Acupuncture reduces mechanical ventilation time in critically ill patients: A systematic review and meta-analysis of randomized control trials.

BACKGROUND: Mechanical Ventilation (MV) is an essential life support machine, frequently utilized in an Intensive Care Unit (ICU). Recently, a growing number of clinical trials have investigated the effect of acupuncture treatment on MV outcomes. OBJECTIVES: This study investigated the safety and efficacy of acupuncture treatment for critically ill patients under MV. METHODS: In this systematic review and meta-analysis of randomized controlled trials, the efficacy of acupuncture related interventions was compared to routine ICU treatments, and sham/control acupuncture as control interventions applied to ICU patients undergoing MV. The databases of PubMed, Cochrane Library, and Web of Science were extensively searched in the month of April 2022. The primary outcome measurements were defined as total MV time, ICU length of stay, and mortality. The Cochrane Collaboration risk of bias tool was employed to analyze the severity of bias. The meta-analysis was conducted using Review Manager 5.3 software. The quality of evidence was evaluated according to the GRADE approach. RESULTS: A total of 10 clinical trials were included in this investigation. When comparing the performance of acupuncture-related interventions to that of the reported control interventions, the results of the meta-analysis revealed a significant reduction in the total number of MV days as well as the duration of ICU length of stay following acupuncture treatment (MD -2.06 [-3.33, -0.79] P = 0.001, I2 = 55 %, MD-1.26 [-2.00, -0.53] P = 0.0008, I2 = 77 %, respectively). A reduction in the total mortality was similarly observed (RR = 0.67 [0.47, 0.94] P = 0.02, I2 = 0 %). CONCLUSION: This systematic review and meta-analysis identified a noteworthy reduction in the total MV days, time spent in the ICU, as well as the total mortality following acupuncture related interventions. However, the small sample size, risk of bias and existing heterogeneity should be taken into consideration. The results of this study are promising and further investigations in this field are warranted.

Is acupuncture safe in the ICU? A systematic review and meta-analysis.

Background and purpose: The safety of interventions for critically ill patients is a crucial issue. In recent years, several studies have treated critically ill patients with acupuncture. However, the safety of acupuncture in this setting remains to be systematically measured. Methods: In May 2022, the electronic databases of PubMed and the Cochrane Library were searched for studies comparing acupuncture interventions to control interventions in critically ill patients. Study outcomes examined the incidence of severe adverse events (AEs), minor AEs, adverse reactions, ICU stays, and 28-day mortality. Results: A total of 31 articles were analyzed, and no serious AEs related to acupuncture treatment were identified. No significant differences were found between the groups in the meta-analysis of minor AEs (risk ratio [RR] 5.69 [0.34, 96.60], P = 0.23, I2 = 76%). A reduced risk in the incidence of adverse reactions following acupuncture intervention was evidenced (RR 0.33 [0.22, 0.50], P = 0.00001, I2 = 44%). The patients in the acupuncture arm spent significantly less time in the intensive care unit (ICU) (Mean difference -1.45 [-11.94, -10.97], P = 0.00001, I2 = 56%) and also exhibited lower 28-day mortality rates (odds ratio 0.61 [0.48, 0.78], P = 0.0001, I2 = 0%). Conclusion: There is no evidence to indicate a higher risk of severe or minor AEs in patients who receive acupuncture. Acupuncture demonstrated favorable results in both ICU stay and 28-day mortality measurements, in addition to presenting with fewer adverse reactions compared to routine ICU care. However, the low certainty of the evidence resulting from a high risk of bias in the included studies merits substantial consideration, and further research is still warranted. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=142131, identifier: CRD42020142131.

Effects of Testosterone Replacement Therapy on Muscle Strength in Older Men with Low to Low-Normal Testosterone Levels: A Systematic Review and Meta-Analysis.

BACKGROUND: Previous studies and meta-analyses have explored the relationship among testosterone, muscle strength, and physical function, to the best of our knowledge, no meta-analysis has investigated the effects of testosterone replacement therapy (TRT) on subgroup of relatively hypogonadal older men. OBJECTIVE: The aim of this study was to evaluate the effect of TRT in older men with low testosterone levels. METHODS: PubMed, Embase, and Web of Science were systematically searched for articles published between January 1990 and April 2020. We included randomized controlled studies that investigated the effect of TRT and included older men (age >60 years) with relatively low testosterone levels. Studies were extracted following the PRISMA flowchart, and the included randomized controlled trials were evaluated using RoB 2.0. Our main outcome was muscle strength changes after TRT evaluated using a metaregression of confounding factors. Secondary outcomes included changes in physical performance and the risk ratio of adverse events. Random-effects meta-analyses of TRT on muscle strength and physical function were performed. RESULTS: Thirteen studies with 2,043 patients were included. The mean age of subjects in various studies ranged from 65.9 years to 76 years. Transdermal testosterone dosages ranged from 5 to 10 g/day, while intramuscular options were 125 mg/week or 200 mg every 2 weeks. Oral testosterone supplementation was given at 160 mg/day in one study. Pooled meta-analyses revealed greater muscle strength improvement after TRT compared with placebo (Hedges' g = 0.21; 95% CI: = 0.15-0.28). Intramuscular administration of TRT had greater efficacy (Hedges' g = 0.74; 95% CI: = 0.34-1.14) than transdermal and oral TRT (p < 0.001). A metaregression revealed that baseline serum total testosterone was associated with muscle strength improvement (ß = -0.004, p = 0.002). The risk ratios of adverse events, including elevated prostate-specific antigen, acute coronary syndrome, and prostate cancer, were not significantly different. CONCLUSION: TRT improved muscle strength in older, relatively hypogonadal men. The effect was more pronounced in populations with lower baseline testosterone levels.

Acupuncture effect on dumping syndrome in esophagus cancer patients with feeding jejunostomy: A study protocol for a single blind randomized control trial.

INTRODUCTION: Esophagus cancer patients are at risk for malnourishment. Feeding jejunostomy is used in advanced esophagus cancer patients in order to support and supplement the patients' nutrition needs. In dumping syndrome, the food is rapidly introduced into the intestine at a rate that is faster than normal, it is associated with both digestive system and vasoactive symptoms. Dumping syndrome has an association with both esophagus cancer patients and feeding jejunostomy. In the mid and long term, dumping syndrome is an important issue that contributes to the risk of malnourishment in advanced esophagus cancer patients. In recent studies, acupuncture was effective in regulating digestive symptoms. Acupuncture is considered to be a safe intervention, that was previously shown to be effective in treating digestive-related symptoms. METHODS: Sixty advanced esophageal cancer patients post-feeding jejunostomy will be divided into 2 equal groups, an intervention group (n = 30) and a control group (n = 30). Patients in the intervention group will receive acupuncture using the following acupoints: ST36 (Zusanli), ST37 (Shangjuxu), ST39 (Xiajuxu), PC6 (Neiguan), LI4 (Hegu), and Liv 3 (Taichung). Patients in the control group will receive shallow acupuncture on 12 non-acupoints (sham points), 1 cm from the above mention points. Patients and assessors will be blind to trial allocation. Both groups will receive acupuncture twice a week for 6 weeks. The main outcome measurements are: body weight, BMI, Sigstad's score, and the Arts' dumping questionnaire. DISCUSSION: There are no previous studies that have examined the use of acupuncture on patients with dumping syndrome. This single-blind randomized control trial will investigate the effect of acupuncture on dumping syndrome in advanced esophagus cancer patients with feeding jejunostomy. The results will determine if verum acupuncture can affect dumping syndrome and prevent weight loss.

Traditional Chinese medicine use in patients with oral cancer: A retrospective longitudinal cohort study in Taiwan.

Oral cancer is frequently associated with smoking, alcohol consumption, and betel quid chewing, which are common harmful behaviors observed in certain cohorts of the Taiwanese population. Some reports have explored the potential therapeutic effect of certain herbal remedies on cancer treatments and the outcomes thereof. However, supportive evidence regarding the specific use of traditional Chinese medicine (TCM) in oral cancer treatment is lacking and deserves further investigation. This study measured the use of TCM therapies for oral cancer in a Taiwanese population-based retrospective longitudinal cohort study. The Taiwan National Health Insurance Research Database was utilized to conduct this study. The study population was limited to oral cancer patients diagnosed between 2000 and 2009, which were followed up for at least 5 years. Therapeutic strategies investigated included acupuncture and the Chinese herbs and formula used. Additionally, the frequency of TCM treatment visits, total medical costs, and all-cause mortality were also analyzed. Between 2000 and 2009, a total of 951 patients were diagnosed with various oral cancers. 13.7% of the diagnosed patients utilized TCM treatment measures. The majority of the patients were males. The top 3 common single herbs used were Xuán shen (Radix Scrophulariae), Shí hú (Herba Dendrobii), and Mài mén dong (Ophiopogon Japonicus). Then, Gan lù yǐn, Zhi bǎi dì huáng wán, and Sàn zhǒng kuì jian tang were the most frequently used herbal formulas. The survival probability was higher in TCM users when compared to non-TCM users in 5- and 12-year all-cause mortality (P < .05). This study explored the use of TCM therapies in oral cancer patients and identified essential information regarding the specifics of conventional herbal medicine used, affiliated medical costs, survival probability, and common symptoms observed in Taiwanese oral cancer patients.

The Use of Traditional Chinese Medicine in Patients with Oral, Oropharynx, Nasopharynx, and Hypopharynx Cancers: A Retrospective Longitudinal Cohort Study in Taiwan.

INTRODUCTION: Given the prevalent use of tobacco and betel nut in the Taiwanese community, an increase risk of oral, oropharynx, and hypopharynx cancers (head and neck cancers) is apparent. The use of Traditional Chinese Medicine (TCM) and acupuncture is both common and conveniently accessible in Taiwan, with treatments being financially supported by the National Health Insurance (NHI). This study aims to investigate the use of TCM in head and neck cancers in Taiwan through a longitudinal cohort study. METHODS: The Taiwan National Health Insurance Research Database (NHIRD) was utilized in order to conduct this study. The study populations consisted of oral, oropharynx, nasopharynx, and hypopharynx cancers (head and neck cancer) patients in 2002, which were then followed up until 2007 in regards to TCM use, until 2013 in regards to acupuncture use and until 2014 for all-cause mortality. Patients were divided into 4 groups. Common symptoms, Chinese herbs and formula used, TCM visits and 5 and 12 years all-cause mortality were analyzed. RESULTS: The use of TCM was increased in the second to fourth-year post-diagnosis. TCM use in nasopharynx cancer patients was higher compared to other cancers. The number of TCM visits per patient was increased post-diagnosis. The findings suggest a non-significant reduction in 5 and 12 years all-cause mortality between TCM II and CON II groups. CONCLUSION: The use of TCM in new patients suffering from head and neck cancers was increased in close proximity to the cancer diagnosis. The relation between TCM use and mortality of head and neck cancer should be investigated through larger scale studies.

Press tack needle stimulation for blunt chest trauma: a randomized double-blind control trial.

OBJECTIVES: Blunt chest trauma is often associated with severe pain, reduced lung function and decreased sleep quality. This study aims to investigate the immediate and long-term effect of acupuncture on these factors using a randomized control double-blind design. METHODS: A total of 72 patients were randomized into 2 groups: treatment group (press tack acupuncture) and control group (press tack placebo). The face rating scale, numerical rating scale (NRS), portable incentive spirometer and Verran Snyder-Halpern sleep scale were measured at baseline, immediately after the intervention, and at the 4th day, with 2-weeks and 3-months follow-ups. RESULTS: There were no significant changes between the groups at the baseline measurements, with the exception of hypertension comorbidity. Immediately after the intervention and on the 4th day follow-up, the patients in the treatment group showed a significantly lower face rating scale when compared to the control (P < 0.05). There were no significant changes in any of the other measurements between the groups (P > 0.05). Subgroup analysis revealed that the NRS for turn over on the 4th day was reduced significantly in the treatment group of patients without lung contusion (P < 0.05). For patients without pleural drainage, cough NRS in the treatment group was significantly reduced in the 2-week follow-up (P < 0.05). CONCLUSIONS: This study showed that press tack acupuncture effects on pain reduction were inconclusive. However, future studies on the effect of acupuncture on blunt chest trauma patients are needed. CLINICAL TRIAL REGISTRATION: clinicaltirl.gov: NCT04318496.

Paradoxical mortality of high estimated glomerular filtration rate reversed by 24-h urine creatinine excretion rate adjustment: sarcopenia matters.

BACKGROUND: Muscle wasting may explain the paradoxical mortality of patients with high estimated glomerular filtration rates (eGFRs) derived from equation methods. However, empirical evidence and solutions remain insufficient. METHODS: In this retrospective cohort study, we compared the performance of equation methods for predicting all-cause mortality; we used 24-h creatinine clearance (24-h CrCl), equation-based eGFRs, and a new eGFR estimating equation weighting for population 24-h urine creatinine excretion rate (U-CER). From 2003 to 2018, we identified 4986 patients whose data constituted the first 24-h CrCl measurement data in the Clinical Research Data Repository of China Medical University Hospital and were followed up for at least 5 years after careful exclusion. Three GFR estimation equations [the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study, and Taiwanese MDRD], 24-h CrCl, and 24-h U-CER-adjusted eGFR were used. RESULTS: A high correlation was observed among the eGFR levels derived from the equation methods (0.995-1.000); however, the correlation decreased to 0.895-0.914 when equation methods were compared with the 24-h CrCl or 24-h U-CER-adjusted equation-based eGFR. In the Bland-Altman plots, the average discrepancy between the equation methods and the 24-h CrCl method was close to zero (maximal bias range: 5.12 for the Taiwanese MDRD equation vs. 24-h CrCl), but the range in limit of agreement was wide, from ±43.7 mL/min/1.73 m2 for the CKD-EPI equation to ±54.3 mL/min/1.73 m2 for the Taiwanese MDRD equation. A J-shaped dose-response relationship was observed between all equation-based eGFRs and all-cause mortality. Only 24-h CrCl exhibited a non-linear negative dose-response relationship with all-cause mortality. After adjustment for 24-h U-CER in the statistical model, the paradoxical increase in mortality risk for an eGFR of >90 mL/min/1.73 m2 returned to null. When 24-h U-CER was used directly to correct eGFR, the monotonic non-linear negative relationship with all-cause mortality was almost identical to that of 24-h CrCl. CONCLUSIONS: The 24-h U-CER-adjusted eGFR and 24-h CrCl are viable options for informing mortality risk. The 24-h U-CER adjustment method can be practically implemented to eGFR-based care and effectively mitigate the inherent confounding biases from individual's muscle mass amount due to both sex and racial differences.

Coffeeberry Activates the CaMKII/CREB/BDNF Pathway, Normalizes Autophagy and Apoptosis Signaling in Nonalcoholic Fatty Liver Rodent Model.

Nonalcoholic fatty liver disease (NAFLD) shows extensive liver cell destruction with lipid accumulation, which is frequently accompanied by metabolic comorbidities and increases mortality. This study aimed to investigate the effects of coffeeberry (CB) on regulating the redox status, the CaMKII/CREB/BDNF pathway, autophagy, and apoptosis signaling by a NAFLD rodent model senescence-accelerated mice prone 8 (SAMP8). Three-month-old male SAMP8 mice were divided into a control group and three CB groups (50, 100, and 200 mg/kg BW), and fed for 12 weeks. The results show that CB reduced hepatic malondialdehyde and carbonyl protein levels. CB significantly enhanced Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) and reduced the phospho-cAMP response element-binding protein (p-CREB)/CREB ratio. In addition, CB increased the silent information regulator T1 level, promoted Beclin 1 and microtubule-associated protein light chain 3 II expressions, and reduced phosphorylated mammalian target of rapamycin and its downstream p-p70s6k levels. CB also inhibited the expressions of apoptosis-related factors poly (ADP-ribose) polymerase-1 and the apoptosis-inducing factor. In conclusion, CB might protect the liver by reducing oxidative stress, activating the CaMKII/CREB/BDNF pathway, and improving autophagic and apoptotic expressions in a dose-dependent manner.

Digestion-Specific Acupuncture Effect on Feeding Intolerance in Critically Ill Post-Operative Oral and Hypopharyngeal Cancer Patients: A Single-Blind Randomized Control Trial.

Malnourishment is prevalent in patients suffering from head and neck cancer. The postoperative period is crucial in terms of nutritional support, especially after composite resection and reconstruction surgery. These patients present with a number of risk factors that aggravate feeding intolerance, including postoperative status, prolonged immobility, decreased head elevation, mechanical ventilation, and applied sedative agents. Routine management protocols for feeding intolerance include prokinetic drug use and post-pyloric tube insertion, which could be both limited and accompanied by detrimental adverse events. This single-blind clinical trial aimed to investigate the effects of acupuncture in postoperative feeding intolerance in critically ill oral and hypopharyngeal cancer patients. Twenty-eight patients were randomized into two groups: Intervention group and Control group. Interventions were administered daily over three consecutive postoperative days. The primary outcome revealed that the intervention group reached 70% and 80% of target energy expenditure (EE) significantly earlier than the control group (4.00 ± 1.22 versus 6.69 ± 3.50 days, p = 0.012), accompanied by higher total calorie intake within the first postoperative week (10263.62 ± 1086.11 kcals versus 8384.69 ± 2120.05 kcals, p = 0.004). Furthermore, the intervention group also needed less of the prokinetic drug (Metoclopramide, 20.77 ± 48.73 mg versus 68.46 ± 66.56 mg, p = 0.010). In conclusion, digestion-specific acupuncture facilitated reduced postoperative feeding intolerance in oral and hypopharyngeal cancer patients.

Acupuncture for blunt chest trauma: A protocol for a double-blind randomized control trial.

INTRODUCTION: Blunt chest trauma (BCT) accounts for up to 65% of polytrauma patients. In patients with 0 to 2 rib fractures, treatment interventions are typically limited to oral analgesics and breathing exercises. Patients suffering from BCT experience symptoms of severe pain, poor sleep, and inability to perform simple daily life activities for an extended period of time thereafter. In this trial, we aim to investigate the efficacy of acupuncture as a functional and reliable treatment option for blunt chest trauma patients. METHODS: The study is designed as a double-blind randomized control trial. We will include 72 patients divided into 2 groups; the acupuncture group (Acu) and placebo group (Con). The acupuncture group will receive true acupuncture using a uniquely designed press tack needle. The control group will receive placebo acupuncture treatment through the use of a similarly designed press tack needle without the needle element. The acupoints selected for both groups are GB 34, GB 36, LI 4, LU 7, ST 36, and TH 5. Both groups will receive 1 treatment only following the initial visit to the medical facility and upon diagnosis of BCT. Patient outcome measurements include: Numerical Rating Scale, Face Rating Scale, respiratory function flowmeter, Verran Snyder-Halpern sleep scale, and the total amount of allopathic medication used. Follow-up time will be scheduled at 4 days, 2 weeks, and lastly 3 months. EXPECTED OUTCOME: The results of this study can potentially provide a simple and cost-effective analgesic solution to blunt chest trauma patients. This novel study design can serve as supporting evidence for future double-blind studies within the field of acupuncture. OTHER INFORMATION: The study will be conducted in the thoracic surgical department and acupuncture department in China Medical University Hospital, Taichung, Taiwan. The study will be conducted on blunt chest trauma patients and is anticipated to have minimum risk of adverse events. Enrollment of the patients and data collection will start from March 2020. Study completion time is expected in March 2022. PROTOCOL REGISTRATION: (CMUH109-REC1-002), (NCT04318496).

The Effectiveness of Acupuncture in the Treatment of Frozen Shoulder: A Systematic Review and Meta-Analysis.

BACKGROUND: Frozen shoulder (FS) is associated with pain, reduced range of motion (ROM), and shoulder function. The condition occurs in 2-5% of the population, and it is especially common around the age of 50 years. FS symptoms will recover after 1-4 years. Many patients turn to acupuncture in order to alleviate the FS symptoms. OBJECTIVE: In this review, we will investigate the efficiency of acupuncture as a FS treatment. METHODS: A literature search of acupuncture and FS-related keywords was performed in the following databases: PubMed, Cochrane Library, Embase, and Web of Science. Thirteen publications were included for a systematic review, and a meta-analysis was done using the following measurements: visual analogue scale (VAS) for pain, Constant-Murley Shoulder Outcome Score (CMS) for shoulder function, and active shoulder ROM including flexion, abduction, and external rotation. The Cochrane Collaboration's risk of bias tool and quality of evidence GRADE recommendations and STRICTA 2010 were used to grade the included publications. RESULTS: A meta-analysis on VAS pain score showed significant pain reduction, restoring CMS shoulder function, and flexion ROM in favor of acupuncture versus the control. In external rotation and abduction ROM, a meta-analysis was not significant. The most used acupoints are Jian Yu (LI15) and Jian Liao (TB14). CONCLUSIONS: The results indicate that acupuncture could be safe and effective for pain reduction, restoring shoulder function, and restoring flexion ROM for FS patients in the short term and midterm. However, the level of evidence was very low. More high-quality and longer studies are needed in order to robust the evidence.

Acupuncture effect on digestion in critically ill postoperative oral and hypopharyngeal cancer patients: A protocol for double-blind randomized control trial.

INTRODUCTION: Head and neck cancer patients are at a high risk to suffer from malnourishment, a risk that increases in postoperative condition and with the use of enteral nutrition (EN). Until now patients who are suffering from indigestion in the intensive care unit (ICU) received treatment in the form of prokinetic drugs, drugs that can lead to serious side effects and only can partially improve digestion functions. Acupuncture was used successfully in several clinical trials to improve postoperative indigestion in cancer patients without any reported adverse events. The study aims are to investigate acupuncture effect in combination with prokinetic drugs in the treatment of indigestion in postoperative oral and hypopharyngeal cancer patients in the ICU. METHODS: Single-center, double-blind randomized control trial will compare between 2 equal groups. A total of 28 patients that will meet the inclusion criteria: age 30 to 80, postplastic surgery for oral cancer or hypopharyngeal cancer, developed feeding intolerance 2 times in the first postoperative day, Apache score <20, and needed EN. Patients will be randomly divided (1:1) into treatment group or control group for 3 treatments in 3 days along with routine ICU treatment. The main outcome measurement will be the number of days a patient needs to reach his total energy expenditure. EXPECTED OUTCOME: The results will shed light on the effectiveness and safety of acupuncture in a double-blind design treating postoperative ICU cancer patients. In addition, the study presents a revolutionary double-blind design that if, will prove as successful might influence the way double-blind acupuncture studies are performed today. OTHER INFORMATION: The study will be conducted in the surgical ICU department, of China medical university hospital, Taichung 404, Taiwan. The study is conducted on stable ICU patients and is anticipated to have minimum risk for adverse events. Patients enrollment and data collection will start from May 15, 2019. The study expected completion time: June 2021.

Evaluation of the necessity for chest drain placement following thoracoscopic wedge resection.

PURPOSE: To evaluate the outcomes of patients who underwent thoracoscopic wedge resection without chest drain placement. METHODS: The subjects of this retrospective study were 89 patients, who underwent thoracoscopic wedge resection at our hospital between January, 2013 and July, 2015. A total of 45 patients whose underlying condition did not meet the following criteria were assigned to the "chest drain placement group" (group A): peripheral lesions, healthy lung parenchyma, no intraoperative air leaks, hemorrhage or effusion accumulation, and no pleural adhesion. The other 44 patients whose underlying condition met the criteria were assigned to the "no chest drain placement group" (group B). Patient characteristics, specimen data, and postoperative conditions were analyzed and compared between the groups. RESULTS: Group A patients had poorer forced expiratory volume in one second (FEV1) values, less normal spirometric results, significantly higher resected lung volume, a greater maximum tumor-pleura distance, and a larger maximum tumor size. They also had a longer postoperative hospital stay. There was no difference between the two groups in postoperative complications. CONCLUSIONS: Avoiding chest drain placement after a thoracoscopic wedge resection appears to be safe and beneficial for patients who have small peripheral lesions and healthy lung parenchyma.

A Mimicking Esophageal Cancer After Liver Transplant for Hepatocellular Carcinoma: A Rare Posttransplant Metastasis.

Liver transplant is now considered to be a successful treatment modality for early hepatocellular carcinoma. In addition, advances in immunosuppressive therapy have greatly prolonged posttransplant survival of patients with hepatocellular carcinoma. However, both the posttransplant physiologic condition and immunosuppressive therapy affect the patient's natural immunity, resulting in accumulating and more problematic complications. Three years after a male patient with hepatocellular carcinoma underwent living-donor liver transplant, he presented with esophageal metastasis from recurrence of hepatocellular carcinoma. This is an extremely rare complication, perhaps with an ominous prognosis, and, to the best of our knowledge, the first such case to be published in the English literature.

Significant Association of Cyclo-oxygenase 2 Genotypes with Upper Tract Urothelial Cancer.

AIM: Reliable biomarkers are in urgent need for diagnosis, outcome prediction and treatment-effect monitoring for upper tract urothelial carcinomas (UTUC). Although up-regulation of cyclo-oxygenase 2 (COX2) is found in stroma and tumor cells in more than half of the patients with UTUC investigated, the genomic contribution of COX2 to UTUC has not been studied. The study aimed to evaluate the association of six polymorphic genotypes of COX2 with UTUC within a Taiwanese population. MATERIALS AND METHODS: A total of 218 patients with UTUC and 580 healthy controls were genotyped for six COX2 polymorphisms, namely A-1195G, G-765C, T+8473C, intron 1, intron 5 and intron 6, and examined for their association with UTUC risk. RESULTS: The distribution of genotypes of COX2 G-765C and intron 5 were significantly different between patient and control groups (p=0.0001 and 0.0016, respectively), while others were not (p>0.05). The haplotype analysis showed that compared to the GG/TT haplotype of COX2 G-765C/intron 5, those carrying GG/AT variants have a significantly increased risk of UTUC (odds ratio=4.83, 95% confidence interval=1.79-13.06), while those carrying CG/TT variants have a decreased risk (odds ratio=0.26, 95% confidence interval=0.14-0.49). CONCLUSION: Our results suggest that individual and combined COX2 G-765C/intron 5 genotypes play a role in controlling COX2 expression and UTUC development.

Inhibition of Toxic IAPP Amyloid by Extracts of Common Fruits.

The aggregation of the 37-amino acid polypeptide islet amyloid polypeptide (IAPP, amylin), as either insoluble amyloid or as small oligomers, appears to play a direct role in the death of pancreatic ß-islet cells in type 2 diabetes. It is believed that inhibiting the aggregation of IAPP may slow down, if not prevent entirely, the progression of this disease. Extracts of thirteen different common fruits were analyzed for their ability to prevent the aggregation of amyloidogenic IAPP. Thioflavin T binding, immuno-detection and circular dichroism assays were performed to test the in vitro inhibitory potential of each extract. Atomic force microscopy was used to visualize the formation of amyloid fibrils with and without each fruit extract. Finally, extracts were tested for their ability to protect living mammalian cells from the toxic effects of amyloid IAPP. Several fruits showed substantial ability to inhibit IAPP aggregation and protect living cells from toxic IAPP amyloid.

IAPP aggregation and cellular toxicity are inhibited by 1,2,3,4,6-penta-O-galloyl-ß-D-glucose.

The polyphenol, 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PGG) has been found to exhibit a host of positive pharmacologic activities, including anti-cancer and anti-diabetic. Little is known about the mode of action of PGG in yielding these positive activities. We show here that PGG is a potent inhibitor of IAPP (islet amyloid polypeptide, amylin) aggregation. Preventing the initial aggregation event of IAPP is one strategy for slowing, and possibly preventing, the toxic effects of IAPP oligomeric intermediates. Equal molar ratios of PGG to IAPP substantially reduced the ability of IAPP to bind thioflavin T. Atomic force microscopy revealed that PGG prevented amyloid-based fiber formation under rigorous conditions conducive to forming IAPP aggregates. PGG was also found to protect PC12 rat cells from toxic IAPP. PGG was compared to the known amyloid inhibitors (and structural relatives); tannic acid and gallic acid. In every test, PGG was far superior to tannic and gallic acids at inhibiting amyloid aggregation. These results indicate that PGG is a potent inhibitor of IAPP amyloid aggregation and a potential lead molecule for development of an amyloid inhibiting therapeutic.