Clinical outcomes of laser hemorrhoidoplasty with feeding vessels suture ligation: a retrospective study in a single center.

BACKGROUND: Laser hemorrhoidoplasty has demonstrated significant therapeutic effectiveness. To diminish postoperative bleeding and enhance overall outcomes, we have additionally adopted suture ligating the feeding vessels. This study aimed to understand the treatment outcomes and any associated complications. METHODS: This study comprised patients with symptomatic grade II-III hemorrhoids who underwent laser hemorrhoidoplasty with feeding vessel suture ligation and Milligan-Morgan hemorrhoidectomy between 1 September 2020, and 31 August 2022. Surgical-related details, postoperative pain, discomfort after discharge, hemorrhoid recurrence, and any complications were collected from inpatient records, outpatient follow-ups, and telephone interviews. Initially, we will analyze the distinctions between the laser group and the traditional group, followed by an investigation into complications and satisfaction within the laser surgery subgroup. RESULTS: The study included 323 patients, with 173 undergoing laser hemorrhoidoplasty (LHP) and 150 undergoing Milligan-Morgan hemorrhoidectomy. Regarding pain assessment, the LHP group exhibited superior performance compared to traditional surgery at postoperative 4 h, before discharge, and during the first and second outpatient visits, with statistically significant differences. Additionally, the LHP group had a lower rate of urinary retention and experienced significantly less pain, with statistically significant differences. CONCLUSIONS: Laser hemorrhoidoplasty with feeding vessels suture ligation has been shown to reduce postoperative pain and appears to be a promising minimally invasive treatment option for symptomatic grade II and III hemorrhoids.

Impact of chemotherapy on surgical outcomes in ileostomy reversal: a propensity score matching study from a single centre.

PURPOSE: In patients with chemotherapy, there is no consensus on the timing of ileostomy closure. Ileostomy reversal could improve the quality of life and minimise the long-term adverse events of delayed closure. In this study, we evaluated the impact of chemotherapy on ileostomy closure and searched for the predictive factors for complications. METHODS: We retrospectively analysed 212 patients with rectal cancer who underwent ileostomy closure surgery during and without chemotherapy and were consecutively enrolled between 2010 and 2016. As a result of the heterogeneity of the two groups, propensity score matching (PSM) was performed with a 1:1 PSM cohort. RESULTS: A total of 162 patients were included in the analysis. The overall stoma closure-related complications (12.4% vs. 11.1%, p = 1.00) and major complications (2.5% vs. 6.2%, p = 0.44) were not significantly different between the two groups. Multivariate analysis demonstrated that chronic kidney disease and bevacizumab use are risk factors for major complications. CONCLUSION: Patients with oral or intravenous chemotherapy can safely have ileostomy closure with an adequate time delay from chemotherapy. When patients use bevacizumab, major complications related to ileostomy closure should still be cautioned.

Localised grey matter atrophy in multiple sclerosis is network-based: a coordinate-based meta-analysis.

AIM: To test the network degeneration hypothesis in multiple sclerosis (MS) with a two-stage coordinate-based meta-analysis by: (1) characterising regional selectivity of grey matter (GM) atrophy and (2) testing for functional connectivity involving these regions. MATERIALS AND METHODS: Meta-analytic sources included 33 journal articles (1,666 MS patients and 1,269 healthy controls) with coordinate-based results from voxel-based morphometry analysis demonstrating GM atrophy. Mass univariate and multivariate coordinate-based meta-analyses were performed to identify a convergent pattern of GM atrophy and determine inter-regional co-activation (as a surrogate of functional connectivity), with anatomical likelihood estimation and functional meta-analytic connectivity modelling, respectively. RESULTS: Localised GM atrophy was demonstrated in the thalamus, putamen, caudate, sensorimotor cortex, insula, superior temporal gyrus, and cingulate gyrus. This convergent pattern of atrophy displayed significant inter-regional functional co-activations. CONCLUSION: In MS, GM atrophy was regionally selective, and these regions were functionally connected. The meta-analytic model-based results of this study are intended to guide future development of quantitative neuroimaging markers for diagnosis, evaluating disease progression, and monitoring treatment response.

Gender difference in clinical and genetic characteristics of Brugada syndrome: SADS-TW BrS registry.

BACKGROUND: Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. AIM: To investigate the gender difference of BrS in Han Chinese. DESIGN: We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. METHODS: Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. RESULTS: The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P = 0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P < 0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P = 0.049), which was mainly attributed to syncope (P < 0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P = 0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P = 0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P = 0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P = 0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. CONCLUSION: Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females.

Reliable sonographic features for nodal thyroglobulin to diagnose recurrent lymph node metastasis from papillary thyroid carcinoma.

OBJECTIVES: Ultrasound-guided aspiration cytology (US-FNAC) was previously used to diagnose lymph node metastasis of papillary thyroid carcinoma (PTC). Combined US-FNAC with nodal thyroglobulin (LN-FNA-Tg) significantly improved the diagnostic rate. However, diagnostic accuracy depends on proper node selection. Therefore, it is crucial to choose the nodes with reliable sonographic features to guide clinician for confirmation. DESIGN AND SETTING: Retrospective cohort study was carried out in one medical centre from 2011 to 2014. PARTICIPANTS: A total of 148 patients with PTC, being treated by total thyroidectomy and radioiodine, were assessed for potential nodal metastases by ultrasound. MAIN OUTCOME MEASURES: Lymph nodes with cystic content, peripheral hypervascularity, calcification, hyperechoic content, the absence of hilum and Solbiati index < 2 indicated risk of malignancy. US-FNAC and LN-FNA-Tg were both performed. Positive nodal metastasis was further confirmed by dissection. Risk impact of these sonographic features on LN-FNA-Tg to diagnose nodal metastasis was tested by logistic regression analysis based on the significance in both univariate and multivariate models. RESULTS: Overall, 49 lymph nodes were documented as recurrent nodal metastasis. LN-FNA-Tg greater than serum thyroglobulin and higher than 1 ng/mL achieved 100% of diagnostic rate for recurrent nodal metastasis. The malignant sonographic features that significantly cohered with positive LN-FNA-Tg were cystic and hyperechoic content and lack hilum, in sequence. CONCLUSIONS: LN-FNA-Tg is an excellent tool to quantitatively diagnose nodal metastasis. To achieve ideal diagnosis, the most reliable sonographic features were cystic content, hyperechoic content and the absence of hilum in lymph nodes, but not calcification or Solbiati index < 2.

The relationship of the anterior articular capsule to the adjacent subscapularis: An anatomic and histological study.

INTRODUCTION: The purpose of this study was to delineate the anatomic relationship between the anterior articular capsule and the adjacent subscapularis by measuring the dimensions of the anterior articular capsule attachment and the subscapularis footprint on the humerus, as well as investigating the interface between the two structures. MATERIALS AND METHODS: Three shoulder specimens underwent histological analysis; for histological analysis, cross-sections through the subscapularis-capsule complex were harvested at the tendinous and muscular insertion sites. The dimensions of the anterior articular capsule attachment and the subscapularis footprint (including the tendinous and muscular insertions) were measured in thirteen cadaveric shoulder specimens. RESULTS: Histologically, the articular capsule has thin and loosely arranged collagen fibers with many interspersing fibroblast nuclei, whereas the outer layer of the articular capsule blends into a layer of more loosely spaced and less organized collagen fibers. This interface between the subscapularis and the underlying articular capsule is filled with more loosely spaced and less organized collagen fibers. The macroscopic evaluation showed that the minimum articular capsule width (4.2mm, SD 2.2mm) was located at its initiation 4.9mm (SD, 2.1mm) inferior to the superior margin of the subscapularis; the corresponding subscapularis footprint width measured 10.1mm (SD, 4.9mm). The maximum articular capsule width was11.1 mm (SD, 3.7mm) and was located 5mm distal to the inferior margin of the tendinous footprint. The maximum subscapularis footprint width was 15.8mm (SD, 2.9mm); the corresponding articular capsule attachment measured 5.2mm (SD, 1.8mm). CONCLUSIONS: Our results suggest that the anterior articular capsule attachment of the glenohumeral joint complements the footprint of the subscapularis and occupies a larger area of the lesser tubercle and metaphysis of the humerus than previously documented. The histological study confirms the presence of a demarcation between the subscapularis and articular capsule, specifically more significant at the region medial to the tendon insertion and at the muscular insertion of the subscapularis.

C-reactive protein gene polymorphism predicts the risk of thromboembolic stroke in patients with atrial fibrillation: a more than 10-year prospective follow-up study.

Essentials We studied the C-reactive protein (CRP) gene on stroke risk in atrial fibrillation (AF) patients. 725 patients with CRP triallelic polymorphism genotype were followed-up for more than 10 years. Patients with the A-390/T-390 allele of the CRP gene were more likely to get ischemic stroke. The triallelic polymorphism of the CRP is related to ischemic stroke in AF patients. SUMMARY: Background Little evidence is available regarding the impact of genetic polymorphisms on the risk of thromboembolic stroke in patients with atrial fibrillation (AF). An increasing body of evidence is demonstrating that inflammatory responses play an important role in the pathophysiology of AF. Objectives To investigate the effect of genetic polymorphisms of the C-reactive protein (CRP) gene on the incidence of thromboembolic stroke in patients with AF. Methods A total of 725 AF patients were longitudinally followed up for > 10 years; this is the largest and longest AF follow-up cohort with genetic data. CRP promoter triallelic polymorphisms (C-390A and C-390T) were genotyped, and CRP levels were divided into four quartiles. Results Patients with higher CRP levels were more likely to develop thromboembolic stroke than those with lower CRP levels (P<0.001, log-rank test for comparison of four quartiles). After adjustment for conventional risk factors, patients with higher CRP levels were more likely to develop thromboembolic stroke than those in the lowest CRP quartile (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.08-4.81; the lowest CRP quartile was the reference group). Patients carrying the A-390 or T-390 allele had higher CRP levels (3.35 ± 2.71 mg L-1 versus 2.43 ± 2.00 mg L-1 ), and were more likely to develop thromboembolic stroke, even after adjustment for conventional risk factors (HR 2.07, 95% CI 1.23-3.48). Conclusion The CRP triallelic polymorphism and the CRP level are associated with the risk of incident thromboembolic stroke in patients with AF.

Enhanced electrochemical supercapacitance of binder-free nanoporous ternary metal oxides/metal electrode.

Free-standing nanoporous Ni-Cu-Mn mixed metal oxides on metal with a high surface area was fabricated by chemically dealloying a Ni8Cu12Mn80 single-phase precursor, followed by electrochemical oxidation in an alkaline solution. Electrochemical analysis shows that first Cu and Mn-based metal oxides formed by the electrochemical oxidation. Ni-based oxides grow later with the increase of electrochemical CV cycles and mix with the Cu/Mn oxides, forming a relatively stable mixed metal oxides thin film on metal ligament network. Due to the different electrochemical properties of each metal and the synergetic effect between them, the mixed ternary metal oxides formed on metal nano-ligament can operate stably between a wide potential window (1.5V) in 1.0M KOH aqueous solution when tested as a free-standing supercapacitor electrode. Due to the high volumetric surface area, wide operating potential window and excellent conductivity, the nanoporous metal oxides@metal composite exhibits a high volumetric capacitance (∼500Fcm(-3)), high energy density (∼38mWhcm(-3)) and good cycling stability.

Statin use reduces the risk of dementia in elderly patients: a nationwide data survey and propensity analysis.

OBJECTIVES: The objective of this study was to examine the association between the use of statins and the risk of newly diagnosed dementia in an elderly population. DESIGN, SETTING AND PARTICIPANTS: Random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included in the analysis. All participants were 65 years or older without dementia and either did or did not start treatment with statins from 1 August 1997 to 31 December 2010. Patients with established dementia before the start of treatment were excluded. Baseline characteristics were matched (by propensity score) in those who did and did not receive statins. RESULTS: A total of 57,669 subjects were included in the analysis with approximately 12 years of follow-up. Propensity score matching identified 2003 patients who received statins and another 2003 patients who did not with comparable baseline characteristics. Adjusted hazard ratios (HRs) for dementia were significantly inversely associated with total or daily equivalent statin dosage (total accumulated dose: HRs 0.829, 0.720 and 0.385 from T1 to T3 vs. control, P < 0.001 for trend; mean daily dose: HRs 0.667, 0.798 and 0.503 from T1 to T3 vs. control, P < 0.001). The results remained robust after propensity adjustment. CONCLUSION: Independent of traditional risk factors, there was a decrease in newly diagnosed cases of dementia in elderly patients who had received a high total or daily dose of statins. The more potent statins (e.g. atorvastatin and rosuvastatin) seemed to be particularly effective in the prevention of dementia.

Cetuximab plus chemotherapy as first-line treatment for metastatic colorectal cancer: effect of KRAS mutation on treatment efficacy in Taiwanese patients.

Cetuximab, either alone or in combination with chemotherapy, is approved for treatment of patients with metastatic colorectal cancer (mCRC). We reviewed retrospectively records of 50 patients with mCRC from a single center in Taiwan. All patients had ECOG performance status grade 2, histological diagnosis of advanced CRC based on RECIST criteria, and were given at least three cycles of chemotherapy plus cetuximab. We compared the effectiveness of therapy in patients with wild-type and mutant KRAS genes, assessed the overall response (OR) rate of patients with locally advanced or metastatic non-resectable CRC, and assessed the progression-free survival (PFS) time. The ten patients with KRAS mutations had poorer response rates than the 40 patients with the wild-type KRAS gene. Patients with the wild-type and mutant genes had similar progression free survival (PFS) status and median time to PFS. The median overall survival time was significantly greater in patients with the wild-type gene than in those with the mutant gene (28.77 ± 6.43 months vs. 15.13 ± 0.50 months, p=0.014). Taiwanese patients with mCRC respond better to a cetuximab plus chemotherapy regime if their tumors have the wild-type KRAS gene.

Phantom rectum following abdominoperineal excision for rectal neoplasm: appearance and disappearance.

AIM: The sensation that the rectum remains or is functioning after abdominoperineal excision (APE) is called phantom rectum (PR). Its postoperative and long-term morbidity are not well documented. Informed consent may not include the risk and consequences of this condition. We assessed the incidence and morbidity of PR after APE and compared those with vs those without vertical rectus abdominis myocutaneous flaps. METHOD: Patients who underwent APE between 1 January 2004 and 31 December 2008 were identified. Preoperative radiation and operative reconstruction by vertical rectus abdominis myocutaneous (VRAM) flaps were noted. Patients were interviewed by telephone to assess the presence and timing of PR symptoms and their effect on quality of life. RESULTS: Thirty-six of 80 patients who underwent APE were available for follow-up. Twenty-three (64%) described PR symptoms including urgency to evacuate [22 (61%)], sensation of faeces in the rectum [19 (52%)] and sensation of passing flatus [17 (48%)]. Eleven (47%) who had VRAM vs 25 who did not, reported having symptoms of PR at < 3 months after APE. Patients described their symptoms as 'unchanged over time' [20 (56%)], 'gradually decreasing and ultimately disappearing' [13 (35%)] or 'worsening' [3 (9%)]. Preoperative radiation and laparoscopic approach were not associated with PR symptoms. Significantly more patients having a VRAM flap reported early PR symptoms [7/11 (64%) vs 4/25 (16%)] (P = 0.008). CONCLUSION: PR sensations were experienced by 23 (64%) patients who underwent APE for rectal cancer. VRAM reconstruction was associated with early PR presentation. The possibility of PR should be discussed preoperatively in patients undergoing APE for anorectal neoplasm.

Recurrent laryngeal nerve injury in video-assisted thyroidectomy: lessons learned from neuromonitoring.

INTRODUCTION: The objective of the study was to assess the mechanism of recurrent laryngeal nerve (RLN) injury during video-assisted thyroidectomy (VAT). METHODS: The study examined 201 nerves at risk (NAR). VAT with laryngeal neuromonitoring (LNM) was outlined according to this scheme: (a) preparation of the operative space; (b) vagal nerve stimulation (V1); (c) ligature of the superior thyroid vessels; (d) visualization, stimulation (R1), and dissection of the RLN; (e) extraction of the lobe; (f) resection of the thyroid lobe; (g) final hemostasis; (h) verification of the electrical integrity of the RLN (V2, R2). The site, cause, and circumstance of nerve injury were elucidated with the application of LNM. Laryngeal nerve injuries were classified into type 1 injury (segmental) and 2 (diffuse). RESULTS: Fourteen nerves (6.9 %) experienced loss of R2 and V2 signals. 80 percent of lesions occurred in the distal 1 cm of the course of the RLN. The incidence of type 1 and 2 injuries was 71 and 29 % respectively. The mechanisms of injury were traction (70 %) and thermal (30 %). Traction lesions were created during the extraction of the lobe from the mini-incision [point (e)]. Thermal injury occurred during energy-based device use in (f) and (g) circumstances. CONCLUSIONS: RLN palsy still occurs with routine endoscopic identification of the nerve, even combined with LNM. LNM has the advantage of elucidating the mechanism of RLN injury. Traction and thermal RLN injuries are the most frequent lesions in VAT.

A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation.

OBJECTIVES: In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. METHODS: A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. RESULTS: Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The -390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. CONCLUSION: A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.

Differential association of proinflammatory cytokines with left ventricular diastolic dysfunction in subjects with and without continuous ambulatory peritoneal dialysis.

BACKGROUND AND AIMS: The association between inflammation and left ventricular (LV) diastolic dysfunction in continuous ambulatory peritoneal dialysis (CAPD) and non-CAPD patients is not established. The objective of this study was to test the above association and whether inflammation interacts with CAPD to increase LV diastolic dysfunction risks. METHODS AND RESULTS: 120 subjects with normal creatinine levels and 101 CAPD patients were recruited. Echocardiographic parameters were assessed in all patients. The participants were classified as having LV diastolic dysfunction by echocardiographic findings including mitral inflow E/A ratio < 1, deceleration time > 220 cm/s, or decreased peak annular early diastolic velocity in tissue Doppler imaging. Blood was sampled at the baseline for measurement of inflammation markers, including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Subjects with LV diastolic dysfunction had higher proinflammation cytokines levels in both groups. Inflamed markers correlated significantly with echocardiography parameters for LV diastolic dysfunction in patients receiving CAPD. In a multivariate regression analysis adjusting for all the factors associated with LV diastolic dysfunction, inflammation is still significantly associated with left ventricular diastolic dysfunction (TNF-alpha, OR: 2.6, 95% CI: 2.0-3.35, p < 0.001; IL-6, OR: 1.26, 95% CI: 1.25-1.26, p = 0.01). In addition, the interaction of CAPD and inflammation significantly contributed to the development of LV diastolic dysfunction (CAPD∗ TNF-α: OR: 1.45, 95% CI: 1.13-1.79, P = 0.004). CONCLUSION: We found inflammation plays a vital role for LV diastolic dysfunction especially in CAPD patients. A synergistic effect between CAPD and inflammation, especially TNF-α, would further aggravate LV diastolic dysfunction.

Implementation of systematic neuromonitoring training for thyroid surgery.

Neural monitoring is increasingly applied to thyroid surgery and yet few surgeons have received formal training in intraoperative neuromonitoring (IONM). Standardized application of neural monitoring is an expected outcome of formal training programs in IONM. This study was designed to document a systematic training course that focuses on standardized state-of-art IONM knowledge. Seventeen 1-day courses were organized by the Department of Surgical Sciences, University of Insubria Medical School (Varese-Como, Italy), between 2009-2010. The course included didactic and practical training sessions. Some specific steps and checklist identified for courses included: knowledge of IONM technology and troubleshooting algorithms; IONM anesthetic perspectives, standards of IONM equipment set up and technique. A total of 75 trainees completed a questionnaire after completion of the respective courses. Questions probed demographic data, operative IONM experience and evaluation of course content. Data gathered showed that 97% of participants had no prior experience with the standardized approach of IONM technique (i.e. stimulation of the vagal nerve). The most useful parts of the course were judged to be (a) algorithms for perioperative IONM problem solving (30%), (b) live surgery with hands-on training (25%), (c) standardization of IONM technique (25%), and (d) IONM equipment set-up (20%). Poor reimbursement for hospital thyroid procedures is the main reason of limitation of IONM technology. The course offered participants novel knowledge and training and gave participants a systematic and standard approach to IONM technique.

Lower ataxia telangiectasia mutated (ATM) mRNA expression is correlated with poor outcome of laryngeal and pharyngeal cancer patients.

BACKGROUND: Ataxia telangiectasia mutated (ATM) kinase is a critical regulator in initiating DNA damage response and activating DNA repair. However, the correlation between ATM expression and the outcome of laryngopharyngeal cancer patients is unknown. We hypothesize that ATM expression is correlated with a worse outcome in laryngopharyngeal cancer patients. PATIENTS AND METHODS: The ATM messenger RNA (mRNA) expression of 80 tumors of laryngeal and pharyngeal cancer was examined by real-time quantitative RT-PCR. Overall survival rates were measured using Kaplan-Meier estimates and the log-rank tests. The adjusted hazard rate ratios (HRRs) were computed by multivariate Cox regressions. RESULTS: Reduced ATM mRNA was found in 65 of 80 studied cases. Lower ATM expression [tumor/normal <0.3, HRR = 2.49; 95% confidence interval (CI) 1.27-4.88], younger age (<55 years, HRR = 2.71; 95% CI 1.16-6.32), and larger tumor (T(3)/T(4), HRR = 2.21; 95% CI 1.10-4.44) were independent risk factors for survival. Patients with lower ATM and younger age (HRR = 6.51; 95% CI 2.05-20.66) or with lower ATM and T(3)/T(4) tumor (HRR = 5.23; 95% CI 2.04-13.40) exhibited the poorest outcome. CONCLUSION: The expression of ATM mRNA, which is frequently downregulated in laryngeal and pharyngeal cancers, could be a valuable prognostic marker.

Demonstrating the pharmacogenetic effects of angiotensin-converting enzyme inhibitors on long-term prognosis of diastolic heart failure.

The objective of this study was to evaluate the effects of angiotensin-converting enzyme (ACE) inhibitors and pharmacogenetic interaction on the survival of the patients with diastolic heart failure (DHF). A total of 285 subjects with DHF confirmed by echocardiography were recruited in the period between 1995 and 2003. Baseline characteristics (age, sex, prior history, medication, and echocardiographic findings) and genetic polymorphisms (ACE gene insertion/deletion (I/D) polymorphism; T174M, M235T, G-6A, A-20C, G-152A, and G-217A polymorphisms of the angiotensinogen (AGT) gene; and A1166C polymorphisms of the angiotensin II type I receptor (AT1R)) were collected and matched (by propensity score) in those who received and those who did not receive ACE inhibitors. The patients were followed up to 10 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival trend. The 85 patients who received ACE inhibitors and the other 85 patients who did not were found to have comparable baseline characteristics and polymorphism distribution. Prescription of ACE inhibitors was associated with a significant decrease in overall mortality (hazard ratio (HR), 0.45; 95% confidence interval (CI), 0.24-0.83; P=0.01), and a lower rate of cardiovascular events at 4000 days (HR, 0.53; 95% CI, 0.32-0.90; P=0.02). In addition, ACE I/D gene D allele was associated with higher overall mortality as compared with the I allele (HR, 2.04; P=0.003). This effect was diminished in those who received ACE inhibitors. The use of ACE inhibitor was associated with a significant decrease in long-term mortality and cardiovascular events in the patients with DHF. Genetic variants in the renin-angiotensin system genes were also associated, but their effects could be modified by the use of ACE inhibitors.