Social and structural determinants of injection drug use-associated bacterial and fungal infections: A qualitative systematic review and thematic synthesis.

BACKGROUND AND AIMS: Injection drug use-associated bacterial and fungal infections are increasingly common, and social contexts shape individuals' injecting practices and treatment experiences. We sought to synthesize qualitative studies of social-structural factors influencing incidence and treatment of injecting-related infections. METHODS: We searched PubMed, EMBASE, Scopus, CINAHL and PsycINFO from 1 January 2000 to 18 February 2021. Informed by Rhodes' 'risk environment' framework, we performed thematic synthesis in three stages: (1) line-by-line coding; (2) organizing codes into descriptive themes, reflecting interpretations of study authors; and (3) consolidating descriptive themes into conceptual categories to identify higher-order analytical themes. RESULTS: We screened 4841 abstracts and included 26 qualitative studies on experiences of injecting-related bacterial and fungal infections. We identified six descriptive themes organized into two analytical themes. The first analytical theme, social production of risk, considered macro-environmental influences. Four descriptive themes highlighted pathways through which this occurs: (1) unregulated drug supply, leading to poor drug quality and solubility; (2) unsafe spaces, influenced by policing practices and insecure housing; (3) health-care policies and practices, leading to negative experiences that discourage access to care; and (4) restrictions on harm reduction programmes, including structural barriers to effective service provision. The second analytical theme, practices of care among people who use drugs, addressed protective strategies that people employ within infection risk environments. Associated descriptive themes were: (5) mutual care, including assisted-injecting and sharing sterile equipment; and (6) self-care, including vein health and self-treatment. Within constraining risk environments, some protective strategies for bacterial infections precipitated other health risks (e.g. HIV transmission). CONCLUSIONS: Injecting-related bacterial and fungal infections are shaped by modifiable social-structural factors, including poor quality unregulated drugs, criminalization and policing enforcement, insufficient housing, limited harm reduction services and harmful health-care practices. People who inject drugs navigate these barriers while attempting to protect themselves and their community.

'More of the same, but worse than before': A qualitative study of the challenges encountered by people who use drugs in Nova Scotia, Canada during COVID-19.

BACKGROUND: To learn about the experiences of people who use drugs, specifically opioids, in the Halifax Regional Municipality (HRM), in Nova Scotia, Canada during the COVID-19 pandemic through qualitative interviews with people who use drugs and healthcare providers (HCP). This study took place within the HRM, a municipality of 448,500 people [1]. During the pandemic many critical services were interrupted while overdose events increased. We wanted to understand the experiences of people who use drugs as well as their HCPs during the first year of the pandemic. METHODOLOGY: We conducted a qualitative study using semi-structured interviews with 13 people who use drugs and 6 HCPs, including physicians who work in addiction medicine (3), a pharmacist, a nurse, and a community-based opioid agonist therapy (OAT) program staff member. Participants were recruited within HRM. Interviews were held via phone or videoconference due to social distancing directives. Interviews focused on the challenges people who use drugs and HCPs faced during the pandemic as well as elicited perspectives on a safe supply of drugs and the associated barriers and facilitators to the provision of a safe supply. RESULTS: Of the 13 people who use drugs who participated in this study, ages ranged from 21-55 years (mean 40). Individuals had spent on average 17 years in HRM. Most people who use drugs (85%, n = 11) utilized income assistance, the Canadian Emergency Response Benefit, or disability support. Many had experienced homelessness (85%, n = 11) and almost half (46%, n = 6) were currently precariously housed in the shelter system. The main themes among interviews (people who use drugs and HCPs) were housing, accessing healthcare and community services, shifts in the drug supply, and perspectives on safe supply. CONCLUSIONS: We identified several challenges that people who use drugs face in general, but especially during the COVID-19 pandemic. Access to services, housing support, and interventions to use safely at home were limited. As many challenges faced by people who use drugs exist outside of COVID-19, we concluded that the formal and informal interventions and changes in practice that were made to support people who use drugs should be sustained well past the end of the pandemic. The need for enhanced community supports and a safe supply of drugs, despite its complicated nature, is essential for the health and safety of people who use drugs in HRM, especially during COVID-19.

Life-threatening presentation of a parahiatal hernia after esophagectomy: a case report and review of the literature.

A woman presented to our hospital with acute abdominal pain 7 months following an oesophagectomy. A chest X-ray revealed a new elevation of the left diaphragm. CT demonstrated a large left diaphragmatic hernia incarcerated with non-enhancing transverse colon and loops of small bowel. She deteriorated rapidly into obstructive shock and was urgently brought to the operating room for a laparotomy. The diaphragmatic orifice was identified in a left parahiatal position, consistent with a parahiatal hernia. Incarcerated necrotic transverse colon and ischaemic loops of small bowel were resected, and the diaphragmatic defect was closed primarily. Because of haemodynamic instability, the abdomen was temporarily closed, and a second look was performed 24 hours later, allowing anastomosis and definitive closure. Parahiatal hernias are rare complications following surgical procedures and can lead to devastating life-threatening complications, such as an obstructive shock. Expeditious diagnosis and management are required in the acute setting.

Intraoesophageal migration of Teflon pledgets used for hiatal hernia repair: a serious adverse event.

11 months following an elective paraoesophageal hernia repair, a female patient presents to the emergency department with severe dysphagia. A CT showed a distention of the distal oesophagus caused by a foreign body and dense material inside and outside the oesophagus wall. A gastroscopy confirmed the presence of a bezoar and secondary oesophagitis due to the intraoesophageal migration of Teflon pledgets. Even when used appropriately, only for the crus repair, the use of Teflon pledgets may result in fistulisation through the oesophagus. This complication suggests that the use of Teflon pledgets to buttress a hiatal hernia repair should be used with caution and that an alternative technique (eg, resorbable pledgets) could be preferred.

Cytomegalovirus-Driven Adaption of Natural Killer Cells in NKG2Cnull Human Immunodeficiency Virus-Infected Individuals.

Expansion of natural killer (NK) cells expressing NKG2C occurs following human cytomegalovirus (HCMV) infection and is amplified by human immunodeficiency virus (HIV) co-infection. These NKG2C-expressing NK cells demonstrate enhanced CD16-dependent cytokine production and downregulate FcεRIγ and promyelocytic leukemia zinc finger protein (PLZF). Lacking NKG2C diminishes resistance to HIV infection, but whether this affects NK cell acquisition of superior antibody-dependent function is unclear. Therefore, our objective was to investigate whether HCMV-driven NK cell differentiation is impaired in NKG2Cnull HIV-infected individuals. Phenotypic (CD2, CD16, CD57, NKG2A, FcεRIγ, and PLZF expression) and functional (cytokine induction and cytotoxicity) properties were compared between HIV⁻infected NKG2Cnull and NKG2C-expressing groups. Cytokine production was compared following stimulation through natural cytotoxicity receptors or through CD16. Cytotoxicity was measured by anti-CD16-redirected lysis and by classical antibody-dependent cell-mediated cytotoxicity (ADCC) against anti-class I human leukocyte antigen (HLA) antibody-coated cells. Our data indicate highly similar HCMV-driven NK cell differentiation in HIV infection with or without NKG2C. While the fraction of mature (CD57pos) NK cells expressing CD2 (p = 0.009) or co-expressing CD2 and CD16 (p = 0.03) was significantly higher in NKG2Cnull HIV-infected individuals, there were no significant differences in NKG2A, FcεRIγ, or PLZF expression. The general phenotypic and functional equivalency observed suggests NKG2C-independent routes of HCMV-driven NK cell differentiation, which may involve increased CD2 expression.

Origins of natural killer cell memory: special creation or adaptive evolution.

The few initial formative studies describing non-specific and apparently spontaneous activity of natural killer (NK) cells have since multiplied into thousands of scientific reports defining their unique capacities and means of regulation. Characterization of the array of receptors that govern NK cell education and activation revealed an unexpected relationship with the major histocompatibility molecules that NK cells originally became well known for ignoring. Proceeding true to form, NK cells continue to up-end archetypal understanding of their ever-expanding capabilities. Discovery that the NK cell repertoire is extremely diverse and can be reshaped by particular viruses into unique subsets of adaptive NK cells challenges, or at least broadens, the definition of immunological memory. This review provides an overview of studies identifying adaptive NK cells, addressing the origins of NK cell memory and introducing the heretical concept of NK cells with extensive antigenic specificity. Whether these newly apparent properties reflect adaptive utilization of known NK cell attributes and receptors or a specially creative allocation from an undefined receptor array remains to be fully determined.

Effects of a Pre-surgery Supervised Exercise Training 1 Year After Bariatric Surgery: a Randomized Controlled Study.

BACKGROUND: We have previously reported on the benefits of Pre-Surgical Exercise Training (PreSET) on physical fitness and social interactions in subjects awaiting bariatric surgery (BS). However, data are needed to know whether these benefits are maintained post-BS. OBJECTIVES: The purpose of this paper was to evaluate the effect of PreSET on physical activity (PA) level, physical fitness, PA barriers, and quality of life (QoL) 1 year (1-Y) after BS. METHODS: Of the 30 participants randomized into two groups (PreSET and usual care), 25 were included in the final analysis. One year after BS, time spent in different PA intensities and number of steps were assessed with an accelerometer. Before BS and until 1-Y after BS, physical fitness was assessed with symptom-limited cardiac exercise test, 6-min walk test (6MWT), and sit-to-stand, half-squat, and arm curl tests. QoL, PA barriers, and PA level were evaluated with questionnaires. RESULTS: The number of steps (7460 vs 4287) and time spent in light (3.2 vs 2.2 h/day) and moderate (0.6 vs 0.3 h/day) PA were higher in the PreSET group 1-Y after BS. The changes in 6MWT heart cost (1.3 vs 0.6 m/beats/min), half-squat test (38.8 vs 10.3 s), and BMI (- 16.8 vs - 13.5 kg/m2) were significantly greater in the PreSET group compared to those in the usual care group. No other significant difference between groups was observed. CONCLUSION: The addition of the PreSET to individual lifestyle counseling seems effective to improve PA level and submaximal physical fitness 1-Y after BS. Studies with larger cohorts are now required to confirm these results. The trial was registered at clinicaltrials.gov (NCT01452230).

NKG2C(+)CD57(+) Natural Killer Cell Expansion Parallels Cytomegalovirus-Specific CD8(+) T Cell Evolution towards Senescence.

Objective. Measuring NKG2C(+)CD57(+) natural killer (NK) cell expansion to investigate NK responses against human cytomegalovirus (HCMV) and assessing relationships with adaptive immunity against HCMV. Methods. Expansion of NKG2C(+)CD57(+) NK was measured in peripheral blood mononuclear cells (PBMC) from groups distinguished by HCMV and human immunodeficiency virus (HIV) infection status. Anti-HCMV antibody levels against HCMV-infected MRC-5 cell lysate were assessed by ELISA and HCMV-specific CD8(+) T cell responses characterized by intracellular flow cytometry following PBMC stimulation with immunodominant HCMV peptides. Results. Median NK, antibody, and CD8(+) T cell responses against HCMV were significantly greater in the HCMV/HIV coinfected group than the group infected with CMV alone. The fraction of CMV-specific CD8(+) T cells expressing CD28 correlated inversely with NKG2C(+)CD57(+) NK expansion in HIV infection. Conclusion. Our data reveal no significant direct relationships between NK and adaptive immunity against HCMV. However, stronger NK and adaptive immune responses against HCMV and an inverse correlation between NKG2C(+)CD57(+) NK expansion and proliferative reserve of HCMV-specific CD8(+) T cells, as signified by CD28 expression, indicate parallel evolution of NK and T cell responses against HCMV in HIV infection. Similar aspects of chronic HCMV infection may drive both NK and CD8(+) T cell memory inflation.

Impacts of Supervised Exercise Training in Addition to Interdisciplinary Lifestyle Management in Subjects Awaiting Bariatric Surgery: a Randomized Controlled Study.

BACKGROUND: Experts recommend physical activity (PA) to optimize bariatric surgery (BS) results. However, evidence on the effect of PA before BS is missing. The aim of this study was to assess the impact of adding a Pre-Surgical Exercise Training (PreSET) to an interdisciplinary lifestyle intervention on physical fitness, quality of life, PA barriers, and anthropometric parameters of subjects awaiting BS. METHODS: Thirty candidates for BS (43.2 ± 9.2 years, 47.5 ± 8.1 kg/m2) have been randomized in two groups: one group following the PreSET (endurance and strength training) and another receiving usual care. Before and after 12 weeks, we assessed physical fitness with a battery of tests (symptom-limited exercise test, 6-min walk test (6MWT), sit-to-stand test, half-squat test, and arm curl test), quality of life with the laval questionnaire, and PA barriers with the physical exercise belief questionnaire. RESULTS: One control group subject abandoned the study. Subjects in the PreSET group participated in 60.0 % of the supervised exercise sessions proposed. Results showed significant improvements in the 6MWT (17.4 ± 27.2 vs. -16.4 ± 42.4 m; p = 0.03), half-squat test (17.1 ± 17.9 vs. -0.9 ± 14.5 s; p = 0.05), arm curl repetitions (4.8 ± 2.3 vs. 1.0 ± 4.1; p = 0.01), social interaction score (10.7 ± 12.5 vs. -2.1 ± 11.0 %; p = 0.02), and embarrassment (-15.6 ± 10.2 vs. -3.1 ± 17.8 %; p = 0.02) in completers (n = 8) compared to the non-completers (n = 21). No significant difference between groups in BMI and other outcomes studied was observed after the intervention. CONCLUSIONS: Adding a PreSET to an individual lifestyle counselling intervention improved physical fitness, social interactions, and embarrassment. Post-surgery data would be interesting to confirm these benefits on the long term.

Early migration of fully covered double-layered metallic stents for post-gastric bypass anastomotic strictures.

INTRODUCTION: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is well recognized for its efficiency in morbidly obese patients. Anastomotic strictures present in 5-15% of cases and have a significant impact on the patient's quality of life. Endoscopic balloon dilation is the recommended treatment but management of refractory cases is challenging. PRESENTATION OF CASE: Two patients with anastomotic stenoses refractory to dilations were treated with fully covered esophageal stents. Both cases presented early stent migration. The first patient finally underwent surgical revision of the anastomosis. For the second patient, a double-layered stent was installed after the first incident. After the migration of this second stent, three sessions of intralesional injection of triamcinolone acetonide were performed. Both patients were free of obstructive symptoms at a follow-up of 9 months. DISCUSSION: Treatment of post-gastric bypass strictures with stents is based on years of successful experience with endoscopic stenting of malignant esophageal strictures, gastric outlet obstruction in addition to anastomotic stenoses after esophageal cancer surgery. The actual prosthesis are however inadequate for the particularities of the LRYGB anastomosis with a high migration rate. Intralesional corticosteroid injection therapy has been reported to be beneficial in the management of refractory benign esophageal strictures and seems to have prevented recurrence of the stenosis in this post-LRYGB. CONCLUSION: Stents are aimed at preventing a complex surgical reintervention but are not yet specifically designed for that indication. Local infiltration of corticosteroids at the time of dilation may prevent recurrence of the anastomotic stricture.