Validation and responsiveness of the English version of the Chemotherapy-Induced Alopecia Distress Scale (CADS) in breast cancer patients.

PURPOSE: This study aimed to validate the Chemotherapy-Induced Alopecia Distress Scale (CADS) in a diverse English-speaking population and patients with endocrine treatment-induced alopecia (EIA). OBJECTIVE: Chemotherapy and endocrine therapy commonly cause alopecia in breast cancer patients, leading to significant psychological and social challenges. The CADS was developed to assess the psychosocial impact of alopecia, but its generalizability beyond Korean patients requires further investigation. METHODS: Data from the CHANCE study (NCT02530177), which focused on non-metastatic breast cancer, was used. The cohort included 256 patients, and CADS data were collected at baseline, 6 months after chemotherapy completion, or 12 months after initiating endocrine therapy. The CADS questionnaire comprised 17 items covering physical and emotional health, daily activities, and relationships. Reliability was assessed using Cronbach's alpha, and responsiveness was measured by effect size. RESULTS: The CADS exhibited good reliability, with Cronbach's alpha of 0.91 for the overall score, indicating acceptable internal consistency in both chemotherapy (0.89) and endocrine therapy (0.86) groups. Longitudinal responsiveness was supported by an effect size of 0.49 between decreasing satisfaction with hair growth and increasing emotional distress. Cross-sectional validity was confirmed, with effect sizes of 0.91 and 0.92 for satisfaction with hair growth and emotional and activity domains, respectively. CONCLUSION: The CADS is a valid and responsive tool for assessing the psychosocial impact of chemotherapy-induced alopecia and endocrine treatment-induced alopecia in a diverse Western patient population.

Non-cardiac comorbid health outcomes and prevalence after myocardial infarction: an umbrella review.

OBJECTIVE: There exists limited comprehensive evidence on the potential association between non-cardiac comorbidities and myocardial infarction (MI). Thus, we conducted an umbrella review of existing meta-analyses to provide a broad understanding of non-cardiac health outcomes associated with MI. MATERIALS AND METHODS: The primary focus on the prevalence of related health outcomes in patients with MI was systemically searched. Each original meta-analysis that was included had its methodological quality evaluated by a Measurement Tool Assessment Systematic Reviews 2 (AMSTAR2). To evaluate the certainty in the evidence for each outcome, we employed GRADE and the Joanna Briggs Institute Prevalence Critical Appraisal Tool. The protocol was registered in PROSPERO (CRD42023458642). RESULTS: We identified seven meta-analyses comprising 126 studies with 336,581 participants from 22 countries and five continents. The pooled prevalence of comorbidities in patients with MI was 39% anxiety [95% confidence interval (CI), 30-48; GRADE, very low certainty], 29% depression (95% CI, 23-36; very low certainty), 39% frailty (95% CI, 24-55; very low certainty), and 23% failure of returning to work (95% CI, 16-29; very low certainty). The diagnosis of MI was associated with an increased risk of cognitive impairment (odds ratio, 1.45; 95% CI, 1.10-1.92; moderate certainty). Among frail patients, MI was associated with an increased risk of major bleeding (relative risk, 1.93; 95% CI, 1.08-3.45; low certainty) and mortality (relative risk, 2.29; 95% CI, 1.48-3.53; moderate certainty). However, we did not find any evidence of cancer risk associated with the development of MI. CONCLUSIONS: Our umbrella meta-analysis provided comprehensive evidence of the association between MI and several non-cardiac health conditions. The robustness of our study is attributed to the integration of evidence across several studies, thus, these insights offer valuable treatment options for policymakers and physicians to develop personalized health strategies.

Dog sperm cryopreservation using cryovials and different dilution steps.

BACKGROUND: The conventional sperm freezing method for dog sperm is with straws and includes two-step dilution and a long equilibration time. OBJECTIVE: To develop a more efficient freezing method using cryovials. MATERIALS AND METHODS: Three freezing protocols using cryovials (0.5 mL) were conducted with dog spermatozoa at 1 x 108 sperm/mL: Group 1 spermatozoa were cooled in cryovials and extender 1 (E1) and extender 2 (E1 +1 M glycerol) at 4 degree C for 50 min and then frozen over LN2 for 20 min; Group 2 sperm was cooled and frozen in cryovials with a mixture of E1 and E2 (1:1) in a deep freezer (-80 degree C) for 30 min; Group 3 sperm in cryovials and E1 were cooled at 4 degree C for 20 min, cooled for an additional 20 min after addition of E2 (E1:E2, 1:1), and then frozen using LN2/ vapour for 20 min. The control (Group 4) consisted of spermatozoa in straws being frozen using the conventional freezing method using two-step dilution. All groups were plunged and stored in LN2 after freezing and their functional performance and gene expression determined. RESULTS: Progressive motility and acrosome integrity were highest (P < 0.05) in Groups 2, 3 and 4 (only acrosome integrity). Viability in Group 3 was significantly better that in the other Groups, and the reactive oxygen species (ROS) level and phosphatidylserine (PS) translocation index were significantly lower in Group 2 than the other Groups. The expression of sperm mitochondria-associated cysteine-rich protein (SMCP) and anti-apoptotic B-cell lymphoma 2 (BCL2) genes was highest (P < 0.05) in Group 2 and the expression of pro-apoptotic Bcl2-associated X protein (BAX) was lowest (P < 0.05) in Group 4. CONCLUSION: The sperm frozen using cryovials, one step dilution and the deep freezer (Group 2) proved to be a simple and suitable cryopreservation method for dog sperm. https://doi.org/10.54680/fr24110110312.

Validation and Responsiveness of the English version of the Chemotherapy-Induced Alopecia Distress Scale (CADS) in Breast Cancer Patients.

Purpose: This study aimed to validate the chemotherapy-induced alopecia distress scale (CADS) in a diverse English-speaking population and patients with endocrine treatment- induced alopecia (EIA). Objective: Chemotherapy and endocrine therapy commonly cause alopecia in breast cancer patients, leading to significant psychological and social challenges. The CADS was developed to assess the psychosocial impact of alopecia, but its generalizability beyond Korean patients requires further investigation. Methods: Data from the CHANCE study ( NCT02530177 ), which focused on non-metastatic breast cancer, was used. The cohort included 256 patients, and CADS data were collected at baseline, six months after chemotherapy completion, or 12 months after initiating endocrine therapy. The CADS questionnaire comprised 17 items covering physical and emotional health, daily activities, and relationships. Reliability was assessed using Cronbach's alpha, and responsiveness was measured by effect size. Results: The CADS exhibited good reliability, with a Cronbach's alpha of 0.91 for the overall score, indicating acceptable internal consistency in both chemotherapy (0.89) and endocrine therapy (0.86) groups. Longitudinal responsiveness was supported by an effect size of 0.49 between decreasing satisfaction with hair growth and increasing emotional distress. Cross-sectional validity was confirmed, with effect sizes of 0.91 and 0.92 for satisfaction with hair growth and emotional and activity domains, respectively. Conclusion: The CADS is a valid and responsive tool for assessing the psychosocial impact of chemotherapy-induced alopecia and endocrine treatment-induced alopecia in a diverse Western patient population.

Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study.

BACKGROUND: Combined therapy with dabrafenib plus trametinib was approved in several countries for treatment of BRAF V600E-mutant anaplastic thyroid cancer (ATC) based on an earlier interim analysis of 23 response-assessable patients in the ATC cohort of the phase II Rare Oncology Agnostic Research (ROAR) basket study. We report an updated analysis describing the efficacy and safety of dabrafenib plus trametinib in the full ROAR ATC cohort of 36 patients with ∼4 years of additional study follow-up. PATIENTS AND METHODS: ROAR (NCT02034110) is an open-label, nonrandomized, phase II basket study evaluating dabrafenib plus trametinib in BRAF V600E-mutant rare cancers. The ATC cohort comprised 36 patients with unresectable or metastatic ATC who received dabrafenib 150 mg twice daily plus trametinib 2 mg once daily orally until disease progression, unacceptable toxicity, or death. The primary endpoint was investigator-assessed overall response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints were duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. RESULTS: At data cutoff (14 September 2020), median follow-up was 11.1 months (range, 0.9-76.6 months). The investigator-assessed ORR was 56% (95% confidence interval, 38.1% to 72.1%), including three complete responses; the 12-month DOR rate was 50%. Median PFS and OS were 6.7 and 14.5 months, respectively. The respective 12-month PFS and OS rates were 43.2% and 51.7%, and the 24-month OS rate was 31.5%. No new safety signals were identified with additional follow-up, and adverse events were consistent with the established tolerability of dabrafenib plus trametinib. CONCLUSIONS: These updated results confirm the substantial clinical benefit and manageable toxicity of dabrafenib plus trametinib in BRAF V600E-mutant ATC. Dabrafenib plus trametinib notably improved long-term survival and represents a meaningful treatment option for this rare, aggressive cancer.

The Potential Impact and Usability of the Eighth Edition TNM Staging Classification in Oral Cavity Cancer.

AIMS: In the current eighth edition head and neck TNM staging, extranodal extension (ENE) is an adverse feature in oral cavity squamous cell cancer (OSCC). The previous seventh edition N1 with ENE is now staged as N2a. Seventh edition N2+ with ENE is staged as N3b in the eighth edition. We evaluated its potential impact on patients treated with surgery and postoperative intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: OSCC patients treated with primary surgery and adjuvant (chemo)radiotherapy between January 2005 and December 2014 were reviewed. Cohorts with pathological node-negative (pN-), pathological node-positive without ENE (pN+_pENE-) and pathological node-positive with ENE (pN+_pENE+) diseases were compared for local control, regional control, distant control and overall survival. The pN+ cohorts were further stratified into seventh edition N-staging subgroups for outcomes comparison. RESULTS: In total, 478 patients were evaluated: 173 pN-; 159 pN+_pENE-; 146 pN+_pENE+. Outcomes at 5 years were: local control was identical (78%) in all cohorts (P = 0.892), whereas regional control was 91%, 80% and 68%, respectively (P < 0.001). Distant control was 97%, 87%, 68% (P < 0.001) and overall survival was 75%, 53% and 39% (P < 0.001), respectively. Overall survival for N1 and N2a subgroups was not significantly different. In the seventh edition N2b subgroup of pENE- (n = 79) and pENE+ (n = 79) cohorts, overall survival was 67% and 37%, respectively. In the seventh edition N2c subgroups, overall survival for pENE- (n = 17) and pENE+ (n = 38) cohorts was 65% and 35% (P = 0.08), respectively. Overall, an additional 128 patients (42% pN+) were upstaged as N3b. CONCLUSIONS: When eighth edition staging was applied, stage migration across the N2-3 categories resulted in expected larger separations of overall survival by stage. Patients treated with primary radiation without surgical staging should have outcomes carefully monitored. Strategies to predict ENE preoperatively and trials to improve the outcomes of pENE+ patients should be explored.

Diagnostic accuracy of the jetting sign and a dilatation ratio of left renal vein in CT urography for detecting anterior nutcracker syndrome.

AIM: To investigate the diagnostic value of computed tomography (CT) urography findings of anterior nutcracker syndrome (NCS). MATERIALS AND METHODS: The study included patients with left renal vein (LRV) compression at the aortomesenteric portion at CT urography who underwent renal venography or cystoscopy. Patients with a renocaval pressure gradient of ≥3 mmHg on renal venography or bloody urine jetting from the left ureteral orifice on cystoscopy were defined as the NCS group; the remaining patients comprised the non-NCS group. CT findings were analysed using the jetting of contrast medium flow from the LRV to the inferior vena cava (jetting sign), aortomesenteric distance, presence of collateral veins, and a dilatation ratio of LRV diameter at the aortomesenteric portion (arterial phase/delayed phases). Clinical findings, including age, gender, and body-mass-index, were also analysed. CT features and clinical findings were compared between the NCS and non-NCS groups. Diagnostic performance of CT parameters was assessed using receiver operating characteristic curve analysis. RESULTS: A total of 70 patients (21 men, mean age 44.4 ± 17.2 years) with NCS (n=13) and non-NCS (n=57) were included. Younger age (<40 years), presence of the jetting sign, and a lower dilatation ratio of LRV diameter between the arterial and delayed phases (<1.7) were found to be significant independent factors for predicting the NCS group (OR 24.5, 18.9, 19.4, respectively, p<0.05 for all). The combination of the presence of the jetting sign and a dilatation ratio of LRV diameter of <1.7 obtained the highest AUC of 0.88. CONCLUSION: The jetting sign and the dilatation ratio of LRV diameter between the arterial and delayed phases can both be very useful in the diagnosis of anterior nutcracker syndrome during CT urography.

Analysis of local invasion and regional spread in malignant sublingual gland tumour: Implications for surgical planning.

Malignant tumours arising from the sublingual glands are very rare, and the extent and frequency of local invasion or regional spread in malignant sublingual gland tumour (MSLT) has not been fully studied due to the disease rarity. To provide comprehensive features of local and regional spread of MSLT, we reviewed 20 surgical cases for detailed pathological analyses among 26 cases diagnosed as having primary MSLT. Adenoid cystic carcinoma (ACC) was the most common pathological subtype, followed by mucoepidermoid carcinoma. Disease-free and overall survivals at 5 years were 76.1 % and 77.7 %, respectively. High-grade malignant tumours and grade 2-3 ACC accounted for 41.7 % and 85.7 %. Clinical and pathological extraparenchymal extensions were found in 34.6 % and 80.0 %, respectively. Tumour invasion to the lingual nerve and submandibular gland/ductal system were also detected in 40.0 % and 28.6 %. The incidences of lingual nerve invasion in ACC and ACC ≥4 cm were 30.8 % and 42.9 %. Regional nodal involvement occurred in seven of 26 cases, and all metastatic lymph nodes were found in neck levels Ib and IIa. In summary, a significant portion of MSLT cases consisted of high-grade tumours and grade 2-3 ACC; therefore local invasion into adjacent structures should be cautiously evaluated in cases of MSLT.

Presenting stage and risk group in men dying of prostate cancer.

Introduction: Prostate cancer remains the 3rd leading cause of cancer-related mortality in Canadian men, and yet screening for prostate cancer continues to be controversial because the majority of men diagnosed with prostate cancer do not die of the disease. It also remains uncertain whether treatment of cases that can be treated with curative intent alters the mortality rate. There are very few studies describing the presenting stage, risk groups, and survival after diagnosis for men dying of prostate cancer in the literature. In this study, we explored these characteristics for all men who died of prostate cancer in British Columbia between 2013 and 2015. Methods: The population-based BC Cancer databases were used to identify all patients diagnosed between January 2013 and December 2015 who died of prostate cancer. Patient, tumour, and treatment characteristics were collected, and the risk grouping for each tumour was determined. The proportion of cases in each risk group at the time of diagnosis was determined. Survival time from diagnosis to death was calculated for all patients and for each risk group using the Kaplan-Meier method. Results: A total of 1256 patients died of prostate cancer. Of patients who presented with metastatic disease, 57.2% presented with a Gleason score of 8 or more, compared with only 35.7% of patients who presented with nonmetastatic disease (p < 0.0001). The presenting stage and risk group of those dying of prostate cancer were as follows: 32% metastatic disease, 3% regional (defined as node-positive), 39% localized high risk, 9% localized intermediate risk, 4% localized low risk, 6% localized not otherwise specified, and 7% unknown. Therefore, 80.3% of those with a known risk group presented with either localized high-risk, regional, or metastatic disease at diagnosis. The median survival times from diagnosis to death were 12 years for localized low-risk, 10 years for localized intermediate-risk, 6.5 years for localized high-risk, 4 years for regional, and 1.7 years for metastatic disease at diagnosis. Conclusions: This population-based analysis demonstrates that patients with localized high-risk, regional, or metastatic disease at diagnosis constitute the overwhelming majority of patients who die of prostate cancer in British Columbia. Unless these disease states can reliably be identified at an earlier low- or intermediate-risk localized state in the future, it is unlikely that treatment of localized low- and intermediate-risk cancer will have an impact on survival. Furthermore, patients with de novo metastatic disease had identifiable risk factors of a higher prostate-specific antigen and Gleason score. Further studies are required to confirm these results.

National health screening may reduce cardiovascular morbidity and mortality among the elderly.

OBJECTIVES: Since 2007, the Korean government has provided a free health screening to the elderly starting at the age of 66 years. The purpose of this study was to evaluate the association between this general health screening and the incidences of stroke and myocardial infarction and mortality. STUDY DESIGN: The study design used in this study is a retrospective cohort study. METHODS: The study was conducted using the universe of insurance claims data of Korea and followed a cohort of individuals aged 66 years in 2009 from 2006 through 2016 (n = 354,194). We assessed the association between receipt of the national health screening and health outcomes using propensity matching and Cox proportional hazard models. RESULTS: We found that the receipt of the national health screening was associated with a reduction in negative health outcomes. The hazard ratio for stroke was 0.89 (P < 0.001), 0.88 (P < 0.001) for myocardial infarction and 0.58 for death (P < 0.001). CONCLUSION: Korea's national health screening was associated with reductions in cardiovascular morbidity and mortality in the elderly.

Phase I trial of alpelisib in combination with concurrent cisplatin-based chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck.

BACKGROUND: Deregulation of the PI3K signalling pathway is frequent in squamous cell carcinoma of the head and neck (SCCHN) and may be implicated in radioresistance. We report on the results from a phase I 3 + 3 dose escalation study of alpelisib, a class I α-specific PI3K inhibitor in combination with concurrent cisplatin-based chemoradiation (CRT) in patients with locoregionally advanced SCCHN (LA-SCCHN). METHODS: Eligible patients had previously untreated LA-SCCHN and were candidates for CRT. The primary objective was to evaluate safety and determine the recommended phase II dose (RP2D). Alpelisib was given orally once daily at two dose levels: 200 mg and 250 mg. CRT consisted of cisplatin 100 mg/m2 IV every three weeks and standard fractionation radiotherapy (IMRT) 70 Gy in 35 fractions. RESULTS: Nine patients were enrolled (six alpelisib 200 mg, three 250 mg). Oropharynx was the primary site in all patients (seven p16-positive; five T1-2N2M0, four T3-4N2-3M0 [AJCC 7th edition]). All patients completed CRT within seven weeks. Grade 3 alpelisib-related toxicities occurred in four patients. No dose-limiting toxicity (DLT) was observed at 200 mg among three DLT-evaluable patients. Two of two DLT-evaluable patients treated at 250 mg experienced DLTs (inability to complete ≥75% alpelisib secondary to radiation dermatitis and febrile neutropenia). Thus, RP2D was declared at 200 mg. After median follow-up of 39.7 months, two patients developed pulmonary metastases despite locoregional control. Three-year overall survival was 77.8% (95% CI 36.5%-93.9%). CONCLUSION: Alpelisib at 200 mg has a manageable safety profile in combination with cisplatin-based CRT in LA-SCCHN.

Robot-assisted orthotopic "W" ileal neobladder in male patients: step-by-step video-illustrated technique and preliminary outcomes.

The objective was to describe our step-by-step technique for robot-assisted orthotopic "W" ileal neobladder (INB) for urinary diversion following radical cystectomy for oncological purpose, and to report the outcomes of this technique for the first six male patients treated at our center. Patients underwent robot-assisted radical cystoprostatectomy for bladder cancer and had a "W" ileal neaobladder as urinary diversion. Our surgical technique is described step by step and video illustrated. Patients and operative data were collected and reported. The Expanded Prostate Cancer Index Composite Short Form (EPIC-26) self-administered questionnaire was used to assess the urinary, sexual and bowel functions outcomes at 90 days postoperatively. The mean operative time was 475 min [420-525] and mean length of stay was 13 days [11-15]. No major complications occurred (Clavien grade ≥ 3). Regarding the continence four patients reported they leaked urine rarely or never and two patients having urine leak once a day. Two patients did not wear any pad, the four others reported using pad at night. Two patients reported urinary function as not a problem, one as a very small problem, two as a small problem and one as a moderate problem. These results from our six first cases using the technique described here are promising with interesting early functional outcomes. This has to be confirmed on larger cohort and with long-term follow-up.

The effect of low body mass index on the development of chronic obstructive pulmonary disease and mortality.

BACKGROUND: Sarcopenia may worsen disease progression and lead to poor outcomes in chronic obstructive pulmonary disease (COPD). OBJECTIVES: We aimed to determine the effect of BMI on the development of COPD and mortality. METHODS: We enrolled 437 584 participants registered in the physical health check-up cohort database of the Korean National Health Interview Survey from 2002 to 2003, and we defined COPD diagnosis based on the ICD-10 code and prescribed medication. BMI (kg m-2 ) classified them to five groups (low BMI < 18.5, normal BMI 18.5-23, overweight 23-25, obesity 25-30, severe obesity ≥30) at baseline. RESULTS: Participants in the low BMI group had a significantly higher rate of COPD development for 13 years (7.6%) than those in other groups (3.4-4.1%, P < 0.0001). Amongst never or light smokers, COPD development in the low BMI group (5.6-6.7%) was significantly higher than that in other groups (2.8-4.7%). Similarly, amongst participants with a smoking history of ≥30 years, COPD development in the low BMI group (20.1%) was higher than those in other groups (8.4-12.4%). On multivariable analysis, normal or higher than normal body weight was significantly protective against the development of COPD (hazard ratio [HR], 0.609-0.739,) compared to low BMI. COPD-free-survival (HR, 0.491-0.622) and overall survival (HR, 0.440-0.585) were also better in them compared to those with low BMI (all P < 0.0001). CONCLUSIONS: Low BMI is an important risk factor for COPD development and mortality. Maintaining adequate body weight may reduce the risk for COPD development and mortality.

The impact of social media on citation rates in coloproctology.

AIM: This study aimed to investigate the association between Twitter exposure and the number of citations for coloproctology articles. METHOD: Original articles from journals using Twitter between June 2015 and May 2016 were evaluated for the following characteristics: publishing journal; article subject; study design; nationality, speciality and affiliation of the author(s); and reference on Twitter. Citation data for these articles were retrieved from Google Scholar (https://scholar.google.com) in January 2018. We performed a univariate analysis using these data followed by a multivariate, logistic regression analysis to search for factors associated with a high citation level, which was defined as accrual of more than five citations. RESULTS: Out of six coloproctology journals listed on the InCites JCR database, three (Diseases of the Colon & Rectum, Colorectal Disease and Techniques in Coloproctology) used Twitter, where 200 (49.5%) out of a total of 404 articles had been featured. Citation rates of articles that featured on Twitter were significantly higher than those that did not (11.4 ± 9.2 vs 4.1 ± 3.1, P < 0.001). In multivariate analysis, Twitter exposure (OR 8.6, P = 0.001), European Union nationality (OR 2.4, P = 0.004), Colorectal Disease journal (OR 3.3, P = 0.005) and systematic review articles (OR 3.4, P = 0.009) were associated with higher citation levels. CONCLUSION: Article exposure on Twitter was strongly associated with a high citation level. Medical communities should encourage journals as well as physicians to actively utilize social media to expedite the spread of new ideas and ultimately benefit medical society as a whole.

Cardiorespiratory fitness is impaired and predicts mid-term postoperative survival in patients with abdominal aortic aneurysm disease.

NEW FINDINGS: What is the central question of this study? To what extent cardiorespiratory fitness is impaired in patients with abdominal aortic aneurysmal (AAA) disease and corresponding implications for postoperative survival requires further investigation. What is the main finding and its importance? Cardiorespiratory fitness is impaired in patients with AAA disease. Patients with peak oxygen uptake of <13.1 ml O2  kg-1  min-1 and ventilatory equivalent for carbon dioxide at anaerobic threshold ≥34 are associated with increased risk of postoperative mortality at 2 years. These findings demonstrate that cardiorespiratory fitness can predict mid-term postoperative survival in AAA patients, which may help to direct care provision. ABSTRACT: Preoperative cardiopulmonary exercise testing is a standard assessment of cardiorespiratory fitness (CRF) and risk stratification. However, to what extent CRF is impaired in patients undergoing surgical repair of abdominal aortic aneurysm (AAA) disease and the corresponding implications for postoperative outcome requires further investigation. We measured CRF during an incremental exercise test to exhaustion using online respiratory gas analysis in patients with AAA disease (n = 124, aged 72 ± 7 years) and healthy sedentary control subjects (n = 104, aged 70 ± 7 years). Postoperative survival was examined for association with CRF, and threshold values were calculated for independent predictors of mortality. Patients who underwent preoperative cardiopulmonary exercise testing before surgical repair had lower CRF [age-adjusted mean difference of 12.5 ml O2  kg-1  min-1 for peak oxygen uptake ( V ̇ O 2 peak ), P < 0.001 versus control subjects]. After multivariable analysis, both V ̇ O 2 peak and the ventilatory equivalent for carbon dioxide at anaerobic threshold ( V ̇ E / V ̇ C O 2 - AT ) were independent predictors of mid-term postoperative survival (2 years). Hazard ratios of 5.27 (95% confidence interval 1.62-17.14, P = 0.006) and 3.26 (95% confidence interval 1.00-10.59, P = 0.049) were observed for V ̇ O 2 peak  < 13.1 ml O2  kg-1  min-1 and V ̇ E / V ̇ C O 2 - AT ≥ 34, respectively. Thus, CRF is lower in patients with AAA, and those with a V ̇ O 2 peak  < 13.1 ml O2  kg-1  min-1 and V ̇ E / V ̇ C O 2 - AT ≥ 34 are associated with a markedly increased risk of postoperative mortality. Collectively, our findings demonstrate that CRF can predict mid-term postoperative survival in AAA patients, which may help to direct care provision.

Letermovir for prophylaxis of cytomegalovirus in allogeneic hematopoietic stem cell recipients.

Letermovir is a new antiviral agent with activity against human cytomegalovirus (CMV). Letermovir works as an inhibitor of the CMV DNA terminase complex which further inhibits viral DNA processing and packaging. Letermovir is available both orally and intravenously in 480-mg and 240-mg dosage forms, and is approved for use in the prophylaxis of CMV infection and disease in CMV-seropositive recipients of allogeneic hematopoietic stem cell transplant (HSCT) over the age of 18. The recommended dose is 480 mg p.o./i.v. once daily initiated between day 0 through day 28 post-allogeneic HSCT and continued through day 100 post-transplantation; the dose should be reduced to 240 mg daily if coadministered with cyclosporine. Letermovir is metabolized primarily by hepatic OATP1B1/3 and is not recommended for patients with severe hepatic impairment (Child-Pugh class C). Renal dosage adjustments are not warranted until a creatinine clearance (CrCl) of less than 10 mL/min; however, serum creatinine should be monitored when administered to patients with a CrCl of less than 50 mL/min. Cross-resistance with other useful antiviral agents in the treatment of CMV has not been observed. Additionally, letermovir is active against DNA polymerase inhibitor-resistant viral strains. Letermovir has shown promising clinical efficacy and is generally well tolerated, thus providing a favorable new option in the prophylaxis of CMV infection and disease.

Return of the tetracyclines: omadacycline, a novel aminomethylcycline antimicrobial.

Omadacycline is a novel aminomethylcycline antimicrobial agent that is available in both oral and intravenous formulations. The distinguishing structural characteristics of omadacycline from other tetracyclines allow for its continued antimicrobial activity in the presence of traditional tetracycline resistance mechanisms (efflux pumps and ribosomal protection proteins). Omadacycline has been found to have potent activity against antibiotic-resistant pathogens including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, extended spectrum beta-lactamase-producing Escherichia coli and multidrug-resistant Streptococcus pneumoniae. Currently available data indicate that omadacycline is generally well tolerated with the most common adverse effects being gastrointestinal symptoms. Omadacycline seems to be a promising new agent for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections. Studies for the treatment of cystitis in adult females are currently underway, and future results of these studies will further help delineate the antibacterial role of omadacycline.

Analysis of efficacy and safety of core-needle biopsy versus fine-needle aspiration cytology in patients with cervical lymphadenopathy and salivary gland tumour.

In this study, we compared the diagnostic accuracy and safety of fine-needle aspiration cytology and core-needle biopsy in patients with cervical lymphadenopathy or salivary gland tumour, and provided a basis for selecting the appropriate diagnostic method in clinical situations. A total of 278 patients were included in this study. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 66.7% and 100%, respectively, and negative predictive values were 92.6% and 100%, respectively, for diagnosing malignancy. In diagnosing lymphoma, fine-needle aspiration cytology gave false-negative results in all patients. In diagnosing tuberculous lymphadenopathy, the sensitivities of fine-needle aspiration cytology and core-needle biopsy were 33.3% and 91.15%, respectively, and the negative predictive values were 90.0% and 95.1%, respectively. The sensitivities of fine-needle aspiration cytology and core-needle biopsy were 42.9% and 100% in diagnosing malignant salivary gland tumours, and the negative predictive values were 91% and 100%, respectively. The results of this study showed that core-needle biopsy was superior in diagnosing and distinguishing critical diseases such as malignant lymphadenopathy and tuberculosis in patients with cervical lymphadenopathy and salivary gland tumour.

Src-type tyrosine kinase p56lck is critical for thymic stromal lymphopoietin-induced allergic rhinitis.

BACKGROUND: Thymic stromal lymphopoietin (TSLP) is a regulator of mast cell-mediated allergic inflammatory reactions, but the manner in which TSLP contributes to allergic rhinitis (AR) remains unclear. OBJECTIVE: Here, we sought to determine that TSLP plays a crucial role in AR by interacting with Src-type tyrosine kinase p56lck and STAT6 and promoting mast cells degranulation. METHODS: The effects of TSLP on mast cell degranulation and AR were analysed in human mast cell line (HMC-1 cells), ovalbumin (OVA)-induced AR animal model, and human subjects. Small interfering RNA experiments were performed in HMC-1 cells and OVA-induced AR model. Immune responses were analysed by enzyme-linked immunosorbent assay, Western blotting, immunoprecipitation, and histological studies. RESULTS: Thymic stromal lymphopoietin levels and mast cell-derived p56lck activation were elevated in human subjects with AR, and in AR mice, exogenous TSLP accelerated TH2-allergic inflammatory reactions by up-regulating p56lck and STAT6. On the other hand, depletion of TSLP, p56lck, and STAT6 ameliorated clinical symptoms in AR mice. The selective inhibitor of p56lck, damnacanthal, inhibits AR reactions. CONCLUSION: Collectively, these observations suggest a role for TSLP/p56lck/STAT6 in AR and offer insight into potential therapeutic strategies.

Insulin Resistance is Associated with Chronic Laryngitis in Korean Women.

OBJECTIVES: The aim of this study was to investigate the association between chronic laryngitis (CL) and insulin resistance (IR) in South Korea using data from the 2010 Korea National Health and Nutrition Examination Surveys (KNHANES). DESIGN, SETTING AND PARTICIPANTS: Cross-sectional data of 4,261 adults who completed KNHANES were analyzed. CL was considered when participants experienced a voice change and demonstrated flexible laryngoscopic findings of diffuse laryngeal inflammation. All participants were assessed for IR using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Among the Korean population older than 19 years, the prevalence of chronic laryngitis was 3.8±0.7%. Univariate analysis demonstrated that CL was significantly associated with smoking and systolic and diastolic blood pressure in men and with age, diastolic blood pressure, HDL cholesterol, insulin, and HOMA-IR in women. Multiple regression analysis demonstrated that the mean value of HOMA-IR was significantly associated with CL in women only. In addition, CL was more prevalent in the highest compared with the lowest HOMA-IR quartile (OR [95% CI]: 2.268 [1.053-4.884] after adjusting for age, OR [95% CI]: 2.235 [1.040-6.181] after adjusting for confounding factors of age, body mass index, smoking status, alcohol intake, regular exercise, education, and income). CONCLUSIONS: These findings indicate that IR characterized by HOMA-IR is significantly associated with CL in Korean women only. Our results suggest that HOMA-IR could be an early predictive factor of increased risk of CL in Korean women.