Treatment of male breast cancer: meta-analysis of real-world evidence.

BACKGROUND: Breast cancer is rare in men and managed by extrapolating from breast cancer in women. The clinicopathological features of male breast cancer, however, differ from those of female breast cancer. Because clinical trials are rare, the synthesis of real-world data is one method of integrating sufficient evidence on the optimal treatment for this patient population. METHODS: PubMed, Embase, and Cochrane Library databases were searched. Clinical studies were included if they evaluated the treatments of interest in male breast cancer; these evaluations included breast-conserving surgery (BCS) versus mastectomy, postmastectomy radiation therapy versus no radiation, the accuracy of sentinel lymph node biopsy (SLNB), and a comparison of various endocrine therapies. RESULTS: Forty studies were retrieved. The pooled estimate of overall survival (OS) revealed no difference between BCS and mastectomy groups. Postmastectomy radiation to the chest wall significantly increased OS relative to no postmastectomy radiation (hazard ratio (HR) 0.67, 95 per cent confidence interval 0.54 to 0.84). The pooled estimates of identification and false-negative rates of SLNB were 97.4 and 7.4 per cent respectively. Tamoxifen treatment was associated with significantly increased OS compared with no tamoxifen intake (HR 0.62, 0.41 to 0.95). CONCLUSION: Identification and false-negative rates for SLNB were comparable to those in female breast cancer. Breast-conserving surgery can be effective and safe; postmastectomy radiation to the chest wall and 5-year tamoxifen treatment improves survival.

Efficacy and safety of high-dose vs low-dose leucovorin in patients with colorectal cancer: systematic review and meta-analysis.

AIM: The clinical benefits of a combination of leucovorin and fluorouracil have been established in the treatment of colorectal cancer. Due to a leucovorin shortage in 2008, many institutions revised their protocols to reduce the dose of leucovorin. After the shortage was resolved, some hospitals still maintained their modified protocols. Thus, we conducted a systematic review to evaluate the efficacy and safety of low- vs high-dose leucovorin in the treatment of colorectal cancer. METHOD: The PubMed, Embase and Cochrane databases were searched for studies published before May 2019. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcomes were median survival time and tumour response rate. Secondary outcomes were haematological and nonhaematological toxicities. RESULTS: Eight randomized controlled trials and four retrospective studies were reviewed. The pooled median survival time was similar between the two dose levels (standard mean difference -0.06, 95% CI -0.19 to 0.08). The pooled tumour response rate was comparatively higher in the high-dose leucovorin regimen (OR 0.81; 95% CI 0.55-1.18). No statistically significant difference was found between the haematological and nonhaematological toxicities of the two groups. However, there were fewer diarrhoea events in the low-dose leucovorin regimen. CONCLUSION: Low-dose leucovorin regimens seemed feasible approaches for colorectal cancer treatment when the shortage happened, because both regimens manifested comparable outcomes in survival time and tumour response rate.

Consensus statements on the clinical usage and characteristics of aripiprazole for Hong Kong.

Aripiprazole, a dopamine partial agonist, is a second-generation anti-psychotic that is widely used for the treatment of schizophrenia and other psychotic disorders. A group of psychiatric experts in Hong Kong developed a set of consensus statements, aiming to facilitate the understanding of clinical properties and usages of aripiprazole among local physicians. Of note, because aripiprazole long-acting injectable has been available locally not long before the establishment of the consensus panel, which limited the discussion on its use in the local context, the consensus statements were focused primarily on oral aripiprazole. To draft the consensus statements, the panellists discussed the published evidence and their clinical experience regarding aripiprazole in a series of meetings based on several areas. At the final meeting, each drafted statement was voted on anonymously by all panellists based on its practicability of recommendation in Hong Kong. A set of consensus statements on the characteristics and clinical use of aripiprazole was established and accepted by the panel. These statements serve to provide a practical reference for physicians in Hong Kong, and possibly other parts of the Asia-Pacific region, on the use of aripiprazole in people with schizophrenia spectrum disorders and other psychotic problems.

A study of human neutrophil antigen genotype frequencies in Hong Kong.

BACKGROUND: Alloantibodies against human neutrophil antigens (HNA) are associated with a variety of clinical conditions. Over the past decade, the allelic and genotypic frequencies of the five HNA systems have been evaluated. Although the HNA system is less polymorphic than human leukocyte antigens (HLA), significant differences in the genotypic and allele frequencies still exist in different populations, even those living in close proximity. OBJECTIVES: To delineate HNA genotypic and allele frequencies to provide vital information on estimating the risk of HNA-associated diseases for our local population. METHODS: Using a validated, in-house-developed assay, genotyping for HNA-1, HNA-3, HLA-4 and HNA-5 was performed on 300 samples from Chinese blood donors from Hong Kong. In addition, the frequency of the HNA-2 c.843A > T allele was also determined. RESULTS: The allele frequencies of HNA-1a, -1b and -1c alleles were 67·8, 31·5 and 0%, respectively, whereas the frequencies of HNA-3a and HNA-3b were 71·0 and 29·0%, respectively. The frequencies of HNA-4a and -4b alleles were 99·5 and 0·5%, respectively, and for HNA-5a and -5b, alleles were 85·2 and 14·8%, respectively. Homozygotes for the HNA-2 c.843 TT variant were absent in our population, whereas only <4% of the population were c.843AT heterozygote carriers. CONCLUSIONS: This is the first study to define HNA genotype and allele frequencies using a validated modified in-house PCR-SSP method in the Hong Kong Chinese blood donor population. Our approach provides a cost-effective assay for conducting routine HNA typing and facilitates the incorporation of these assays into routine clinical service. Our results are comparable with those reported in the Guangzhou Chinese population, but the allele frequencies in our Hong Kong Chinese population are significantly different from the reported European frequencies, confirming that a geographical difference exists for HNA allele frequencies.

Diabetes in older people: position statement of The Hong Kong Geriatrics Society and the Hong Kong Society of Endocrinology, Metabolism and Reproduction.

Following a survey on the clinical practice of geriatricians in the management of older people with diabetes and a study of hypoglycaemia in diabetic patients, a round-table discussion with geriatricians and endocrinologists was held in January 2015. Consensus was reached for six domains specifically related to older diabetic people: (1) the considerations when setting an individualised diabetic management; (2) inclusion of geriatric syndrome screening in assessment; (3) glycaemic and blood pressure targets; (4) pharmacotherapy; (5) restrictive diabetic diet; and (6) management goals for nursing home residents.

The importance of the Pseudomonas aeruginosa type III secretion system in epithelium traversal depends upon conditions of host susceptibility.

Pseudomonas aeruginosa is invasive or cytotoxic to host cells, depending on the type III secretion system (T3SS) effectors encoded. While the T3SS is known to be involved in disease in vivo, how it participates remains to be clarified. Here, mouse models of superficial epithelial injury (tissue paper blotting with EGTA treatment) and immunocompromise (MyD88 deficiency) were used to study the contribution of the T3SS transcriptional activator ExsA to epithelial traversal. Corneas of excised eyeballs were inoculated with green fluorescent protein (GFP)-expressing PAO1 or isogenic exsA mutants for 6 h ex vivo before bacterial traversal and epithelial thickness were quantified by using imaging. In the blotting-EGTA model, exsA mutants were defective in capacity for traversal. Accordingly, an ∼16-fold variability in exsA expression among PAO1 isolates from three sources correlated with epithelial loss. In contrast, MyD88-/- epithelia remained susceptible to P. aeruginosa traversal despite exsA mutation. Epithelial lysates from MyD88-/- mice had reduced antimicrobial activity compared to those from wild-type mice with and without prior antigen challenge, particularly 30- to 100-kDa fractions, for which mass spectrometry revealed multiple differences, including (i) lower baseline levels of histones, tubulin, and lumican and (ii) reduced glutathione S-transferase, annexin, and dermatopontin, after antigen challenge. Thus, the importance of ExsA in epithelial traversal by invasive P. aeruginosa depends on the compromise enabling susceptibility, suggesting that strategies for preventing infection will need to extend beyond targeting the T3SS. The data also highlight the importance of mimicking conditions allowing susceptibility in animal models and the need to monitor variability among bacterial isolates from different sources, even for the same strain.

Effect of daily short-duration weight-bearing on disuse-induced deterioration of musculoskeletal system.

OBJECTIVES: To investigate deterioration of musculoskeletal system due to prolonged disuse and the potential of daily short-duration weight-bearing as countermeasures. METHODS: Twenty-four adult male Sprague-Dawley rats were divided into Control Group (CG, no intervention), Tail-suspension Group (TG, tail-suspension without treatment), and Weight-Bearing Group (WBG, tail-suspension with 20 min/day, 5 days/week body weight loading). After four weeks of treatment, femur and tibia, soleus and extensor digitorum longus were evaluated for bone and muscle quality respectively. Tensile properties of bone-tendon insertion (BTI) were evaluated using patella-patellar tendon complex. RESULTS: Disuse induced deterioration on bone, muscle, and BTI after four weeks. Compared with CG, TG and WBG showed significant decrease in bone mineral density (BMD) of trabecular bone in distal femur (4.3-15.2%), muscle mass (31.3-52.3%), muscle cross-sectional area (29.1-35%), and failure strength of BTI (23.9-29.4%). Tensile test showed that the failure mode was avulsion of bone at the BTI. No significant difference was detected between TG and WBG for all assessments on bone, muscle, and BTI. CONCLUSIONS: Disuse caused deterioration of bone, muscle, and BTI while daily short-duration of weight-bearing did not prevent this deterioration. Mechanical stimulation with higher intensity and longer duration may be necessary to prevent musculoskeletal deterioration resulted from prolonged disuse.

Pseudomonas aeruginosa Survival at Posterior Contact Lens Surfaces after Daily Wear.

PURPOSE: Pseudomonas aeruginosa keratitis is a sight-threatening complication of contact lens wear, yet mechanisms by which lenses predispose to infection remain unclear. Here, we tested the hypothesis that tear fluid at the posterior contact lens surface can lose antimicrobial activity over time during lens wear. METHODS: Daily disposable lenses were worn for 1, 2, 4, 6, or 8 hours immediately after removal from their packaging or after presoaking in sterile saline for 2 days to remove packaging solution. Unworn lenses were also tested, some coated in tears "aged" in vitro for 1 or 8 hours. Lenses were placed anterior surface down into tryptic soy agar cradles containing gentamicin (100 µg/mL) to kill bacteria already on the lens and posterior surfaces inoculated with gentamicin-resistant P. aeruginosa for 3 hours. Surviving bacteria were enumerated by viable counts of lens homogenates. RESULTS: Posterior surfaces of lenses worn by patients for 8 hours supported more P. aeruginosa growth than lenses worn for only 1 hour, if lenses were presoaked before wear (∼ 2.4-fold, p = 0.01). This increase was offset if lenses were not presoaked to remove packaging solution (p = 0.04 at 2 and 4 hours). Irrespective of presoaking, lenses worn for 8 hours showed more growth on their posterior surface than unworn lenses coated with tear fluid that was aged for 8 hours in vitro (∼ 8.6-fold, presoaked, p = 0.003; ∼ 5.4-fold from packaging solution, p = 0.004). Indeed, in vitro incubation did not impact tear antimicrobial activity. CONCLUSIONS: This study shows that postlens tear fluid can lose antimicrobial activity over time during contact lens wear, supporting the idea that efficient tear exchange under a lens is critical for homeostasis. Additional studies are needed to determine applicability to other lens types, wearing modalities, and relevance to contact lens-related infections.

Acute appendicitis complicating Amyand's hernia: imaging features and literature review.

Acute appendicitis complicating Amyand's hernia is an extremely rare condition, in which the appendix herniates into the inguinal sac and, subsequently, gets inflamed. The condition is difficult to diagnose clinically. Imaging is valuable for its diagnosis and detection of the associated complications. In this article, we will discuss the imaging features of acute appendicitis complicating Amyand's hernia and the results of a literature review on the condition.

The optimal duration of compression therapy following varicose vein surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: The optimal duration of compression therapy following varicose vein surgery of the great saphenous vein (GSV) remains controversial. Therefore, the aim of this study was to evaluate different durations of compression therapy after varicose vein surgery and their outcomes. DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: Outcomes from short-duration (3-10 d) and long-duration (3-6 wk) compression therapy after GSV stripping and phlebectomies were evaluated. Pain was assessed post surgery using a visual analog scale. Secondary outcomes included leg volume, complications, and the duration of absenteeism from work. RESULTS: We identified 4 RCTs published between 1991 and 2009 that evaluated 686 patients. We observed non-significant differences in postoperative pain scores between the long-duration and short-duration groups, with a weighted mean difference of -0.03 (95% confidence interval (CI): -0.53 to 0.47) at 4 weeks, and -0.01 (95% CI: -0.31 to 0.33) at 6 weeks, postoperatively. We also observed non-significant differences in the incidence of postoperative complications (risk ratio: 0.84, 95% CI: 0.60-1.18), and changes in leg volume, 4 weeks postoperatively (P = .18) between the groups. CONCLUSION: Our study results indicate that there are no benefits to long-term compression therapy after varicose vein surgery of the GSV regarding postoperative pain, leg volume, incidence of complications, and duration of absenteeism from work.

Development and validation of perceived rehabilitation require questionnaires for caregivers of people with schizophrenia.

OBJECTIVE: This study aimed at developing and validating the Perceived Rehabilitation Needs Questionnaires for Caregivers (PRNQ-Cs) of people with schizophrenia. METHODS: The items of PRNQ-C were generated based on focus group discussion and literature review. A validation study was conducted to examine its psychometric properties among 98 caregivers who were recruited via convenience sampling. RESULTS: Through the use of direct oblique rotation, exploratory factor analysis yielded an eight-factor solution which accounted for 64.39% of the total variance. Its internal consistency and test-retest reliability were satisfactory. CONCLUSION: Through cross-cultural validation, the PRNQ-C is applicable in other Chinese communities with huge population of schizophrenia.

Resistive vibration exercise retards bone loss in weight-bearing skeletons during 60 days bed rest.

UNLABELLED: Countermeasures are desirable to retard bone loss during long-term space flight. We evaluated the effect of an intervention protocol on bed rest-induced bone loss. INTRODUCTION: We developed a resistive vibration exercise (RVE) platform to test if an intervention RVE protocol would be effective to protect bed rest-induced bone loss. METHODS: Fourteen male subjects were assigned randomly to either the RVE group (n = 7) that performed daily supervised resistive vibration exercise or to the no any exercise control (CON) group (n = 7). Both dual-energy X-ray absorptiometry and peripheral quantitative computed tomography were used to monitor changes in bone mineral density. RESULTS: RVE significantly prevented bone loss at multiple skeletal sites, including calcaneus, distal tibia, hip, and lumbar spine (L2-L4). The ratio of urinary calcium and creatinine was found higher after starting bed rest in CON group while no significant changes were observed in RVE group. No significant temporal change was found for osteocalcin-N during and after bed rest in CON group. However, a significant increase was shown after bed rest in RVE group. In both groups, the urinary concentration of bone resorption markers, such as C-telopeptide of type I collagen (CTX-I) and deoxypyridinoline (DPD), were significantly elevated after bed rest. In the CON group, no significant temporal effect was found for hydroxyproline (HOP), CTX-I, and DPD during bed rest and the serum concentration of HOP and TGF-ß significantly increased about 52.04% and 24.03%, respectively only after bed rest. However, all these markers tended to decrease in the RVE group. CONCLUSIONS: Our results might imply that the intervention of RVE retarded bone loss induced by simulated microgravity in humans that was mainly attributed to its anabolic effects.

Development, reliability, and validity of the Posttraumatic Stress Disorder Interview for Vietnamese refugees: a diagnostic instrument for Vietnamese refugees.

The Posttraumatic Stress Disorder Interview for Vietnamese Refugees (PTSD-IVR) was created specifically to assess for the presence of current and lifetime history of premigration, migration, encampment, and postmigration traumas in Vietnamese refugees. The purpose of the present study was to describe the development of and investigate the interrater and test-retest reliability of the PTSD-IVR and its validity in relation to the diagnoses obtained from the Longitudinal, Expert, and All Data (LEAD; Spitzer, 1983) standard. Clinicians conducted the diagnosis process with 127 Vietnamese refugees using the LEAD standard and the PTSD-IVR. Assessment of the reliability and validity of the PTSD-IVR yielded good to excellent AUC (area under the receiver operating characteristic curve; .86, .87) and κ values (.66, .74) indicating the reliability of the PTSD-IVR and the agreement between the LEAD procedure and the PTSD-IVR. The results of the present study suggest that the PTSD-IVR performs successfully as a diagnostic instrument specifically created for Vietnamese refugees in their native language.

[Ultraviolet Mie lidar observations of aerosol extinction in a dust storm case over Macao].

Atmospheric aerosol over Macao was monitored by using a 355 nm Mie scattering lidar during the dust event on March 22nd, 2010. Vertical profiles of aerosol extinction coefficients were obtained and correlated with local PM10 concentration. The near-surface aerosol extinction coefficients have good agreement with PM10 concentration values. The aerosol extinction vertical profiles showed that there were distinct layers of dust aerosol concentration. The source and tracks of dust aerosol were analyzed by back-trajectory simulation. Observations showed that this lidar could run well even in dust storm episode, and it would help to further the study on aerosol properties over Macao.

Phosphoregulation of DSB-1 mediates control of meiotic double-strand break activity.

In the first meiotic cell division, proper segregation of chromosomes in most organisms depends on chiasmata, exchanges of continuity between homologous chromosomes that originate from the repair of programmed double-strand breaks (DSBs) catalyzed by the Spo11 endonuclease. Since DSBs can lead to irreparable damage in germ cells, while chromosomes lacking DSBs also lack chiasmata, the number of DSBs must be carefully regulated to be neither too high nor too low. Here, we show that in Caenorhabditis elegans, meiotic DSB levels are controlled by the phosphoregulation of DSB-1, a homolog of the yeast Spo11 cofactor Rec114, by the opposing activities of PP4PPH-4.1 phosphatase and ATRATL-1 kinase. Increased DSB-1 phosphorylation in pph-4.1 mutants correlates with reduction in DSB formation, while prevention of DSB-1 phosphorylation drastically increases the number of meiotic DSBs both in pph-4.1 mutants and in the wild-type background. C. elegans and its close relatives also possess a diverged paralog of DSB-1, called DSB-2, and loss of dsb-2 is known to reduce DSB formation in oocytes with increasing age. We show that the proportion of the phosphorylated, and thus inactivated, form of DSB-1 increases with age and upon loss of DSB-2, while non-phosphorylatable DSB-1 rescues the age-dependent decrease in DSBs in dsb-2 mutants. These results suggest that DSB-2 evolved in part to compensate for the inactivation of DSB-1 through phosphorylation, to maintain levels of DSBs in older animals. Our work shows that PP4PPH-4.1, ATRATL-1, and DSB-2 act in concert with DSB-1 to promote optimal DSB levels throughout the reproductive lifespan.

Synthesis and self-assembly of stimuli-responsive poly(2-(dimethylamino) ethyl methacrylate)-block-fullerene (PDMAEMA-b-C60) and the demicellization induced by free PDMAEMA chains.

Well-defined poly(2-(dimethylamino) ethyl methacrylate)-block-fullerene [60] ((PDMAEMA)-b-C(60)) with a galactose targeting moiety was prepared by atom-transfer radical polymerization (ATRP). This copolymer was designed for possible use as a targeted drug carrier. The chemical composition and the self-assembly behavior were characterized using different techniques, including GPC, NMR, UV, and DLS. The self-assembly of the galactose-functionalized PDMAEMA-b-C(60) structure in aqueous solutions was investigated using dynamic light scattering (DLS) under different pH conditions. At pH 3 and 10, the DLS results showed the presence of both polymeric micelles and unimers. However, a smaller R(h) was observed at pH 10 than at pH 3 because of electrostatic repulsion at low pH values. In addition, free PDMAEMA chains induced the demicellization of self-assembled nanostructures caused by the formation of a charge-transfer complex between PDMAEMA and C(60.) This phenomenon offers possible applications for free-polymer-triggered drug release.

Heart rate variability (HRV) and posttraumatic stress disorder (PTSD): a pilot study.

Exposure to combat experiences is associated with increased risk of developing Post Traumatic Stress Disorder. Prolonged exposure therapy and cognitive processing therapy have garnered a significant amount of empirical support for PTSD treatment; however, they are not universally effective with some patients continuing to struggle with residual PTSD symptoms. Heart rate variability (HRV) is a measure of the autonomic nervous system functioning and reflects an individual's ability to adaptively cope with stress. A pilot study was undertaken to determine if veterans with PTSD (as measured by the Clinician-Administered PTSD Scale and the PTSD Checklist) would show significantly different HRV prior to an intervention at baseline compared to controls; specifically, to determine whether the HRV among veterans with PTSD is more depressed than that among veterans without PTSD. The study also aimed at assessing the feasibility, acceptability, and potential efficacy of providing HRV biofeedback as a treatment for PTSD. The findings suggest that implementing an HRV biofeedback as a treatment for PTSD is effective, feasible, and acceptable for veterans. Veterans with combat-related PTSD displayed significantly depressed HRV as compared to subjects without PTSD. When the veterans with PTSD were randomly assigned to receive either HRV biofeedback plus treatment as usual (TAU) or just TAU, the results indicated that HRV biofeedback significantly increased the HRV while reducing symptoms of PTSD. However, the TAU had no significant effect on either HRV or symptom reduction. A larger randomized control trial to validate these findings appears warranted.

Neutrophils exposed to A. phagocytophilum under shear stress fail to fully activate, polarize, and transmigrate across inflamed endothelium.

Anaplasma phagocytophilum is an obligate intracellular bacterium that has evolved mechanisms to hijack polymorphonuclear neutrophil (PMN) receptors and signaling pathways to bind, infect, and multiply within the host cell. E-selectin is upregulated during inflammation and is a requisite endothelial receptor that supports PMN capture, rolling, and activation of integrin-mediated arrest. Ligands expressed by PMN that mediate binding to endothelium via E-selectin include sialyl Lewis x (sLe(x))-expressing ligands such as P-selectin glycoprotein ligand-1 (PSGL-1) and other glycolipids and glycoproteins. As A. phagocytophilum is capable of binding to sLe(x)-expressing ligands expressed on PMN, we hypothesized that acute bacterial adhesion to PMN would subsequently attenuate PMN recruitment during inflammation. We assessed the dynamics of PMN recruitment and migration under shear flow in the presence of a wild-type strain of A. phagocytophilum and compared it with a strain of bacteria that binds to PMN independent of PSGL-1. Acute bacterial engagement with PMN resulted in transient PMN arrest and minimal PMN polarization. Although the wild-type pathogen also signaled activation of beta2 integrins and elicited a mild intracellular calcium flux, downstream signals including PMN transmigration and phosphorylation of p38 mitogen-activated protein kinase (MAPK) were inhibited. The mutant strain bound less well to PMN and failed to activate beta2 integrins and induce a calcium flux but did result in decreased PMN arrest and polarization that may have been partially mediated by a suppression of p38 MAPK activation. This model suggests that A. phagocytophilum binding to PMN under shear flow during recruitment to inflamed endothelium interferes with normal tethering via E-selectin and navigational signaling of transendothelial migration.