Advances and challenges in regenerative therapies for abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a significant source of mortality worldwide and carries a mortality of greater than 80% after rupture. Despite extensive efforts to develop pharmacological treatments, there is currently no effective agent to prevent aneurysm growth and rupture. Current treatment paradigms only rely on the identification and surveillance of small aneurysms, prior to ultimate open surgical or endovascular repair. Recently, regenerative therapies have emerged as promising avenues to address the degenerative changes observed in AAA. This review briefly outlines current clinical management principles, characteristics, and pharmaceutical targets of AAA. Subsequently, a thorough discussion of regenerative approaches is provided. These include cellular approaches (vascular smooth muscle cells, endothelial cells, and mesenchymal stem cells) as well as the delivery of therapeutic molecules, gene therapies, and regenerative biomaterials. Lastly, additional barriers and considerations for clinical translation are provided. In conclusion, regenerative approaches hold significant promise for in situ reversal of tissue damages in AAA, necessitating sustained research and innovation to achieve successful and translatable therapies in a new era in AAA management.

Characterization of a phenol-based model for denervation of the abdominal aorta and its implications for aortic remodeling.

Objective: Sympathetic innervation plays a pivotal role in regulating cardiovascular health, and its dysregulation is implicated in a wide spectrum of cardiovascular diseases. This study seeks to evaluate the impact of denervation of the abdominal aorta on its morphology and wall homeostasis. Methods: Male and female Sprague-Dawley rats (N = 12), aged 3 months, underwent midline laparotomy for infrarenal aorta exposure. Chemical denervation was induced via a one-time topical application of 10% phenol (n = 6), whereas sham controls received phosphate-buffered saline (n = 6). Animals were allowed to recover and subsequently were sacrificed after 6 months for analysis encompassing morphology, histology, and immunohistochemistry. Results: At 6 months post-treatment, abdominal aortas subjected to phenol denervation still exhibited a significant reduction in nerve fiber density compared with sham controls. Denervated aortas demonstrated reduced intima-media thickness, increased elastin fragmentation, decreased expression of vascular smooth muscle proteins (α-SMA and MYH11), and elevated adventitial vascular density. Sex-stratified analyses revealed additional dimorphic responses, particularly in aortic collagen and medial cellular density in female animals. Conclusions: Single-timepoint phenol-based chemical denervation induces alterations in abdominal aortic morphology and vascular remodeling over a 6-month period. These findings underscore the potential of the sympathetic nervous system as a therapeutic target for aortic pathologies. Clinical Relevance: Aortic remodeling remains an important consideration in the pathogenesis of aortic disease, including occlusive, aneurysmal, and dissection disease states. The paucity of medical therapies for the treatment of aortic disease has driven considerable interest in elucidating the pathogenesis of these conditions; new therapeutic targets are critically needed. Here, we show significant remodeling after phenol-induced denervation with morphologic, histologic, and immunohistochemical features. Future investigations should integrate sympathetic dysfunction as a potential driver of pathologic aortic wall changes with additional consideration of the sympathetic nervous system as a therapeutic target.

Ectopic Crossed Testis: A Rare Anomaly of Testicular Migration.

Ectopic crossed testis is a rare condition in which both testes descend through the same inguinal canal. The most common presentation is an ipsilateral inguinal hernia with contralateral cryptorchidism. This is a case report of a six-year-old male child who had an empty right scrotal sac. Diagnostic laparoscopy is useful for both diagnosis and management. Management is determined by the anatomy of the vas, vessels, and testis discovered during surgical exploration. Transseptal contralateral orchidopexy results in good tension-free testicular fixation in the scrotum.

Hematuria as a Sign of Kidney Stone Disease Evaluated Using Computed Tomography: A Review.

Kidney stone is a common cause of acute pain in the abdomen in patients presenting to casualty. Being present in roughly 12% of the world's population makes it the most prevalent pathology of the urinary system. The ureters, kidneys, and bladder frequently develop calculi, resulting in hematuria. The most effective imaging technique for evaluating calculi is unenhanced helical computed tomography. The population, intervention, control, and outcomes (PICO)-formatted question was used to generate methodological medical subject heading (MeSH) phrases, which increased the search strategy's sensitivity in finding research. Some of these names ("hematuria") included "renal calculi" (MeSH) and "cone-beam computed tomography" (MeSH). Studies that satisfied these requirements were subjected to critical evaluation. The merits of the listed studies were evaluated using a unique quality assessment scale. The most accurate imaging diagnostic test for people with hematuria is multidetector computed tomography. If a patient over 40 presents with microscopic hematuria, a non-contrast computed tomography or ultrasound study should be performed, and if gross hematuria is observed, cystoscopy should be added. Pre- and post-contrast computed tomography scans and cystoscopy should be carried out on elderly patients.

Radiological Evaluation of a Rare Case of Rib Caries and Cold Abscess in a Young Male Patient With Miliary Tuberculosis: A Case Report With Review of Literature.

Rib caries with a cold abscess is a rare presentation of tuberculosis (TB) and is tricky to diagnose. It is rarer in young patients, especially in conjunction with active miliary TB. We present one such case of a 23-year-old male patient who presented with swelling over the left lower chest. Rib caries and cold abscess were initially detected by ultrasonography and elastography. The rib involvement and the extent of the cold abscess were further evaluated on a computed tomography scan, which also showed active pulmonary miliary TB. The patient was treated by aspiration of the cold abscess and anti-tuberculosis therapy. The fact that the patient had no history of diabetes, alcoholism, human immunodeficiency virus infection, or immunodeficiency disorder increases the rarity of this case. This case highlights the role of imaging in diagnosing rib caries, cold abscess, and miliary TB.

Randomised controlled trials for COVID-19: evaluation of optimal randomisation methodologies-need for data validation of the completed trials and to improve ongoing and future randomised trial designs.

During the emerging COVID-19 (coronavirus disease 2019) pandemic, initially there were no proven treatment options. With the release of randomised controlled trial (RCT) results, we are beginning to see possible treatment options for COVID-19. The RECOVERY trial showed an absolute risk reduction in mortality by 2.8% with dexamethasone, and the ACTT-1 trial showed that treatment with remdesivir reduced the time to recovery by 4 days. Treatment with hydroxychloroquine (HCQ) and lopinavir/ritonavir did not show any mortality benefit in either the RECOVERY or World Health Organization (WHO) Solidarity trials. The National Institutes of Health (NIH) and Brazilian HCQ trials did not show any benefit for HCQ based on the seven-point ordinal scale outcomes. The randomisation methodologies utilised in these controlled trials and the quality of published data were reviewed to examine their adaptability to treat patients. We found that the randomisation methodologies of these trials were suboptimal for matching the studied groups based on disease severity among critically-ill hospitalised COVID-19 patients with high mortality rates. The published literature is very limited regarding the disease severity metrics among the compared groups and failed to show that the data are without fatal sampling errors and sampling biases. We also found that there is a definite need for the validation of data in these trials along with additional important disease severity metrics to ensure that the trials' conclusions are accurate. We also propose proper randomisation methodologies for the design of RCTs for COVID-19 as well as guidance for the publication of COVID-19 trial results.

Resveratrol Downregulates Biomarkers of Sepsis Via Inhibition of Proteasome's Proteases.

Lipopolysaccharide (LPS) is the main agonist of gram-negative bacteria and initiates inflammation. We recently reported that plasmas from sepsis patients revealed increased levels of following group of biomarkers; VCAM-1, ICAM1, CRP, resistin, and proteasome LMP subunits. Our objective here was to compare effects of resveratrol (shown to be a nonspecific proteasome inhibitor by us) and a known LMP7 inhibitor (ONX-0914, specific inhibitor) on proteasome's activities, as well as on inflammatory markers mentioned above in human blood monocytes. Using fluorescence-based assays on blood monocytes purified proteasomes, resveratrol (0-100 µM) inhibited all three protease activities, predominantly LMP7. Similarly, resveratrol inhibited all three protease activities using cell-based luminescence assay. In contrast, ONX-0914 was more selective and potent for LMP7 activity. Resveratrol and ONX-0914, both significantly inhibited expression of LPS-induced biomarkers mentioned above in CD14 monocytes. Moreover, resveratrol itself, as well as in combination with LPS, accumulated pIκBα in CD14 monocytes. Collectively, our data suggest that resveratrol is a less potent inhibitor of all three; CT-like (predominantly LMP7), T-like and PA protease activities and is less toxic to human monocytes than ONX-0914 (a selector inhibitor of only LMP7) as observed by an autophagy detection kit. Also, resveratrol reduces LPS-induced inflammatory cytokine expression by decreasing the translocation of NF-κB due to an increase in inhibitor pIκBα. Therefore, resveratrol can be used to curb inflammation in diseased states like sepsis and other disorders.

Bowel ultrasound for predicting surgical management of necrotizing enterocolitis: a systematic review and meta-analysis.

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating inflammatory disease of the intestinal tract that represents a significant source of morbidity and mortality in preterm infants. Imaging of the abdomen is valuable for timely diagnosis and close monitoring of disease progression in NEC. Bowel ultrasound (US) is increasingly being recognized as an important imaging tool for evaluating NEC that provides additional detail than plain abdominal radiographs. OBJECTIVE: To identify bowel US findings associated with surgical management or death in infants with NEC. MATERIALS AND METHODS: We searched Embase, PubMed, and the Cumulative Index to Nursing and Allied Health Literature for studies investigating the association between bowel US findings and surgical management or death in NEC. Selected articles were evaluated for quality of study methodology using the Newcastle-Ottawa Scale, and aggregate statistics for odds ratio (OR) and 95% confidence interval were calculated. RESULTS: Of 521 articles reviewed, 11 articles comprising 748 infants were evaluated for quality. Nine of the studies were retrospective and from single-center experiences. Pooled analysis showed that focal fluid collections (OR 17.9, 3.1-103.3), complex ascites (OR 11.3, 4.2-30.0), absent peristalsis (OR 10.7, 1.7-69.0), pneumoperitoneum (OR 9.6, 1.7-56.3), bowel wall echogenicity (OR 8.6, 3.4-21.5), bowel wall thinning (OR 7.11.6-32.3), absent perfusion (OR 7.0, 2.1-23.8), bowel wall thickening (OR 3.9, 2.4-6.1) and dilated bowel (OR 3.5, 1.8-6.8) were associated with surgery or death in NEC. In contrast, portal venous gas (OR 3.0, 0.8-10.6), pneumatosis intestinalis (OR 2.1, 0.9-5.1), increased bowel perfusion (OR 2.6, 0.6-11.1) and simple ascites (OR 0.54, 0.1-2.5) were not associated with surgery or death. CONCLUSION: This meta-analysis identified several bowel US findings that are associated and not associated with surgery or death in NEC. Bowel US may be useful for early identification of high-risk infants with NEC who may benefit from more aggressive treatment, including surgery. Future studies are needed to determine whether the addition of bowel US in NEC evaluation would improve outcomes.