Nevin Manimala

J Shoulder Elbow Surg. 2024 Mar 22:S1058-2746(24)00215-5. doi: 10.1016/j.jse.2024.01.054. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of this study is to systematically review the evidence in the literature to ascertain the functional outcomes, recurrence rates, and subsequent revision rates following type V superior labrum anterior-posterior (SLAP) repair.

METHODS: Two independent reviewers performed a literature search based on PRISMA guidelines, utilizing the EMBASE, MEDLINE, and The Cochrane Library Databases. Studies were included if they had clinical outcomes on the patients undergoing type V SLAP repair. Statistical analysis was performed using SPSS (IBM, Armonk, NY, USA). A P value of < 0.05 was considered to be statistically significant.

RESULTS: Our review found 13 studies, including 451 shoulders meeting our inclusion criteria. The majority of patients were male (89.3%), with an average age of 25.9 years (range 15-58) and a mean follow-up of 53.8 months. The Rowe score was the most utilized functional outcome score, with a weighted mean of 88.5. Additionally, the mean Constant score was 91.0, the mean ASES score was 88.3, the mean SSV score was 85.5%, and the mean VAS pain score was 1.2. The overall rate of return to play was 84.8%, with 80.2% returning to the same level of play. The overall reoperation rate was 6.1%, with a recurrent dislocation rate of 8.2%. In the studies comparing type V SLAP and isolated Bankart repair, there were statistically insignificant differences in VAS pain scores (MD; 0.15, 95% CI, -0.13 to 0.44, I² = 0%, p = 0.29) and recurrence rates (RR; 1.38, 95% CI, 0.88 to 2.15, I² = 0%, p = 0.16).

CONCLUSION: Arthroscopic repair of type V SLAP tears results in excellent functional outcomes, with high return to play rates in athletes. There are low rates of reoperations and recurrent dislocations. Additionally, in comparison to an isolated Bankart repair, SLAP repair does not increase recurrence rates or postoperative pain.

PMID:38522776 | DOI:10.1016/j.jse.2024.01.054

J Heart Lung Transplant. 2024 Mar 22:S1053-2498(24)01536-5. doi: 10.1016/j.healun.2024.03.016. Online ahead of print.

ABSTRACT

BACKGROUND: Identification of differences in mortality risk between female and male heart transplant recipients may prompt sex-specific management strategies. Because worldwide, males of all ages have higher absolute mortality rates than females, we aimed to compare the excess risk of mortality (risk above the general population) in female versus male heart transplant recipients.

METHODS: We used relative survival models conducted separately in SRTR and CTS cohorts from 1988-2019, and subsequently combined using two-stage individual patient data meta-analysis, to compare the excess risk of mortality in female versus male first heart transplant recipients, accounting for the modifying effects of donor sex and recipient current age.

RESULTS: We analyzed 108,918 patients. When the donor was male, female recipients 0-12 years (Relative excess risk (RER) 1.13, 95% CI 1.00-1.26), 13-44 years (RER 1.17, 95% CI 1.10-1.25), and ≥45 years (RER 1.14, 95% CI 1.02-1.27) showed higher excess mortality risks than male recipients of the same age. When the donor was female, only female recipients 13-44 years showed higher excess risks of mortality than males (RER 1.09, 95% CI 1.00-1.20), though not significantly (p= 0.05).

CONCLUSIONS: In the setting of a male donor, female recipients of all ages had significantly higher excess mortality than males. When the donor was female, female recipients of reproductive age had higher excess risks of mortality than male recipients of the same age, though this was not statistically significant. Further investigation is required to determine the reasons underlying these differences.

PMID:38522764 | DOI:10.1016/j.healun.2024.03.016

Pharmacol Res. 2024 Mar 22:107142. doi: 10.1016/j.phrs.2024.107142. Online ahead of print.

ABSTRACT

ZLDI-8 is an A disintegrin and metalloproteinase domain 17 (ADAM17) inhibitor that suppresses the shedding of Notch1 to the Notch1 intracellular domain (NICD). In previous studies, we found that ZLDI-8 was able to sensitize HCC to sorafenib, but the mechanism of action remains unclear. The sensitizing effects of ZLDI-8 were tested both in vitro and in vivo. EMT-related factors, sorafenib sensitivity-related proteins and ECM-related gene expression were assessed using immunohistochemistry, RTPCR and Western blotting. Knockdown assays were conducted to determine the relationship between the Notch and Integrin pathways. CoIP assays, nuclear and cytoplasmic fractionation and immunofluorescence colocalization were applied to explore the interaction between the Notch and Integrin pathways. Appropriate statistical analysis methods were used to assess the significance of the experimental results and to ensure the scientific validity and reliability of the experimental design. We found that ECM- and EMT-related proteins were downregulated after ZLDI-8 treatment (P<0.05). ZLDI-8 significantly downregulated Integrinβ1 and Integrinβ3 in HCC in vitro and in vivo (P<0.05), possibly through Foxc2-dependent regulation. Mechanistically, interfering with the expression of both Integrin-linked kinase (ILK) and the NICD may downregulate the expression of proteins targeted by sorafenib, thereby sensitizing cells to sorafenib. The retroregulation of Integrinβ by ILK may occur through the interaction between the NICD and ILK and may be the result of the translocation of the complexus. Our study indicates that blocking the Notch pathway may affect Integrinβ through crosstalk between the Notch1 and Integrinβ/ILK signaling pathways, thus providing a potential therapeutic strategy for HCC.

PMID:38522759 | DOI:10.1016/j.phrs.2024.107142

J Stroke Cerebrovasc Dis. 2024 Mar 22:107686. doi: 10.1016/j.jstrokecerebrovasdis.2024.107686. Online ahead of print.

ABSTRACT

OBJECTIVE: Cross-sectional and cohort studies have found insufficient evidence of a causal relationship between sex hormone-binding globulin and ischemic stroke, only associations. Here, we performed a sex-stratified, bidirectional, two-sample Mendelian randomization analysis to evaluate whether a causal relationship exists between sex hormone-binding globulin and ischemic stroke.

METHODS: Single-nucleotide polymorphisms associated with sex hormone-binding globulin and ischemic stroke were screened from genome-wide association studies summary data as instrumental variables to enable a bidirectional, two-sample Mendelian randomization study design. Inverse-variance weighted analysis was used as the main method to evaluate potential causality, and additional methods, including the weighted median and MR-Egger tests, were used to validate the Mendelian randomization results. Cochran’s Q statistic, MR-Egger intercept test, and Mendelian Randomization-Pleiotropy Residual Sum and Outlier global test were used as sensitivity analysis techniques to assure the reliability of the results. Multivariable analysis was used to show the robustness of the results with key theorized confounders.

RESULTS: Inverse-variance weighted analysis showed that genetically predicted higher serum sex hormone-binding globulin levels were associated with significantly decreased risk of ischemic stroke in males (odds radio = 0.934, 95% confidence interval = 0.885-0.985, P = 0.012) and females (odds radio = 0.924, 95% confidence interval = 0.868-0.983, P = 0.013). In an analysis of ischemic stroke subtypes, genetically predicted higher serum sex hormone-binding globulin levels were also associated with significantly decreased risk of small-vessel occlusion in both males (odds radio = 0.849, 95% confidence interval = 0.759-0.949, P = 0.004) and females (odds radio = 0.829, 95% confidence interval = 0.724-0.949, P = 0.006). The association remained in sensitivity analyses and multivariable analyses. The reverse analysis suggested an association between genetically predicted risk of cardioembolism and increased serum sex hormone-binding globulin in females (Beta = 0.029 nmol/L, Standard Error = 0.010, P = 0.003).

CONCLUSION: Our findings provide new insight into the etiology of ischemic stroke and suggest that modulating serum sex hormone-binding globulin may be a therapeutic strategy to protect against ischemic stroke.

PMID:38522757 | DOI:10.1016/j.jstrokecerebrovasdis.2024.107686

J Stroke Cerebrovasc Dis. 2024 Mar 22:107685. doi: 10.1016/j.jstrokecerebrovasdis.2024.107685. Online ahead of print.

ABSTRACT

OBJECTIVES: Increased plasma gamma-glutamyl transferase (GGT1) has been identified as a robust and independent risk factor for ischemic stroke (IS), but the molecular mechanisms of the enzyme-disease association are unclear. The present study investigated whether polymorphisms in the GGT1 gene contribute to IS susceptibility.

MATERIALS AND METHODS: DNA samples obtained from 1288 unrelated individuals (600 IS patients and 688 controls) were genotyped for common single nucleotide polymorphisms of GGT1 using the MassArray-4 platform.

RESULTS: The rs5751909 polymorphism was significantly associated with decreased risk of ischemic stroke regardless sex and age (P_perm≤0.01, dominant genetic model). The haplotype rs4820599A-rs5760489A-rs5751909A showed strong protection against ischemic stroke (OR 0.53, 95%CI 0.36 – 0.77, P_perm≤0.0001). The protective effect of SNP rs5751909 in the stroke phenotype was successfully replicated in the UK Biobank, SiGN, and ISGC cohorts (P≤0.01). GGT1 polymorphisms showed joint (epistatic) effects on the risk of ischemic stroke, with some known IS-associated GWAS loci (e.g., rs4322086 and rs12646447) investigated in our population. In addition, SNP rs5751909 was found to be strongly associated with a decreased risk of ischemic stroke in non-smokers (OR 0.54 95%CI 0.39-0.75, P_perm=0.0002) and non-alcohol abusers (OR 0.43 95%CI 0.30-0.61, P_perm=2.0 × 10^-6), whereas no protective effects of this SNP against disease risk were observed in smokers and alcohol abusers (P_perm<0.05).

CONCLUSIONS: We propose mechanisms underlying the observed associations between GGT1 polymorphisms and ischemic stroke risk. This pilot study is the first to demonstrate that GGT1 is a novel susceptibility gene for ischemic stroke and provides additional evidence of the genetic contribution to impaired redox homeostasis underlying disease pathogenesis.

PMID:38522756 | DOI:10.1016/j.jstrokecerebrovasdis.2024.107685

Resuscitation. 2024 Mar 22:110189. doi: 10.1016/j.resuscitation.2024.110189. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: In case of out-of-hospital cardiac arrest (OHCA) personnel of the emergency medical services (EMS) are regularly confronted with advanced directives (AD) and do-not-attempt-resuscitation (DNACPR) orders. The authors conducted a retrospective analysis of EMS operation protocols to examine the prevalence of DNACPR in case of OHCA and the influence of a presented DNACPR on CPR-duration, performed Advanced-Life-Support (ALS) measures and decision making.

MATERIALS AND METHODS: Retrospective analysis of prehospital medical documentation of all resuscitation incidents in a German county with 250,000 inhabitants from 1 January 2016 to 31 December 2022. Combined with data from the structured CPR team-feedback database patients characteristics, measures and course of the CPR were analysed. Statistic testing with significance level p<0.05.

RESULTS: In total n=1,474 CPR events were analysed. Patients with DNACPR vs. no DNACPR: n=263 (17.8%) vs. n=1,211 (82.2%). Age: 80.0±10.3 years vs. 68.0±13.9 years; p<0.001. Patients with ASA-status III/IV: n=214 (81.3%) vs. n=616 (50.9%); p<0.001. Initial layperson-CPR: n=148 (56.3%) vs. n=647 (55.7%); p=0.86. Airway management: n=185 (70.3%) vs. n=1,069 (88.3%); p<0.001. With DNACPR CPRduration initiated layperson-CPR vs. no layperson-CPR: 19:14min (10:43-25:55min) vs. 12:40min (06:35-20:03min); p<0.001.

CONCLUSION: In case of CPR EMS-personnel are often confronted with DNACPRorders. Patients are older and have more previous diseases than patients without DNACPR. Initiated layperson-CPR might lead to misinterpretation of patients will with impact on CPR-duration and unwanted measures. Awareness of this issue should be created through measures such as training programs in particular to train staff in the interpretation and legal admissibility of ADs.

PMID:38522733 | DOI:10.1016/j.resuscitation.2024.110189

J Vasc Surg Venous Lymphat Disord. 2024 Mar 22:101874. doi: 10.1016/j.jvsv.2024.101874. Online ahead of print.

ABSTRACT

OBJECTIVE: Telangiectasias, characterized by dilated venules, are frequently observed in the lower extremities. Sclerotherapy stands out as the predominant treatment for these vascular lesions. The integration of laser therapy with a mild sclerosing agent, serving as an osmotic sclerosant, presents an enhanced cosmetic treatment approach, aiming to optimize outcomes while minimizing potential adverse effects. This study sought to evaluate the feasibility, efficacy, and safety of cryo-laser and cryo-sclerotherapy (CLaCS) and compare it with injection sclerotherapy for the treatment of telangiectasia and reticular veins.

METHODS: In this randomized controlled trial, individuals expressing concerns about telangiectasia and reticular veins were recruited for aesthetic treatment. Enrolled patients were prospectively randomized according to the chosen treatment technique. Group A included patients undergoing CLaCS treatment with 70% dextrose, focusing on a single area measuring 20 cm by 20 cm. Group B comprised patients receiving polidocanol injection sclerotherapy for a single area of the same dimensions.

RESULTS: A total of 195 patients were enrolled in Group A, while Group B comprised 197 patients. Following three treatment sessions, The rates of complete lesion elimination after first, second and third treatment sessions were 64.6%, 86.2%, and 100% in Group A and 50.3%, 74.1%, and 85.3% in group B respectively. Notably, Group A exhibited a significantly higher complete elimination rate compared to Group B at the conclusion of the study (p<0.001). Furthermore, Group A demonstrated a statistically significant lower incidence of postprocedural pigmentation and other complications when compared to Group B (p<0.001). These findings underscore the enhanced efficacy and safety profile associated with the CLaCS technique utilizing 70% dextrose in comparison to injection sclerotherapy with polidocanol.

CONCLUSION: CLaCS, combining cryo-laser and cryo-sclerotherapy, demonstrated superior efficacy and safety compared to traditional polidocanol sclerotherapy for treating telangiectasia and reticular veins.

PMID:38522666 | DOI:10.1016/j.jvsv.2024.101874

Cryobiology. 2024 Mar 22:104891. doi: 10.1016/j.cryobiol.2024.104891. Online ahead of print.

ABSTRACT

Nowadays the significant role of biobanks in medical, diagnostic, industrial, and environmental research is well known. Bacterial biobanks could be used as a good resource for designing new treatments, biomedical and industrial researches, and laboratory diagnostics. To have a collection of bacteria from clinical samples and maintain their long-term viability, their preservation needs appropriate protective agents, like cryoprotectants and lyoprotectants. In this study, we collected and characterized Gram-negative and Gram-positive bacteria carrying important antibiotic resistance markers from different clinical samples of hospitalized children. Sucrose (10%), skimmed milk (10%), skimmed milk plus sodium glutamate (10% + 1%), and bovine serum albumin (BSA, 10%) were used as lyoprotectants during the freeze-drying procedure. The survival rate of the lyophilized samples was calculated by dilution plating and measuring the colony forming unit (CFU) after 3 months of storage. The culture analysis results indicated that 25 of the 27 studied bacterial genera (Dilutions 10^-3 to 10^-6), including Shigella, Methicillin-resistant S. aureus, Acinetobacter spp., Escherichia spp., Pseudomonas spp., Klebsiella spp., Enterococcus spp., were recovered in cultured fractions from all preservation conditions, while 2 genera were only detected in a single preservation condition (2/27, 7.4%). Based on the results, sucrose (10%) and skimmed milk (10%) presented the most protective features. The survival rates varied significantly according to types of the bacteria. Collectively, our results showed a diversity in the recovery of different bacterial genera after lyophilization. While statistically no significant difference was detected among the studied protective agents, sucrose (10%) and skimmed milk (10%) exhibited more effective lyoprotective properties for both Gram-positive and Gram-negative bacteria among the clinical isolates in our study.

PMID:38522663 | DOI:10.1016/j.cryobiol.2024.104891

Biosystems. 2024 Mar 22:105193. doi: 10.1016/j.biosystems.2024.105193. Online ahead of print.

ABSTRACT

We derive the classic, ubiquitous, but enigmatic Yerkes-Dodson effect of applied stress on real-world performance in a highly natural manner from fundamental assumptions on cognition and its dynamics, as constrained by the asymptotic limit theorems of information and control theories. We greatly extend the basic approach by showing how differences in an underlying probability model can affect the dynamics of decision across a broad range of cognitive enterprise. Most particularly, however, this development may help inform our understanding of the different expressions of human psychopathology. A ‘thin tailed’ underlying distribution appears to characterize expression of ‘ordinary’ situational depression/anxiety symptoms of conditions like burnout induced by toxic stress. A ‘fat tailed’ underlying distribution appears to be associated with brain structure and function abnormalities leading to serious mental illness and poor decision making where symptoms are not only emerging in the setting of severe stress but may also appear in a highly punctuated manner at relatively lower levels of stress. A simple hierarchical optimization shows how environmental ‘shadow price’ constraints can buffer or aggravate the effects of stress and arousal. Extension of the underlying theory to other patterns of pathology, like immune disorders and premature aging, seems apt. Applications to the punctuated dynamics of institutional cognition under stress also appear possible. Ultimately, the probability models studied here can be converted to new statistical tools for the analysis of observational and experimental data.

PMID:38522638 | DOI:10.1016/j.biosystems.2024.105193

Ophthalmol Retina. 2024 Mar 22:S2468-6530(24)00121-0. doi: 10.1016/j.oret.2024.03.017. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine the molecular causes of Schubert-Bornschein (S-B) congenital stationary night blindness (CSNB), clinically characterize in detail, and assess genotype-phenotype correlations for retinal function and structure.

DESIGN: Retrospective, longitudinal, single center case series.

PARTICIPANTS: 122 patients with S-B CSNB attending Moorfields Eye Hospital, United Kingdom.

METHODS: All case notes, results of molecular genetic testing, and optical coherence tomography (OCT) were reviewed.

MAIN OUTCOME MEASURES: Molecular genetics, presenting complaints, rates of nystagmus, nyctalopia, photophobia, strabismus, color vision defects and spherical error of refraction (SER). Retinal thickness, outer nuclear layer thickness (ONL) and ganglion cell layer + inner plexiform layer (GCL+IPL) thickness from OCT imaging.

RESULTS: X-linked (CACNA1F and NYX) and autosomal recessive (TRPM1, GRM6, GPR179 and CABP4) genotypes were identified. The mean reported age of onset was 4.94 ± 8.99 years. Over the follow-up period, 95.9% of patients reported reduced visual acuity (VA), half had nystagmus and 64.7% reported nyctalopia. Incomplete CSNB (iCSNB) patients more frequently had nystagmus and photophobia. Nyctalopia was similar for iCSNB and complete CSNB (cCSNB). Color vision data was limited but more defects were found in iCSNB. None of these clinical differences met statistical significance. There was no significant difference between groups in VA, with a mean of 0.46 LogMAR, and remained stable over the course of follow-up. cCSNB patients, specifically those with NYX and TRPM1 variants, were more myopic. CACNA1F patients showed the largest refractive variability and the CABP4 patient was hyperopic. No significant differences were found in OCT structural analysis during the follow-up period.

CONCLUSIONS: Retinal structure in CSNB is stationary and no specific genotype – structure correlates were identified. VA appears to be relatively stable, with rare instances of progression.

PMID:38522615 | DOI:10.1016/j.oret.2024.03.017