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1.  A rare instance of retrosternal goitre presenting with obstructive sleep apnoea in a middle-aged person 
In endemic goitre areas, 20% of the population over 70 will have retrosternal goitre.12 Obstructive sleep apnoea (OSA) occurs when there are repeated episodes of complete or partial blockage of the upper airway during sleep.
A 55-year-old man was being treated for obstructive sleep apnoea, came with stridor worsening over the 2 and was advised CPAP ventilation. In our institution, he was diagnosed to have goitre with retrosternal extension with no hypo/hyperthyroidism. He was an obese (BMI – 30 Kg/m2) male with a short, broad neck and clinically no obvious swelling in the neck. He had stridor, with positive Kocher's test as well as Pemberton's sign. His TFT's were normal and CT scan revealed widening of superior mediastinum. Patient was pre-medicated with low dose (0.1 μg) fentanyl, and induced with inhalational anaesthesia (sevoflourane). Endotracheal intubation was done using 6 no. ET tube, without muscle relaxation, and the thyroid was removed through a conventional Kocher's incision. Thyroid was enlarged 25 cm by 10 cm in retrosternal position. Postoperatively, pt was reversed and shifted to ICU, was monitored for the next 24 hours. He was extubated uneventfully the next morning. Patient had a good post-op recovery and was discharged on the 7th post-op day.
Terms such as retrosternal, substernal, intrathoracic, or mediastinal have been used to describe a goitre that extends beyond the thoracic inlet. However, there is a lack of consensus regarding the exact definition of a retrosternal goitre (RSG).1 The majority of patients present with shortness of breath or asthma like symptoms (68.8%), as was the case in the studied patient. Other modes of presentation include neck mass (75%), hoarseness of voice (37.5%), dysphagia (31.3%), stridor/wheezing (19%), or SVC obstruction. Upper airway obstruction due to thyroid gland has been reported up to 31%2 and difficulty in intubation has been reported in 11%.3 Central airway obstruction produces symptoms of dyspnoea, stridor, or obstructive pneumonia and is often misdiagnosed as asthma.4 The CT scan was the most useful tool showing the nature and extent of the lesion in the reported case. In a recent publication, the CT scan was considered the gold-standard preoperative radiological investigation.5 Surgery is the only effective treatment for retrosternal goitres. In most cases, suppressive therapy with thyroxine is ineffective in reducing the size of multinodular goitres;7,8 radio-iodine therapy is both generally ineffective in large goitres8 and may induce acute inflammation and swelling of the gland with the potential for airway obstruction. The operation of choice is usually a total thyroidectomy. Only around 2% of patients undergoing thyroidectomy for retrosternal goitre will require surgical access other than a standard collar incision (either manubriotomy, sternotomy or thoracotomy).9
Despite all the advances in investigative modalities, retrosternal goitre still exists in 20% of patients over 70 years in endemic regions. It has to be recognised that it can be a cause of obstructive sleep apnoea. Early detection and prompt management goes a long way in decreasing the morbidity and mortality in patients with RSG.
PMCID: PMC3860032  PMID: 24212758
Retrosternal goitre; Obstructive sleep apnoea
2.  Rosiglitazone, a PPAR gamma agonist, Attenuates Inflammation After Surgical Brain Injury in Rodents 
Brain research  2008;1215:218-224.
Surgical brain injury (SBI) is unavoidable during many neurosurgical procedures. This inevitable brain injury can result in postoperative complications including brain edema, blood-brain barrier disruption (BBB) and cell death in susceptible areas. Rosiglitazone (RSG), a PPAR-γ agonist, has been shown to reduce inflammation and provide neuroprotection in experimental models of ischemia and intracerebral hemorrhage. This study was designed to evaluate the neuroprotective effects of RSG in a rodent model of SBI.
65 adult male Sprague-Dawley rats were randomly divided into sham, vehicle and treatment groups. RSG was administered intraperitoneally in two dosages (1mg/kg/dose, 6mg/kg/dose) 30 minutes before surgery, and 30 minutes and 4 hours after surgery. Animals were euthanized 24 hrs following neurological evaluation to assess brain edema and BBB permeability by IgG staining. Inflammation was examined using myeloperoxidase (MPO) assay and double-labeling fluorescent immunohistochemical analysis of IL-1β and TNF-α.
Localized brain edema was observed in tissue surrounding the surgical injury. This brain edema was significantly higher in rats subjected to SBI than sham animals. Increased IgG staining was present in affected brain tissue; however, RSG reduced neither IgG staining nor brain edema. RSG also did not improve neurological status observed after SBI. RSG, however, significantly attenuated MPO activity and qualitatively decreased IL-1β and TNF-α expression compared to vehicle-treated group.
SBI causes increased brain edema, BBB disruption and inflammation localized along the periphery of the site of surgical resection. RSG attenuated inflammatory changes, however, did not improve brain edema, BBB disruption and neurological outcomes after SBI.
PMCID: PMC2505191  PMID: 18479673
Rosiglitazone; surgical brain injury; inflammation; brain edema; blood brain barrier; myeloperoxidase
3.  Changes in endotoxin levels in T2DM subjects on anti-diabetic therapies 
Chronic low-grade inflammation is a significant factor in the development of obesity associated diabetes. This is supported by recent studies suggesting endotoxin, derived from gut flora, may be key to the development of inflammation by stimulating the secretion of an adverse cytokine profile from adipose tissue.
The study investigated the relationship between endotoxin and various metabolic parameters of diabetic patients to determine if anti-diabetic therapies exerted a significant effect on endotoxin levels and adipocytokine profiles.
Fasting blood samples were collected from consenting Saudi Arabian patients (BMI: 30.2 ± (SD)5.6 kg/m2, n = 413), consisting of non-diabetics (ND: n = 67) and T2DM subjects (n = 346). The diabetics were divided into 5 subgroups based on their 1 year treatment regimes: diet-controlled (n = 36), metformin (n = 141), rosiglitazone (RSG: n = 22), a combined fixed dose of metformin/rosiglitazone (met/RSG n = 100) and insulin (n = 47). Lipid profiles, fasting plasma glucose, insulin, adiponectin, resistin, TNF-α, leptin, C-reactive protein (CRP) and endotoxin concentrations were determined.
Regression analyses revealed significant correlations between endotoxin levels and triglycerides (R2 = 0.42; p < 0.0001); total cholesterol (R2 = 0.10; p < 0.001), glucose (R2 = 0.076; p < 0.001) and insulin (R2 = 0.032; p < 0.001) in T2DM subjects. Endotoxin showed a strong inverse correlation with HDL-cholesterol (R2 = 0.055; p < 0.001). Further, endotoxin levels were elevated in all of the treated diabetic subgroups compared with ND, with the RSG treated diabetics showing significantly lower endotoxin levels than all of the other treatment groups (ND: 4.2 ± 1.7 EU/ml, RSG: 5.6 ± 2.2 EU/ml). Both the met/RSG and RSG treated groups had significantly higher adiponectin levels than all the other groups, with the RSG group expressing the highest levels overall.
We conclude that sub-clinical inflammation in T2DM may, in part, be mediated by circulating endotoxin. Furthermore, that whilst the endotoxin and adipocytokine profiles of diabetic patients treated with different therapies were comparable, the RSG group demonstrated significant differences in both adiponectin and endotoxin levels. We confirm an association between endotoxin and serum insulin and triglycerides and an inverse relationship with HDL. Lower endotoxin and higher adiponectin in the groups treated with RSG may be related and indicate another mechanism for the effect of RSG on insulin sensitivity.
PMCID: PMC2674418  PMID: 19368716
4.  AB 61. Resection of a giant bilateral retrovascular intrathoracic goiter causing severe upper airway obstruction, 2 years after subtotal thyroidectomy a case report and review of the literature 
Journal of Thoracic Disease  2012;4(Suppl 1):AB61.
The intrathoracic (substernal) goiter (1-15% of all thyroidectomies) is usually benign; but it can be malignant in 3-17%. There is history of thyroid surgery in 13-30% of patients. Intrathoracic goiters cause adjacent structure compression more frequently than the cervical goiters, due to the limited space of the thoracic cage. Compression of trachea, oesophagus, vascular and neural structures may cause dyspnoea, dysphagia, superior vena cava syndrome, subclavian vein thrombosis, dysphonia, and Horner’s syndrome. There is usually progressive deterioration, but acute exacerbation may occur. We present successful surgical management of a gigantic benign intrathoracic goiter, causing severe respiratory distress.
Patients and methods
A 63 year old male with history of subtotal thyroidectomy 2 years ago, presented with progressively increasing dyspnoea and inspiratory stridor. A large cervical, and prespinal superior and posterior mediastinal mass was revealed on computed tomography. Two retrovascular, pre- para- and retro-tracheal lobes were displacing the aortic arch, the anonymous vein, and the trachea, descending to the carina, severely compressing the trachea at the level of the aortic arch. Two lobes [maximum length: 12 cm (right), 14 cm (left), total weight: 290 gr] were resected en block through a cervical collar incision and a median sternotomy. Histology revealed multinodular goiter without malignancy.
The operation and the postoperative course were uneventful, without: bleeding, infection, recurrent laryngeal nerve palsy, cardiorespiratory, endocrine, or wound complications. Airway stenosis was immediately relieved, although a minor degree of stenosis, attributed to tracheomalacia due to chronic compression, remained. No intervention was required, and improvement was noted at follow-up.
Thoracic goiter (>50% of the mass below the thoracic inlet) is per se an indication for resection. Tracheal compression by (cervical or thoracic) goiter is also an indication for resection; early tracheal decompression is recommended particularly in symptomatic patients. In severe respiratory distress, intubation and semi-urgent operation may be required. With early intervention, most intrathoracic goiters (91-99%) can be removed through a cervical approach, while tracheomalacia is avoided. Re-operation and resection of a goiter descending to the carina, adjacent to the aortic arch, the descending aorta and the thoracic spine required a median sternotomy that was not associated with morbidity.
PMCID: PMC3537438
5.  Fish oil decreases inflammation and reduces cardiac remodeling in rosiglitazone treated aging mice 
Pharmacological Research  2010;63(4):300-307.
Clinical studies suggest that rosiglitazone (RSG) treatment may increase the incidence of heart failure in diabetic patients. In this study, we examined whether a high corn oil diet with RSG treatment in insulin resistant aging mice exerted metabolic and pro-inflammatory effects that stimulate cardiac dysfunction. We also evaluated whether fish oil attenuated these effects. Female C57BL/6J mice (13 months old) were divided into 5 groups: (1) lean control (LC), (2) corn oil, (3) fish oil, (4) corn oil + RSG and (5) fish oil + RSG. Mice fed a corn oil enriched diet and RSG developed hypertrophy of the left ventricle (LV) and decreased fractional shortening, despite a significant increase in total body lean mass. In contrast, LV hypertrophy was prevented in RSG treated mice fed a fish oil enriched diet. Importantly, hyperglycemia was controlled in both RSG groups. Further, fish oil + RSG decreased LV expression of atrial and brain natriuretic peptides, fibronectin and the pro-inflammatory cytokines interleukin-6 and tumor necrosis factor-α, concomitant with increased interleukin-10 and adiponectin levels compared to the corn oil + RSG group. Fish oil + RSG treatment suppressed inflammation, increased serum adiponectin, and improved fractional shortening, attenuating the cardiac remodeling seen in the corn oil + RSG diet fed C57BL/6J insulin resistant aging mice. Our results suggest that RSG treatment has context-dependent effects on cardiac remodeling and serves a negative cardiac role when given with a corn oil enriched diet.
PMCID: PMC3326603  PMID: 21193042
Aging; Corn oil; Fish oil; Cardiac remodeling; Inflammation; Left ventricle hypertrophy; Rosiglitazone
6.  Comparison of Three Treatment Approaches to Decreasing Cardiovascular Disease Risk in Nondiabetic, Insulin Resistant, Dyslipidemic Individuals 
The efficacy of fenofibrate (FEN), rosiglitazone (RSG), or a calorie-restricted diet (CRD) to reduce cardiovascular disease risk was compared in 37 overweight/obese, insulin resistant, nondiabetic individuals. Measurements were made of insulin sensitivity, fasting lipid and lipoprotein concentrations, and postprandial plasma glucose, insulin, free fatty acid, and triglyceride concentrations, before and after three months of treatment with FEN, RSG, or the CRD. Weight fell in the CRD group, but did not change significantly following treatment with either drug. Insulin sensitivity improved significantly in the CRD and RSG-treated groups, but to a greater extent in those given RSG, without a significant difference when comparing FEN treatment to the CRD. Total cholesterol concentrations were significantly lower following FEN and CRD. Fasting plasma triglyceride concentrations decreased significantly in FEN-treated and CRD groups, but postprandial concentrations decreased only in the FEN-treated subjects. Significant decreases in postprandial glucose and insulin concentrations were only seen in the RSG-treated and CRD groups. FEN administration improved the dyslipidemia in these subjects, without changing insulin sensitivity, whereas insulin sensitivity was enhanced in RSG-treated patients, without improvement in the dyslipidemia. Weight loss in the CRD group led to improvements in both insulin sensitivity and dyslipidemia, but the change in the former was less than in RSG-treated individuals, and the improvement in lipid metabolism not as great as with administration of FEN. In conclusion, there does not appear to be one therapeutic intervention that effectively treats all the metabolic abnormalities present in these patients at greatly increased risk of cardiovascular disease.
PMCID: PMC2603622  PMID: 18572037
dyslipidemia; insulin resistance; fenofibrate; rosiglitazone
7.  Effect of Rosiglitazone on Bone Quality in a Rat Model of Insulin Resistance and Osteoporosis 
Diabetes  2011;60(12):3271-3278.
Rosiglitazone (RSG) is an insulin-sensitizing drug used to treat type 2 diabetes mellitus. The A Diabetes Outcome Progression Trial (ADOPT) shows that women taking RSG experienced more fractures than patients taking other type 2 diabetes drugs. These were not osteoporotic vertebral fractures but, rather, occurred in the limbs. The purpose of this study was to investigate how RSG treatment alters bone quality, which leads to fracture risk, using the Zucker fatty rat as a model.
A total of 61 female 4-month-old rats were divided into six groups. One Sham group was a control and another was administered oral RSG 10 mg/kg/day. Four ovariectomized (OVX) groups were dosed as follows: controls, RSG 10 mg/kg, alendronate (ALN, injected at 0.7 mg/kg/week), and RSG 10 mg/kg plus ALN. After 12 weeks of treatment, bone quality was evaluated by mechanical testing. Microarchitecture, bone mineral density (BMD), cortical bone porosity, and bone remodeling were also measured.
OVX RSG 10 mg/kg rats had lower vertebral BMD and compromised trabecular architecture versus OVX controls. Increased cortical bone porosity and decreased mechanical properties occurred in these rats. ALN treatment prevented decreased BMD and architectural and mechanical properties in the OVX model. Reduced bone formation, increased marrow adiposity, and excess bone resorption were observed in RSG-treated rats.
RSG decreases bone quality. An unusual finding was an increase in cortical bone porosity induced by RSG, consistent with its effect on long bones of women. ALN, an inhibitor of bone resorption, enhanced mechanical strength and may provide an approach to partially counter the deleterious skeletal effects of RSG.
PMCID: PMC3219933  PMID: 21998400
8.  Emergency thyroidectomy: Due to acute respiratory failure 
•CT scan has a great value for retrosternally extended giant goiter cases.•If the general status of the patient prevents CT scan, bedside ultrasound can be used instead.•Nasal awake intubiation is an appropriate choice for the patients with destructed trachea.•Emergency thyroidectomy is a common option for the treatment of giant goiter causing airway obstruction.
Giant cervical and mediastinal goiter may lead to acute respiratory failure caused by laryngotracheal compression and airway obstruction. Here, we present a case admitted to the emergency service with a giant goiter along with respiratory failure and poor general health status, which required urgent surgical intervention.
A 71-year-old female admitted to the emergency room with shortness of breath and poor general health status resulting from a giant cervical swelling progressively increased during the last 7 years and constituted severe respiratory failure which has become severe in the last one month. A giant nodular goiter of the left thyroid lobe extending retrosternally, causing tracheal compression, limiting the neck movements was detected with clinical examination and bedside ultrasound. Emergency thyroidectomy was planned. Fiberoptic-assisted awake nasal intubation was performed in the operating room. Emergency total thyroidectomy was performed for the life-threatening respiratory failure. Postoperative period was uneventful. She was transferred from intensive care unit to the ward on postoperative day 3 and was discharged from the hospital on the postoperative 7th day. Benign multinodular hyperplasia was reported on the histopathological report. Patient was included in routine follow-up.
In the present case tracheal destruction due to compression of the giant goiter was found in agreement with previous reports. Emergency thyroidectomy was performed after awake intubation since it is a common surgical option for the treatment of giant goiter causing severe airway obstruction.
Respiratory failure due to giant nodular goiter is a life-threatening situation and should be treated immediately by performing awake endotracheal intubation following emergency total thyroidectomy.
PMCID: PMC4276272  PMID: 25437688
Retrosternal; Giant goiter; Thyroidectomy; Awake intubation; Laryngotracheal compression; Respiratory failure
9.  Combination of peroxisome proliferator-activated receptor α/γ agonists may benefit type 2 diabetes patients with coronary artery disease through inhibition of inflammatory cytokine secretion 
Patients with type 2 diabetes mellitus (T2DM) have a higher risk of cardiovascular disease (CVD). Peroxisome proliferator-activated receptors (PPARs) play an important role in the regulation of energy homeostasis. Therefore, we aimed to observe the effects of combined PPARα/γ agonists on T2DM patients with coronary artery disease (CAD). Patients were randomly divided into a rosiglitazone (RSG) group (n=20), a bezafibrate (BEZ) group (n=20), a combination of RSG and BEZ group (n=20) and a control group (n=20). Plasma C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay before and 12 weeks after treatment. Fasting blood glucose (FBG), fasting insulin, insulin resistance index (IRI), hemoglobin A1c (HbA1c), lipid levels and body mass index were also investigated. At the end of the treatment, FBG, insulin, IRI, HbA1c and triglyceride levels decreased and the level of high-density lipoprotein cholesterol increased in the RSG, BEZ and combination groups. A decrease in low-density lipoprotein cholesterol was only observed in the combination group. Although the total cholesterol levels in all groups decreased, no significant difference was noted. The levels of CRP and MCP-1 were reduced in patients in the RSG, BEZ and combination groups. In addition, RSG, BEZ and the combination of RSG and BEZ also inhibited MCP-1 secretion. The combination of RSG and BEZ was more efficient than RSG or BEZ alone in downregulating cytokines. In conclusion, our results suggest that a combination of RSG and BEZ may be more efficient than RSG or BEZ alone in the treatment of T2DM patients with CAD.
PMCID: PMC3570181  PMID: 23408783
diabetes mellitus; coronary heart disease; peroxisome proliferator-activated receptor α; peroxisome proliferator-activated receptor γ; inflammatory cytokine
10.  Peri-Operative Treatment of Giant Nodular Goiter 
Objective: To summarize the experience in the peri-operative treatment of giant nodular goiter.
Methods: A total of 123 patients with giant nodular goiter sized 6~20 cm were admitted into our hospital from 1990 to 2011 and the clinical data were retrospectively analyzed. These patients underwent total or subtotal thyroidectomy.
Results: All patients underwent surgical intervention. Unilateral subtotal thyroidectomy was performed in 40 patients, unilateral total thyroidectomy in 1 patient, bilateral subtotal thyroidectomy in 79 patients, and unilateral total thyroidectomy, removal of entire isthmus and contralateral subtotal thyroidectomy in 3 patients. Nodular goiter was pathologically proven post-operatively. No short-term complications such as dyspnea or thyroid storm were found postoperatively. Post-operative follow up was done for 9 months to 6 years and no recurrence was observed.
Conclusion: Comprehensive pre-operative preparation, pre-operative evaluation, complete exposure of the operative field, meticulous operation, effective control and prevention of hemorrhage and prevention against damage to superior and recurrent laryngeal nerves are crucial for the successful surgical intervention of giant nodular goiter.
PMCID: PMC3491437  PMID: 23136541
nodular goiter; peri-operative treatment; surgical intervention.
11.  Surgical approach to retrosternal goitre: do we still need sternotomy? 
Retrosternal goitre is defined as a goitre with a portion of its mass ≥ 50% located in the mediastinum. Surgical removal is the treatment of choice and, in most cases, the goitre can be removed via a cervical approach. Aim of this retrospective study was to analyse personal experience in the surgical management of retrosternal goitres, defining, in particular, the features requiring sternotomy. Over a 5-year period (2004-2008), 986 patients underwent thyroidectomy in the ENT Department of the University Hospital of Udine, Italy; in 53 patients, 37 females, 16 males (mean age: 64 years, range: 35-85), thyroidectomy was performed for a retrosternal goitre, which extended, at computed tomography at least 3 cm below the cervico-thoracic isthmus. Retrosternal goitres were removed via a cervical approach in 49 patients; a sternotomy was necessary in 4 patients (7.5%), due to an ectopic intra-thoracic thyroid in one patient, and a very large thyroid reaching the main bronchial bifurcation in the other 3 (mean weight of goitres: 883 g, range: 520-1600). Histo-pathological studies revealed a benign lesion in 50 patients and a carcinoma in 2 (3.7%). The incidence of transient and permanent hypoparathyroidism was 13% and 3.7%, respectively. Transient recurrent laryngeal nerve palsy occurred in one patient (1.8%), post-operative bleeding in 3 patients (5.6%) and respiratory complications, requiring a tracheotomy in one case, in 2 patients (3.7%). Surgical removal of a retrosternal goitre is a challenging procedure; it can be performed safely, in most cases, via a cervical approach, with a complication rate slightly higher than the average rate for cervical goitre thyroidectomy, especially concerning hypoparathyroidism and post-operative bleeding. The most significant criteria for selecting patients requiring sternotomy are computed tomography features, in particular the presence of an ectopic goitre, the thyroid gland volume and the extent of the goitre to or below the tracheae carina. In conclusion, if retrosternal goitre thyroidectomy is performed by a skilled surgical team, familiar with its unique pitfalls, the assistance of a thoracic surgeon may be required only in a few selected cases.
PMCID: PMC2868211  PMID: 20463839
Thyroid; Retrosternal goitre; Surgical treatment; Sternotomy; Complications
12.  The “forgotten” goiter after total thyroidectomy 
“Forgotten” goiter is an extremely rare disease which is defined as a mediastinal thyroid mass found after total thyroidectomy.
We report two cases with forgotten goiter. One underwent total thyroidectomy due to thyroid papillary cancer and TSH level was in normal range one month after surgery. The thyroid scintigraphy scan revealed mediastinal thyroid mass. The second case underwent total thyroidectomy due to Graves’ disease and TSH level was low after surgery. At postoperative seventh year, patients were admitted to our Endocrinology Division due to persistent hyperthyroidism and CT scan revealed forgotten thyroid at mediastinum. Both patients underwent median sternotomy and mass excision, there was no morbidity detected after second surgical procedures.
In the majority of cases forgotten goiter is the consequence of the incomplete removal of a plunging goiter. Although in some cases, it may be attributed to a concomitant, unrecognized mediastinal goiter which is not connected to the thyroid with a thin fibrous band or vessels. Absence of signs like mediastinal mass or tracheal deviation in preoperative chest X-ray do not excluded the substernal goiter.
Retrosternal goiter should be suspected if the lower poles could not be palpated on physical examination and when postoperative TSH levels remained unchanged.
PMCID: PMC3604653  PMID: 23336990
Forgotten goiter; Retrosternal goiter; Substernal goiter; Total thyroidectomy
13.  Benign Nodular Goiter Causing Upper Airway Obstruction 
Benign nodular goiter (BNG) can cause narrowing of the upper airway. In some rare cases, obstruction of the upper airway also occurs. The following paper reports our experiences with regard to BNG patients who experienced obstruction of the upper airway.
Materials and Methods.
We retrospectively investigated the records of 13 patients with acute airway obstruction due to BNG who were admitted to the General Surgery Department of Ataturk University Medical School between January 2000 and December 2007.
Thirteen patients with airway obstruction secondary to BNG were hospitalized during this period. There were two males and 11 females, and the mean age was 58.5 years (range 37–74 years). For all patients, the primary symptom upon admission was defined as respiratory distress; all patients had varying degrees of respiratory distress upon admission. Three of the patients underwent emergent endotracheal intubation in the emergency room.
A preoperative radiological evaluation was performed with thyroid ultrasonography (US) and computed tomography (CT). There were retrosternal or substernal components of the BNG in nine patients. Twelve patients underwent operations, while one patient with mild respiratory distress elected not to be operated on. Ten patients underwent total thyroidectomies, while two patients underwent near-total thyroidectomies. One patient with retrosternal goiter also underwent a median sternotomy. Three patients received a tracheostomy after the operation.
Suction drains were utilized in all operations. During the post-operative period, two patients suffered from voice impairment, and seven patients experienced hypocalcemia. Two patients died. Pathological examination of the thyroidectomy tissue revealed BNG in all cases. In addition, two patients had micropapillary carcinomas.
Although BNG causing upper airway obstruction is rare, it is an important clinical entity because of the need for emergent operation, the increased rate of complications, and high mortality.
PMCID: PMC4261473  PMID: 25610072
Nodular goiter; Upper airway; Obstruction
14.  Correlation of Circulating Acid-Labile Subunit Levels with Insulin Sensitivity and Serum LDL Cholesterol in Patients with Type 2 Diabetes: Findings from a Prospective Study with Rosiglitazone 
PPAR Research  2014;2014:917823.
Silencing of acid-labile subunit (ALS) improved glucose metabolism in animal models. The aim of this study is to evaluate the effects of rosiglitazone (RSG) on ALS levels in individuals with type 2 diabetes. A randomized, double-blind, placebo-controlled trial was conducted. Subjects with type 2 diabetes mellitus were randomly distributed to an RSG-treated (n = 30) or a placebo (n = 31) group. Patients were evaluated prior to treatment at baseline and at 12 and 24 weeks after treatment. At baseline, ALS levels were negatively associated with low-density lipoprotein cholesterol (LDLc) levels and homeostatic model assessment version 2 insulin sensitivity (HOMA2-%S). Over 24 weeks, there was a significantly greater reduction in ALS levels in the nonobese RSG-treated individuals than placebo-treated group. The effect of RSG on ALS was not significant in obese individuals. Fasting plasma glucose and hemoglobin A1c were reduced, but total cholesterol and LDLc were increased, in patients on RSG. Change in ALS levels predicted changes in total cholesterol and HOMA2-%S over time. This study suggested a BMI-dependent effect of RSG treatment on ALS levels. Reduction of ALS by RSG increases the risk of atherosclerosis in individuals with type 2 diabetes.
PMCID: PMC4055636  PMID: 24966876
15.  Recurrent Laryngeal Nerve Injury in Thyroid Surgery 
Oman Medical Journal  2011;26(1):34-38.
Vocal cord paresis or paralysis due to iatrogenic injury of the recurrent laryngeal nerve (RLNI) is one of the main problems in thyroid surgery. Although many procedures have been introduced to prevent the nerve injury, still the incidence of recurrent laryngeal nerve palsy varies between 1.5-14%. The aim of the present study is to assess the risk factors of recurrent laryngeal nerve injury during thyroid surgery.
Patients who had thyroid surgery between 1990 and 2005 and were admitted to the surgical department of King Fahd hospital of the University, Al-Khobar, Saudi Arabia were enrolled for this retrospective review, Factors predisposing to recurrent laryngeal nerve injury were evaluated such as pathology of the lesions and the type of operations and identification of recurrent laryngeal nerve intra-operatively. Preoperative and postoperative indirect laryngoscopic examinations were performed for all patients.
340 patients were included in this study. Transient unilateral vocal cord problems occurred in 11 (3.2%) cases, and in 1 (0.3%) case, it became permanent (post Rt. Hemithyroidectomy). Bilateral vocal cord problems occurred in 2 cases (0.58%), but none became permanent. There were significant increases in the incidence of recurrent laryngeal nerve injury in secondary operation (21.7% in secondary vs. 2.8% in primary, p=0.001), total/near total thyroidectomy (7.2% in total vs. 1.9% in subtotal, p=0.024), non-identification of RLN during surgery (7.6% in non-identification vs. 2.6% in identification, p=0.039) and in malignant disease (12.8% in malignant vs. 2.9% in benign, p=0.004). However, there was no significant difference in the incidence of recurrent laryngeal nerve injury with regards to gender (4.1% in male vs 3.8% in female, p=0.849).
The present study showed that thyroid carcinoma, re-operation for recurrent goiter, non-identification of RLN and total thyroidectomy were associated with a significantly increased risk of operative recurrent laryngeal nerve injury.
PMCID: PMC3191623  PMID: 22043377
Thyroidectomy; recurrent laryngeal nerve injury; carcinoma of thyroid
16.  An unusual recurrent bilateral posterior mediastinal goiter after subtotal thyroidectomy: Case report 
Surgical treatment of benign thyroid diseases need to be followed up closely, since recurrent thyroid nodules can be seen after subtotal thyroidectomy. Intrathoracic goiter (ITG) occurs in 10–30% of patients following subtotal thyroidectomy. In general these goiters are benign, having a malignant rate of only 2–22%. ITG grows slowly but steadily and in its process of development, it narrows the thoracic inlet by compressing the surrounding structures. Most of these can not located in the anterior mediastinum, others located in posterior retrovascular area. Bilateral posterior retrovascular goiters are very rare.
We report a case involving a 61-year-old woman with history of gradual-onset dyspnea who was referred to us for evaluation of a large mediastinal mass. She had undergone bilateral thyroid lobectomy for a cervical goiter 10 years ago. The mass was removed successfully via median sternotomy without complication. The patient recovered well and was discharged in 1 week.
Most anterior mediastinal goiters can be resected through a transcervical approach, but if those extending beyond the aortic arch into the posterior mediastinum are better dealt with by sternotomy or lateral thoracotomy.
Bilateral recurrent posterior mediastinal and retrovascular large goiters are better resected via sternotomy rather than lateral thoracotomy. The reason for that are the possibility of injury to large vascular structures and the difficulty of their management through lateral thoracotomy when cardiopulmonary bypass needed.
PMCID: PMC4147647  PMID: 24973529
Intrathoracic goiter; Mediastinum; Median sternotomy
17.  A new complication of retained surgical gauze: development of malignant fibrous histiocytoma – report of a case with a literature review 
Primary visceral malignant fibrous histiocytoma (MFH) is a rare disease, and few cases have been reported in the English literature. However, retained foreign bodies in the abdomen after surgical procedures are important causes of intra-abdominal infections. For legal and ethical reasons, there are few publications in the literature. In this article, we describe for the first time a case of malign abdominal fibrous histiocytoma associated with a surgical sponge forgotten in the abdominal cavity a long time ago.
Case presentation
A 64-year-old male presented to our surgical department with cachexia, abdominal pain, distention and pyrexia of unknown origin. He had a medical history of abdominal surgery for peptic ulcer perforation 32 years ago. Clinical examination revealed fever with a distended and painful abdominal wall. Radiological imaging of the abdomen showed multiple heterogeneous masses in one large cystic cavityalmost completely filling the abdomen. The patient underwent a laparotomy, and interestingly, opening the cyst revealed retained surgical gauze (RSG). The origin of the tumor was the visceral peritoneum, and it was excised totally.
Primary intra-abdominal MFH can present as a complication of long-lasting RSG. Therefore, clinicians must remember this while establishing the differential diagnosis for patients with a history of previous abdominal surgery and presenting with symptoms associated with both the tumor and systemic inflammatory response.
PMCID: PMC3411509  PMID: 22776249
Malignant fibrous histiocytoma; Retained surgical gauze; Gossypiboma; Textiloma; Retained foreign body; Soft tissue sarcoma
18.  Rosiglitazone Monotherapy in Mild-to-Moderate Alzheimer's Disease: Results from a Randomized, Double-Blind, Placebo-Controlled Phase III Study 
A phase II study of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone extended release (RSG XR) in mild-to-moderate Alzheimer's disease (AD) detected a treatment benefit to cognition in apolipoprotein E (APOE)-∊4-negative subjects. The current phase III study with prospective stratification by APOE genotype was conducted to confirm the efficacy and safety of RSG XR in mild-to-moderate AD. An open-label extension study assessed the long-term safety and tolerability of 8 mg RSG XR.
This double-blind, randomized, placebo-controlled study enrolled 693 subjects. Within 2 APOE allelic strata (∊4-positive, ∊4-negative), subjects were randomized (2:2:2:1) to once-daily placebo, 2 mg RSG XR, 8 mg RSG XR or 10 mg donepezil (control). Coprimary endpoints were change from baseline to week 24 in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score, and week 24 Clinician's Interview-Based Impression of Change plus caregiver input (CIBIC+).
At week 24, no significant differences from placebo in change from baseline in coprimary endpoints were detected with either the RSG XR dose in APOE-∊4-negative subjects or overall. For donepezil, no significant treatment difference was detected in ADAS-Cog; however, a significant difference was detected (p = 0.009) on the CIBIC+. Peripheral edema was the most common adverse event for 8 mg RSG XR (15%) and placebo (5%), and nasopharyngitis for 2 mg RSG XR (7%).
No evidence of efficacy of 2 mg or 8 mg RSG XR monotherapy in cognition or global function was detected in the APOE-∊4-negative or other analysis populations. The safety and tolerability of RSG XR was consistent with its known pharmacology.
PMCID: PMC3214882  PMID: 20733306
Rosiglitazone, extended release; Monotherapy; Alzheimer's disease; Peroxisome proliferator-activated receptor-γ; Cognition; Apolipoprotein E allele ∊4; Health outcomes; Donepezil
19.  Surgical Indications for Goiter with Background Hashimoto’s Thyroiditis: Institutional Experience 
The Indian Journal of Surgery  2011;73(6):414-418.
Hashimoto’s thyroiditis (HT) is usually treated conservatively with thyroxine. Its incidence is higher in Iodine sufficient areas and may require surgery for associated nodularity or complications. A retrospective study on surgically treated HT cases was conducted in a teritiary care teaching hospital in an Iodine sufficient area of Southern India. 34 cases of goiter with associated HT, who underwent thyroidectomy between 2007 and 2010 were analysed for indications of surgery. Minimum follow-up period was 6 months. F:M ratio was 31:3 with mean age of 41.3 years. Goiter was diffuse in 41% and nodular in 59%. 16 (47%) of patients were hypothyroid. Autoimmune association was found in 35%. Commonest surgery done was hemithyroidectomy in 12 (35%) followed by subtotal thyroidectomy in 10 cases. Most frequent indication for surgery was nodular goiter in 12 (35%) followed by associated malignancy, persistent goiter, pressure symptoms and painful thyroiditis. Histopathology showed diffuse HT alone in 12 (35%) and rest of the cases had HT as a component synchronous with other pathologies. Associated pathologies were benign multinodular goiter (6), colloid nodule (6), papillary cancer (5), follicular adenoma (4), cyst (1). Surgery for HT is primarily indicated for associated pathologies like dominant nodule, suspicious or proven malignancy, persistent goiter, painful thyroiditis, pressure symptoms and rarely for HT perse. Rate of surgery for HT associated goiter appears to be higher in Iodine sufficient areas, the cause of which needs to be studied further.
PMCID: PMC3236274  PMID: 23204697
Hashimoto’s thyroiditis; Thyroxine; Surgery
20.  Adiponectin: An Indispensable Molecule in Rosiglitazone Cardioprotection Following Myocardial Infarction 
Circulation research  2009;106(2):409.
Patients treated with peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist manifest favorable metabolic profiles associated with increased plasma adiponectin (APN). However, whether increased APN production as a result of PPAR-γ agonist treatment is an epiphenomenon or is causatively related to PPAR-γ’s cardioprotective actions remains completely unknown.
To determine the role of APN in rosiglitazone (RSG) cardioprotection against ischemic heart injury.
Methods and Results
Adult male wild type (WT) and APN knockdown/knockout (APN+/− and APN−/−) mice were treated with vehicle or rosiglitazone (RSG, 20 mg/kg/day), and subjected to coronary artery ligation 3 days after beginning treatment. In WT mice, RSG (7 days) significantly increased adipocyte APN expression, elevated plasma APN levels (2.6-fold), reduced infarct size (17% reduction), decreased apoptosis (0.23±0.02% vs. 0.47±0.04% TUNEL positive in remote non-ischemia area), attenuated oxidative stress (48.5% reduction), and improved cardiac function (P<0.01). RSG-induced APN production and cardioprotection were significantly blunted (P<0.05 vs. WT) in APN+/−, and completely lost in APN−/− (P>0.05 vs. vehicle-treated APN−/− mice). Moreover, treatment with RSG for up to 14 days significantly improved the post-ischemic survival rate of WT mice (P<0.05 vs. vehicle group), but not APN knockdown/knockout mice.
PPAR-γ agonists’ cardioprotective effects are critically dependent on its APN stimulatory action, suggesting that under pathologic conditions where APN expression is impaired (such as advanced type-2 diabetes), the harmful cardiovascular effects of PPAR-γ agonists may outweigh its cardioprotective benefits.
PMCID: PMC2818803  PMID: 19940263
Diabetes; Myocardial infarction; Adipocytokine; Signaling
21.  Resection of a giant bilateral retrovascular intrathoracic goiter causing severe upper airway obstruction, 2 years after subtotal thyroidectomy: a case report and review of the literature 
Journal of Thoracic Disease  2012;4(Suppl 1):41-48.
The intrathoracic (or substernal) goiter is more often benign; but it can be malignant in 2-22% of patients. There is history of prior thyroid surgery in 10% to more than 30% of patients. Intrathoracic goiters cause adjacent structure compression more frequently than the cervical goiters, due to the limited space of the thoracic cage. Compression of trachea, oesophagus, vascular and neural structures may cause dyspnoea, dysphagia, superior vena cava syndrome, subclavian vein thrombosis, hoarseness, and Horner’s syndrome. There is usually progressive deterioration, but acute exacerbation may occur. The presence of a thoracic goiter (>50% of the mass below the thoracic inlet) is per se an indication for resection. Tracheal compression by (cervical or thoracic) goiter is also an indication for resection; early tracheal decompression is recommended particularly in symptomatic patients. In severe respiratory distress, intubation and semi-urgent operation may be required. With early intervention, most intrathoracic goiters can be removed through a cervical approach, while tracheomalacia is avoided. We hereby present successful and uncomplicated total thyroidectomy, through a median sternotomy, of a benign, gigantic, bilateral, retrovascular, posterior mediastinal, intrathoracic goiter, encircling the trachea, and causing severe respiratory distress in a 63 year old man with history of previous subtotal thyroidectomy.
PMCID: PMC3537381  PMID: 23304440
Airway obstruction/etiology; airway obstruction/surgery; thyroidectomy; goiter; substernal/surgery; goiter/intrathoracic
22.  Rosiglitazone-loaded Nanospheres for Modulating Macrophage-Specific Inflammation in obesity 
PPARγ nuclear receptor agonists have been shown to attenuate macrophage inflammatory responses implicated in the metabolic complications of obesity and in atherosclerosis. However, PPARγ agonists currently in clinical use, including rosiglitazone (RSG), are often associated with severe side effects that limit their therapeutic use. Here, 200 nm PLGA/PVA nanospheres were formulated for the systemic delivery of RSG specifically to macrophages. RSG was encapsulated with over 50% efficiency in the hydrophobic PLGA core and released specifically within the acidifying macrophage phagosomes. In bone marrow derived macrophages, RSG-loaded nanoparticles (RSG-NPs) induce a dose dependent upregulation (1.5 to 2.5-fold) of known PPARγ target genes, with maximal induction at 5 μM; and downregulate the expression of genes related to the inflammatory process, with maximum effect at 10 μM. In Ldlr-/- mice fed high fat diet, treatment with RSG-NPs alleviated inflammation in white adipose tissue and liver but, unlike treatment with free RSG, did not alter genes associated with lipid metabolism or cardiac function, indicating a reduction in the RSG side effect profile. These biocompatible, biodegradable RSG-NPs represent a preliminary step towards the specific delivery of nuclear receptor agonists for the treatment of macrophage-mediated inflammatory conditions associated with obesity, atherosclerosis and other chronic disease states.
PMCID: PMC4076002  PMID: 23791978
PPARγ agonists; macrophage targeting; PLGA/PVA nanospheres; inflammatory diseases
23.  Coordinate Transcriptomic and Metabolomic Effects of the Insulin Sensitizer Rosiglitazone on Fundamental Metabolic Pathways in Liver, Soleus Muscle, and Adipose Tissue in Diabetic db/db Mice 
PPAR Research  2010;2010:679184.
Rosiglitazone (RSG), developed for the treatment of type 2 diabetes mellitus, is known to have potent effects on carbohydrate and lipid metabolism leading to the improvement of insulin sensitivity in target tissues. To further assess the capacity of RSG to normalize gene expression in insulin-sensitive tissues, we compared groups of 18-day-treated db/db mice with increasing oral doses of RSG (10, 30, and 100 mg/kg/d) with untreated non-diabetic littermates (db/+). For this aim, transcriptional changes were measured in liver, inguinal adipose tissue (IAT) and soleus muscle using microarrays and real-time PCR. In parallel, targeted metabolomic assessment of lipids (triglycerides (TGs) and free fatty acids (FFAs)) in plasma and tissues was performed by UPLC-MS methods. Multivariate analyses revealed a relationship between the differential gene expressions in liver and liver trioleate content and between blood glucose levels and a combination of differentially expressed genes measured in liver, IAT, and muscle. In summary, we have integrated gene expression and targeted metabolomic data to present a comprehensive overview of RSG-induced changes in a diabetes mouse model and improved the molecular understanding of how RSG ameliorates diabetes through its effect on the major insulin-sensitive tissues.
PMCID: PMC2953354  PMID: 20953342
24.  Effect and cardiovascular safety of adding rosiglitazone to insulin therapy in type 2 diabetes: A meta-analysis 
Recently, the use of rosiglitazone has been limited or withdrawn from the market as a result of cardiovascular risk. However, theoretically adding rosiglitazone to insulin could help insulin to decrease the glucose level. The present meta-analysis was designed to investigate the effect and safety of adding rosiglitazone to insulin therapy in type 2 diabetes.
Materials and Methods
We searched published and unpublished databases through to March 2012. Randomized controlled trials (RCTs) comparing rosiglitazone in combination with insulin (RSG + INS) vs insulin alone (INS) in type 2 diabetes with outcomes including glycated hemoglobin levels, insulin dose, lipid parameters, blood pressure, edema and cardiovascular adverse events were selected.
Nine RCTs with durations of 24–26 weeks involving 1,916 patients were included. The RSG + INS group showed significantly decreased glycated hemoglobin levels by 0.89% (P < 0.00001) with an 8.48-U reduction in daily insulin dose (P <0.00001). However, the risks of hypoglycemia and edema were more frequent in the RSG+INS group (P < 0.0001; P = 0.03, respectively). Total cholesterol level was significantly increased in the RSG+INS group (P < 0.00001), but none of the high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol or triglyceride levels were significantly different between groups. There were no significant differences between groups with regard to the risks of myocardial infarction, heart failure, cardiovascular death or all-cause death.
Rosiglitazone could help type 2 diabetes patients with poorly controlled glucose with insulin therapy to decrease glucose levels and reduce their daily insulin dose, but at the cost of increased total cholesterol level, hypoglycemia and edema risk. Compared with insulin therapy, adding rosiglitazone to insulin did not increase the risks of myocardial infarction, heart failure, cardiovascular death or all-cause death.
PMCID: PMC4296706  PMID: 25621136
Insulin; Rosiglitazone; Type 2 diabetes
25.  The Factors Related with Postoperative Complications in Benign Nodular Thyroid Surgery 
The Indian Journal of Surgery  2010;73(1):32-36.
Thyroid gland is an important endocrine organ because of its functions. Although the morbidity and mortality of thyroid surgery have decreased markedly, serious complications may still occur. The aim of this retrospective study was to identify the factors influencing the complications in benign nodular thyroid surgery. A total of 332 patients who underwent thyroid surgery between April 2004 and May 2008 were evaluated retrospectively to identify the factors influencing the complications. We found that in surgery lasting more than 90 minutes the risk of permanent recurrent laryngeal nerve (RLN) injury was high, daily drainage more than 50 cc increases the risk of seroma formation, retrosternal goiter surgery have higher risk for bleeding. The flap edema rates were high found in the operations made by resident surgeon and patients with size 3–4 thyroid glands. Low complication rates can be achieved after thyroidectomy with better knowledge of the surgical anatomy of the neck, thyroid pathology and required surgical treatment.
PMCID: PMC3077179  PMID: 22211035
Thyroidectomy; Complications; Influencing factors

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