Nonhealing Surgical Wounds in a Patient with Plasminogen Deficiency Type 1 Successfully Treated with Intravenous Plasminogen: A Case Report.

ABSTRACT: Intravenous plasminogen replacement therapy for patients with plasminogen deficiency type 1 (hypoplasminogenemia) was recently approved for marketing in the US. In this case report, the authors describe a 33-year-old man with hypoplasminogenemia who developed nonhealing postsurgical wounds following trauma to his right hand despite receiving standard treatment for 4 months. The patient was enrolled in a compassionate-use protocol with intravenous plasminogen replacement therapy and experienced prompt resolution of surgical wounds. He was the first human patient to receive replacement therapy with plasminogen, human-tvmh in the US and first to demonstrate cutaneous wound healing in addition to resolution of ligneous lesions attributable to plasminogen deficiency type 1.

Temporal and Spatial Assessment of the Corneal Response to UV Cross-Linking Using 3-Dimensional In Vivo Confocal Microscopy.

ABSTRACT: The goal of this study was to evaluate the temporal and spatial pattern of wound healing following UV corneal cross-linking (CXL) using 3-dimensional (3-D) confocal imaging in vivo. Using a modified Heidelberg Retinal Tomograph with Rostock Corneal Module confocal microscope, we performed 3-D scans on two patients at multiple time points after CXL. Patient 1 showed a normal post-CXL wound healing response, with initial subbasal nerve loss and keratocyte apoptosis in the anterior stroma, followed by partial restoration of both the nerve plexus and stromal keratocytes by 6 months. In patient 2, in addition to anterior corneal damage, pyknotic nuclei were observed in the posterior stroma 7 days after CXL. Acellular areas were present in the posterior stroma at 3 months, with only partial keratocyte repopulation at 6 months. Regeneration of the subbasal nerve plexus was also delayed. Three-dimensional confocal imaging allowed these unusual wound healing responses to be identified in the absence of any corresponding clinical observations.

The importance of promoting physical activity and exercise training as adjuvant therapy for people with multiple sclerosis

Abstract Aim: This review aimed to provide evidence and highlight the importance of including physical activity (PA) and/or exercise training (ET) as part of the comprehensive multiple sclerosis (MS) care. Methods: Using the current literature on the subject, we provide a brief overview of MS incorporating its definition, common symptoms, prevalence, and potential disease consequences. We further succinctly describe MS as the first line of treatment, as well as the role of PA and ET in the disease. We end the commentary highlighting important recommendations from an international initiative to improve MS-related physical activity research that we believe will help not only improve the area of study but also best practices within this population. Results: There is compelling evidence for the beneficial effects of PA and/or ET on MS-related symptoms and consequently health and quality of life. There is preliminary evidence suggesting the potential for a disease-modifying effect. Conclusion: Fomenting this discussion is timely due to the increased prevalence of MS in different regions of the globe, and people with MS report low levels of PA participation and high amounts of sedentary time. The consequences of inactivity in this population can be drastic. The current body of evidence supports the notion that PA and ET are safe health behaviors that should be adopted as an adjuvant treatment option within the comprehensive and complex MS care due to its benefits on a variety of disease-related symptoms and its potential for improving health and quality of life in this population.

Exercise Training for Multiple Sclerosis: A Narrative Review of History, Benefits, Safety, Guidelines, and Promotion.

BACKGROUND: There have been significant advances in the medical treatment and management of multiple sclerosis pathogenesis, relapse and disease progression over the past 30 years. There have been advancements in the symptomatic treatment of multiple sclerosis, including management of secondary multiple sclerosis expressions such as walking, cognitive dysfunction, fatigue and depression. Scientific evidence and expert opinion suggest that exercise may be the single most effective non-pharmacological symptomatic treatment for multiple sclerosis. This article presents the historical context of exercise training within the multidisciplinary management of multiple sclerosis. We guide neurologists and healthcare providers on the recommended prescription of exercise and practical, theoretical methods to overcome barriers to exercise. METHOD: We undertook a critical search of the historical and current literature regarding exercise and multiple sclerosis from the viewpoint of exercise promotion by neurologists and the multidisciplinary care team. RESULTS: We highlight the ever-strengthening body of research indicating that exercise is safe and effective for improving symptoms of multiple sclerosis. Further, exercise training may be necessary for reducing disease progression. CONCLUSION: We seek to encourage neurologists and specialists in multidisciplinary healthcare teams to prescribe and promote exercise at diagnosis and across all stages of the disease trajectory using prescriptive guidelines as part of comprehensive MS care. Available tools include clinical education to dispel any historical myths related to exercise in multiple sclerosis, clinical exercise guidelines and behaviour change theory to overcome patients barriers to exercise.

Maxillomandibular Advancement and Upper Airway Stimulation: Extrapharyngeal Surgery for Obstructive Sleep Apnea.

There are many ways to categorize surgery for obstructive sleep apnea (OSA), one of which is to distinguish between intrapharyngeal and extrapharyngeal procedures. While the general otolaryngologist treating OSA is familiar with intrapharyngeal procedures, such as uvulopalatopharyngoplasty and tongue base reduction, extrapharyngeal sleep operations such as maxillomandibular advancement (MMA) and upper airway stimulation (UAS) have evolved rapidly in the recent decade and deserve a dedicated review. MMA and UAS have both shown predictable high success rates with low morbidity. Each approach has unique strengths and limitations, and for the most complex of OSA patients, the two in combination complement each other. Extrapharyngeal airway operations are critical for achieving favorable outcomes for sleep surgeons.

Surgical Algorithm for Obstructive Sleep Apnea: An Update.

Sleep surgery is part of a continuum of care for obstructive sleep apnea (OSA) that involves medical, pharmacologic, and behavioral therapy. Upper airway surgery for OSA can significantly improve stability by way of modulating the critical negative closing pressure. This is the same mechanism of action as positive airway pressure or oral appliance therapy. The updated surgical algorithm in this review adds precision in three areas: patient selection, identification of previously unaddressed anatomic phenotypes with associated treatment modality, and improved techniques of previously established procedures. While the original Riley and Powell phase 1 and 2 approach to sleep surgery has focused on individual surgical success rate, this algorithm strives for an overall treatment success with multi-modal and patient-centric treatments.

Surgical Algorithm for Obstructive Sleep Apnea: An Update

Sleep surgery is part of a continuum of care for obstructive sleep apnea (OSA) that involves medical, pharmacologic, and behavioral therapy. Upper airway surgery for OSA can significantly improve stability by way of modulating the critical negative closing pressure. This is the same mechanism of action as positive airway pressure or oral appliance therapy. The updated surgical algorithm in this review adds precision in three areas: patient selection, identification of previously unaddressed anatomic phenotypes with associated treatment modality, and improved techniques of previously established procedures. While the original Riley and Powell phase 1 and 2 approach to sleep surgery has focused on individual surgical success rate, this algorithm strives for an overall treatment success with multi-modal and patient-centric treatments.

Maxillomandibular Advancement and Upper Airway Stimulation: Extrapharyngeal Surgery for Obstructive Sleep Apnea

There are many ways to categorize surgery for obstructive sleep apnea (OSA), one of which is to distinguish between intrapharyngeal and extrapharyngeal procedures. While the general otolaryngologist treating OSA is familiar with intrapharyngeal procedures, such as uvulopalatopharyngoplasty and tongue base reduction, extrapharyngeal sleep operations such as maxillomandibular advancement (MMA) and upper airway stimulation (UAS) have evolved rapidly in the recent decade and deserve a dedicated review. MMA and UAS have both shown predictable high success rates with low morbidity. Each approach has unique strengths and limitations, and for the most complex of OSA patients, the two in combination complement each other. Extrapharyngeal airway operations are critical for achieving favorable outcomes for sleep surgeons.

High resolution continuous arterial spin labeling of human cerebral perfusion using a separate neck tagging RF coil.

For standard clinical applications, ASL images are typically acquired with 4-8 mm thick slices and 3-4 mm in-plane resolution. However, in this paper we demonstrate that high-resolution continuous arterial spin labeling (CASL) perfusion images can be acquired in a clinically relevant scan time using current MRI technology. CASL was implemented with a separate neck coil for labeling the arterial blood on a 4.7T MRI using standard axial 2D GE-EPI. Typical-resolution to high-resolution (voxels of 95, 60, 45, 27, or 7 mm3) images were compared for qualitative and quantitative cerebral blood flow analysis (CBF) in nine healthy volunteers (ages: 24-32 years). The highest resolution (1.5x1.5x3 = 7 mm3) CASL implementation yielded perfusion images with improved cortex depiction and increased cortical CBF measurements (53 ± 8 ml/100g/min), consistent with reduced partial volume averaging. The 7 mm3 voxel images were acquired with 6 cm brain coverage in a clinically relevant scan of 6 minutes. Improved spatial resolution facilitates CBF measurement with reduced partial volume averaging and may be valuable for the detection of perfusion deficits in small lesions and perfusion measurement in small brain regions.

Maxillomandibular Advancement: Contemporary Approach at Stanford.

Maxillomandibular advancement (MMA) for the treatment of obstructive sleep apnea (OSA) has remained a reliable and highly effective surgical intervention since its introduction in 1989. Modifications have been made to maximize skeletal movement and upper airway stability without compromising facial balance. Contemporary indications of recommending MMA prior to other soft tissue surgery are described. MMA poses unique challenges to surgeons. There are patient-related factors, including OSA, a chronic inflammatory condition with associated cardiovascular and metabolic comorbidity. Perioperative management is more complex than routine orthognathic patients. Key details are shared from a 3-decade experience at Stanford.

Continuing the Original Stanford Sleep Surgery Protocol From Upper Airway Reconstruction to Upper Airway Stimulation: Our First Successful Case.

In 1993, a surgical protocol for dynamic upper airway reconstruction in patients with obstructive sleep apnea (OSA) was published, and it became commonly known as the Stanford phase 1 and 2 sleep surgery protocol. It served as a platform on which research and clinical studies have continued to perfect the surgical care of patients with OSA. However, relapse is inevitable in a chronic condition such as OSA, and a subset of previously cured surgical patients return with complaints of excessive daytime sleepiness. This report describes a patient who was successfully treated with phase 1 and 2 operations more than a decade previously. He returned at 65 years of age with relapse of moderate OSA, and after workup with polysomnography and drug-induced sleep endoscopy, he underwent upper airway stimulation of the hypoglossal nerve that resulted in a cure of OSA. This case shows why upper airway stimulation is an appropriate option for patients with OSA relapse, after previously successful maxillomandibular advancement.

HIV testing behaviour and use of risk reduction strategies by HIV risk category among MSM in Vancouver.

We carried out an analysis of a serobehavioural study of men who have sex with men >19 years of age in Vancouver, Canada to examine HIV testing behaviour and use of risk reduction strategies by HIV risk category, as defined by routinely gathered clinical data. We restricted our analysis to those who self-identified as HIV-negative, completed a questionnaire, and provided a dried blood spot sample. Of 842 participants, 365 (43.3%) were categorised as lower-risk, 245 (29.1%) as medium-risk and 232 (27.6%) as higher-risk. The prevalence of undiagnosed HIV infection was low (lower 0.8%, medium 3.3%, higher 3.9%; p = 0.032). Participants differed by risk category in terms of having had an HIV test in the previous year (lower 46.5%, medium 54.6%, higher 67.0%; p < 0.001) and in their use of serosorting (lower 23.3%, medium 48.3%, higher 43.1%; p < 0.001) and only having sex with HIV-positive men if those men had low viral loads or were taking HIV medication (lower 5.1%, medium 4.8%, higher 10.9%; p = 0.021) as risk reduction strategies. These findings speak to the need to consider segmented health promotion services for men who have sex with men with differing risk profiles. Risk stratification could be used to determine who might benefit from tailored multiple health promotion interventions, including HIV pre-exposure prophylaxis.

Seroprevalence of hepatitis C and correlates of seropositivity among men who have sex with men in Vancouver, Canada: a cross-sectional survey.

OBJECTIVES: We sought to determine the prevalence of hepatitis C virus (HCV) infection among men who have sex with men (MSM) in Vancouver, Canada, and associations of risk behaviours with HCV serostatus. METHODS: We used data from the ManCount Study, a cross-sectional survey of MSM selected through a venue-based, time-location sampling method. Bivariate analyses and multivariate logistic regression modelling were used to determine correlates of HCV seropositivity. Bivariate analyses of participants who reported no history of injection drug use (IDU) were used to explore sexual behaviours associated with HCV seropositivity. RESULTS: HCV seroprevalence was 4.9% (56/1132). Among HCV-seropositive participants who responded to the question, 22.4% (11/49) were unaware of their HCV-seropositive status, 84.9% (45/53) reported a history of IDU and 60.7% (34/56) were HIV positive by dried blood spot. Multivariate modelling found previous IDU (adjusted OR (AOR): 26.30, 95% CI 11.15 to 62.03), receiving goods, drugs or money for sex (AOR 4.98, 95% CI 2.43 to 10.20) and current smoking (AOR 3.46, 95% CI 1.47 to 8.16) were associated with HCV seropositivity. Among MSM who reported no history of IDU, HCV seropositivity was associated with bleeding after receptive anal sex (p=0.001) and a previous diagnosis of gonorrhoea (p=0.007). CONCLUSIONS: HCV seroprevalence among a sample of MSM is higher than the general population and associated with a history of IDU. Among those who did not report IDU, we found evidence that suggests sexual exposure could be the route of transmission.

Relationship between disclosure of same-sex sexual activity to providers, HIV diagnosis and sexual health services for men who have sex with men in Vancouver, Canada.

OBJECTIVES: Men who have sex with men (MSM) report challenges to accessing appropriate health care. We sought to understand the relationship between disclosure of same-sex sexual activity to a health care practitioner (HCP), sexual behaviour and measures of sexual health care. METHODS: Participants recruited through community venues and events completed a questionnaire and provided a blood sample. This analysis includes only individuals with self-reported HIV negative or unknown serostatus. We compared participants who had disclosed having same-sex partners with those who had not using chi-square, Wilcoxon Rank Sum and Fisher's exact tests and used logistic regression to examine those variables associated with receiving an HIV test. RESULTS: Participants who had disclosed were more likely to have a higher level of education (p<0.001) and higher income (p<0.001), and to define themselves as "gay" or "queer" (p<0.001). Those who had not disclosed were less likely to report having risky sex (p=0.023) and to have been tested for HIV in the previous two years (adjusted odds ratio 0.23, 95% confidence interval: 0.16-0.34). There was no difference in undiagnosed HIV infection (3.9% versus 2.6%, p=0.34). Individuals who had disclosed were also more likely to have been tested for gonorrhea and syphilis, and more likely to have ever been vaccinated against hepatitis A and hepatitis B (p<0.001 for all). CONCLUSIONS: While generally reporting lower risk behaviour, MSM who did not disclose same-sex sexual activity to their HCP did have undiagnosed HIV infections and were less likely to have been tested or vaccinated. Strategies to improve access to appropriate sexual health care for MSM are needed.

Risks for HIV and other sexually transmitted infections among Asian men who have sex with men in Vancouver, British Columbia: a cross-sectional survey.

BACKGROUND: Individuals of Asian heritage represent the largest ethnic minority in Canada. Approximately 10% of the new HIV diagnoses in men in British Columbia occur among Asian-Canadians. However, the HIV risk patterns of Asian men who have sex with men (MSM) have not been extensively studied. METHODS: Participants aged ≥ 19 years were enrolled in a venue-based HIV serobehavioural survey of MSM in Vancouver, Canada. We compared the demographic characteristics, risk behaviours, and prevalence of HIV and other sexual and blood borne infections between Asian and non-Asian MSM using bivariate analysis and logistic regression confounder modelling. RESULTS: Amongst 1132 participants, 110 (9.7%) self-identified as Asian. Asian participants were younger than non-Asian participants (median age 29 vs. 32 years; p < 0.001), but otherwise did not differ from other study participants. HIV prevalence was lower among Asian MSM compared to Non-Asian MSM (3.7% vs 19.0%, p <0.001). Among men who self-reported as HIV negative or unknown we found no differences in unprotected anal intercourse (UAI) with a discordant or unknown serostatus partner in the previous six months (11 vs. 13%; p = 0.503). However, Asian MSM were less likely to report ever using injection drugs (10.8% vs. 19.2%; p = 0.043) or using alcohol before having sex (52% vs. 64.4%; p = 0.017). CONCLUSIONS: Asian MSM in our study reported similar rates of UAI as non-Asian MSM, but had a lower prevalence of HIV infection. Other factors, such as the use of drugs and alcohol, in relation to sex, may partly explain these differences. However this requires further investigation.

Targeting screening and social marketing to increase detection of acute HIV infection in men who have sex with men in Vancouver, British Columbia.

OBJECTIVES: The contribution of acute HIV infection (AHI) to transmission is widely recognized, and increasing AHI diagnosis capacity can enhance HIV prevention through subsequent behavior change or intervention. We examined the impact of targeted pooled nucleic acid amplification testing (NAAT) and social marketing to increase AHI diagnosis among men who have sex with men (MSM) in Vancouver. DESIGN: Observational study. METHODS: We implemented pooled NAAT following negative third-generation enzyme immunoassay (EIA) testing for males above 18 years in six clinics accessed by MSM, accompanied by two social marketing campaigns developed by a community gay men's health organization. We compared test volume and diagnosis rates for pre-implementation (April 2006-March 2009) and post-implementation (April 2009-March 2012) periods. After implementation, we used linear regression to examine quarterly trends and calculated diagnostic yield. RESULTS: After implementation, the AHI diagnosis rate significantly increased from 1.03 to 1.84 per 1000 tests, as did quarterly HIV test volumes and acute to non-acute diagnosis ratio. Of the 217 new HIV diagnoses after implementation, 54 (24.9%) were AHIs (25 detected by pooled NAAT only) for an increased diagnostic yield of 11.5%. The average number of prior negative HIV tests (past 2 years) increased significantly for newly diagnosed MSM at the six study clinics compared to other newly diagnosed MSM in British Columbia, per quarter. CONCLUSION: Targeted implementation of pooled NAAT at clinics accessed by MSM is effective in increasing AHI diagnoses compared to third-generation EIA testing. Social marketing campaigns accompanying pooled NAAT implementation may contribute to increasing AHI diagnoses and frequency of HIV testing.

Impact of statistical adjustment for frequency of venue attendance in a venue-based survey of men who have sex with men.

Venue sampling is a common sampling method for populations of men who have sex with men (MSM); however, men who visit venues frequently are more likely to be recruited. While statistical adjustment methods are recommended, these have received scant attention in the literature. We developed a novel approach to adjust for frequency of venue attendance (FVA) and assess the impact of associated bias in the ManCount Study, a venue-based survey of MSM conducted in Vancouver, British Columbia, Canada, in 2008-2009 to measure the prevalence of human immunodeficiency virus and other infections and associated behaviors. Sampling weights were determined from an abbreviated list of questions on venue attendance and were used to adjust estimates of prevalence for health and behavioral indicators using a Bayesian, model-based approach. We found little effect of FVA adjustment on biological or sexual behavior indicators (primary outcomes); however, adjustment for FVA did result in differences in the prevalence of demographic indicators, testing behaviors, and a small number of additional variables. While these findings are reassuring and lend credence to unadjusted prevalence estimates from this venue-based survey, adjustment for FVA did shed important insights on MSM subpopulations that were not well represented in the sample.

A new species of Kukri Snake (Oligodon Fitzinger, 1826; Squamata: Colubridae) from the Cat Tien National Park, southern Vietnam.

We describe a new species of the genus Oligodon from the lowland forests of Cat Tien National Park, Dong Nai Province, in southern Vietnam. Oligodon cattienensis sp. nov. is distinguished from the remaining Southeast Asian kukri snakes by the combination of the following characters: medium-sized, deeply forked hemipenes without spines, 17-17-15 dorsal scale rows, nasal entire, 2 small postoculars, almost equal in size, 167-178 ventrals, 31-35 subcaudals, 24-35 + 5 large dark-edged vertebral blotches in combination with a yellow-orange or red vertebral stripe between blotches, head pattern including ocular band, temporal bands and elongated chevron, ventrals pink or whitish (reddish in juveniles) in life, some bearing a quadrangular dark blotch on each lateral side, or ventrals being entirely dark. Based on the hemipenial morphology the new species is assigned to the Oligodon cyclurus species group. A comparison table for all Indochinese Oligodon is provided.

A new species of Sphenomorphus Fitzinger, 1843 (Squamata: Sauria: Scincidae) from Vietnam .

A new forest skink species of the genus Sphenomorphus is described from Kon Tum Plateau, southern Central Vietnam. Sphenomorphus sheai sp. nov. is similar to the other montane skink species from the Indochina region, Lygosoma veunsaiensis, Scincella apraefrontalis, Sphenomorphus tetradactylus, and Sphenomorphus tridigitus, in having a small size and the absence of external ear openings. However, the new species is differentiated from aforementioned species and other members of Sphenomorphus from China and mainland Southeast Asia by a unique suite of morphological characters. The discovery of S. sheai brings the total species number of Sphenomorphus known from Vietnam to twelve.

Implications for HIV prevention programs from a serobehavioural survey of men who have sex with men in Vancouver, British Columbia: the ManCount study.

BACKGROUND: We examined HIV prevalence, awareness of HIV serostatus and HIV risk behaviour among a sample of men who have sex with men (MSM) in Vancouver. METHODS: MSM > or = 18 years were recruited from August 2008 to February 2009 through community venues. Participants completed a questionnaire and provided a dried blood spot (DBS) for HIV and other STI testing. We performed descriptive statistics and bivariate analyses of key explanatory variables. RESULTS: A total of 1,169 participants completed questionnaires; of these, 1,138 (97.3%) provided DBS specimens suitable for testing. The median age was 33 years (IQR 26-44). A total of 206 (18%) were HIV-positive by DBS, of whom 86% were aware they were positive. HIV seropositivity increased from 7.1% in those < 30 years of age to 19% in those 30-44 years and 34% among those > or = 45 years (p < 0.001 for test of trend). Of the 933 who self-reported as HIV-negative or unknown, 28 (3.0%) tested HIV-positive. Among those not tested for HIV in the previous 2 years, the reasons for not testing differed between participants with undiagnosed HIV infection and those who were HIV-negative. A total of 62% of study participants who self-reported as HIV-negative reported using a condom the last time they had anal sex. The use of risk-reduction measures was reported by 91.1% of all study participants (72% if excluding consistent condom use). CONCLUSION: The majority of MSM in Vancouver have adopted behaviours that reduce their HIV-related risk. However, prevention programs must continue to promote condom use, increase HIV testing, and better inform MSM of the value and limitations of other risk-reduction strategies.