Risk and timing of isotretinoin-related laboratory disturbances: a population-based study.

INTRODUCTION: Uncertainty surrounds the optimal routine laboratory monitoring in acne patients treated with isotretinoin. OBJECTIVE: Our aim was to evaluate the risk of mild and severe laboratory abnormalities in patients with acne starting isotretinoin versus oral antibiotic treatment. METHODS: A global population-based retrospective cohort study assigned two groups of patients with acne-prescribed isotretinoin (n = 79,012) and oral antibiotics (n = 79,012). Comprehensive propensity-score matching was conducted. RESULTS: Compared to acne patients treated with oral antibiotics, those under isotretinoin demonstrated an increased risk of grade ≥3 hypertriglyceridemia (hazard ratio [HR], 7.85; 95% confidence interval [CI], 5.58-11.05; P < 0.001) and grade ≥3 elevated aspartate transaminase (AST) levels (HR, 1.45; 95% CI, 1.13-1.85; P = 0.003) within the initial 3 months of treatment. The absolute risk of these abnormalities among isotretinoin initiators was 0.4% and 0.2%, respectively. The risk difference of these findings was clinically marginal: 3 and 1 additional cases per 1,000 patients starting isotretinoin, respectively. There was no significant risk of grade ≥3 impairment in cholesterol, alanine transaminase, gamma-glutamyl transferase, or creatinine levels under isotretinoin. Most laboratory abnormalities were documented 1-3 months after drug initiation in time-stratified analysis. CONCLUSION: Isotretinoin is associated with a clinically marginal increased risk of severe hypertriglyceridemia and hypertransaminasemia. Routine blood testing should be performed 1-3 months after commencing therapy.

eCLIPs bifurcation remodeling system for treatment of wide-neck bifurcation aneurysms: A systematic review and meta-analysis of safety and efficacy.

BACKGROUND: Wide neck bifurcation aneurysms (WNBAs) are a subtype of aneurysms that are especially complex to treat. We aim to conduct a systematic review and meta-analysis to synthesize the available literature on the safety and efficacy of employing endovascular clip system (eCLIPs) in the treatment of WNBAs. METHODS: We report this study in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 guidelines. PubMed, Embase, Web of Science, and Scopus were queried for this review. Screening and extraction were performed by at least two authors to ensure accuracy and completeness, and a senior author arbitrated any discrepancies. All data were analyzed using R software version 4.3.0. and random-effects model. RESULTS: Four studies were finally included, of which three were prospective and one was retrospective. Successful adjunctive coiling occurred in 91.38% (95% CI = 70.71-97.9) of cases and overall technical success was achieved in 88.61% (95 CI = 75.54-95.15) of cases. The pooled complete occlusion (Raymond-Roy Class I) was 50.65% (95% CI = 39.63-61.60) and adequate occlusion (Raymond-Roy Class I/II) was 84.42% (95% CI = 74.53-90.93). Thrombo-embolic complication had a pooled rate of 1.22% (95% CI = 0.17-8.15), retreatment rate was 6.10% (95% CI = 2.56-13.83), and mortality reported in 3.66% (95% CI = 1.18-10.74) of patients. CONCLUSION: The use of eCLIPs may be a safe and efficacious treatment for WNBAs. Future randomized controlled trials are needed for further validation of the findings.

Intensive vs Conventional Blood Pressure Control After Thrombectomy in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Importance: Endovascular thrombectomy (EVT) is standard treatment for acute ischemic stroke (AIS) due to large-vessel occlusion (LVO), but optimal post-EVT blood pressure (BP) control remains debated. Objective: To assess the association of different systolic BP targets following EVT with functional outcomes, mortality, and complications in patients with AIS due to LVO. Data Sources: Systematic review and meta-analysis of databases (PubMed, Embase, Web of Science, Scopus, and Cochrane Library) to September 8, 2023. Study Selection: Inclusion criteria consisted of randomized clinical trials examining post-EVT management of systolic BP in patients with AIS and LVO comparing intensive vs conventional targets. Nonrandomized studies, observational studies, noninterventional trials, meeting abstracts, duplicate studies, studies with overlapping data, and non-English language studies were excluded. Two authors independently applied these criteria through a blinded review, with discrepancies resolved through consensus. The risk of bias in the included studies was assessed using the revised tool for assessing risk of bias in randomized trials. Data Extraction and Synthesis: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline. Three authors extracted data regarding study characteristics, baseline patient data, and outcomes of interest. The pooled data were analyzed using a random-effects meta-analysis. Main Outcomes and Measures: Rates of functional independence, 90-day mortality, symptomatic intracranial hemorrhage, and hypotensive events. Results: A total of 4 randomized clinical trials with 1571 initially enrolled patients were included in the analysis. Lower functional independence rates were observed in the intensive control group (relative risk [RR], 0.81 [95% CI, 0.67-0.98]). No significant differences were found in 90-day mortality (RR, 1.18 [95% CI, 0.92-1.52]), symptomatic intracranial hemorrhage (RR, 1.12 [95% CI, 0.75-1.67]), or hypotensive events (RR, 1.80 [95% CI, 0.37-8.76]). There was minimal heterogeneity among the studies included in the functional independence outcome (I2 = 13% and τ2 = 0.003), which was absent among other outcomes (I2 = 0 and τ2 = 0). Conclusions and Relevance: These findings suggest that intensive post-EVT BP reduction does not yield benefits and may carry risks. While awaiting the results of additional ongoing trials, a conservative BP management strategy after endovascular recanalization is favored in daily practice.

Low circulatory levels of total cholesterol, HDL-C and LDL-C are associated with death of patients with sepsis and critical illness: systematic review, meta-analysis, and perspective of observational studies.

BACKGROUND: Mechanistic studies have established a biological role of sterol metabolism in infection and immunity with clinical data linking deranged cholesterol metabolism during sepsis with poorer outcomes. In this systematic review we assess the relationship between biomarkers of cholesterol homeostasis and mortality in critical illness. METHODS: We identified articles by searching a total of seven electronic databases from inception to October 2023. Prospective observational cohort studies included those subjects who had systemic cholesterol (Total Cholesterol (TC), HDL-C or LDL-C) levels assessed on the first day of ICU admission and short-term mortality recorded. Meta-analysis and meta-regression were used to evaluate overall mean differences in serum cholesterol levels between survivors and non-survivors. Study quality was assessed using the Newcastle-Ottawa Scale. FINDINGS: From 6469 studies identified by searches, 24 studies with 2542 participants were included in meta-analysis. Non-survivors had distinctly lower HDL-C at ICU admission -7.06 mg/dL (95% CI -9.21 to -4.91, p < 0.0001) in comparison with survivors. Corresponding differences were also seen less robustly for TC -21.86 mg/dL (95% CI -31.23 to -12.49, p < 0.0001) and LDL-C -8.79 mg/dL (95% CI, -13.74 to -3.83, p = 0.0005). INTERPRETATION: Systemic cholesterol levels (TC, HDL-C and LDL-C) on admission to critical care are inversely related to mortality. This finding is consistent with the notion that inflammatory and metabolic setpoints are coupled, such that the maladaptive-setpoint changes of cholesterol in critical illness are related to underlying inflammatory processes. We highlight the potential of HDL-biomarkers as early predictors of severity of illness and emphasise that future research should consider the metabolic and functional heterogeneity of HDLs. FUNDING: EU-ERDF-Welsh Government Ser Cymru programme, BBSRC, and EU-FP7 ClouDx-i project (PG).

Cutaneous Sarcoidosis.

Sarcoidosis is a multisystem disease that most commonly affects the lungs, lymphatic system, eyes, and skin but any organ may be involved. Cutaneous sarcoidosis most commonly presents as pink-red to red-brown papules and plaques that commonly affect the head and neck. With the skin being readily accessible for evaluation and biopsy, when sarcoidosis is suspected, dermatologic evaluation may be helpful for establishing a definitive diagnosis. Treatment strategy depends on the severity and distribution of skin lesions and should incorporate patient preference and treatment considerations for other organs that may be involved.

Are interleukin 17 and interleukin 23 inhibitors associated with malignancies?-Insights from an international population-based study.

BACKGROUND: Cancer risk after long-term exposure to interleukin (IL)-23 inhibitors (IL-23i) and IL-17 inhibitors (IL-17i) remains to be delineated. OBJECTIVE: To evaluate the risk of malignancies in patients with psoriasis treated with IL-23i and IL-17i relative to those prescribed tumour necrosis factor inhibitors (TNFi) during the first 5 years following drug initiation. METHODS: A global population-based cohort study included two distinct analyses comparing patients with psoriasis under different therapeutic modalities; (i) new users of IL-17i(n = 15,331) versus TNFi (n = 15,331) and (ii) new users of IL-23i (n = 5832) versus TNFi (n = 5832). RESULTS: Patients prescribed IL-17i experienced a decreased risk of non-Hodgkin lymphoma (NHL; HR, 0.58; 95% CI, 0.40-0.82; p = 0.002), colorectal cancer (HR, 0.68; 95% CI, 0.49-0.95; p = 0.024), hepatobiliary cancer (HR, 0.68; 95% CI, 0.58-0.80; p < 0.001), ovary cancer (HR, 0.48; 95% CI, 0.29-0.81; p = 0.005), melanoma (HR, 0.52; 95% CI, 0.37-0.73; p < 0.001), and basal cell carcinoma (BCC; HR, 0.57; 95% CI, 0.48-0.67; p < 0.001). IL-23i was associated with a reduced risk of NHL (HR, 0.39; 95% CI, 0.19-0.78; p = 0.006), hepatobiliary cancer (HR, 0.44; 95% CI, 0.31-0.62; p < 0.001) and BCC (HR, 0.76; 95% CI, 0.57-0.99; p = 0.046). In a sensitivity analysis comparing patients managed by IL-17i and IL-23i with their biologic-naïve counterparts, these classes were associated with decreased risk of several malignancies. CONCLUSION: IL-17i and IL-23i are associated with decreased risk of several malignancies. These findings should be considered prior to the prescription of biologics.

TEM Classification of Aortic Dissection-The Evolving Scoring System: A Literature Review.

Aortic dissection is an acute presentation that, if unnoticed, poses a significant risk to life. Anatomically, it is defined as a tear in the intimal layer of the aorta, but management differs significantly based on the location of this tear. Traditionally the Stanford and DeBakey classifications have been used to distinguish tear types and thus guide the most favourable management option, be it medical optimisation or surgery. Recently, a new Type-Entry-Malperfusion classification has been proposed to more accurately define and thus risk stratify patients with aortic dissection. This review summarises the Type-Entry-Malperfusion classification and highlights its potential advantages and limitations compared to other classifications. Clinical insights and potential barriers to adopting this classification are also described in this review.

The impact of off-hour mechanical thrombectomy therapy on outcomes for acute ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: The impact of off-hours and on-hours mechanical thrombectomy (MT) treatment for acute ischemic stroke (AIS) is not well understood. We conducted a systematic review and met-analysis comparing outcomes between patients undergoing off-hours MT versus on-hours MT. METHODS: This study is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses recommendations. A systematic literature review of the English language literature was conducted using Web of Science, Embase, Scopus, and PubMed databases. We included all original studies comparing off-hour and on-hour outcomes or time metrics in AIS undergoing MT. R software version 4.3.1 and the 'meta' statistical package were used to analyze all the data presented in this study. RESULTS: We included 26 studies with 82,850 patients. Patients undergoing MT during off-hours achieved lower rates of 90-day functional independence (OR 0.92, 95% CI 0.86-0.99; p = 0.04) and successful recanalization (OR 0.89, 95% CI 0.81-0.98; p = 0.014). Patients undergoing off-hours MT experienced similar rates of 90-day mortality (OR 1.07, 95% CI 0.96-1.19; p = 0.21) and sICH (OR 1.04, 95% CI 0.85-1.28; p = 0.674). Patients in the off-hour group experienced longer onset to door time (MD = 12.23 min; 95% CI 4.53-19.93; p = 0.002), imaging to puncture time (MD = 10.59 min; 95% CI 4.00-17.19; p = 0.002), and door to recanalization time (MD = 13.31 min; 95% CI 4.60-22.03; p = 0.003). CONCLUSIONS: Patients undergoing MT for AIS during off-hours experienced lower rates of functional independence. This may be attributed to treatment delays during off-hours. Future studies should work to optimize hospital workflows and identify factors which may contribute to treatment delays.

Molecularly Targeted Therapies for Inflammatory Cutaneous Granulomatous Disorders: A Review of the Evidence and Implications for Understanding Disease Pathogenesis.

Inflammatory cutaneous granulomatous diseases, including granuloma annulare, cutaneous sarcoidosis, and necrobiosis lipoidica, are distinct diseases unified by the hallmark of macrophage accumulation and activation in the skin. There are currently no Food and Drug Administration-approved therapies for these conditions except prednisone and repository corticotropin injection for pulmonary sarcoidosis. Treatment of these diseases has generally been guided by low-quality evidence and may involve broadly immunomodulatory medications. Development of new treatments has in part been limited by an incomplete understanding of disease pathogenesis. Recently, there has been substantial progress in better understanding the molecular pathogenesis of these disorders, opening the door for therapeutic innovation. Likewise, reported outcomes of treatment with immunologically targeted therapies may offer insights into disease pathogenesis. In this systematic review, we summarize progress in deciphering the pathomechanisms of these disorders and discuss this in the context of emerging evidence on the use of molecularly targeted therapies in treatment of these diseases.

Does vitamin D deficiency predispose to keloids via dysregulation of koebnerisin (S100A15)? A case-control study.

Keloids result from uncontrolled inflammation and fibrosis during wound healing. Vitamin D can regulate skin proliferation and inflammation. Fibroblasts are vitamin D-responsive target cells and are source of koebnerisin (an antimicrobial peptide released during inflammation and wound healing). This study aimed to assess the levels and correlations between the serum and tissue 25-Hydroxyvitamin D, tissue vitamin D receptors, and serum and tissue koebnerisin (S100A15) in patients with keloids. Nineteen patients with keloids and 20 matched controls were recruited. From each keloid patient, a serum sample and two biopsies were taken from the keloid (lesional) (Tissue A) and from normal skin (non-lesional) (Tissue B). From controls, a serum sample and a tissue biopsy from normal skin were taken. Serum and tissue 25-Hydroxyvitamin D, tissue vitamin D receptors, and serum and tissue koebnerisin were measured in retrieved samples using ELISA. Results revealed a significantly lower serum 25-Hydroxyvitamin D, tissue vitamin D receptors, as well as, serum and tissue koebnerisin in keloid patients compared to controls. Tissue 25-Hydroxyvitamin D was significantly lower in keloidal skin biopsy (Tissue A) compared to non-lesional normal skin biopsy (Tissue B). Tissue koebnerisin showed a significant positive correlation with tissue vitamin D receptors, and a significant negative correlation with tissue 25-Hydroxyvitamin D. There was a significant negative correlation between serum 25-Hydroxyvitamin D and duration of keloid. Accordingly, low serum and tissue 25-Hydroxyvitamin D and deficient tissue vitamin D receptors contribute to the pathogenesis of keloids. This can be partly mediated by dysregulation of the antimicrobial peptide; koebnerisin. Artificial antimicrobial peptides and koebnerisin-modifying drugs, for example, vitamin D and TNF-α inhibitors can have a role in keloid prevention and treatment.