Material deprivation is associated with liver stiffness and liver-related outcomes in people with HIV.

BACKGROUND: Socioeconomic status (SES) is a driver of health disparities and chronic diseases. People with HIV (PWH) are at risk for chronic liver diseases. We evaluated the association between low SES and hepatic outcomes in PWH. METHODS: We included PWH from a prospective cohort. SES was assessed by the Pampalon material and social deprivation index to classify the cohort into quintiles of deprivation. Multivariable linear regression was used to investigate associations of material and social deprivation with liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) as markers of hepatic fibrosis and steatosis, respectively. Incidence of outcomes was evaluated through survival analysis. RESULTS: Among the 804 PWH included, 45% and 72% were living in areas of the highest material and social deprivation, respectively. Materially deprived PWH were more frequently female and of non-white ethnicity and had higher prevalence of metabolic comorbidities. After adjustments, material deprivation correlated with increased LSM (ß = 1.86, 95% CI 0.53-3.17) but not with CAP (ß = 6.47, 95% CI -5.55-18.49). Patients were observed for a median follow-up of 3.8 years. Incidence of liver-related events was higher in most materially deprived compared to most privileged PWH (hazard ratio 3.03, 95% CI 1.03-8.92), while there was no difference in extrahepatic outcomes or all-cause mortality. Social deprivation showed no association with either LSM or clinical outcomes. CONCLUSIONS: Living in materially deprived neighbourhoods as a proxy for lower SES, is associated with LSM and liver-related events in PWH. Future strategies should explore mechanisms underlying these relationships and whether enhanced material security improves hepatic outcomes.

Surgical Treatment of the Intraspinal Rib Head Dislocation in Children With Dystrophic Scoliosis Secondary to Type 1 Neurofibromatosis.

BACKGROUND: The purpose of this study was to explore the surgical treatment of intraspinal rib head dislocation (IRH) in children with dystrophic scoliosis secondary to type 1 neurofibromatosis (NF1-DS). METHODS: From 2006 to 2019, 32 of 128 patients with NF1-DS were found to have IRH and enrolled in this study. There were 19 boys and 13 girls with an average age of 8.8±2.6 years. Patients were divided into 2 groups: group A (n=25) without IRH resection and group B (n=7) with IRH resection. The intraspinal rib proportion (IRP), apical vertebra rotation, apical vertebral translation, main thoracic curve Cobb angle, trunk shift and thoracic kyphosis, lumbar lordosis, and sagittal vertebral axis were measured before and after the operation. Spinal injury was graded based on the American Spinal Injury Association (ASIA) Impairment Scale. RESULTS: The study group had a total of 42 IRH. The mean follow-up duration was 46.1±28.7 months. The preoperative IRP in both groups was similar (35.5±14.3% vs. 31.2±15.3%, P=0.522). The postoperative IRP was lower in group B (18.5±11.2% vs. 0%, P=0.002). The IRP in group A decreased from preoperative (31.2±15.3%) to postoperative (18.5±11.2%) (P<0.05). There was no significant difference in the apical vertebra rotation, apical vertebral translation, main thoracic curve Cobb angle, trunk shift, thoracic kyphosis, lumbar lordosis, and sagittal vertebral axis between the 2 groups before surgery and after surgery. Four patients with nerve injury caused by the IRH had full neurological recovery postoperatively. All patients were ASIA grade E at the last follow-up. CONCLUSIONS: The surgical treatment of IRH in children with NF1-DS should be determined on the basis of the presence of preoperative neurological symptoms. This study supports the practice of correcting spinal deformities only in patients with mild or no spinal cord injury. If there are obvious neurological symptoms, IRH resection is necessary to relieve spinal cord compression to recover nerve function. LEVEL OF EVIDENCE: Level III.

TRPM2 Silencing Causes G2/M Arrest and Apoptosis in Lung Cancer Cells via Increasing Intracellular ROS and RNS Levels and Activating the JNK Pathway.

BACKGROUND/AIMS: The oxidative stress sensor transient receptor potential melastatin-2 (TRPM2) ion channel has recently gained attention in many types of cancer. The lung tissue is highly susceptible to oxidative stress-mediated injury and diseases; therefore, we aimed to determine whether TRPM2 plays an essential role in protecting lung cancer cells from oxidative damage while promoting cancer cell survival and metastasis. METHODS: We used two non-small cell lung (NSCLC) cell lines A549 and H1299 as a lung cancer model. We investigated the functional expression of TRPM2 using electrophysiology, qRT-PCR and Western blots. CFSE and flow cytometry were used to study TRPM2 role in proliferation, cell cycle and apoptosis. Gap closure chambers and Three-Tiered Chemotaxis Chamber were used to study the role of TRPM2 in metastasis. SCID mice were used to study the role of TRPM2 in lung tumor growth and metastasis. RESULTS: we demonstrate that TRPM2 is functionally expressed in NSCLC cells and that its downregulation significantly inhibits cell proliferation and promotes apoptosis. These results were concomitant with an induction in DNA damage and G2/M cell cycle arrest. TRPM2 silencing inhibits also lung cancer cells invasion ability and alters EMT processes. Mechanistically, TRPM2 downregulation causes an increase in the intracellular levels of reactive oxygen (ROS) and nitrogen (RNS) species, which in turn causes DNA damage and JNK activation leading to G2/M arrest, and an ultimate cell death. Finally, TRPM2 downregulation suppresses the growth of human lung tumour xenograft in SCID mice and TRPM2 depleted tumours exhibited a significant reduction in the mRNA expression level of EMT markers compared to the control tumors. CONCLUSION: Our data provide new insights on the functional expression of TRPM2 in lung cancer, its essential role in tumour growth and metastasis through the control of JNK signaling pathway, and that TRPM2 could be exploited for targeted lung cancer therapies.

Haemophagocytic Lymphohistiocytosis Following the anti-PD-1 Nivolumab in a Patient with Gastric Cancer and Ankylosing Spondylitis.

Background: Autoimmune diseases are not contraindications for immune checkpoint inhibitors (ICI) therapy in patients with cancer. However, immune-related adverse events (irAEs) are frequently observed in patients receiving ICIs including dermatitis, thyroiditis, colitis, and pneumonitis. Thrombocytopenic purpura, aplasia, and haemophagocytic lymphohistiocytosis (HLH) are rarely observed during ICIs. Case description: We report the case of a male patient with pre-existing untreated HLA B27 and ankylosing spondylitis with gastric cancer and liver metastases. The 79-year-old man was treated with anti-HER2 trastuzumab and anti-PD-1 nivolumab. Seventeen days after the seventh cycle of treatment, he presented at the emergency department with acute fever, confusion, and hypotension. Laboratory results showed pancytopenia, and elevation of ferritin and triglyceride. No infections were detected. Although not seen in a bone marrow biopsy, clinical presentation, and absence of infection, together with an H-score of 263, indicated HLH. The patient was treated with dexamethasone for four days and discharged on a tapering dose of steroids. At the two-month follow-up, clinical presentation was normal and blood test almost normalised. At 8 months, no liver metastases were observed. Conclusions: In a patient with a pre-existing autoimmune condition, immunotherapy led to the development of HLH, which was controlled by glucocorticoid. Absence of the feature of haemophagocytosis in the bone marrow biopsy did not exclude the diagnosis, as HLH can occur in the spleen or in the liver. Glucocorticoid therapy did not prevent the anti-cancer effect of ICIs, and liver metastases disappeared 8 months post-HLH. This case warrants further research on the interplay between autoimmunity and ICI response, as well as ICI-induced irAEs. LEARNING POINTS: Haemophagocytic lymphohistiocytosis (HLH) post seventh cycle of trastuzumab (anti-HER2) and nivolumab (anti-PD-1) was controlled with glucocorticoid.Breach of tolerance was due to immunotherapy-induced HLH in a patient with pre-existing autoimmune condition (HLA B27- positive ankylosing spondylitis).There was a complete disappearance of liver metastases 8 months post-HLH.

Community Power-Building Groups And Public Health NGOs: Reimagining Public Health Advocacy.

Public health frameworks have grappled with the inequitable distribution of power as a driver of the social conditions that determine health. However, these frameworks have not adequately considered building community power as a strategy to shift the distribution of power. Community power-building organizations build and organize a base of affected people to take collective action to transform their material conditions, using advocacy and other tactics. We conducted qualitative interviews with representatives of twenty-two national nongovernmental public health organizations (public health NGOs) and thirteen community power-building organizations to explore the nature and potential of partnerships between public health and community power-building organizations. Our findings suggest ways to close advocacy gaps within the public health ecosystem and ways in which public health can strategically leverage its power, resources, and expertise to support social justice campaigns and movements.

Fixed Drug Eruption to Trimethoprim-Sulfamethoxazole and Doxycycline.

Fixed drug eruption (FDE) is a common cutaneous drug eruption. We are the first to report a case of polysensitive FDE to both trimethoprim-sulfamethoxazole (TMP-SMX) and doxycycline. Diagnosis of FDE is largely clinical, and it is important to establish a good medication history to identify the causative agent. Treatment depends on avoidance of the implicated drug.

How Should Health Professionals and Policy Makers Respond to Substandard Care of Detained Immigrants?

More people, including children and pregnant women, are being detained for longer periods in a patchwork of over 200 detention centers around the country, most of which are private facilities or county jails. Human Rights Watch has documented systemic medical care failures at these facilities, including incompetent treatment, which is linked to patient deaths. Clinicians working in these facilities face formidable obstacles to providing adequate care, two of which are the Department of Homeland Security's lack of reasonable alternatives to detention and insufficient staffing. Harm caused by these conditions and detention itself should be enough to prompt clinicians to insist that the government enable provision of care consistent with generally accepted standards, including through reducing the detained population.

Building a better virus trap.

The concept of ecological 'traps' is based in theory from ecology and conservation biology that has now found application to infectious diseases with a study from Paul Turner's group. This study is important because it offers a mathematical model of ecological traps, applies this model to viruses, and tests the model in a bacteria-phage system. Although there will be technical hurdles to overcome, this concept might lead to benefits for both health and industry.

Evidence of a robust resident bacteriophage population revealed through analysis of the human salivary virome.

Viruses are the most abundant known infectious agents on the planet and are significant drivers of diversity in a variety of ecosystems. Although there have been numerous studies of viral communities, few have focused on viruses within the indigenous human microbiota. We analyzed 2 267 695 virome reads from viral particles and compared them with 263 516 bacterial 16S rRNA gene sequences from the saliva of five healthy human subjects over a 2- to 3-month period, in order to improve our understanding of the role viruses have in the complex oral ecosystem. Our data reveal viral communities in human saliva dominated by bacteriophages whose constituents are temporally distinct. The preponderance of shared homologs between the salivary viral communities in two unrelated subjects in the same household suggests that environmental factors are determinants of community membership. When comparing salivary viromes to those from human stool and the respiratory tract, each group was distinct, further indicating that habitat is of substantial importance in shaping human viromes. Compared with coexisting bacteria, there was concordance among certain predicted host-virus pairings such as Veillonella and Streptococcus, whereas there was discordance among others such as Actinomyces. We identified 122 728 virulence factor homologs, suggesting that salivary viruses may serve as reservoirs for pathogenic gene function in the oral environment. That the vast majority of human oral viruses are bacteriophages whose putative gene function signifies some have a prominent role in lysogeny, suggests these viruses may have an important role in helping shape the microbial diversity in the human oral cavity.

Bacterial diversity in the oral cavity of 10 healthy individuals.

The composition of the oral microbiota from 10 individuals with healthy oral tissues was determined using culture-independent techniques. From each individual, 26 specimens, each from different oral sites at a single point in time, were collected and pooled. An 11th pool was constructed using portions of the subgingival specimens from all 10 individuals. The 16S ribosomal RNA gene was amplified using broad-range bacterial primers, and clone libraries from the individual and subgingival pools were constructed. From a total of 11,368 high-quality, nonchimeric, near full-length sequences, 247 species-level phylotypes (using a 99% sequence identity threshold) and 9 bacterial phyla were identified. At least 15 bacterial genera were conserved among all 10 individuals, with significant interindividual differences at the species and strain level. Comparisons of these oral bacterial sequences with near full-length sequences found previously in the large intestines and feces of other healthy individuals suggest that the mouth and intestinal tract harbor distinct sets of bacteria. Co-occurrence analysis showed significant segregation of taxa when community membership was examined at the level of genus, but not at the level of species, suggesting that ecologically significant, competitive interactions are more apparent at a broader taxonomic level than species. This study is one of the more comprehensive, high-resolution analyses of bacterial diversity within the healthy human mouth to date, and highlights the value of tools from macroecology for enhancing our understanding of bacterial ecology in human health.

The competitive cost of antibiotic resistance in Mycobacterium tuberculosis.

Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates.