual primary and nodal disease, particularly after a response to chemotherapy; patterns of locoregional control or failure related to treatment variables. The issues subsequently addressed include: how does chemotherapy affect the operative candidacy and resectability of proposed surgical patients? Could, or should surgery be eliminated in the management of some patients treated with induction chemotherapy? Can less radical surgery be contemplated in patients significantly "downstaged" by prior chemotherapy treatment? Is increased locoregional or distant metastatic control observed in these patients? What is the role of surgery in the responder to chemotherapy?

Subglottic stenosis is a recognized complication of prolonged intubation. To date, there is no uniformly successful operative procedure for severe subglottic stenosis, fulfilling the criteria of decannulation and a serviceable voice. The surgical ideals for such a procedure should include the use of autogenous grafting material, avoidance of internal stenting, and limited manipulation of the mucosa. This study was intended to assess the fate of isolated hyoid and thyroid alar grafts interposed in the posterior cricoid lamina. Additionally, anterior/posterior splits with and without anterior grafting were evaluated. Seventeen dogs were used in the determinate animal model. Vocal cord mobility was evaluated by direct laryngoscopy prior to sacrifice. Graphic gross anatomical specimens depict the effects of anterior/posterior splitting on the cricoid cartilage. Clinical correlations are suggested.

The incidence of chemical hypothyroidism, as manifested by elevated thyroid stimulating hormone (TSH) levels, has been estimated to be as high as 25% after radiation therapy and 45% after radiation therapy and surgery to the neck for treatment of nodal metastases from squamous carcinoma of the head and neck. We prospectively evaluated 43 previously untreated patients seen in the Dana Farber Cancer Institute Interdisciplinary Head and Neck Service who were treated with aggressive combination chemotherapy in addition to standard surgery and/or radiotherapy. All patients were serially monitored for serum TSH, serum T4, and clinical evidence of hypothyroidism. Following cis-platinum, bleomycin, and methotrexate chemotherapy and subsequent surgery and/or radiotherapy, decreased thyroid reserve appeared in 37% of patients at a median follow-up of 9 months. Thirty percent of patients receiving radiotherapy alone and 43% of patients receiving surgery and radiotherapy developed elevated TSH levels. Only one patient developed clinical symptoms. Other patients were asymptomatic despite persistently elevated TSH levels. Abnormalities appeared within the first 4 months after completion of all therapy and were slowly progressive. The addition of combination chemotherapy does not appear to increase the incidence or severity of thyroid dysfunction following radiation therapy and surgery to the neck. In view of the extended survival seen in patients treated with interdisciplinary regimens, we recommend that all patients receiving irradiation to the neck--particularly those patients having neck dissections or total laryngectomies--have routine thyroid function studies performed following the cessation of treatment.