Fat embolism syndrome (FES) in sickle cell disease (SCD) remains a significant diagnostic and therapeutic challenge, often associated with high morbidity and mortality. While red blood cell exchange (RCE) is the standard first-line therapy, some cases continue to deteriorate despite aggressive management. Emerging evidence suggests that therapeutic plasma exchange (TPE) may serve as valuable salvage therapy, potentially improving survival in refractory cases. We present two cases of FES in SCD, both marked by an attack of profound hypotension and multiorgan dysfunction, yet with distinct trajectories and responses to therapy. The first case involved a 34-year-old female with FES refractory to conventional treatment, including RCE. A single session of TPE led to rapid clinical stabilization and recovery. The second case described a 28-year-old female with a more severe disease course, requiring five cycles of combined RCE and TPE before achieving clinical improvement and recovery. These cases underscore the potential role of TPE as an adjunct to RCE in managing FES in SCD and highlight the need for further research to establish its efficacy in this critical setting.
Respiratory failure following extubation is a major contributor to patient morbidity and death in intensive care settings. While various methods exist, the relative effectiveness of high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and conventional oxygen therapy (COT) in preventing reintubation remains an area of active research. This systematic review and network meta-analysis assessed these techniques in adult patients after scheduled extubation. A search of MEDLINE, Embase, and Cochrane CENTRAL was performed for relevant randomized controlled trials (RCTs) available up to December 2025. Data extraction was performed independently by two researchers. To synthesize findings, a random-effects network meta-analysis was employed, focusing on reintubation rates within a 72-hour window as the primary endpoint. Results were expressed as risk ratios (RR) accompanied by 95% confidence intervals (CI), and the Confidence in Network Meta-Analysis (CINeMA) tool was used to evaluate evidence quality. The analysis included 14 RCTs involving a total of 4,146 participants. Results indicated that both NIV (RR 0.56; 95% CI 0.34-0.94) and HFNC (RR 0.68; 95% CI 0.47-0.97) significantly decreased the reintubation risk when compared to COT. No significant difference in efficacy was observed between HFNC and NIV (RR 1.20; 95% CI 0.76-1.89). Based on surface under the cumulative ranking curve (SUCRA) rankings, NIV emerged as the most effective intervention (88% probability), followed by HFNC (60%) and then COT (2%). The certainty of evidence was moderate for comparisons involving COT, but low for the HFNC versus NIV comparison because of imprecision. HFNC and NIV are more effective than COT at preventing reintubation in the ICU. HFNC serves as a dependable preventative measure due to its ease of application and performance comparable to NIV. These findings support a shift away from standard COT toward more advanced noninvasive respiratory support.
PURPOSE:Gene-disease relationship (GDR) is a key concept in monogenic disease diagnostics. Although functional analysis and disease modeling play important supporting roles, human genetics evidence remains key to supporting or challenging a proposed GDR. Such evidence typically comes from individual publications that address one GDR at a time. We hypothesized that a large cohort composed primarily of Mendelian phenotypes and enriched for consanguinity and founder effect can accelerate evidence generation by enabling high-throughput discovery of homozygous loss-of-function (LOF) variants as well as strong segregation data. METHODS:To test this hypothesis, we analyzed our Lifera Omics Database (LODB) for homozygous high-impact missense variants that are observed in 2 or more unrelated individuals to exploit the power of founder variants, as well as homozygous presumptive LOF variants. The search spanned 2904 genes with tentative GDRs in the literature. RESULTS:The analysis revealed 154 individuals with 119 homozygous LOF variants that support GDRs for 95 genes. Additionally, we identified 13 founder missense variants (33 homozygous individuals) that support GDR for 13 genes. Our data expand the mode of inheritance (MOI) of 19 genes for which the tentative GDRs were based on dominant variants. Phenotypic expansion was encountered in 18 of the supported GDRs, including those in which the full syndromic constellation has not been previously delineated. We also report four novel allelic disorders of reported GDRs. CONCLUSION:This work highlights the potential of diagnostic laboratories to accelerate GDR refinement through data sharing and working closely with referring physicians. It also showcases the added advantage concerning autosomal recessive GDR when the study population is enriched for consanguinity and founder effect.
Allergic rhinitis is a common condition that is characterized by the presence of inflammation in the nasal mucosa in response to allergen exposure. Several subjective tools were developed to evaluate and diagnose this condition. One of these tools is the total nasal symptoms score (TNSS), which is a quick and validated tool that is being used to evaluate the severity of allergic rhinitis. Hence, this study aims to translate and validate the TNSS into the Arabic language. The questionnaire was translated using three steps, including forward translation, backward translation, and pilot study. After the questionnaire was translated to Arabic, the score was distributed to allergic rhinitis patients and the healthy population to assess its reliability and validity. A total of 160 allergic rhinitis patients and 145 healthy participants were involved in the study. These two groups were comparable in regard to the socio-demographic characteristics. The Cronbach’s alpha scores for the translated TNSS showed an excellent internal consistency with a score of 0.912. Additionally, the translated TNSS has shown a high reliability when the questionnaire was repeated again (p < 0.0001). In comparison to the control group, the allergic rhinitis group showed significantly higher scores (p < 0.0001), indicating a good discriminant validity of the translated TNSS. The Arabic version of the TNSS was a reliable and valid tool to measure and evaluate the severity of allergic rhinitis patients. Thus, this instrument can be used in clinical practice and outcome studies for Arabic-speaking patients.
Guillain–Barré syndrome is a clinical syndrome manifesting as immune-mediated polyneuropathy. Approximately one-third of affected patients develop respiratory failure, necessitating intensive care unit admission and invasive mechanical ventilation. Multiple factors present at the onset and during intensive care unit stay are established predictors of the requirement for invasive mechanical ventilation. These include the rapid progression of motor weakness, concurrent involvement of peripheral limb and axial muscles, ineffective cough, bulbar muscle weakness, and the decline in rapid vital capacity. However, no reliable criteria currently exist to predict the duration of muscle weakness progression and plateau phases or the time to recovery. We herein report a case of a 55-year-old male admitted to the intensive care unit following a 5-day history of progressive ascending generalized weakness. His condition progressed to quadriplegia, diaphragmatic paralysis, and autonomic dysfunction. A diagnosis of Guillain–Barré syndrome–acute motor axonal neuropathy variant was confirmed via neurological examination, imaging, cerebrospinal fluid analysis, and nerve conduction studies. The patient exhibited no clinical improvement following two courses of five sessions each of plasma exchange and intravenous immunoglobulin. Owing to the refractory nature of his condition, he required more than 5 months of step-down intensive care unit care prior to transfer to a general medical ward and subsequent discharge home on hospital day 182.
