Impact of age, obesity, and renal impairment on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma.

INTRODUCTION: There remains a need to determine whether certain subgroups of newly diagnosed multiple myeloma (NDMM) derive the same benefit from high-dose chemotherapy-autologous stem cell transplant (HDT-ASCT). We describe our institutional experience highlighting the impact of age, obesity, and renal impairment on outcomes after HDT-ASCT for patients with NDMM in a real-world setting. METHODS: A total of 449 consecutive patients were included in this retrospective analysis. RESULTS: No difference in median progression free survival or overall survival was seen for patients with age > 65, body mass index (BMI) > 30 kg/m2, or estimated glomerular filtration rate < 60 mL/min/1.73 m2 when compared to those without these characteristics. From a safety standpoint, there were no differences in the incidence of transplant-related mortality or secondary malignancy among subgroups. CONCLUSION: For patients with NDMM undergoing HDT-ASCT, there is no difference in outcomes based on age, BMI, or renal function, and the presence of one or more of these factors should not preclude patients from HDT-ASCT.

Impact of race and ethnicity on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma.

Non-Hispanic Black patients are disproportionally affected by multiple myeloma (MM) and whether efficacy outcomes after autologous stem cell transplant (ASCT) differ by race and ethnicity remains an area of active investigation. This study included 449 patients enriched with a large proportion of non-Hispanic Black patients and sought to highlight the impact of race and ethnicity on outcomes after HDT-ASCT for patients with newly diagnosed MM. We found induction chemotherapy followed by high-dose therapy-ASCT and maintenance chemotherapy is associated with long-term PFS and OS, regardless of race or ethnicity.

The 'comeback' of Selinexor: From toxic to tolerable.

Selinexor is a novel XPO1 inhibitor approved for patients with relapsed refractory multiple myeloma. When used as twice weekly dosing, selinexor is associated with significant toxicities, prohibiting its use in clinical practice. Newer combinations with other chemotherapeutic agents have evaluated less frequent and lower doses of Selinexor with aggressive supportive care. These novel combinations appear to have tolerable safety profiles while preserving drug efficacy, making Selinexor a reasonable option for patients with heavily pretreated relapsed refractory multiple myeloma.

Host apoplastic cysteine protease activity is suppressed during the mutualistic association of Lolium perenne and Epichloë festucae.

Plants secrete various defence-related proteins into the apoplast, including proteases. Papain-like cysteine proteases (PLCPs) are central components of the plant immune system. To overcome plant immunity and successfully colonize their hosts, several plant pathogens secrete effector proteins inhibiting plant PLCPs. We hypothesized that not only pathogens, but also mutualistic microorganisms interfere with PLCP-meditated plant defences to maintain endophytic colonization with their hosts. Epichloë festucae forms mutualistic associations with cool season grasses and produces a range of secondary metabolites that protect the host against herbivores. In this study, we performed a genome-wide identification of Lolium perenne PLCPs, analysed their evolutionary relationship, and classified them into nine PLCP subfamilies. Using activity-based protein profiling, we identified four active PLCPs in the apoplast of L. perenne leaves that are inhibited during endophyte interactions. We characterized the L. perenne cystatin LpCys1 for its inhibitory capacity against ryegrass PLCPs. LpCys1 abundance is not altered during the mutualistic interaction and it mainly inhibits LpCP2. However, since the activity of other L. perenne PLCPs is not sensitive to LpCys1, we propose that additional inhibitors, likely of fungal origin, are involved in the suppression of apoplastic PLCPs during E. festucae infection.

From conventional to disruptive: upturning the HIV testing status quo among men who have sex with men in Vietnam.

INTRODUCTION: HIV prevalence among men who have sex with men (MSM) in Vietnam is increasing, while annual HIV testing uptake has remained consistently low, posing a significant challenge to reaching the 90-90-90 goals. Barriers to MSM seeking HIV testing include concerns regarding confidentiality and lack of convenient testing options. Two new HIV testing strategies-HIV lay provider and HIV self-testing (HIVST)-were piloted alongside intensive social media outreach to increase access to and uptake of HIV testing among MSM not actively engaged in services. METHODS: We measured the proportion of first-time MSM HIV testers opting for HIV lay or self-testing, and factors that were associated with first-time testing, as part of a larger HIV lay and self-testing study among key populations in Vietnam. We also assessed MSM satisfaction with HIV lay or self-testing, and testing location and provider preferences. Finally, we calculated linkage to care cascade among MSM that were diagnosed and enrolled in anti-retroviral therapy (ART) services. RESULTS: Among MSM that sought HIV lay and self-testing, 57.9% (n = 320) and 51.3% (n = 412) were first-time testers respectively. In the final adjusted models, the odds of being a first-time tester and opting for HIV lay testing were higher among MSM who were young, had lower levels of income and had never exchanged sex for money; for HIVST, the odds of being a first-time HIV tester were higher among MSM that had attained lower levels of education. HIV lay and self-testing resulted in higher detection of new HIV cases (6.8%) compared to conventional HIV testing among key populations (estimated at 1.6% in 2016), while MSM linked to testing through social media interventions presented with even higher HIV-positivity (11%). Combined, 1655 HIV cases were diagnosed and more than 90% were registered for ART services. CONCLUSIONS: Our findings suggest that MSM-delivered HIV testing and self-testing, promoted through online or face-to-face interactions, offer important additions to MSM HIV testing services in Vietnam, and could significantly contribute to epidemic control by increasing HIV testing among harder-to-reach and higher-risk MSM, effectively enrolling them in ART, and reducing onward transmission.

Lay provider HIV testing: A promising strategy to reach the undiagnosed key populations in Vietnam.

BACKGROUND: In Vietnam, reaching the remaining one-third of undiagnosed people living with HIV and facilitating their antiretroviral therapy (ART) enrollment requires breakthrough approaches. We piloted lay provider HIV testing as an innovative approach to reach at-risk populations that never or infrequently HIV test at facility-based services. METHODS: We conducted a cross-sectional survey and analysis of routine program data in two urban provinces (Hanoi and Ho Chi Minh City) and two rural mountainous provinces (Nghe An and Dien Bien) from October 2015 through September 2017. Acceptability of lay provider testing was defined as the proportion of first-time HIV testers utilizing the service, and effectiveness was measured by HIV positivity and ART initiation rates. Univariate and multivariate analyses were used to determine lay provider testing preference and factors associated with that preference. RESULTS: Among 1,230 individuals recruited for face-to-face interviews, 74% belonged to key populations: people who inject drugs accounted for 31.4%; men who have sex with men, 60.4%; and female sex workers, 8.2%. Most clients (67%) reported being first-time HIV testers, and the majority (85.8%) preferred lay provider testing to facility-based testing. Multivariate analysis found that clients in urban areas (adjusted odds ratio [aOR] = 2.50; 95% confidence interval [CI]: 1.30-4.90) and those who had a university or higher education (aOR = 1.83; 95% CI: 1.05-3.20) were more likely to prefer lay provider testing. Lay provider testing yielded a higher HIV positivity rate (4.1%), particularly among first-time testers (6.8%), compared to facility-based testing (nationally estimated at 1.6% in 2016) and had a high ART initiation rate (91%). CONCLUSIONS: Our findings suggest that lay provider HIV testing is an effective approach to reach previously unreached at-risk populations, and, therefore, a critical addition to accelerating Vietnam's attainment of the Joint United Nations Programme on HIV/AIDS 90-90-90 goals.

Cigarette Smoking and Musculoskeletal Pain Severity Among Male and Female Afghanistan/Iraq Era Veterans.

OBJECTIVE: Cigarette smoking and musculoskeletal pain are prevalent among Department of Veterans Affairs (VA) health care system users. These conditions frequently co-occur; however, there is limited empirical information specific to Afghanistan/Iraq era veterans. The present study sought to examine gender differences in the association between cigarette smoking and moderate to severe musculoskeletal pain in US veterans with Afghanistan/Iraq era service. METHODS: A random sample of 5,000 veterans with service after November 11, 2001, participated in a survey assessing health care needs and barriers to care. One thousand ninety veterans completed the survey assessing post-traumatic stress disorder (PTSD) symptoms, depressive symptoms, and current pain severity. Multivariate logistic regression was used to examine the association between gender, cigarette smoking status, and current moderate to severe musculoskeletal pain. RESULTS: Findings indicated a significant gender by smoking interaction on moderate/severe musculoskeletal pain, adjusting for age, self-reported race/ethnicity and weight status, combat exposure, probable PTSD, depressive symptoms, service-connected injury during deployment, and VA health care service utilization. Deconstruction of the interaction indicated that female veteran smokers, relative to female nonsmokers, had increased odds of endorsing moderate to severe musculoskeletal pain (odds ratio [OR] = 2.73, 95% confidence interval [CI] = 1.16-6.41), whereas this difference was nonsignificant for male veterans (OR = 1.03, 95% CI = 0.69-1.56). CONCLUSIONS: Survey data from Operation Enduring Freedom/Operation Iraqi Freedom veterans suggest an association between current smoking, gender, and moderate to severe musculoskeletal pain. The stronger relationship between smoking and pain in women supports the need for interventional and longitudinal research that can inform gender-based risk factors for pain in veteran cigarette smokers.

IDC2 and IDC3, two genes involved in cell non-autonomous signaling of fruiting body development in the model fungus Podospora anserina.

Filamentous ascomycetes produce complex multicellular structures during sexual reproduction. Little is known about the genetic pathways enabling the construction of such structures. Here, with a combination of classical and reverse genetic methods, as well as genetic mosaic and graft analyses, we identify and provide evidence for key roles for two genes during the formation of perithecia, the sexual fruiting bodies, of the filamentous fungus Podospora anserina. Data indicate that the proteins coded by these two genes function cell-non-autonomously and that their activity depends upon conserved cysteines, making them good candidate for being involved in the transmission of a reactive oxygen species (ROS) signal generated by the PaNox1 NADPH oxidase inside the maturing fruiting body towards the PaMpk1 MAP kinase, which is located inside the underlying mycelium, in which nutrients are stored. These data provide important new insights to our understanding of how fungi build multicellular structures.

HIV service delivery models towards 'Zero AIDS-related Deaths': a collaborative case study of 6 Asia and Pacific countries.

BACKGROUND: In the Asia-Pacific region, limited systematic assessment has been conducted on HIV service delivery models. Applying an analytical framework of the continuum of prevention and care, this study aimed to assess HIV service deliveries in six Asia and Pacific countries from the perspective of service availability, linking approaches and performance monitoring for maximizing HIV case detection and retention. METHODS: Each country formed a review team that provided published and unpublished information from the national HIV program. Four types of continuum were examined: (i) service linkages between key population outreach and HIV diagnosis (vertical-community continuum); (ii) chronic care provision across HIV diagnosis and treatment (chronological continuum); (iii) linkages between HIV and other health services (horizontal continuum); and (iv) comprehensive care sites coordinating care provision (hub and heart of continuum). RESULTS: Regarding the vertical-community continuum, all districts had voluntary counselling and testing (VCT) in all countries except for Myanmar and Vietnam. In these two countries, limited VCT availability was a constraint for referring key populations reached. All countries monitored HIV testing coverage among key populations. Concerning the chronological continuum, the proportion of districts/townships having antiretroviral treatment (ART) was less than 70% except in Thailand, posing a barrier for accessing pre-ART/ART care. Mechanisms for providing chronic care and monitoring retention were less developed for VCT/pre-ART process compared to ART process in all countries. On the horizontal continuum, the availability of HIV testing for tuberculosis patients and pregnant women was limited and there were sub-optimal linkages between tuberculosis, antenatal care and HIV services except for Cambodia and Thailand. These two countries indicated higher HIV testing coverage than other countries. Regarding hub and heart of continuum, all countries had comprehensive care sites with different degrees of community involvement. CONCLUSIONS: The analytical framework was useful to identify similarities and considerable variations in service availability and linking approaches across the countries. The study findings would help each country critically adapt and adopt global recommendations on HIV service decentralization, linkages and integration. Especially, the findings would inform cross-fertilization among the countries and national HIV program reviews to determine county-specific measures for maximizing HIV case detection and retention.

Piloting a Social Networks Strategy to Increase HIV Testing and Counseling Among Men Who Have Sex with Men in Greater Accra and Ashanti Region, Ghana.

The 2011 Ghana Men's Study identified a high prevalence of HIV among men who have sex with men (MSM) in Accra/Tema (34.4 %) and in Kumasi (13.6 %), whereas the HIV rate among MSM referred through peer educators (PEs) to HIV testing and counseling (HTC) services in these two sites was substantially lower (8.4 %). These findings raised questions about possible limitations of the peer-education strategy to reach high-risk MSM. Therefore, a pilot study was conducted to assess the feasibility of using a social network strategy (SNS) to identify and refer MSM to HTC services. Within 3 months, 166 MSM were reached and referred to HTC services: 62.7 % reported no recent exposure to PEs; 61.5 % were unaware of their recent HIV serostatus; and 32.9 % were newly diagnosed HIV positive. This pilot study suggests that an SNS could be an important strategy to reach MSM and to increase the uptake of HTC.

A short history of HIV prevention programs for female sex workers in Ghana: lessons learned over 3 decades.

BACKGROUND: Female sex workers (FSWs) in Ghana have a 10-fold greater risk for acquiring HIV than the general adult population, and they contribute a substantial proportion of the new HIV infections in the country. Although researchers have conducted behavioral and biological surveys, there has been no review of the contextual, programmatic, and epidemiological changes over time. METHODS: The authors conducted a historical review of HIV prevention programs in Ghana. We reviewed the use of different interventions for HIV prevention among FSWs and data from program monitoring and Integrated Biological and Behavioral Surveillance Surveys. In particular, we looked at changes in service access and coverage, the use of HIV testing and counseling services, and the changing prevalence of HIV and other sexually transmitted infections. RESULTS: HIV prevention interventions among FSWs increased greatly between 1987 and 2013. Only 72 FSWs were reached in a pilot program in 1987, whereas 40,508 FSWs were reached during a national program in 2013. Annual condom sales and the proportion of FSWs who used HIV testing and counseling services increased significantly, whereas the prevalence of gonorrhea and chlamydia decreased. The representation of FSWs in national HIV strategic plans and guidelines also improved. CONCLUSIONS: Ghana offers an important historical example of an evolving HIV prevention program that-despite periods of inactivity-grew in breadth and coverage over time. The prevention of HIV infections among sex workers has gained momentum in recent years through the efforts of the national government and its partners-a trend that is critically important to Ghana's future.

Integrating palliative care into HIV outpatient clinical settings: preliminary findings from an intervention study in Vietnam.

Symptom assessment and treatment for people living with HIV (PLHIV) cannot only lead to improvements in quality of life but contribute to combination antiretroviral adherence and early detection of virologic rebound. The majority of PLHIV in Vietnam receive their care in HIV outpatient settings, whereas very few clinics provide palliative care. The Ministry of Health has called for palliative care to be incorporated into existing HIV and cancer services, but there is limited guidance regarding how to operationalize integration. An HIV outpatient clinic palliative care intervention was tested in northern Vietnam to explore the accessibility, acceptability, and feasibility of integrated services. Primary outcome measures included changes in identification and treatment of pain and other symptoms, the prevalence of depression and anxiety, and perceived social support. The palliative care intervention included introduction of tools and mentoring to assess and treat pain and other symptoms as well as mental health and social support screening, counseling, and treatment services. The intervention resulted in significant changes in provider practice and service delivery. Providers and patients reported overall satisfaction with the intervention and resulting improvements in quality of care.

Vietnam: integrating palliative care into HIV/AIDS and cancer care.

Vietnam is struggling to meet the growing need for both disease-modifying and palliative care for people with life-threatening chronic diseases such as HIV/AIDS and cancer. Recently, Vietnam initiated rapid development of a national palliative care program for HIV/AIDS and cancer patients that builds on existing palliative care programs and experience and integrates palliative care into standard HIV/AIDS and cancer care. National palliative care guidelines have been issued by the Ministry of Health based on a rapid situation analysis. Plans now call for review and revision of opioid laws and regulations to increase availability of opioids for medical use, training in palliative care for clinicians throughout the country, and development of palliative care programs both in the community and in inpatient referral centers.

Fine-needle aspiration of a primary mediastinal large B-cell lymphoma: a case report with cytologic, histologic, and flow cytometric considerations.

Fine-needle aspiration (FNA) cytology and immunophenotyping by flow cytometry (FCM) are increasingly being used for diagnosing and subclassifying lymphoma in the REAL/WHO classification. Herein, we report a case of primary mediastinal large B-cell lymphoma (PMBL), a subtype of diffuse large B-cell lymphoma in the WHO classification, diagnosed by FNA cytology in conjunction with FCM. This, to our knowledge, has not previously been reported. A 57-yr-old woman presented with bilateral axillary lymphadenopathy and intermittent shortness of breath. CT scan revealed a 5-cm anterior mediastinal mass and mediastinal lymphadenopathy. Endoscopic ultrasound-guided FNA of a 4.5-cm subcarinal lymph node showed medium to large atypical lymphocytes with scant to moderate finely vacuolated cytoplasm. Nuclei were enlarged, cleaved, noncleaved, lobulated, and hyperchromatic. The background showed lymphoglandular bodies. Malignant large cell lymphoma was cytologically diagnosed. FCM, performed on a portion of the FNA specimen, demonstrated large B cells devoid of surface immunoglobulin expression, the characteristic immunophenotype of PMBL. The histologic diagnosis was PMBL. Touch-imprint cytology of the histologic specimen showed large cells with a narrow rim of clear cytoplasm and prominent outer cell border. Nuclear features were similar to the FNA specimen. In the presence of a mediastinal mass, FNA cytology in conjunction with FCM can effectively diagnose PMBL in the appropriate clinical setting.