Global impact of COVID-19 on surgeons and team members (GlobalCOST): a cross-sectional study.

OBJECTIVES: To investigate the impact of COVID-19 on the well-being of surgeons and allied health professionals as well as the support provided by their institutions. DESIGN: This cross-sectional study involved distributing an online survey through medical organisations, social media platforms and collaborators. SETTING: It included all staff based in an operating theatre environment around the world. PARTICIPANTS: 1590 complete responses were received from 54 countries between 15 July and 15 December 2020. The average age of participants was 30-40 years old, 64.9% were men and 32.5% of a white ethnic background. 79.5% were surgeons with the remainder being nurses, assistants, anaesthetists, operating department practitioners or classified other. MAIN OUTCOME MEASURES: Participants that had experienced any physical illness, changes in mental health, salary or time with family since the start of the pandemic as well as support available based on published recommendations. RESULTS: 32.0% reported becoming physically ill. This was more likely in those with reduced access to personal protective equipment (OR 4.62; CI 2.82 to 7.56; p<0.001) and regular breaks (OR 1.56; CI 1.18 to 2.06; p=0.002). Those with a decrease in salary (29.0%) were more likely to have an increase in anxiety (OR 1.50; CI 1.19 to 1.89; p=0.001) and depression (OR 1.84; CI 1.40 to 2.43; p<0.001) and those who spent less time with family (35.2%) were more likely to have an increase in depression (OR 1.74; CI 1.34 to 2.26; p<0.001). Only 36.0% had easy access to occupational health, 44.0% to mental health services, 16.5% to 24/7 rest facilities and 14.2% to 24/7 food and drink facilities. Fewer measures were available in countries with a low Human Development Index. CONCLUSIONS: This work has highlighted a need and strategies to improve conditions for the healthcare workforce, ultimately benefiting patient care.

Gestational Trophoblastic Neoplasia: Experience from a Tertiary Care Center of India.

AIMS: Gestational trophoblastic neoplasia (GTN) comprise a spectrum of interrelated conditions originating from the placenta. With sensitive assays for human chorionic gonadotropin (ß-hCG) and current approaches to chemotherapy, most women with GTN can be cured with preservation of reproductive potential. The purpose of this analysis was to address the outcome of GTN in patients from a tertiary care center of India. MATERIALS AND METHODS: We undertook a retrospective and prospective review of GTN cases treated at our center over a period of 7 years from 2008 to 2014. Patients of GTN were assigned to low-risk or high-risk categories as per the FIGO scoring system. The low-risk group was treated with combination of actinomycin-D and methotrexate and the high-risk group received the Etoposide, Methotrexate, Actinomycin-D/ Cyclophosphamide, Vincristine (EMA/CO) regimen. Salvage therapy was Etoposide, Paclitaxel /Paclitaxel, Cisplatin (EP/TP). Treatment was continued for three cycles after normalization of ß-hCG level, after which the patients were followed up regularly. RESULTS: In total, 41 GTN patients were treated at our institution during the above period; 17 were in the low-risk and 24 were in the high-risk category. The lung was the most common site of metastasis. All low-risk patients achieved complete remission. Among high-risk patients, one patient died while receiving first cycle chemotherapy, one patient relapsed, and 22 patients achieved complete remission. The single relapsed patient also achieved remission with second-line chemotherapy. CONCLUSION: Risk-stratified treatment of GTN was associated with acceptable toxicity and resulted in outcome that was comparable with international standards. The use of two-drug combination in low-risk patients is a better option especially in developing countries.

Development of a geographic information system-based decision support toolset to assess the feasibility of on-site wastewater treatment and disposal options in low permeability subsoils.

Traditional on-site wastewater treatment systems have proven to be unsuitable in areas of low permeability subsoils, representing a risk to human health and the environment. With large areas being covered by low permeability tills, Ireland needs to consider alternative treatment and disposal options to be able to allow further development in these areas and to deal with polluting legacy sites. The paper describes the development and structure of a geographic information system (GIS)-based decision support toolset to evaluate possible alternative strategies for these sites. The programme takes as its initial input the location of an existing house located in an area of low permeability subsoils. Through a series of interconnected GIS geoprocesses the model outputs appropriate solutions for a site, ranking them in terms of environmental sustainability and cost. However, the final decisions are still dependent on on-site constraints so that each solution is accompanied by an alert message that provides additional information for the user to refine the output list according to the available local site-specific information.

Transient nature of long-term nonprogression and broad virus-specific proliferative T-cell responses with sustained thymic output in HIV-1 controllers.

BACKGROUND: HIV-1(+) individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+) T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression. METHODOLOGY/PRINCIPAL FINDINGS: CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+) individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+) patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years. CONCLUSIONS: Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory.

Assessment of adipokine expression and mitochondrial toxicity in HIV patients with lipoatrophy on stavudine- and zidovudine-containing regimens.

OBJECTIVES: Despite evidence for the role of adipokines such as adiponectin in the metabolic toxicities of protease inhibitor (PI)-treated patients, little is known about their role in nucleoside reverse transcriptase inhibitor (NRTI)-induced lipoatrophy (LA). We analyzed the relations between mitochondrial toxicity, adipokine expression, and clinical LA in peripheral blood mononuclear cells (PBMCs) and adipose samples from individuals treated with stavudine (d4T) or zidovudine (ZDV) in comparison to patients undergoing highly active antiretroviral therapy (HAART) as well as HIV-negative individuals. METHODS: In this cross-sectional analysis, we studied 18 PI-naive HIV-infected patients with LA treated with d4T (d4T+LA+ [n = 12]) or zidovudine (ZDV+LA+ [n = 6]) in comparison to HAART-treated patients with (HAART+LA+ [n = 8]) and without (HAART+LA- [n = 8]) LA as well as HIV-negative controls (n = 12). Adipose samples were assessed for protein and/or messenger RNA (mRNA) levels of adiponectin, tumor necrosis factor-alpha (TNFalpha), interleukin (IL)-6, and sterol regulatory element-binding protein (SREBP) 1a/c in all groups, whereas adipose and PBMC samples from the d4T+LA+, ZDV+LA+, and HIV-negative subgroups were assessed for mitochondrial DNA (mtDNA) depletion and cytochrome c-oxidase (COX) II/COX IV ratios. RESULTS: There was no change in mtDNA levels in adipose or PBMC samples in NRTI-treated patients with LA, although patients treated with d4T had reduced COX II/COX IV ratios in adipose and PBMC samples. Adipose tissue adiponectin mRNA and plasma levels were reduced in the d4T- and ZDV-treated patients regardless of the use of PIs. Tissue SREBP1c mRNA levels were also significantly reduced in both NRTI groups when compared with the HIV-negative controls. Significant reductions in SREBP1c levels were also evident with the HAART+LA+ group when compared with HAART+LA- controls. CONCLUSIONS: Patients with LA on d4T-based regimens show evidence of mitochondrial respiratory chain dysfunction, whereas the d4T- and ZDV-based regimens also demonstrated reduced SREBP1c and adiponectin levels, findings that have previously been shown with PIs.

Case report. Severe cutaneous ulceration secondary to cytomegalovirus inclusion disease during successful immune reconstitution with HAART.

Restoration of the immune system following HAART is not without its adverse effects. We describe a case of severe cutaneous ulceration secondary to cytomegalovirus (CMV) infection in an HIV-1-seropositive man following the initiation of HAART in the absence of active CMV retinitis and discuss the likely mechanisms associated with its development.

Lopinavir/ritonavir (ABT-378/r).

Despite major advances in HIV research, eradication of HIV from the body is not yet possible. However, current antiretroviral (ARV) therapy can achieve disease control via viral suppression below the limits of detection of currently available assays. This has led to a marked decline in morbidity and mortality associated with the development of opportunistic infections and malignancies. Since viral suppression appears to be the most achievable goal of current therapy, there arises a need for new and more potent ARV agents in order to maintain viral suppression. Many of the currently available protease inhibitors (PIs) have a high protein-binding ability, short plasma half-life [1] and pharmacokinetic interactions with food or other drugs [2]. This can result in sub-optimal plasma drug concentrations, which may allow the virus to break through and replicate, leading to the development of resistant mutants [1]. Lopinavir/ritonavir (LPV/r; Kaletra, Abbott Laboratories) is a new PI consisting of a co-formulation of lopinavir and low-dose ritonavir. The sub-therapeutic dose of ritonavir (a potent cytochrome P450 [CYP] 3A4 inhibitor) inhibits the metabolism of lopinavir, resulting in higher lopinavir concentrations than when lopinavir is administered alone [3]. This pharmacokinetic interaction is associated with a high lopinavir trough level:wild type median effective concentration (EC(50)) ratio and good general tolerability when compared with other currently licensed PIs [4]. The concept of pharmacokinetic enhancement - boosting - is not new as ritonavir has previously been utilised in this context with other PIs. The relationship between plasma and intracellular drug levels has yet to be clarified. What has been ascertained from pharmacokinetic studies thus far is the correlation between ARV trough plasma concentrations (C(min)) and virological outcome [5,6]. LPV/r exemplifies how the pharmacokinetic profile of a drug can be modified to attain sufficient C(min) to suppress pheno- and genotypically resistant viral strains, as well as provide a pharmacological barrier to the emergence of resistance [7]. LPV/r reduces pill-burden and aids compliance, as shown by encouraging results in the treatment of both ARV-naive and -experienced patients.