Muscle degeneration in chronic massive rotator cuff tears of the shoulder: Addressing the real problem using a graphene matrix.

Massive rotator cuff tears (MRCTs) of the shoulder cause disability and pain among the adult population. In chronic injuries, the tendon retraction and subsequently the loss of mechanical load lead to muscle atrophy, fat accumulation, and fibrosis formation over time. The intrinsic repair mechanism of muscle and the successful repair of the torn tendon cannot reverse the muscle degeneration following MRCTs. To address these limitations, we developed an electroconductive matrix by incorporating graphene nanoplatelets (GnPs) into aligned poly(l-lactic acid) (PLLA) nanofibers. This study aimed to understand 1) the effects of GnP matrices on muscle regeneration and inhibition of fat formation in vitro and 2) the ability of GnP matrices to reverse muscle degenerative changes in vivo following an MRCT. The GnP matrix significantly increased myotube formation, which can be attributed to enhanced intracellular calcium ions in myoblasts. Moreover, the GnP matrix suppressed adipogenesis in adipose-derived stem cells. These results supported the clinical effects of the GnP matrix on reducing fat accumulation and muscle atrophy. The histological evaluation showed the potential of the GnP matrix to reverse muscle atrophy, fat accumulation, and fibrosis in both supraspinatus and infraspinatus muscles at 24 and 32 wk after the chronic MRCTs of the rat shoulder. The pathological evaluation of internal organs confirmed the long-term biocompatibility of the GnP matrix. We found that reversing muscle degenerative changes improved the morphology and tensile properties of the tendon compared with current surgical techniques. The long-term biocompatibility and the ability of the GnP matrix to treat muscle degeneration are promising for the realization of MRCT healing and regeneration.

Metal-Organic Framework-Based Surface-Enhanced Raman Scattering Sensing Platform for Trace Malondialdehyde Detection in Tears.

Disease biomarkers in tears are crucial for clinical diagnosis and health monitoring. However, the limited volume of tear samples, low concentration of tear biomarkers, and complex tear composition present challenges for precise testing. We introduce a spot-on testing platform of metal-organic framework (MOF)-based surface-enhanced Raman scattering (SERS) capillary column, which is capable of target molecules selective separation and enrichment for tear biomarkers in situ detection. It consists of Au nanostars for effective SERS signal and a porous MOF shell for separating impurities through molecular sieving effect. This platform allows for simultaneous collection and detection of tear, capturing the disease biomarker malondialdehyde in tears with a 9.38 × 10-9 mol/L limit of detection. Moreover, we designed a hand-held device based on this tubular SERS sensor, successfully diagnosing patients with dry eye disease. This functional capillary column enables noninvasive and rapid diagnosis of biomarkers in biofluids, providing potential for disease diagnosis and healthcare monitoring.

Two Artificial Tears Outbreak-Associated Cases of Extensively Drug-Resistant Pseudomonas aeruginosa Detected Through Whole Genome Sequencing-Based Surveillance.

We describe 2 cases of extensively drug-resistant Pseudomonas aeruginosa infection caused by a strain of public health concern, as it was recently associated with a nationwide outbreak of contaminated artificial tears. Both cases were detected through database review of genomes in the Enhanced Detection System for Hospital-Associated Transmission (EDS-HAT), a routine genome sequencing-based surveillance program. We generated a high-quality reference genome for the outbreak strain from an isolate from our center and examined the mobile elements encoding blaVIM-80 and bla-GES-9 carbapenemases. We used publicly available Pseudomonas aeruginosa genomes to explore the genetic relatedness and antimicrobial resistance genes of the outbreak strain.

Tear Proteins Altered in Patients with Persistent Eye Pain after Refractive Surgery: Biomarker Candidate Discovery.

Some patients develop persistent eye pain after refractive surgery, but factors that cause or sustain pain are unknown. We tested whether tear proteins of patients with pain 3 months after surgery differ from those of patients without pain. Patients undergoing refractive surgery (laser in situ keratomileusis or photorefractive keratectomy ) were recruited from 2 clinics, and tears were collected 3 months after surgery. Participants rated their eye pain using a numerical rating scale (NRS, 0-10; no pain-worst pain) at baseline, 1 day, and 3 months after surgery. Using tandem mass tag proteomic analysis, we examined tears from patients with pain [NRS ≥ 3 at 3 months (n = 16)] and patients with no pain [NRS ≤ 1 at 3 months (n = 32)] after surgery. A subset of proteins (83 of 2748 detected, 3.0%) were associated with pain 3 months after surgery. High-dimensional statistical models showed that the magnitude of differential expression was not the only important factor in classifying tear samples from pain patients. Models utilizing 3 or 4 proteins had better classification performance than single proteins and represented differences in both directions (higher or lower in pain). Thus, patterns of protein differences may serve as biomarkers of postsurgical eye pain as well as potential therapeutic targets.

Discovery and Verification of Sjögren's Syndrome Protein Biomarkers in Tears by Targeted LC-MRM.

Sjögren's syndrome (SS) is an autoimmune rheumatic disorder characterized by exocrine gland dysfunction, mainly from the lacrimal and salivary glands. The disease causes severe aqueous dry eye syndrome (DED) and is associated with high rates of complications, including corneal ulceration, scaring, and perforation. Systemic complications may occur as well as a higher risk of developing lymphoma. Diagnosis of SS-DED is often delayed and difficult to establish. With the aim of discovering biomarkers to help discriminate SS-DED patients, a combination of untargeted and targeted LC-MS/MS analyses were performed on tear samples collected on Schirmer strips and subjected to tryptic digestion. Following the analysis of three cohorts and the development of two targeted LC-sMRM methods for the verification of putative biomarkers found in the first cohort of samples, 64 proteins could be linked to Sjögren's syndrome, in the hopes of helping to confirm diagnoses as well as potentially stratifying the severity of disease in these patients. Proteins that were increased in SS-DED showed activation of the immune system and alterations in homeostasis. Several proteases and protease inhibitors were found to be significantly changing in SS-DED, as well as a consistent decrease in specific proteins known to be secreted by the lacrimal gland.

Extensively Drug-Resistant Pseudomonas aeruginosa Outbreak Associated With Artificial Tears.

BACKGROUND: Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) are extensively drug-resistant bacteria. We investigated the source of a multistate CP-CRPA outbreak. METHODS: Cases were defined as a US patient's first isolation of P. aeruginosa sequence type 1203 with carbapenemase gene blaVIM-80 and cephalosporinase gene blaGES-9 from any specimen source collected and reported to the Centers for Disease Control and Prevention during 1 January 2022-15 May 2023. We conducted a 1:1 matched case-control study at the post-acute care facility with the most cases, assessed exposures associated with case status for all case-patients, and tested products for bacterial contamination. RESULTS: We identified 81 case-patients from 18 states, 27 of whom were identified through surveillance cultures. Four (7%) of 54 case-patients with clinical cultures died within 30 days of culture collection, and 4 (22%) of 18 with eye infections underwent enucleation. In the case-control study, case-patients had increased odds of receiving artificial tears versus controls (crude matched OR, 5.0; 95% CI, 1.1-22.8). Overall, artificial tears use was reported by 61 (87%) of 70 case-patients with information; 43 (77%) of 56 case-patients with brand information reported use of Brand A, an imported, preservative-free, over-the-counter (OTC) product. Bacteria isolated from opened and unopened bottles of Brand A were genetically related to patient isolates. Food and Drug Administration inspection of the manufacturing plant identified likely sources of contamination. CONCLUSIONS: A manufactured medical product serving as the vehicle for carbapenemase-producing organisms is unprecedented in the United States. The clinical impacts from this outbreak underscore the need for improved requirements for US OTC product importers.

Healthy Tendon Stem Cell-Derived Exosomes Promote Tendon-To-Bone Healing of Aged Chronic Rotator Cuff Tears by Breaking the Positive-Feedback Cross-Talk between Senescent Tendon Stem Cells and Macrophages through the Modulation of Macrophage Polarization.

The re-tear rate of rotator cuff tears (RCT) after surgical repair is high, especially in aged patients with chronic tears. Senescent tendon stem cells (s-TSCs) generally exist in aged and chronically torn rotator cuff tendons and are closely associated with impaired tendon-to-bone healing results. The present study found a positive feedback cross-talk between s-TSCs and macrophages. The conditioned medium (CM) from s-STCs can promote macrophage polarization mainly toward the M1 phenotype, whose CM reciprocally accelerated further s-TSC senescence. Additional healthy tendon stem-cells derived exosomes (h-TSC-Exos) can break this positive feedback cross-talk by skewing macrophage polarization from the M1 phenotype to the M2 phenotype, attenuating s-TSCs senescence. S-TSC senescence acceleration or attenuation effects induced by M1 or M2 macrophages are associated with the inhibition or activation of the bone morphogenetic protein 4 signaling pathway following RNA sequencing analysis. Using an aged-chronic rotator cuff tear rat model, it is found that h-TSC-Exos can shift the microenvironment in the tendon-to-bone interface from a pro-inflammatory to an anti-inflammatory type at the acute postoperative stage and improve the tendon-to-bone healing results, which are associated with the rejuvenated s-TSCs. Therefore, this study proposed a potential strategy to improve the healing of aged chronic RCT.

Post-traumatic and OA-related lesions in the knee at baseline and 2 years after traumatic meniscal injury: Secondary analysis of a randomized controlled trial.

OBJECTIVE: To assess the presence of early degenerative changes on Magnetic Resonance Imaging (MRI) 24 months after a traumatic meniscal tear and to compare these changes in patients treated with arthroscopic partial meniscectomy or physical therapy plus optional delayed arthroscopic partial meniscectomy. DESIGN: We included patients aged 18-45 years with a recent onset, traumatic, MRI verified, isolated meniscal tear without radiographic osteoarthritis. Patients were randomized to arthroscopic partial meniscectomy or standardized physical therapy with optional delayed arthroscopic partial meniscectomy. MRIs at baseline and 24 months were scored using the MRI Osteoarthritis Knee Score (MOAKS). We compared baseline MRIs to healthy controls aged 18-40 years. The outcome was the progression of bone marrow lesions (BMLs), cartilage defects and osteophytes after 24 months in patients. RESULTS: We included 99 patients and 50 controls. At baseline, grade 2 and 3 BMLs were present in 26% of the patients (n = 26), compared to 2% of the controls (n = 1) (between group difference 24% (95% CI 15% to 34%)). In patients, 35% (n = 35) had one or more cartilage defects grade 1 or higher, compared to 2% of controls (n = 1) (between group difference 33% (95% CI 23% to 44%)). At 24 months MRI was available for 40 patients randomized to arthroscopic partial meniscectomy and 41 patients randomized to physical therapy. At 24 months 30% (n = 12) of the patients randomized to arthroscopic partial meniscectomy showed BML worsening, compared to 22% (n = 9) of the patients randomized to physical therapy (between group difference 8% (95% CI -11% to 27%)). Worsening of cartilage defects was present in 40% (n = 16) of the arthroscopic partial meniscectomy group, compared to 22% (n = 9) of the physical therapy group (between group difference 18% (95% CI -2% to 38%)). Of the patients who had no cartilage defect at baseline, 33% of the arthroscopic partial meniscectomy group had a new cartilage defect at follow-up compared to 14% of the physical therapy group. Osteophyte worsening was present in 18% (n = 7) of the arthroscopic partial meniscectomy group and 15% (n = 6) of the physical therapy group (between group difference 3% (95% CI -13% to 19%)). CONCLUSIONS: Our results might suggest more worsening of BMLs and cartilage defects with arthroscopic partial meniscectomy compared to physical therapy with optional delayed arthroscopic partial meniscectomy at 24-month follow-up in young patients with isolated traumatic meniscal tears without radiographic OA.

Human tear film protein sampling using soft contact lenses.

BACKGROUND: Human tear protein biomarkers are useful for detecting ocular and systemic diseases. Unfortunately, existing tear film sampling methods (Schirmer strip; SS and microcapillary tube; MCT) have significant drawbacks, such as pain, risk of injury, sampling difficulty, and proteomic disparities between methods. Here, we present an alternative tear protein sampling method using soft contact lenses (SCLs). RESULTS: We optimized the SCL protein sampling in vitro and performed in vivo studies in 6 subjects. Using Etafilcon A SCLs and 4M guanidine-HCl for protein removal, we sampled an average of 60 ± 31 µg of protein per eye. We also performed objective and subjective assessments of all sampling methods. Signs of irritation post-sampling were observed with SS but not with MCT and SCLs. Proteomic analysis by mass spectrometry (MS) revealed that all sampling methods resulted in the detection of abundant tear proteins. However, smaller subsets of unique and shared proteins were identified, particularly for SS and MCT. Additionally, there was no significant intrasubject variation between MCT and SCL sampling. CONCLUSIONS: These experiments demonstrate that SCLs are an accessible tear-sampling method with the potential to surpass current methods in sampling basal tears.

Extracellular vesicle biomarkers in ocular fluids associated with ophthalmic diseases.

Extracellular vesicles (EVs) are released as highly stable lipid bilayer particles carrying proteins, lipids, glycans and miRNAs. The contents of EVs vary based on the cellular origin, biogenesis route and the functional state of the cell suggesting certain diseased conditions. A growing body of evidence show that EVs carry important molecules implicated in the development and progression of ophthalmic diseases. EVs associated with ophthalmic diseases are mainly carried by one of the three ocular biofluids which include tears, aqueous humor and vitreous humor. This review summarizes the list of EV derived biomarkers identified thus far in ocular fluids for ophthalmic disease diagnosis. Further, the methods used for sample collection, sample volume and the sample numbers used in these studies have been highlighted. Emphasis has been given to describe the EV isolation and the characterization methods used, EV size profiled and the EV concentrations analyzed by these studies, thus providing a roadmap for future EV biomarker studies in ocular fluids.

Characterizing the Myoarchitecture of the Supraspinatus and Infraspinatus Muscles With MRI Using Diffusion Tensor Imaging.

BACKGROUND: The societal cost of shoulder disabilities in our aging society keeps rising. Providing biomarkers of early changes in the microstructure of rotator cuff (RC) muscles might improve surgical planning. Elevation angle (E1A) and pennation angle (PA) assessed by ultrasound change with RC tears. Furthermore, ultrasounds lack repeatability. PURPOSE: To propose a repeatable framework to quantify the myocyte angulation in RC muscles. STUDY TYPE: Prospective. SUBJECTS: Six asymptomatic healthy volunteers (1 female aged 30 years; 5 males, mean age 35 years, range 25-49 years), who underwent three repositioned scanning sessions (10 minutes apart) of the right infraspinatus muscle (ISPM) and supraspinatus muscle (SSPM). FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted and diffusion tensor imaging (DTI; 12 gradient encoding directions, b-values of 500 and 800 s/mm2 ). ASSESSMENT: Each voxel was binned in percentage of depth defined by the shortest distance in the antero-posterior direction (manual delineation), i.e. the radial axis. A second order polynomial fit for PA across the muscle depth was used, while E1A described a sigmoid across depth: E 1 A sig = E 1 A range × sigmf 1 : 100 % depth , - EA 1 grad   ,   E 1 A asym + E 1 A shift . STATISTICAL TESTS: Repeatability was assessed with the nonparametric Wilcoxon's rank-sum test for paired comparisons across repeated scans in each volunteer for each anatomical muscle region and across repeated measures of the radial axis. A P-value <0.05 was considered statistically significant. RESULTS: In the ISPM, E1A was constantly negative, became helicoidal, then mainly positive across the antero-posterior depth, respective at the caudal, central and cranial regions. In the SSPM, posterior myocytes ran more parallel to the intramuscular tendon ( PA ≈ 0 ° ), while anterior myocytes inserted with a pennation angle ( PA ≈ - 20 ° ). E1A and PA were repeatable in each volunteer (error < 10%). Intra-repeatability of the radial axis was achieved (error < 5%). DATA CONCLUSION: ElA and PA in the proposed framework of the ISPM and SSPM are repeatable with DTI. Variations of myocyte angulation in the ISPM and SSPM can be quantified across volunteers. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Safety and efficacy of the OdonAssist inflatable device for assisted vaginal birth: the BESANCON ASSIST study.

BACKGROUND: The first feasibility study of the OdonAssist inflatable device for use in clinically indicated assisted vaginal birth reported a success rate of 48% with no significant safety concerns. Additional studies exploring the device performance in other clinical settings are warranted before definitive conclusions can be drawn about its safety and efficacy in current practice. OBJECTIVE: This study aimed to investigate the safety and efficacy of the OdonAssist before conducting a randomized controlled trial. STUDY DESIGN: This was an open-label, nonrandomized study of 104 women with a clinically indicated assisted vaginal birth using the OdonAssist at the Besancon University Hospital, France. Data, including those of a nested cohort group of women who had an assisted vaginal birth using vacuum or spatulas because a trained OdonAssist device operator was not available at the time of delivery, were collected. The primary outcome measure was the proportion of successful assisted vaginal births using the OdonAssist. Neonatal outcome data were reviewed at days 1 and 28, and maternal outcomes were investigated up to day 90. RESULTS: Between December 2019 and May 2021, 2191 pregnant women were approached, and 83% (1636/1973) of them consented to participate in the study. Among them, 10.7% (176/1636) required an assisted vaginal birth owing to a vertex presentation at +1 and below. The OdonAssist was used in 59% of births (104/176), and 41.1% (72/176) of the participants were included in the nested cohort group. The rate of successful assisted vaginal births using the OdonAssist was 88.5% (92/104). No emergency cesarean deliveries were performed in the OdonAssist group. There were no serious adverse maternal or neonatal reactions related to the use of the device. The rate of third- and fourth-degree perineal tears with the OdonAssist was 3.8% (4/104). The maternal perception ratings of the birth experience with the OdonAssist (collected on days 1, 7, and 28 using a 15-point scale) were high. In addition, the operators reported a positive perception of the device, with ease of use across the different steps of the procedure. One single technique was used for all vertex fetal head positions. CONCLUSION: The OdonAssist is a safe and effective alternative to other current devices for assisted vaginal births. The high acceptance rate (83%) among pregnant women and the high rate of successful assisted vaginal births using the OdonAssist confirm the feasibility of a future randomized controlled trial.

Closed- or open-glottis pushing for vaginal delivery: a planned secondary analysis of the TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery study.

BACKGROUND: The effect on obstetrical outcomes of closed- or open-glottis pushing is uncertain among both nulliparous and parous women. OBJECTIVE: This study aimed to assess the association between open- or closed-glottis pushing and mode of delivery after an attempted singleton vaginal birth at or near term. STUDY DESIGN: This was an ancillary planned cohort study of the TRAAP (TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery) randomized controlled trial, conducted in 15 French maternity units from 2015 to 2016 that enrolled women with an attempted singleton vaginal delivery after 35 weeks' gestation. After randomization, characteristics of labor and delivery were prospectively collected, with special attention to active second-stage pushing and a specific planned questionnaire completed immediately after birth by the attending care provider. The exposure was the mode of pushing, classified into 2 groups: closed- or open-glottis. The main endpoint was operative vaginal delivery. Secondary endpoints were items of maternal morbidity, including severe perineal laceration, episiotomy, postpartum hemorrhage, duration of the second stage of labor, and a composite severe neonatal morbidity outcome. We also assessed immediate maternal satisfaction, experience of delivery, and psychological status 2 months after delivery. The associations between mode of pushing and outcome were analyzed by multivariate logistic regression to control for confounding bias, with multilevel mixed-effects analysis, and a random intercept for center. RESULTS: Among 3041 women included in our main analysis, 2463 (81.0%) used closed-glottis pushing and 578 (19.0%) open-glottis pushing; their respective operative vaginal delivery rates were 19.1% (n=471; 95% confidence interval, 17.6-20.7) and 12.5% (n=72; 95% confidence interval, 9.9-15.4; P<.001). In an analysis stratified according to parity and after controlling for available confounders, the rate of operative vaginal delivery did not differ between the groups among nulliparous women: 28.7% (n=399) for the closed-glottis and 27.5% (n=64) for the open-glottis group (adjusted odds ratio, 0.93; 95% confidence interval, 0.65-1.33; P=.7). The operative vaginal delivery rate was significantly lower for women using open- compared with closed-glottis pushing in the parous population: 2.3% (n=8) for the open- and 6.7% (n=72) for the closed-glottis groups (adjusted odds ratio, 0.43; 95% confidence interval, 0.19-0.90; P=.03). Other maternal and neonatal outcomes did not differ between the 2 modes of pushing among either the nulliparous or parous groups. CONCLUSION: Among nulliparous women with singleton pregnancies at term, the risk of operative vaginal birth did not differ according to mode of pushing. These results will inform shared decision-making about the mode of pushing during the second stage of labor.

Correlation between serum cytokine levels and the effect of allogeneic serum-based eye drops.

INTRODUCTION: The Institute of Hematology and Transfusion Medicine (IHTM) in Warsaw has produced autologous serum eye drops (ASEDs) for the treatment of Dry Eye Syndrome (DES) since 1991. In 2019, IHTM introduced allogeneic tears (alloSEDs) for patients on long-term treatment. MATERIALS AND METHODS: 114 patients who applied alloSEDs were included in the study.They were asked to complete the OSDI questionnaire before and after using ASEDs and 100 units of alloSEDs drops from each donation. The OSDI index rates DES severity (0 no symptoms; 100 severe). We also compared the content of IL-1ß, IL-2, IL- 6, IL-10 and VEGF in ASEDs (38 samples) and alloSEDs (15 serum samples). The study data covered the 2019-2022 period. RESULTS: 114 patients participated in the study. We compared the the effectiveness of ASEDs and alloSEDs. The average, OSDI dropped from 68.42 ± 5,86 (before application) to 51.05 ± 19,06 (after application). Data from the questionnaires (prepared at IHTM) completed and returned (41/114) present the most common indications for the use of serum drops, including DES with no underlying disease, DES secondary to GvHD (Graft versus Host Disease), Sjögren's Syndrome (SS). The study reported higher cytokine levels associated with disease entities such as SS. After application of drops with high cytokine levels, patients reported adverse reactions such as sand under the eyelids, impaired visual acuity, and worse eye lubrication. CONCLUSIONS: AlloSEDs with acceptably low values of pro-inflammatory cytokines and sufficiently high levels of VEGF growth factor may contribute to alleviation of inflammatory eye symptoms.

Incidence of and Risk Factors for Post-Operative Urinary Retention Following Surgery for Perineal Tears Among Ugandan Women: A Prospective Cohort Study.

INTRODUCTION AND HYPOTHESIS: We aimed to determine the incidence and risk factors for post-operative urinary retention (POUR) following surgery for perineal tears, and to determine the time to normal voiding after POUR. METHODS: This was a prospective cohort study of women who underwent surgery for old (≥ 3 months) obstetric perineal tears from January 2022 to December 2023. The diagnosis of POUR was made in a woman who completely failed to void despite a full bladder or, one who had post-void residual (PVR) > 150 ml within 10 min of voiding. Return to normal voiding was considered if a patient with POUR had two consecutive PVRs of ≤ 150 ml. Descriptive analyses and multivariable logistic regression were performed to determine risk factors for POUR. RESULTS: A total of 153 participants were enrolled in this study with a mean age of 35.9 (SD ± 10.8) years. The incidence of POUR was 19.6% (30/153, 95% CI 14.02-26.7), and the median time to normal voiding for these patients was 42.4 h (range 24-72). Risk factors for POUR included repeat perineal tear surgery (RR = 4.24; 95% CI 1.16-15.52; p = 0.029) and early urinary catheter removal (RR = 2.89; 95% CI 1.09-7.67; p = 0.033). CONCLUSION: Post-operative urinary retention following surgery for perineal tears is common. The time to return to normal voiding in patients with POUR is short. Women having repeat perineal tear surgery and those in whom the urinary catheter is removed early were more likely to experience POUR. Delayed urinary catheter removal could be considered, especially in patients undergoing repeat perineal tear surgery.

MicroRNA expression profiling in tears and blood as predictive biomarkers for anti-VEGF treatment response in wet age-related macular degeneration.

PURPOSE: This study aimed to investigate the potential of microRNAs (miRNAs) in tears, blood, and aqueous humor as biomarkers for predicting treatment response in wet age-related macular degeneration (AMD) patients undergoing anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: In a single-center prospective cohort study, treatment-naïve wet AMD patients and age-matched controls were enrolled. Clinical data and miRNA levels (miR-199a-3p, miR-365-3p, miR-200b-3p, miR-195-5p, miR-335-5p, and miR-185-5p) in tears, blood, and aqueous humor were collected. Treatment response was categorized into responders and non-responders based on visual acuity and central subfield thickness. MiRNA levels were quantified using reverse-transcription PCR. Statistical analyses were performed, including ROC analysis, to evaluate predictive accuracy. RESULTS: Dysregulated miRNA profiles were observed in wet AMD tears and blood compared to controls. Specifically, miR-199a-3p, miR-195-5p, and miR-185-5p were upregulated, while miR-200b-3p was downregulated in tears. All six miRNAs were elevated in wet AMD blood samples. Notably, responders showed higher tear expression of miR-195-5p and miR-185-5p. Combining these miRNAs yielded the highest predictive power (AUC = 0.878, p = 0.006) for anti-VEGF responders. CONCLUSIONS: Dysregulated miRNA profiles in tears and blood suggest their potential as biomarkers for wet AMD. MiR-195-5p and miR-185-5p in tears demonstrate predictive value for anti-VEGF treatment responders. This study underscores the non-invasive prediction potential of miRNA tear analysis in wet AMD treatment responses.

Pelvic floor function after third and fourth degree perineal lacerations: a case-control study on quality of life.

BACKGROUND: The primary aim of this study was to compare the quality of life between women with obstetric anal sphincter injury (OASI) and women with intact perineum or minor vaginal tears following their first vaginal birth through a validated urogynaecological questionnaire. As a secondary aim, we wanted to identify the specific symptoms for pelvic floor dysfunction after a vaginal birth. METHODS: One hundred thirty-three cases (III- and IV-degree vaginal tears) and 133 controls (intact perineum or I- and II-degree vaginal tear) were asked to fill the PFDI-20 condition-specific and quality of life survey at three and 12 months after vaginal delivery. The survey evaluates pelvic floor dysfunction symptoms through three subsections: the Pelvic Organ Prolapse Distress Inventory (POPDI), the Colorectal-Anal Distress Inventory (CRADI), and Urinary Distress Inventory, (UDI). The scoring system ranges from 0 (no distress) to 100 (maximum distress) for each subsection, subsequently summed up to obtain the summary score (0 to 300). The patients recruited were asked to complete the survey at 3- and 12-months follow-up visit. Accordingly, data collection started. Categorical variables were subjected to Chi-square test or Fisher's Exact test. Quantitative variables were compared through Student's t-test or Mann-Whitney test. RESULTS: All surveys have shown statistically significant differences when comparing the cases to the control group. Consequently, PFDI-20 has shown a strong correlation between III- and IV-grade lacerations and pelvic floor dysfunction persistence at 12 months after delivery. Intestinal symptoms were the most reported disturbances among women with previous OASI. CONCLUSIONS: Major vaginal tears have demonstrated to have a strong impact on women's quality of life up to a follow-up of 12 months. The use of PFDI-20 questionnaire is a useful and valid tool in the diagnosis and follow-up of genital prolapse, fecal and urinary incontinence in primiparous women with a history of OASI. Thus, its application in clinical practice can help offering the most adequate rehabilitative treatment.

Occurrence and risk factors for second-degree perineal tears: A prospective cohort study using a detailed classification system.

BACKGROUND: The amount of tissue trauma within second-degree perineal tears varies widely. Therefore, subcategorization of second-degree tears and a better understanding of their occurrence and risk factors are needed. The aim of this study was to assess the occurrence of perineal tears when second-degree tears were subcategorized. Furthermore, we aimed to assess the association between variables related to perineal anatomy and other potential risk factors, with second-degree tear subcategories. METHODS: This prospective cohort study included 880 primiparous and multiparous women giving birth to one child vaginally. Perineal tears were categorized using the classification system recommended by the Royal College of Obstetricians and Gynaecologists. In addition, second-degree tears were subcategorized as 2A, 2B, or 2C according to the percentage of damage to the perineal body. Selected variables related to perineal anatomy were as follows: length of genital hiatus; perineal body length; and previous perineal trauma. Risk factors for second-degree tear subcategories were analyzed using a multinominal regression model. RESULTS: Perineal tears occurred as follows: first-degree: 35.6% (n = 313), 2A: 16.3% (n = 143), 2B: 9.1% (n = 80), 2C: 6.6% (n = 58), and third- or fourth-degree: 1.6% (n = 14). In total, 169/880 participants underwent an episiotomy. When episiotomies were excluded, the risk for 2B, or 2C tears increased with smaller genital hiatus, larger perineal body, previous perineal trauma, primiparity, higher gestational age, instrumental vaginal delivery and fetal presentation other than occiput anterior. CONCLUSION: The occurrence of second-degree tear subcategories was 16.3% for 2A tears, 9.1% for 2B tears, and 6.6% for 2C tears. Factors related to perineal anatomy increased the odds for experiencing a second-degree tear in a more severe subcategory.

Giant retinal pigment epithelium tears with membranous nephropathy: a case report and literature review.

BACKGROUND: Kidney and eye diseases may be closely linked. Tears of the retinal pigment epithelium (RPE) have been reported to be related to kidney diseases, such as IgA nephropathy and light-chain deposition disease. However, pigment epithelium tears associated with membranous nephropathy have not been reported or systematically analysed. CASE PRESENTATION: A 68-year-old man presented with decreased right eye visual acuity. Optical coherence tomography (OCT) revealed cystic macular edema, localized serous detachment of the retina and loss of the outer retinal structure in the right eye and retinal pigment epithelium detachment (PED) combined with serous detachment of the retina in the left eye. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) revealed giant RPE tears in the right eye and exudative age-related macular degeneration in the left eye. The patient also suffered from severe membranous nephropathy-autoimmune glomerulonephritis. Renal biopsy immunofluorescence revealed a roughly granular pattern, with immunoglobulin G (IgA), immunoglobulin G (IgG), IgM, complement C3(Components 3), λ light chain and κ light chain subepithelial staining. CONCLUSIONS: It is hypothesized that severe membranous nephropathy caused immune complex deposition on the surface of Bruch membrane, resulting in weakened adhesion between the RPE and Bruch membrane and impaired RPE pump function, combined with age-related macular degeneration, leading to giant RPE tears in the right eye. Close attention should be given to the ocular condition of patients with membranous nephropathy to facilitate timely treatment and avoid serious consequences.

'If he thought that I was going to go and hurt myself, he had another thing coming': Treatment experiences of those with large to massive rotator cuff tears and the perspectives of healthcare practitioners.

OBJECTIVE: To explore the treatment experiences of those diagnosed with large to massive rotator cuff tears and the perspectives of healthcare practitioners providing their care. DESIGN: A qualitative descriptive study using reflexive thematic analysis. SETTING: In-person focus groups were undertaken in a clinical setting (private practice [n = 1]; public outpatient [n = 2]). Semi-structured interviews were conducted online via Microsoft Teams. PARTICIPANTS: Patients diagnosed with these tears (n = 12) and healthcare practitioners (n = 11). RESULTS: Two interlinking themes were identified based on the care received and provided for patients with symptomatic large to massive rotator cuff tears:1) Positive treatment experiences and management: Education, clear communication and reassurance around prognosis were the foundation of positive patient-clinician care. Sub-themes of pain relief, exercise prescription and confidence in their pathway underpinned this experience. This proficiency in care was affirmed by some healthcare practitioners who spoke about the importance of confidence and experience in their management plan even in times of poor progress.2) Negative treatment experiences and management: Uncertainty, delays and exacerbation of pain flawed the patient-clinician care. Sub-themes of inappropriate pain relief, inappropriate exercise prescription and uncertainty impacted their care. Some healthcare practitioners acknowledged knowledge gaps led to uncertainty especially when choosing the next step of care and were quick to escalate care to deflect this uncertainty. CONCLUSIONS: The findings suggest discordance exists between the patient's experiences and expectations when the delivery of care was by less experienced and confident healthcare practitioners in the management of this condition. This highlights the need for improved education and support for healthcare practitioners.