OBJECTIVE: To evaluate the relationship between the timing of thoracic endovascular aortic repair (TEVAR) for blunt thoracic aortic injury (BTAI) and prognosis.
METHODS: This is a single-center retrospective cohort study. Patients who received TEVAR for BTAI at our institution from October 2016 to September 2023 were divided into 2 categories depending on the injury severity score (ISS) (≤ 25 vs. > 25) and when the TEVAR was performed for BTAI (within 24 h vs. after 24 h), respectively. The analysis included all patients who received TEVAR treatment after being diagnosed with BTAI through whole-body CT angiography. Patients treated with open repair and non-operative management were excluded. After propensity-score matching for various factors, outcomes during hospitalization and follow-up were compared. These factors included demographics, comorbidities, concomitant injuries, cause and location of aortic injury, Glasgow coma scale score, society for vascular surgery grading, hemoglobin concentration, creatinine concentration, shock, systolic blood pressure, and heart rate at admission. The comparison was conducted using SPSS 26 software. Continuous variables were presented as either the mean ± standard deviation or median (Q1, Q3), and were compared using either the t-test or the Mann-Whitney U test. Categorical variables were expressed as n (%), and comparisons were made between the 2 groups using the χ2 test or Fisher\'s exact test. Statistical significance was defined as a 2-sided p < 0.05.
RESULTS: In total, 110 patients were involved in the study, with 65 (59.1%) patients having ISS scores > 25 and 32 (29.1%) receiving immediate TEVAR. The perioperative overall mortality rate in the group with ISS > 25 was significantly higher than that in the group with ISS ≤ 25 (11 (16.9%) vs. 2 (4.4%), p < 0.001). Upon admission, the elective group exhibited a notably higher Glasgow coma scale score (median (Q1, Q3)) compared to the immediate group (15 (12, 15) vs. 13.5 (9, 15), p = 0.039), while the creatinine concentration (median (Q1, Q3)) at admission was significantly higher in the immediate group (90.5 (63.8, 144.0) vs. 71.5 (58.3, 80.8), p = 0.012). The final sample included 52 matched patients. Complications occurred significantly less frequently in the elective group compared to the immediate group (16 (50.0%) vs. 3 (10.0%), p < 0.001). Single-factor analysis of variance showed that complications in hospitalized patients were significantly associated with immediate TEVAR as the sole independent risk factor (odds ratio: 9.000, 95% confidence interval: 2.266 - 35.752, p = 0.002).
CONCLUSIONS: In this propensity-score matched analysis of patients undergoing TEVAR for BTAI, elective TEVAR was significantly associated with a lower risk of complication rates. In this study using propensity-score matching, patients who underwent elective TEVAR for BTAI had lower complication rates than immediate TEVAR.

BACKGROUND: Thymosin drugs are commonly used for the treatment of viral infections due to their immunomodulatory effects. The comprehensive clinical efficacy of Thymalfasin therapy for COVID-19 associated pneumonia is not yet fully researched, another issue, whether the use of thymosin drugs can reduce the rate of COVID-19 progression to severe pneumonia has not been well documented. The aim of the present study was to multi-angle evaluate the clinical efficacy of Thymalfasin therapy for COVID-19 pneumonia by retrospective review of the clinical data of 338 inpatients with common COVID-19 infection who received treatment in our hospital.
METHODS: The primary index of observation was whether progression to severe pneumonia occurred within a week after admission, and the secondary indexes were the length of hospital stay, time of negative conversion of COVID-19 antigen, the number of peripheral lymphocytes and white blood cells (WBC), and C-reactive protein (CRP) and procalcitonin (PCT) levels,and the control of pneumonia related symptoms, for example, fever, listlessness, inflammatory exudate area shown on lung CT (%).
RESULTS: The length of hospital stay of patients in Thymalfasin group was significantly shorter than that of patients in the control group (p < 0.01). The proportion of relief of pneumonia related symptoms (fever, fatigue) in the Thymalfasin therapy group was significantly higher than that in the control group, and the inflammatory exudate area shown on CT was significantly lower than that in the control group (p < 0.05). Multivariate logistic regression analysis showed that the use of Thymalfasin was an independent protective factor affecting the progression to severe pneumonia. Multifactorial Cox model analysis indicated that negative conversion of COVID-19 antigen was significantly faster in patients using Thymalfasin and younger patients.
CONCLUSIONS: Thymalfasin therapy has shown excellent clinical efficacy in the treatment of COVID-19 pneumonia, it can reduce inflammatory reactions, promote the relief of COVID-19 pneumonia related symptoms such as fever and fatigue, facilitate effusion absorption, and accelerate COVID-19 pneumonia recovery. Thymalfasin can prevent progression of common COVID-19 infection to severe pneumonia via multiple immunity-enhancing and anti-inflammatory protective mechanisms.

Trauma patients with blunt abdominal solid organ injuries are at high risk for venous thromboembolism (VTE), but the optimal time to safely administer chemical thromboprophylaxis is controversial, especially for patients who are managed nonoperatively due to increased risk of hemorrhage. We sought to compare failure of nonoperative management (NOM) and VTE events based on timing of chemical thromboprophylaxis initiation.
A systematic review was conducted in PubMed and Embase databases. Studies were included if they evaluated timing of initiation of chemical thromboprophylaxis in trauma patients who underwent NOM of blunt solid organ injuries. Outcomes included failure of NOM and incidence of VTE. A random-effects meta-analysis was performed comparing patients who received late (>48 h) versus early thromboprophylaxis initiation.
Twelve retrospective cohort studies, comprising 21,909 patients, were included. Three studies, including 6375 patients, provided data on adjusted outcomes. Pooled adjusted analysis demonstrated no difference in failure of NOM in patients receiving late versus early thromboprophylaxis (odds ratio [OR] 0.92, 95% confidence interval [CI]:0.4-2.14). When including all unadjusted studies, even those at high risk of bias, there remained no difference in failure of NOM (OR 1.16, 95% CI:0.72-1.86). In the adjusted analysis for VTE events, which had 6259 patients between two studies, patients receiving late chemical thromboprophylaxis had a higher risk of VTE compared with those who received early thromboprophylaxis (OR 1.89, 95% CI:1.15-3.12).
Based on current observational evidence, initiation of prophylaxis before 48 h is associated with lower VTE rates without higher risk of failure of NOM.

Cerebral infarction is a major contributor to poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Timing of treatment has been discussed as a possible contributor. We aimed to analyze the impact of treatment timing on the risk of cerebral infarction and poor outcome after aSAH.
Consecutive cases of patients with aSAH treated at our institution between January 2003 and June 2016 were included. The cohort was divided into 2 groups, depending on the treatment during (day 4-14 after ictus) or beyond the vasospasm phase. Statistical assessment included a 1:1 propensity score matching analysis and multivariable logistic regression analysis within the whole cohort.
Of 943 patients with aSAH, 111 underwent treatment in the vasospasm phase. In the propensity score matching analysis, patients treated during the vasospasm phase were at higher risk of vasospasm requiring intra-arterial spasmolysis (P < 0.0001), cerebral infarction distal to the treated vessel (P < 0.0001), and poor outcome (modified Rankin Scale score >2) at 6 months follow-up (P = 0.025). In the multivariable analysis, aneurysm treatment in the vasospasm phase was independently associated with higher risk of cerebral vasospasm necessitating intra-arterial spasmolysis (P < 0.0001; adjusted odds ratio [aOR], 3.62), cerebral infarction distal to the treated aneurysm (P = 0.01; aOR, 2.02), and poor outcome (P = 0.03; aOR, 2.05).
Our data confirm a considerable risk of cerebral infarction and poor outcome in cases of aneurysm treatment between day 4 and 14 after aSAH. A more intense surveillance and prophylactic treatment of cerebral vasospasm might be necessary in cases of aneurysm treatment in the vasospasm phase.

The etiology and pathogenesis of osteoarthritis (OA) have been intensely investigated; however, the disease course and progression are not completely understood. A prominent role for interstitial collagenases is recognized in this degenerative process; hence, strategies to target them are of major interest.
The pathogenesis of OA, the role of interstitial collagenases (MMP-1, -8, and -13), and collagenase modifying drugs are examined and discussed. We reviewed relevant papers from PubMed and Google Scholar.
There is strong evidence for the therapeutic potential of MMP inhibitors in OA; however, they are not expected to impact the inflammatory process. Therefore, there is a need for a relative inhibitor of MMP-13 collagenase, which possesses anti-inflammatory properties. The identification of novel broad-spectrum relative to multiple peptidase inhibitors could provide desirable tools for the prophylaxis, cure, or treatment of diseases involving articular cartilage (AC) degradation, in particular OA.

Melatonin has been proven to reduce myocardial ischemia-reperfusion (MI/R) injury. However, in most studies, melatonin was administered before MI/R, thus, the results lack clinical significance in patients with acute myocardial infarction. We hypothesize that melatonin posttreatment at different times has different curative effects. Administered of Melatonin (150 μM) at different times after the onset of reoxygenation (t = -15, 0, 5, 10, 15, and 30 min). Cellular apoptosis, oxidative stress, and mitochondrial function were assessed. Mitophagy-related protein levels, mitochondrial membrane potential (MMP), and mitochondrial permeability transition pore (mPTP) activity were also measured. A/R injury upregulated mitophagy, which was associated with increased cellular apoptosis, oxidative stress, and mitochondrial dysfunction. Melatonin posttreatment (t = -15, 0, 5, 10, 15, and 30 min) significantly inhibited excessive mitophagy after A/R injury, reduced cellular apoptosis and oxidative stress, restored mitochondrial function and MMP, and restrained mPTP opening. The therapeutic time window in which melatonin posttreatment protected H9c2 cells against A/R injury was large (from -15 to 30 min after the onset of reperfusion), but the earlier the melatonin administration was, the better its protective effect was. This mechanism is likely due to a reduction in mPTP activity and MMP collapse, which lead to the inhibition of mitophagy.

BACKGROUND: There remains controversy regarding the outcomes resulting from treatment versus conservative management of patent ductus arteriosus (PDA) among preterm infants. The effects of extreme prematurity, hemodynamic status of the PDA, and age at treatment remain poorly defined.
METHODS: This retrospective case-control study including infants <  1250 gm who were categorized into 3 groups: Group 1: without PDA, Group 2: with untreated PDA, and Group 3: treated PDA. Diagnosis and treatment of PDA extracted from the medical records. Demographics, clinical characteristics, and outcomes compared using chi-square and analysis of variance. Logistic regression used to estimate adjusted odds ratios.
RESULTS: The study included 734 infants, with 141(19%) in Group 1, 329 (45%) in 2, and 264 (36%) in 3. Group 3 had higher incidence of bronchopulmonary dysplasia (BPD) (aOR, 2.9; 95%CI 1.7-4.8). Infant treated for hemodynamically significant PDA (HSPDA) had higher incidence of BPD (aOR, 1.9; 95%CI 1.0-3.8) and retinopathy of prematurity (ROP) (aOR, 3.4; 95%CI 1.6-6.9). There were no differences in outcome associated with treatment among≤26 weeks gestation and the age when treated.
CONCLUSIONS: Infants with PDA who were treated had higher incidence of BPD. Among those who were treated, those with HSPDA had a higher incidence of BPD and ROP.

Small-cell lung cancer (SCLC) is an aggressive disease with poor survival and rapid doubling time. Current practice is to treat SCLC as soon as possible but evidence on appropriate timing of treatment from diagnosis (TTD) is lacking. This is a retrospective analysis of SCLC patients from the 2012 to 2015 Kentucky Cancer Registry. Data collected included age at diagnosis, stage, gender, race, insurance and treatment. Factors and survival associated with TTD were identified with logistic regression analyses and Cox proportional hazards models. Among the 2992 SCLC patients, 2371 (79%) of SCLC patients were treated with one or more treatment modalities. Among treated patients, 93% received chemotherapy ± radiation with the mean TTD of 18 days. Most patients (80%) have TTD of ≤ 4 weeks with 33% treated within 1 week, 20% 1-2 weeks, and 27% 2-4 weeks from diagnosis. Delay in treatment (TTD > 4 weeks) was less in stage III and IV disease (odds ratio: 0.33 and 0.27 respectively, p < 0.01) but not significantly associated with age, race, gender, and insurance. One and two-year survival of patients with TTD ≤ 4 weeks was significantly worse when compared to > 4 weeks (hazard ratio = 1.43, 95% CI 1.2-1.6, p < 0.01; HR = 1.45, 95% CI 1.3-1.6, p < 0.01 respectively). These results show a trend toward better survival with late treatment of SCLC. Therefore, a general urgency to treat SCLC needs to be re-evaluated with consideration of patients needing more optimization before treatment. Further studies are needed to better clarify the appropriate timing of treatment from diagnosis in SCLC and who will benefit from early versus late treatment.

Hypospadias is one of the most common congenital anomalies in men. The condition is typically characterized by proximal displacement of the urethral opening, penile curvature, and a ventrally deficient hooded foreskin. In about 70%, the urethral meatus is located distally on the penile shaft; this is considered a mild form that is not associated with other urogenital deformities. The remaining 30% are proximal and often more complex. In these cases, endocrinological evaluation is advised to exclude disorders of sexual differentiation, especially in case of concomitant unilateral or bilateral undescended testis. Although the etiology of hypospadias is largely unknown, many hypotheses exist about genetic predisposition and hormonal influences. The goal of hypospadias repair is to achieve cosmetic and functional normality, and currently, surgery is recommended between 6 and 18 months of age. Hypospadias can be corrected at any age with comparable complication risk, functional, and cosmetic outcome; however, the optimal age of repair remains conclusive. Although long-term overall outcome concerning cosmetic appearance and sexual function is fairly good, after correction, men may more often be inhibited in seeking sexual contact. Moreover, lower urinary tract symptoms occur twice as often in patients undergoing hypospadias repair and can still occur many years after the initial repair.
CONCLUSIONS: This study explores the most recent insights into the management of hypospadias. What is Known: • Guidelines advise referral for treatment between 6 and 18 months of age. • Cosmetic outcome is considered satisfactory in over 70% of all patients. What is New: • Long-term complications include urinary tract symptoms and sexual and cosmetic issues. • New developments allow a more individualized approach, hopefully leading to less complications and more patient satisfaction.

Allogenic lymphocyte immunotherapy (LIT) as a treatment for unexplained recurrent spontaneous abortion (URSA) is still controversial due to the lack of enough controls to evaluate its effectiveness. Eighteen randomized, placebo-controlled trials with LIT for URSA were included in the meta-analysis. Live birth rates for each group were extracted, and the overall odds ratio (OR) for LIT was calculated. The success rate of treatment group was significantly higher (OR 3.74, 95% CI 3.07 ~ 4.57). LIT performed before and during pregnancy had dramatically improved the live birth rate in women with URSA (OR 4.67, 95% CI 3.70 ~ 5.90). The overall OR was 5.25 (95% CI 4.16 ~ 6.64), which supports a low dose of lymphocytes for treating URSA. Our results indicate that LIT provides a significantly beneficial effect over placebo for URSA. LIT given before and during pregnancy is superior to LIT given only before pregnancy, and the lower doses per treatment (less than 100 × 106 lymphocytes or 100 mL peripheral blood) achieved a better outcome.