Trends in toxicological findings in unintentional opioid or stimulant toxicity deaths in Québec, Canada, 2012-2021: Has Québec entered a new era of drug-related deaths?

INTRODUCTION: We aimed to describe rates and toxicological findings of unintentional opioid and stimulant toxicity deaths, 2012-2021. METHODS: The dataset included accidental deaths determined by the Coroner to be due to opioids or stimulants. We calculated annual crude mortality rates and described combinations of drugs identified in toxicological examinations of these deaths. We described temporal trends in the detection of specific opioids, stimulants, benzodiazepines (including novel benzodiazepines), gabapentinoids and z-drugs in deaths due to opioids and stimulants. RESULTS: Mortality rates increased over time, reaching their peak in 2020 and remaining high in 2021. In deaths due to opioids, there was a decline in the proportion of deaths involving pharmaceutical opioids after 2019, and a corresponding increase in the proportion of deaths with fentanyl detected. Benzodiazepines were often present in deaths due to opioids, with novel benzodiazepines increasing rapidly from 2019 onwards. Cocaine was the most frequently detected drug in deaths due to stimulants, but amphetamine/methamphetamine was detected in around half of all stimulant deaths from 2016 onwards. DISCUSSION AND CONCLUSIONS: Despite availability of a multitude of overdose prevention interventions, mortality rates due to drug toxicity have increased in Québec. Toxicological findings of these deaths suggest concerning shifts in the illicit drug market, with Québec potentially having entered a new era of elevated overdose mortality. Intervention scale-up is essential, but unlikely to be sufficient, to reduce drug-related mortality. Policy reform to address the root causes of drug toxicity deaths, including an unpredictable drug supply, strained health systems and socio-economic precarity, is essential.

Factor H-related protein 1 in systemic lupus erythematosus.

Background: Factor H (FH) is a major soluble inhibitor of the complement system and part of a family comprising five related proteins (FHRs 1-5). Deficiency of FHR1 was described to be linked to an elevated risk of systemic lupus erythematosus (SLE). As FHR1 can partially antagonize the functionality of FH, an altered FHR1/FH ratio could not only enhance SLE vulnerability but also affect the disease expression. This study focuses on the analysis of FH and FHR1 at a protein level, and the occurrence of anti-FH autoantibodies (anti-FH) in a large cohort of SLE patients to explore their association with disease activity and/or expression. Methods: We assessed FH and FHR1 levels in plasma from 378 SLE patients compared to 84 healthy controls (normal human plasma, NHP), and sera from another cohort of 84 healthy individuals (normal human serum, NHS), using RayBio® CFH and CFHR1 ELISA kits. Patients were recruited by the Swiss SLE Cohort Study (SSCS). Unmeasurable FHR1 levels were all confirmed by Western blot, and in a subgroup of patients by PCR. Anti-FH were measured in SLE patients with non-detectable FHR1 levels and matched control patients using Abnova's CFH IgG ELISA kit. Results: Overall, FH and FHR1 levels were significantly higher in healthy controls, but there was no significant difference in FHR1/FH ratios between SLE patients and NHPs. However, SLE patients showed a significantly higher prevalence of undetectable FHR1 compared to all healthy controls (35/378 SLE patients versus 6/168 healthy controls; p= 0.0214, OR=2.751, 95% CI = 1.115 - 8.164), with a consistent trend across all ethnic subgroups. Levels of FH and FHR1, FHR1/FH ratios and absence of FHR1 were not consistently associated with disease activity and/or specific disease manifestations, but absence of FHR1 (primarily equivalent to CFHR1 deficiency) was linked to the presence of anti-FH in SLE patients (p=0.039). Conclusions: Deficiency of FHR1 is associated with a markedly elevated risk of developing SLE. A small proportion of FHR1-deficient SLE patients was found to have autoantibodies against FH but did not show clinical signs of microangiopathy.

Magnesium matters: unveiling hidden risks in kidney transplant patients through total and ionized magnesium profiling.

Background: In kidney transplant (KT) patients, magnesium (Mg2+) deficiency is widespread. It is often encountered early after KT, may persist longer, and is frequently promoted by calcineurin inhibitors (CNIs) and tubular leakage. Studies demonstrated an association between post-KT hypomagnesemia and allograft dysfunction. The concentration of the active form, the ionized Mg2+ (iMg2+), is not measured clinically, and total Mg2+ (tMg2+) and iMg2+ correlations are conflicting. We assess the cross-sectional prevalence of hypomagnesemia in KT patients. The correlation of demographic and anthropometric parameters was also studied. Methods: A prospective, single-center analysis of KT patients was conducted at the University Hospital of Bern, Switzerland (March 2023-August 2023). Blood samples were collected at least twice for the majority of patients. tMg2+ has been quantified from a plasma sample at the Clinical Chemistry Department of the University Hospital of Bern. The PRIME® ES analyzer (Nova Biomedical, USA) provided results for iMg2+. The following co-variables were considered: age, comorbidities, kidney disease, KT history, estimated glomerular filtration rate (eGFR), and treatment (including Mg2+ supplementation and immunosuppression). Results: A total of 208 measurements in 104 patients were performed [once in 9/104 patients (8.7%), twice in 86/104 (82.7%), and three times in 9/104 (8.7%)]. Compared to that in healthy volunteers (51 measurements in 51 participants), mean iMg2+ was significantly lower in KT patients {KT: 0.46 mmol/L [interquartile range (IQR): 0.40-0.50], volunteers: 0.57 mmol/L (IQR 0.54-0.61), p < 0.01}. Overall, iMg2+ and tMg2+ showed strong category agreement (r2 = 0.93, p < 0.01). In linear regression, low iMg2+ correlated with CNI exposure. For 110/208 measurements (52.9%), a reduced iMg2+ (cutoff: 0.42 mmol/L) was shown. In 58/208 (27.9%), both values were reduced, and 52/208 (25%) had isolated reduced iMg2+. In principal component analysis, patients with isolated low iMg2+ clustered with patients with low iMg2+ and tMg2+. Conclusion: iMg2+ and tMg2+ were strongly correlated. A substantial proportion of patients show isolated low iMg2+. Currently, it is unclear if these patients suffer from Mg2+ deficiency.

Corrigendum: Effectiveness of perindopril/amlodipine fixed-dose combination in the treatment of hypertension: a systematic review.

[This corrects the article DOI: 10.3389/fphar.2023.1156655.].

Tailored synthesis of pH-responsive biodegradable microcapsules incorporating gelatin, alginate, and hyaluronic acid for effective-controlled release.

In response to escalating environmental concerns and the urgent need for sustainable drug delivery systems, this study introduces biodegradable pH-responsive microcapsules synthesized from a blend of gelatin, alginate, and hyaluronic acid. Employing the coacervation process, capsules were created with a spherical shape, multicore structure, and small sizes ranging from 10 to 20 µm, which exhibit outstanding vitamin E encapsulation efficiency. With substantial incorporation of hyaluronic acid, a pH-responsive component, the resulting microcapsules displayed noteworthy swelling behavior, facilitating proficient core ingredient release at pH 5.5 and 7.4. Notably, these capsules can effectively deliver active substances to the dermal layer under specific skin conditions, revealing promising applications in topical medications and cosmetics. Furthermore, the readily biodegradable nature of the designed capsules was demonstrated through Biochemical Oxygen Demand (BOD) testing, with over 80 % of microcapsules being degraded by microorganisms after one week of incubation. This research contributes to the development of responsive microcapsules and aligns with broader environmental initiatives, offering a promising pathway to mitigate the impact of microplastics while advancing various applications.

Opioid prescribing practices in breast oncologic surgery-A retrospective cohort study.

BACKGROUND: In breast oncologic surgery, 75% of patients receive a postoperative opioid prescription at discharge, and 10%-20% will develop persistent opioid use. To inform future institutional guidelines, the objective of this study was to determine baseline opioid prescribing patterns in a single high-volume, referral-based breast center. We hypothesized that opioid prescribing practices varied between procedures and operating surgeons. METHODS: A retrospective analysis of all women undergoing breast cancer surgery between January and December 2019. Opioid prescriptions at discharge were converted to morphine milligram equivalents (MME). The primary outcome of interest was MME prescribed at discharge. Multiple linear regression was used to identify factors independently associated with MME prescribed. RESULTS: 392 patients met inclusion criteria; 68.3% underwent partial mastectomy. Median age was 61 (interquartile range [IQR] 51-70). Median MME prescribed at discharge was 112.5 (IQR 75-150); 83.9% of patients were prescribed co-analgesia. The prescriber was a trainee in 37.7% of cases. 15 patients (3.8%) required opioid renewal. On multivariate analysis, axillary procedure was associated with increased MME (ß = 17, 95% CI 5.5-28 and ß = 32, 95% CI 17-47, for sentinel node and axillary dissection, respectively). However, the factor with the greatest impact on MME was operating surgeon (ß = 72, 95% CI 58-87). Residents prescribed less MME compared to attending surgeons (ß = 11, 95% CI -22; -0.06). CONCLUSION: In a tertiary care center, the operating surgeon had the greatest influence on opioid prescribing practices, and trainees tended to prescribe less MME. These findings support the need for a standardized approach to optimize prescribing and reduce opioid-related harms after oncologic breast surgery.

SABRE hyperpolarization of nicotinamide derivatives and their molecular dynamics properties.

Signal amplification by reversible exchange hyperpolarization explores the chemical structure and kinetic properties of nicotinamide derivatives. N-Benzyl nicotinamide and nicotinic acid hydrazide compounds display relatively fast dissociation rates of approximately 7-8 s-1 and long proton T1 relaxation times of 5-20 s, respectively. Consequently, these substrates exhibit remarkable signal enhancements, reaching approximately 175 and 102 fold, respectively, underscoring the efficacy of the hyperpolarization technique in elucidating the behavior of these compounds.

Immune Monitoring-Guided Versus Fixed Duration of Antiviral Prophylaxis Against Cytomegalovirus in Solid-Organ Transplant Recipients: A Multicenter, Randomized Clinical Trial.

BACKGROUND: The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation. METHODS: In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus. RESULTS: Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001). CONCLUSIONS: Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection. CLINICAL TRIALS REGISTRATION: NCT02538172.

Immunogenicity of High-Dose Versus MF59-Adjuvanted Versus Standard Influenza Vaccine in Solid Organ Transplant Recipients: The Swiss/Spanish Trial in Solid Organ Transplantation on Prevention of Influenza (STOP-FLU Trial).

BACKGROUND: The immunogenicity of the standard influenza vaccine is reduced in solid-organ transplant (SOT) recipients, so new vaccination strategies are needed in this population. METHODS: Adult SOT recipients from 9 transplant clinics in Switzerland and Spain were enrolled if they were >3 months after transplantation. Patients were randomized (1:1:1) to a MF59-adjuvanted or a high-dose vaccine (intervention), or a standard vaccine (control), with stratification by organ and time from transplant. The primary outcome was vaccine response rate, defined as a ≥4-fold increase of hemagglutination-inhibition titers to at least 1 vaccine strain at 28 days postvaccination. Secondary outcomes included polymerase chain reaction-confirmed influenza and vaccine reactogenicity. RESULTS: A total of 619 patients were randomized, 616 received the assigned vaccines, and 598 had serum available for analysis of the primary endpoint (standard, n = 198; MF59-adjuvanted, n = 205; high-dose, n = 195 patients). Vaccine response rates were 42% (84/198) in the standard vaccine group, 60% (122/205) in the MF59-adjuvanted vaccine group, and 66% (129/195) in the high-dose vaccine group (difference in intervention vaccines vs standard vaccine, 0.20; 97.5% confidence interval [CI], .12-1); P < .001; difference in high-dose vs standard vaccine, 0.24 [95% CI, .16-1]; P < .001; difference in MF59-adjuvanted vs standard vaccine, 0.17 [97.5% CI, .08-1]; P < .001). Influenza occurred in 6% of the standard, 5% in the MF59-adjuvanted, and 7% in the high-dose vaccine groups. Vaccine-related adverse events occurred more frequently in the intervention vaccine groups, but most of the events were mild. CONCLUSIONS: In SOT recipients, use of an MF59-adjuvanted or a high-dose influenza vaccine was safe and resulted in a higher vaccine response rate. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov NCT03699839.

Lectin-mediated, time-efficient, and high-yield sorting of different morphologically intact nephron segments.

The kidney is a highly complex organ equipped with a multitude of miniscule filter-tubule units called nephrons. Each nephron can be subdivided into multiple segments, each with its own morphology and physiological function. To date, conventional manual approaches to isolate specific nephron segments are very laborious, time-consuming, often limited to only a specific segment, and typically have low yield. Here, we describe a novel, unconventional method that is superior in many aspects to previous protocols by combining low-cost fluorophore-conjugated lectins or agglutinins (Flaggs) with flow sorting. This allows the simultaneous separation of different nephron segments with preserved 3D morphology from mouse or human samples in under 3 h. Using a 200-µm nozzle and 5 psi, glomeruli, proximal, or distal convoluted tubules are sorted with Cy3-labeled Sambucus Nigra agglutinin (SNA-Cy3), Fluorescein-labeled Lotus Tetragonolobus lectin (LTL-FITC), or Pacific Blue-labeled soybean agglutinin (SBA-PB), respectively. Connecting tubules and collecting ducts are sorted by double-positive SBA-PB and SNA-Cy3 signals, while thick ascending limb segments are characterized by the absence of any Flaggs labeling. From two mouse kidneys, this yields 37-521 ng protein/s or 0.71-16.71 ng RNA/s, depending on the specific nephron segment. The purity of sorted segments, as assessed by mRNA expression level profiling of 15 genes, is very high with a 96.1-fold median enrichment across all genes and sorted segments. In summary, our method represents a simple, straightforward, cost-effective, and widely applicable tool yielding high amounts of pure and morphologically largely intact renal tubule materials with the potential to propel nephron segment-specific research.

Worse cardiovascular and renal outcome in male SLE patients.

Systemic lupus erythematosus (SLE) in males is rare and poorly understood. Thus, still little is known about sex differences in SLE. We set out to identify sex differences regarding clinical manifestations as well as renal and cardiovascular outcomes of SLE. We analyzed patient data from the Swiss SLE Cohort Study. Cumulative clinical manifestations according to the updated American College of Rheumatology criteria were recorded at inclusion. Cardiovascular events were recorded within Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC-SDI). Renal failure was defined as eGFR < 15 ml/min/1.73 m2, initiation of renal replacement therapy or doubling of serum creatinine which were all assessed yearly or documented as end stage renal disease in SLICC-SDI. Risk differences were calculated using logistic regression and cox regression models. We analyzed 93 men and 529 women with a median follow up time of 2 years. Males were significantly older at diagnosis (44.4 versus 33.1 years, p < 0.001) and had less often arthritis (57% versus 74%, p = 0.001) and dermatological disorders (61% versus 76%, p < 0.01). In multivariate analysis female sex remained a significantly associated with arthritis and dermatological disorders. In multivariate analysis men had a significantly higher hazard ratio of 2.3 for renal failure (95% confidence interval (95%-CI) 1.1-5.2, p < 0.04). Total SLICC-SDI Score was comparable. Men had significantly more coronary artery disease (CAD) (17% versus 4%, p < 0.001) and myocardial infarction (10% versus 2%, p < 0.01). In multivariate analysis, male sex remained a significant risk factor for CAD (odds ratio (OR) 5.6, 95%-CI 2.3-13.7, p < 0.001) and myocardial infarction (OR 8.3, 95%-CI 2.1-32.6, p = 0.002). This first sex study in a western European population demonstrates significant sex differences in SLE. Male sex is a risk factor for cardiovascular events and renal failure in SLE. Potential etiological pathomechanisms such as hormonal or X-chromosomal factors remain to be further investigated.

Screening of cognitive performance in kidney transplant recipients: a mini review.

Why should we screen?: The prevalence of cognitive impairment in kidney transplant recipients (KTRs) is up to 58%. The 10-year graft loss and mortality rates are above 30% and 50%, respectively, and executive malfunctioning increases disadvantageous outcomes. What causes cognitive impairment in KTRs?: Strong risk factors are older age and chronic kidney disease. However, causes are multifactorial and include cardiovascular, cerebrovascular, neurodegenerative, inflammatory, uremic, psychiatric, and lifestyle-related susceptibilities. How should we screen?: KTR-specific validated instruments or strategies do not exist. The central element should be a multidomain cognitive screening test that is sensitive to mild cognitive impairment, corrects for age and education, and includes executive functions testing. Cognitive trajectories, effects on everyday life and psychiatric comorbidities should be assessed by integrating the perspectives of both patients and knowledgeable informants. When should we screen?: Screening should not be postponed if there is suspicion of impaired cognition. Different time points after transplantation tend to have their own characteristics. Who should conduct the screening?: Screening should not be limited to specialists. It can be carried out by any healthcare professional who has received a limited amount of training. What are the benefits of screening?: Screening does not provide a diagnosis. However, suggestive results change care in multiple ways. Goals are: Initiation of professional dementia work-up, securing of adherence, anticipation of potential complications (delirium, falls, frailty, functional impairment, malnutrition, etc.), mitigation of behavioral disorders, adjustment of diagnostic and therapeutic "load", reduction of caregiver burden and meeting of changing needs. We summarize data on the prevalence, risk factors and sequelae of cognitive impairment in KTRs. We also discuss the requirements for appropriate screening strategies and provide guiding principles regarding appropriate and safe care.

Pharmacological Activities and Safety of Ganoderma lucidum Spores: A Systematic Review.

Ganoderma lucidum is traditionally used to prevent and treat some diseases such as liver disorders, hypertension, insomnia, diabetes, and cancer. G. lucidum spore extracts are also reported to share similar bioactivities as extracts from its other parts. However, there is no systematic review that elucidates its pharmacological effect. Our aim is to comprehensively summarise current evidence of G. lucidum spore extracts to clarify its benefits to be applied in further studies. We searched five primary databases: PubMed, Virtual Health Library (VHL), Global Health Library (GHL), System for Information on Grey Literature in Europe (SIGLE), and Google Scholar on September 13, 2021. Articles were selected according to inclusion and exclusion criteria. A manual search was applied to find more relevant articles. Ninety studies that reported the pharmacological effects and/or safety of G. lucidum spores were included in this review. The review found that G. lucidum spore extracts showed quite similar effects as other parts of this medicinal plant including anti-tumor, anti-inflammatory, antioxidant effects, and immunomodulation. G. lucidum sporoderm-broken extract demonstrated higher efficiency than unbroken spore extract. G. lucidum extracts also showed their effects on some genes responsible for the body's metabolism, which implied the benefits in metabolic diseases. The safety of G. lucidum should be investigated in depth as high doses of the extract could increase levels of cancer antigen (CA)72-4, despite no harmful effect shown on body organs. Generally, there is a lot of potential in the studies of compounds with pharmacological effects and new treatments. Sporoderm breaking technique could contribute to the production of extracts with more effective prevention and treatment of diseases. High doses of G. lucidum spore extract should be used with caution as there was a concern about the increase in CA.

Impact of enhanced recovery pathways on patient-reported outcomes after abdominal surgery: a systematic review.

INTRODUCTION: Evidence supports that enhanced recovery pathways (ERPs) reduce length of stay and complications; however, these measures may not reflect the perspective of patients who are the main stakeholders in the recovery process. This systematic review aimed to appraise the evidence regarding the impact of ERPs on patient-reported outcomes (PROs) after abdominal surgery. METHODS: Five databases (Medline, Embase, Biosis, Cochrane, and Web of Science) were searched for randomized controlled trials (RCTs) addressing the impact of ERPs on PROs after abdominal surgery. We focused on distinct periods of recovery: early (within 7 days postoperatively) and late (beyond 7 days). Risk of bias was assessed using Cochrane's RoB 2.0. Results were appraised descriptively as heterogeneity hindered meta-analysis. Certainty of evidence was evaluated using GRADE. RESULTS: Fifty-six RCTs were identified [colorectal (n = 18), hepatopancreaticobiliary (HPB) (n = 11), upper gastrointestinal (UGI) (n = 10), gynecological (n = 7), urological (n = 7), general surgery (n = 3)]. Most trials had 'some concerns' (n = 30) or 'high' (n = 25) risk of bias. In the early postoperative period, ERPs improved patient-reported general health (colorectal, HPB, UGI, urological; very low to low certainty), physical health (colorectal, gynecological; very low to low certainty), mental health (colorectal, gynecological; very low certainty), pain (all specialties; very low to moderate certainty), and fatigue (colorectal; low certainty). In the late postoperative period, ERPs improved general health (HPB, UGI, urological; very low certainty), physical health (UGI, gynecological, urological; very low to low certainty), mental health (UGI, gynecological, urological; very low certainty), social health (gynecological; very low certainty), pain (gynecological, urological; very low certainty), and fatigue (gynecological; very low certainty). CONCLUSION: This review supports that ERPs may have a positive impact on patient-reported postoperative health status (i.e., general, physical, mental, and social health) and symptom experience (i.e., pain and fatigue) after abdominal surgery; however, data were largely derived from low-quality trials. Although these findings contribute important knowledge to inform evidence-based ERP implementation, there remains a great need to improve PRO assessment in studies focused on postoperative recovery.

Outcomes of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked disorder characterized by combined immunodeficiency, eczema, microthrombocytopenia, autoimmunity, and lymphoid malignancies. Gene therapy (GT) to modify autologous CD34+ cells is an emerging alternative treatment with advantages over standard allogeneic hematopoietic stem cell transplantation for patients who lack well-matched donors, avoiding graft-versus-host-disease. We report the outcomes of a phase 1/2 clinical trial in which 5 patients with severe WAS underwent GT using a self-inactivating lentiviral vector expressing the human WAS complementary DNA under the control of a 1.6-kB fragment of the autologous promoter after busulfan and fludarabine conditioning. All patients were alive and well with sustained multilineage vector gene marking (median follow-up: 7.6 years). Clinical improvement of eczema, infections, and bleeding diathesis was universal. Immune function was consistently improved despite subphysiologic levels of transgenic WAS protein expression. Improvements in platelet count and cytoskeletal function in myeloid cells were most prominent in patients with high vector copy number in the transduced product. Two patients with a history of autoimmunity had flares of autoimmunity after GT, despite similar percentages of WAS protein-expressing cells and gene marking to those without autoimmunity. Patients with flares of autoimmunity demonstrated poor numerical recovery of T cells and regulatory T cells (Tregs), interleukin-10-producing regulatory B cells (Bregs), and transitional B cells. Thus, recovery of the Breg compartment, along with Tregs appears to be protective against development of autoimmunity after GT. These results indicate that clinical and laboratory manifestations of WAS are improved with GT with an acceptable safety profile. This trial is registered at clinicaltrials.gov as #NCT01410825.

ITGAM rs1143679 Variant in Systemic Lupus Erythematosus Is Associated with Increased Serum Calcification Propensity.

OBJECTIVES: CD11B/ITGAM (Integrin Subunit α M) mediates the adhesion of monocytes, macrophages, and granulocytes and promotes the phagocytosis of complement-coated particles. Variants of the ITGAM gene are candidates for genetic susceptibility to systemic lupus erythematosus (SLE). SNP rs1143679 (R77H) of CD11B particularly increases the risk of developing SLE. Deficiency of CD11B is linked to premature extra-osseous calcification, as seen in the cartilage of animals with osteoarthritis. Serum calcification propensity measured by the T50 test is a surrogate marker for systemic calcification and reflects increased cardiovascular (CV) risk. We aimed to assess whether the CD11B R77H gene variant is associated with a higher serum calcification propensity (i.e., a lower T50 value) in SLE patients compared to the wild-type allele (WT). METHODS: Cross-sectional study incorporating adults with SLE genotyped for the CD11B variant R77H and assessed for serum calcification propensity with the T50 method. Participants were included in a multicenter trans-disciplinary cohort and fulfilled the 1997 revised American College of Rheumatology (ACR) criteria for SLE. We used descriptive statistics for comparing baseline characteristics and sequential T50 measurements in subjects with the R77H variant vs. WT CD11B. RESULTS: Of the 167 patients, 108 (65%) were G/G (WT), 53 (32%) were G/A heterozygous, and 6 (3%) were A/A homozygous for the R77H variant. A/A patients cumulated more ACR criteria upon inclusion (7 ± 2 vs. 5 ± 1 in G/G and G/A; p = 0.02). There were no differences between the groups in terms of global disease activity, kidney involvement, and chronic renal failure. Complement C3 levels were lower in A/A individuals compared to others (0.6 ± 0.08 vs. 0.9 ± 0.25 g/L; p = 0.02). Baseline T50 did not differ between the groups (A/A 278 ± 42' vs. 297 ± 50' in G/G and G/A; p = 0.28). Considering all sequential T50 test results, serum calcification propensity was significantly increased in A/A individuals compared to others (253 ± 50 vs. 290 ± 54; p = 0.008). CONCLUSIONS: SLE patients with homozygosity for the R77H variant and repeated T50 assessment displayed an increased serum calcification propensity (i.e., a lower T50) and lower C3 levels compared to heterozygous and WT CD11B, without differing with respect to global disease activity and kidney involvement. This suggests an increased CV risk in SLE patients homozygous for the R77H variant of CD11B.

Multidisciplinary recommendations for essential baseline functional and laboratory tests to facilitate early diagnosis and management of immune-related adverse events among cancer patients.

Immune checkpoint inhibitors (ICIs) have fundamentally changed the treatment landscape of various cancers. While ICI treatments result in improved survival, quality of life and are cost-effective, the majority of patients experience at least one immune-related adverse event (irAE). Many of these side effects cause little discomfort or are asymptomatic; however, irAEs can affect any organ and are potentially life-threatening. Consequently, early diagnosis and appropriate treatment of irAEs are critical for optimizing long-term outcomes and quality of life in affected patients. Some irAEs are diagnosed according to typical symptoms, others by abnormal findings from diagnostic tests. While there are various guidelines addressing the management of irAEs, recommendations for the early recognition of irAEs as well as the optimal extent and frequency of laboratory tests are mostly lacking. In clinical practice, blood sampling is usually performed before each ICI administration (i.e., every 2-3 weeks), often for several months, representing a burden for patients as well as health care systems. In this report, we propose essential laboratory and functional tests to improve the early detection and management of irAEs and in cancer patients treated with ICIs. These multidisciplinary expert recommendations regarding essential laboratory and functional tests can be used to identify possible irAEs at an early time point, initiate appropriate interventions to improve patient outcomes, and reduce the burden of blood sampling during ICI treatment.

Bosma Arhinia Microphthalmia Syndrome (BAMS): First Report from Vietnam.

Bosma arhinia microphthalmia syndrome (BAMS) is a rare condition, with about 100 cases identified worldwide. It is characterized by nasal and ophthalmic abnormalities, as well as disturbances in puberty and sexual development. The cardinal sign is arhinia, though some cases have partial aplasia of the external nose. In addition, several reports have revealed abnormal brain structure, including changes to the olfactory bulbs. This case describes a 29-year-old female who has suffered from BAMS since birth. On presentation, she was noted to have congenital arhinia, bilateral microphthalmia, vision loss, mouth-breathing, an unclear speaking voice, a high arched or cleft palate, and a hypoplastic maxilla. Her paranasal sinuses were ossified and underdeveloped. This syndrome occurs rarely, both within Vietnam and worldwide. It is characterized by four major features: arrhinia, complete absence of the paranasal sinuses, eye defects, and absent sexual maturation. This case report describes the presentation of the disorder to improve otolaryngologists' understanding of BAMS. Criteria for diagnosis consist of arhinia, midface hypoplasia (with a hypoplastic maxilla), hypogonadotropic hypogonadism, and normal intellectual abilities. Additional important findings are microphthalmia with or without coloboma, anosmia, maxillary hypoplasia, a high-arched palate, and absence of paranasal sinuses and olfactory bulbs.

Accurate detection of enzymatic degradation processes of gelatin-alginate microcapsule by 1H NMR spectroscopy: Probing biodegradation mechanism and kinetics.

With an increase in the severity of environmental pollution caused by microbeads, the development of biodegradable microcapsules that can be applied in diverse fields has attracted significant attention. The degradation processes are directly related to biodegradable microcapsule creation with high stability and persistence. In this study, biodegradable microcapsules are synthesized via a complex coacervation approach using gelatin and alginate as the capsule main wall materials; additionally, enzyme-induced decomposition mechanisms are proposed by observing spectral changes in proton nuclear magnetic resonance (1H NMR) analyses. Additional analytical techniques confirm the chemical structure, morphology, and size distribution of the synthesized capsules; these uniform spherical microcapsules are 20-30 µm in size and possess a smooth surface. In addition to characterization, the microcapsules were exposed to targeted enzymes to investigate enzymatic effects using short-term and long-term degradation kinetics. Close inspection reveals that determination of the degradation rate constant of the major components in the capsule is feasible, and suggests two types of 4-stage degradation mechanisms that are enzyme-specific. These investigations demonstrate that capsule degradation can be explored in detail using 1H NMR spectroscopy to provide a viable strategy for monitoring degradation properties in the development of new biodegradable polymers.