CT-derived lung vessel morphology correlates with prognostic markers in precapillary pulmonary hypertension.

BACKGROUND: While computed tomography pulmonary angiography (CTPA) is an integral part of the work-up in patients with suspected pulmonary hypertension (PH), there is no established CTPA-derived prognostic marker. We aimed to assess whether quantitative readouts of lung vessel morphology correlate with established prognostic indicators in PH. METHODS: We applied a fully-automatic in-house developed algorithm for segmentation of arteries and veins to determine lung vessel morphology in patients with precapillary PH who underwent right heart catheterization and CTPA between May 2016 and May 2019. Primary endpoint of this retrospective study was the calculation of receiver operating characteristics for identifying low and high mortality risk according to the 3-strata risk assessment model presented in the current guidelines. RESULTS: We analyzed 73 patients, median age 65 years (interquartile range (IQR): 54-76), female/male ratio 35/38, median mean pulmonary arterial pressure 37 mm Hg (IQR: 30-46), and found significant correlations with important prognostic factors in pulmonary arterial hypertension. N-terminal pro-brain natriuretic peptide, cardiac index, mixed venous oxygen saturation, and 6-minute walking distance were correlated with the ratio of the number of arteries over veins with vessel diameters of 6-10 mm (Spearman correlation coefficients ρ = 0.64, p < 0.001; ρ = -0.60, p < 0.001; ρ = -0.47, p = 0.005; ρ = -0.45, p = 0.001, respectively). This ratio predicted a low- and high-risk score with an area under the curve of 0.73 (95% confidence interval (CI): 0.56-0.90) and 0.86 (95% CI: 0.74-0.97), respectively. CONCLUSIONS: The ratio of the number of arteries over veins with diameters between 6 and 10 mm is significantly correlated with prognostic markers in pulmonary hypertension and predicts low and high mortality risk.

Identification of Normal Fornix Depth Dataset Generated with a Validated Fornix Meter in Healthy Turkish Population.

PURPOSE: To provide an age and sex-classified reference dataset for normal fornix depth by measuring the lower and upper conjunctival fornix depth (FD) in healthy volunteers. METHODS: An epidemiological, prospective, cross-sectional study evaluates conjunctival FDs in 301 healthy Turkish volunteers aged 20-83. Fornix measurements were made using a validated fornix depth measurer (FDM). RESULTS: The mean age was 49.2 ± 19 in males and 48.6 ± 16.2 in females. The mean upper and lower conjunctival FDs were 15.9 (12-21) mm and 10.1 (6-13) mm, respectively. The mean upper and lower FDs were 15.4 (13-20) mm and 9.7 (6-13) mm in females, and 16.3 (12-21) mm and 10.5 (8-13) mm in males, respectively. . CONCLUSION: When the normative dataset created in healthy Turkish volunteers, it was observed that both the upper and lower FDs were shallower in females and that they gradually became shallower with age. Accordingly, when an evaluation for conjunctival pathology is to be made, the expected normal FD value for both age and sex should be considered.

Unusual Inflammatory Clinical Presentation After Cataract Surgery and that Thought-provoking Question: Is this Infection or Toxic Anterior Segment Syndrome?

PURPOSE: Toxic anterior segment syndrome (TASS) is a noninfectious anterior chamber reaction caused by ocular surgeries. It usually develops within the first 12-48 h after surgery. In case of clinical suspicion of TASS, endophthalmitis as a devastating disease should always be excluded. However, the fact that TASS and endophthalmitis can look the same, but the treatment for each is different. Therefore, distinguishing between the two conditions is an important factor in coping with both diseases. It was aimed to describe the features and clinical management that are considered when distinguishing the cause of unexpected inflammatory response after cataract surgery. METHODS: A retrospective review of medical records of 13 patients who developed TASS in our clinic at Ege University Ophthalmology Department on three different days between July 2022 and December 2022 were included in this study. Anterior segment photographs of those 13 patients and the records of ophthalmological examinations of those patients, including best-corrected visual acuity (BCVA), ocular pressure, biomicroscopic, and fundoscopic examination, were collected. Medical data were evaluated retrospectively. RESULTS: The mean time to onset of clinical symptoms was 27.6 h. The main complaint was pain in nine patients. The primary symptom in the remainder of the patients was blurred vision. Severe hypopyon was seen in 5 cases. Despite the presence of pain and hypopyon, patients who were treated with topical steroids were closely followed up (every 2 h) because they were consecutive patients and had relatively acute onset complaints. Inflammation was regressed after an average of 4 h. No factor causing TASS was found. The BCVA was at the minimum level of 8/10 on the 5th day of surgery. CONCLUSION: When distinguishing TASS from endophthalmitis, severe pain, relatively late onset, hyperemia, and the presence of severe hypopyon usually lead ophthalmologists to the clinical diagnosis of endophthalmitis. However, in this study, most of the patients diagnosed with TASS had severe pain, a significant portion of them had hypopyon, and the onset of the symptoms was relatively late. Close follow-up immediately after suspicion plays a vital role in clinical diagnosis and management accordingly.

Systematic characterization of chromatin modifying enzymes identifies KDM3B as a critical regulator in castration resistant prostate cancer.

Androgen deprivation therapy (ADT) is the standard care for prostate cancer (PCa) patients who fail surgery or radiotherapy. While initially effective, the cancer almost always recurs as a more aggressive castration resistant prostate cancer (CRPC). Previous studies have demonstrated that chromatin modifying enzymes can play a critical role in the conversion to CRPC. However, only a handful of these potential pharmacological targets have been tested. Therefore, in this study, we conducted a focused shRNA screen of chromatin modifying enzymes previously shown to be involved in cellular differentiation. We found that altering the balance between histone methylation and demethylation impacted growth and proliferation. Of all genes tested, KDM3B, a histone H3K9 demethylase, was found to have the most antiproliferative effect. These results were phenocopied with a KDM3B CRISPR/Cas9 knockout. When tested in several PCa cell lines, the decrease in proliferation was remarkably specific to androgen-independent cells. Genetic rescue experiments showed that only the enzymatically active KDM3B could recover the phenotype. Surprisingly, despite the decreased proliferation of androgen-independent cell no alterations in the cell cycle distribution were observed following KDM3B knockdown. Whole transcriptome analyses revealed changes in the gene expression profile following loss of KDM3B, including downregulation of metabolic enzymes such as ARG2 and RDH11. Metabolomic analysis of KDM3B knockout showed a decrease in several critical amino acids. Overall, our work reveals, for the first time, the specificity and the dependence of KDM3B in CRPC proliferation.