Behçet's Disease, Pathogenesis, Clinical Features, and Treatment Approaches: A Comprehensive Review.

Behçet's disease is a systemic inflammatory disorder of unknown etiology. The disease manifests with diverse clinical symptoms, most commonly recurrent oral and genital ulcers, skin lesions, and uveitis, though it can affect multiple organ systems. Diagnosis is primarily clinical due to the lack of a definitive diagnostic test, and management involves a multidisciplinary approach to control inflammation and manage symptoms. Current treatment strategies involve corticosteroids, immunosuppressive agents, and, increasingly, biological therapies. Behçet's disease exhibits a higher prevalence along the Silk Road, suggesting a role of environmental and genetic factors. Despite significant progress in understanding its clinical characteristics and treatment approaches, gaps remain in our understanding of its pathogenesis. Future research is needed to elucidate the disease's pathophysiology and optimize treatment strategies.

Real-Time Ultrasound Guidance as Compared With Landmark Technique for Subclavian Central Venous Cannulation: A Systematic Review and Meta-Analysis With Trial Sequential Analysis.

OBJECTIVES: We conducted a systematic review and meta-analysis to assess the effectiveness of real-time dynamic ultrasound-guided subclavian vein cannulation as compared to landmark technique in adult patients. DATA SOURCES: PubMed and EMBASE until June 1, 2022, with the EMBASE search restricted to the last 5 years. STUDY SELECTION: We included randomized controlled trials (RCTs) comparing the two techniques (real-time ultrasound-guided vs landmark) for subclavian vein cannulation. The primary outcomes were overall success rate and complication rate, whereas secondary outcomes included success at first attempt, number of attempts, and access time. DATA EXTRACTION: Independent extraction by two authors according to prespecified criteria. DATA SYNTHESIS: After screening, six RCTs were included. Two further RCTs using a static ultrasound-guided approach and one prospective study were included in the sensitivity analyses. The results are presented in the form of risk ratio (RR) or mean difference (MD) with 95% CI. Real-time ultrasound guidance increased the overall success rate for subclavian vein cannulation as compared to landmark technique (RR = 1.14; [95% CI 1.06-1.23]; p = 0.0007; I2 = 55%; low certainty) and complication rates (RR = 0.32; [95% CI 0.22-0.47]; p < 0.00001; I2 = 0%; low certainty). Furthermore, ultrasound guidance increased the success rate at first attempt (RR = 1.32; [95% CI 1.14-1.54]; p = 0.0003; I2 = 0%; low certainty), reduced the total number of attempts (MD = -0.45 [95% CI -0.57 to -0.34]; p < 0.00001; I2 = 0%; low certainty), and access time (MD = -10.14 s; [95% CI -17.34 to -2.94]; p = 0.006; I2 = 77%; low certainty). The Trial Sequential Analyses on the investigated outcomes showed that the results were robust. The evidence for all outcomes was considered to be of low certainty. CONCLUSIONS: Real-time ultrasound-guided subclavian vein cannulation is safer and more efficient than a landmark approach. The findings seem robust although the evidence of low certainty.

Agreement between Capillary Refill Time measured at Finger and Earlobe sites in different positions: a pilot prospective study on healthy volunteers.

BACKGROUND: Capillary Refill Time (CRT) is a marker of peripheral perfusion usually performed at fingertip; however, its evaluation at other sites/position may be advantageous. Moreover, arm position during CRT assessment has not been fully standardized. METHODS: We performed a pilot prospective observational study in 82 healthy volunteers. CRT was assessed: a) in standard position with participants in semi-recumbent position; b) at 30° forearm elevation, c and d) at earlobe site in semi-recumbent and supine position. Bland-Altman analysis was performed to calculate bias and limits of agreement (LoA). Correlation was investigated with Pearson test. RESULTS: Standard finger CRT values (1.04 s [0.80;1.39]) were similar to the earlobe semi-recumbent ones (1.10 s [0.90;1.26]; p = 0.52), with Bias 0.02 ± 0.18 s (LoA -0.33;0.37); correlation was weak but significant (r = 0.28 [0.7;0.47]; p = 0.01). Conversely, standard finger CRT was significantly longer than earlobe supine CRT (0.88 s [0.75;1.06]; p < 0.001) with Bias 0.22 ± 0.4 s (LoA -0.56;1.0), and no correlation (r = 0,12 [-0,09;0,33]; p = 0.27]. As compared with standard finger CRT, measurement with 30° forearm elevation was significantly longer (1.17 s [0.93;1.41] p = 0.03), with Bias -0.07 ± 0.3 s (LoA -0.61;0.47) and with a significant correlation of moderate degree (r = 0.67 [0.53;0.77]; p < 0.001). CONCLUSIONS: In healthy volunteers, the elevation of the forearm significantly prolongs CRT values. CRT measured at the earlobe in semi-recumbent position may represent a valid surrogate when access to the finger is not feasible, whilst earlobe CRT measured in supine position yields different results. Research is needed in critically ill patients to evaluate accuracy and precision at different sites/positions.

Red Blood Cell Transfusion Guided by Hemoglobin Only or Integrating Perfusion Markers in Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis With Trial Sequential Analysis.

OBJECTIVE: Strategies for red blood cell (RBC) transfusion in patients undergoing cardiac surgery have been traditionally anchored to hemoglobin (Hb) targets. A more physiologic approach would consider markers of organ hypoperfusion. DESIGN: The authors conducted a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials (RCTs). SETTING: Cardiac surgery. PARTICIPANTS: Adult patients. INTERVENTION: RBC transfusion targeting only Hb levels compared with strategies combining Hb values with markers of organ hypoperfusion. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were the number of RBC units transfused, the number of patients transfused at least once, and the average number of transfusions. Secondary outcomes were postoperative complications, intensive care (ICU) and hospital lengths of stay, and mortality. Only 2 RCTs were included (n = 257 patients), and both used central venous oxygen saturation (ScvO2) as a marker of organ hypoperfusion (cut-off: <70% or ≤65%). A transfusion protocol combining Hb and ScvO2 reduced the overall number of RBC units transfused (risk ratio [RR]: 1.57 [1.33-1.85]; p < 0.0001, I2 = 0%), and the number of patients transfused at least once (RR: 1.33 [1.16-1.53]; p < 0.0001, I2 = 41%), but not the average number of transfusions (mean difference [MD]: 0.18 [-0.11 to 0.47]; p = 0.24, I2 = 66%), with moderate certainty of evidence. Mortality (RR: 1.29, [0.29-5.77]; p = 0.73, I2 = 0%), ICU length-of-stay (MD: -0.06 [-0.58 to 0.46]; p = 0.81, I2 = 0%), hospital length-of-stay (MD: -0.05 [-1.49 to 1.39];p = 0.95, I2 = 0%), and all postoperative complications were not affected. CONCLUSIONS: In adult patients undergoing cardiac surgery, a restrictive protocol integrating Hb values with a marker of organ hypoperfusion (ScvO2) reduces the number of RBC units transfused and the number of patients transfused at least once without apparent signals of harm. These findings were preliminary and warrant further multicentric research.

Use of ketamine in patients with refractory severe asthma exacerbations: systematic review of prospective studies.

PURPOSE: Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring emergency department visits. In addition to conventional strategies for SAEs (inhaled ß-agonists, anticholinergics, and systemic corticosteroids), another pharmacological option is represented by ketamine. We performed a systematic review to explore the role of ketamine in refractory SAEs. METHODS: We performed a systematic search on PubMed and EMBASE up to August 12th, 2021. We selected prospective studies only, and outcomes of interest were oxygenation/respiratory parameters, clinical status, need for invasive ventilation and effects on weaning. RESULTS: We included a total of seven studies, five being randomized controlled trials (RCTs, population range 44-92 patients). The two small prospective studies (n = 10 and n = 11) did not have a control group. Four studies focused on adults, and three enrolled a pediatric population. We found a large heterogeneity regarding sample size, age and gender distribution, inclusion criteria (different severity scores, if any) and ketamine dosing (bolus and/or continuous infusion). Of the five RCTs, three compared ketamine to placebo, while one used fentanyl and the other aminophylline. The outcomes evaluated by the included studies were highly variable. Despite paucity of data and large heterogeneity, an overview of the included studies suggests absence of clear benefit produced by ketamine in patients with refractory SAE, and some signals towards side effects. CONCLUSION: Our systematic review does not support the use of ketamine in refractory SAE. A limited number of prospective studies with large heterogeneity was found. Well-designed multicenter RCTs are desirable.

Use of nafamostat mesilate for anticoagulation during extracorporeal membrane oxygenation: A systematic review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) represents an advanced option for supporting refractory respiratory and/or cardiac failure. Systemic anticoagulation with unfractionated heparin (UFH) is routinely used. However, patients with bleeding risk and/or heparin-related side effects may necessitate alternative strategies: among these, nafamostat mesilate (NM) has been reported. METHODS: We conducted a systematic literature search (PubMed and EMBASE, updated 12/08/2021), including all studies reporting NM anticoagulation for ECMO. We focused on reasons for starting NM, its dose and the anticoagulation monitoring approach, the incidence of bleeding/thrombosis complications, the NM-related side effects, ECMO weaning, and mortality. RESULTS: The search revealed 11 relevant findings, all with retrospective design. Of these, three large studies reported a control group receiving UFH, the other were case series (n = 3) or case reports (n = 5). The main reason reported for NM use was an ongoing or high risk of bleeding. The NM dose varied largely as did the anticoagulation monitoring approach. The average NM dose ranged from 0.46 to 0.67 mg/kg/h, but two groups of authors reported larger doses when monitoring anticoagulation with ACT. Conflicting findings were found on bleeding and thrombosis. The only NM-related side effect was hyperkalemia (n = 2 studies) with an incidence of 15%-18% in patients anticoagulated with NM. Weaning and survival varied across studies. CONCLUSION: Anticoagulation with NM in ECMO has not been prospectively studied. While several centers have experience with this approach in high-risk patients, prospective studies are warranted to establish the optimal space of this approach in ECMO.

Full and simplified assessment of left ventricular diastolic function in covid-19 patients admitted to ICU: Feasibility, incidence, and association with mortality.

PURPOSE: Left ventricular diastolic dysfunction (LVDD) is associated with poor outcomes in the intensive care unit (ICU). Nonetheless, precise reporting of LVDD in COVID-19 patients is currently lacking and assessment could be challenging. METHODS: We performed an echocardiography study in COVID-19 patients admitted to ICU with the aim to describe the feasibility of full or simplified LVDD assessment and its incidence. We also evaluated the association of LVDD or of single echocardiographic parameters with hospital mortality. RESULTS: Between 06.10.2020 and 18.02.2021, full diastolic assessment was feasible in 74% (n = 26/35) of patients receiving a full echocardiogram study. LVDD incidence was 46% (n = 12/26), while the simplified assessment produced different results (incidence 81%, n = 21/26). Nine patients with normal function on full assessment had LVDD with simplified criteria (grade I = 2; grade II = 3; grade III = 4). Nine patients were hospital-survivors (39%); the incidence of LVDD (full assessment) was not different between survivors (n = 2/9, 22%) and non-survivors (n = 10/17, 59%; p = .11). The E/e' ratio lateral was lower in survivors (7.4 [3.6] vs. non-survivors 10.5 [6.3], p = .03). We also found that s' wave was higher in survivors (average, p = .01). CONCLUSION: In a small single-center study, assessment of LVDD according to the latest guidelines was feasible in three quarters of COVID-19 patients. Non-survivors showed a trend toward greater LVDD incidence; moreover, they had significantly worse s' values (all) and higher E/e' ratio (lateral).

Hemoperfusion and blood purification strategies in patients with COVID-19: A systematic review.

BACKGROUND: Coronavirus disease-19 (COVID-19) ranges from asymptomatic infection to severe cases requiring admission to the intensive care unit. Together with supportive therapies (ventilation in particular), the suppression of the pro-inflammatory state has been a hypothesized target. Pharmacological therapies with corticosteroids and interleukin-6 (IL-6) receptor antagonists have reduced mortality. The use of extracorporeal cytokine removal, also known as hemoperfusion (HP), could be a promising non-pharmacological approach to decrease the pro-inflammatory state in COVID-19. METHODS: We conducted a systematic review of PubMed and EMBASE databases in order to summarize the evidence regarding HP therapy in COVID-19. We included original studies and case series enrolling at least five patients. RESULTS: We included 11 articles and describe the characteristics of the populations studied from both clinical and biological perspectives. The methodological quality of the included studies was generally low. Only two studies had a control group, one of which included 101 patients in total. The remaining studies had a range between 10 and 50 patients included. There was large variability in the HP techniques implemented and in clinical and biological outcomes reported. Most studies described decreasing levels of IL-6 after HP treatment. CONCLUSION: Our review does not support strong conclusions regarding the role of HP in COVID-19. Considering the very low level of clinical evidence detected, starting HP therapies in COVID-19 patients does not seem supported outside of clinical trials. Prospective randomized data are needed.

Epidural analgesia during labour and stress markers in the newborn.

Labour and modes of delivery can influence the plasma levels of stress hormones and cytokines involved in pathophysiologic cascade, potentially damaging brain development of the newborn. This prospective observational, single-centre, case-control, non-profit study aimed to detect potential differences in foetal well-being such as stress neuroendocrine responses. Quantitative determinations of the stress markers interleukin (IL)-1ß, IL-8, and ß-endorphin were compared between the control group and the epidural analgesia group. We found higher IL1-ß levels but lower IL-8 and ß-endorphin levels in the epidural analgesia group than in the control group. No significant inter-group differences were observed for any parameters. Our findings demonstrate that epidural analgesia for pain relief during labour does not result in significant differences in blood stress response markers.IMPACT STATEMENTWhat is already known on this subject? We already know that plasma levels of stress hormones and cytokines are influenced by labour and delivery modes. This has a deep impact on the newborn in terms of brain damage, immune system deficits, and altered hypothalamic-pituitary axis responses. We also know that epidural analgesia is a widespread practice that offers pain relief to the woman in labour, but there are few studies on the potentially negative effects of epidural labour analgesia on the unborn child.What do the results of this study add? This study found no significative differences in blood stress response markers between the epidural analgesia group and the control group. Under this study circumstances we found out that epidural analgesia does not significantly influence the newborn's well-being during labour and delivery.What are the implications of these findings for clinical practice and/or further research? These findings must be confirmed by further studies to verify whether epidural analgesia is safe for the newborn's development.

Re-Expansion Pulmonary Edema as a Life-Threatening Complication in Massive, Long-Standing Pneumothorax: A Case Series and Literature Review.

Re-expansion pulmonary edema is a rare and potentially life-threatening complication that can occur after the rapid re-expansion of a collapsed lung due to pneumothorax or pleural effusion. It has a multifactorial pathogenesis, and risk factors for re-expansion pulmonary edema, such as chronic lung collapse, rapid re-expansion, and changes in pulmonary vascular permeability, have been identified. Clinical manifestations vary, ranging from almost asymptomatic to a rapidly fatal condition, and its incidence may be more common and less fatal than previously believed. The literature emphasizes the importance of early recognition and management to ensure favorable outcomes. However, there is ongoing debate regarding the indications for ventilatory support and the timing of non-invasive or invasive ventilation. Herein, we report a case series of three paradigmatic examples of massive re-expansion pulmonary edema occurring over a period of 10 years in our institution among a population of 815 patients with spontaneous pneumothorax. We also conducted a literature review on re-expansion pulmonary edema, with a particular focus on diagnosis and management. In each case, despite initially normal clinical parameters, severe respiratory distress developed following the insertion of a thoracic drainage tube for a massive spontaneous pneumothorax. Two patients required High-Flow Nasal Oxygen, and one was addressed to intensive management, including CPAP. In all cases, the patient's outcome was optimal.

Loco-Regional Anesthesia for Pain Management in Robotic Thoracic Surgery.

Robotic thoracic surgery is a prominent minimally invasive approach for the treatment of various thoracic diseases. While this technique offers numerous benefits including reduced blood loss, shorter hospital stays, and less postoperative pain, effective pain management remains crucial to enhance recovery and minimize complications. This review focuses on the application of various loco-regional anesthesia techniques in robotic thoracic surgery, particularly emphasizing their role in pain management. Techniques such as local infiltration anesthesia (LIA), thoracic epidural anesthesia (TEA), paravertebral block (PVB), intercostal nerve block (INB), and erector spinae plane block (ESPB) are explored in detail regarding their methodologies, benefits, and potential limitations. The review also discusses the imperative of integrating these anesthesia methods with robotic surgery to optimize patient outcomes. The findings suggest that while each technique has unique advantages, the choice of anesthesia should be tailored to the patient's clinical status, the complexity of the surgery, and the specific requirements of robotic thoracic procedures. The review concludes that a multimodal analgesia strategy, potentially incorporating several of these techniques, may offer the most effective approach for managing perioperative pain in robotic thoracic surgery. Future directions include refining these techniques through technological advancements like ultrasound guidance and exploring the long-term impacts of loco-regional anesthesia on patient recovery and surgical outcomes in the context of robotic thoracic surgery.

Taste and Smell Disorders: A Critical Look at Olfactory and Gustatory Dysfunction.

In an era where modern medicine has made remarkable advances in managing diseases in the head and neck region, we present this Special Issue to provide a spotlight on the new research advances on olfactory and gustatory disorders [...].