Faecal Immunochemical Test (FIT) Value-Based Algorithm to Triage Symptomatic Colorectal Patients: A Retrospective Study From a Tertiary Care Hospital.

Background The aim was to evaluate the diagnostic accuracy of quantitative faecal immunochemical testing (FIT) in diagnosing colorectal cancer in symptomatic patients and using it to prioritize patients for urgent colorectal investigations. Methods A retrospective review was done of all symptomatic, FIT-positive patients referred from primary care to the colorectal clinic as per the National Institute for Health and Care Excellence (NICE) DG30 pathway from November 1, 2021, to February 11, 2022. Patients under 18 years of age were excluded. All patients were triaged to test (TTT) or booked in face-to-face (F2F) clinics according to a local algorithm. The data was collected in Microsoft Excel (Microsoft Corporation, Redmond, Washington, United States), and statistical analysis was performed using IBM SPSS Statistics for Windows (IBM Corp., Armonk, New York, United States). Results Out of 915 FIT-positive patients, 774 (84.5%) patients were TTT and 70 (7.65%) were booked in F2F clinics. The mean age was 71 years, and the majority were females (n=488 (F:M = 53:47)). However, a higher prevalence of positive FIT test was observed in men than in women at higher cut-off values of >100 and >200 µg Hb/g faeces (18.79 % vs 17.48% and 12.78% vs 11.69%, respectively). The number needed to scope was 10.8, 6.03, and 5.20 at cut-off values of ≥10, >100, and >200 µg Hb/g, respectively. At cut-off values of ≥10, >100, and >200 µg Hb/g, the specificity for colorectal cancer (CRC) with a 95% confidence interval (95% CI) was 63.75 %, 88.10%, and 92.27 %, respectively, and the positive predictive value (PPV) was 9.63, 18.20, and 21.24, respectively. The majority of the patients (30.9%) had no pathology on colonoscopy, whereas CRC was detected in 9.8%. Conclusion Quantitative FIT in symptomatic colorectal patients can be used to triage patients to investigations more appropriately, reducing the burden on outpatient and endoscopy units and improving the overall efficacy of health provision.

Systematic review on buparvaquone resistance associated with non-synonymous mutation in drug binding genes site of Theileria annulate.

Theileria annulata (T. annulata) is intra-erythrocytic protozoan parasite which is more prevalent in tropical and sub-tropical countries. It has a significant economic impact on the productivity of the dairy industry, and buparvaquone is used to treat infected animals in the prevalent regions of the world. Systematically, buparvaquone targets the cyto-b gene to break the electron transport chain (ETC) and Theileria annulata peptidyl-prolyl isomerase 1 (TaPIN1) gene to destabilize transcription factor JUN (c-JUN) to inhibit proliferation of infected cells, which ultimately leads to the death of T. annulata. The reported studies on drug resistance is due to inappropriate drug application, evolutionary characteristics of the cytochrome b (cyto-b) gene and oncogenic signaling pathways gene (TaPIN1) make the parasite resistant against buparvaquone. Hence, this systematic review was designed to find out non-synonymous mutation in genes (cyto-b and TaPIN1) responsible for drug resistance reported from Tunisia, Turkey, Egypt, Sudan, Iran, Pakistan, China and Germany with reference to the T. annulata Ankara strain of cyto-b (accession no. XM_949625.1) and TaPIN1 (accession no. TA18945) wild type genes. Non-synonymous point mutations were found in cyto-b (Q01 at 130-148 and Q02 at 253-262 regions) and TaPIN1 (A53P and A53T) genes. These point mutations are responsible for developing buparvaquone resistance against T. annulata infection. These genes can be used as biomarkers for the identification of drug resistance in any endemic area. To avoid the complication of drug resistance, development of genetically resistant cattle breeds, potent vaccines and anti-theilerial drugs (Trifloxystrobin and anti-cancerous) are currently required to control proliferating economically important T. annulata parasites.

Humoral and cellular immunity in response to an in silico-designed multi-epitope recombinant protein of Theileria annulata.

Tropical theileriosis is a lymphoproliferative disease caused by Theileria annulata and is transmitted by Ixodid ticks of the genus Hyalomma. It causes significant losses in livestock, especially in exotic cattle. The existing methods for controlling it, chemotherapeutic agents and a vaccine based on an attenuated schizont stage parasite, have several limitations. A promising solution to control this disease is the use of molecular vaccines based on potential immunogenic proteins of T. annulata. For this purpose, we selected five antigenic sequences of T. annulata, i.e. SPAG-1, Tams, TaSP, spm2, and Ta9. These were subjected to epitope prediction for cytotoxic T lymphocytes, B-cells, and helper T lymphocytes. CTL and B-cell epitopes with a higher score whereas those of HTL with a lower score, were selected for the construct. A single protein was constructed using specific linkers and evaluated for high antigenicity and low allergenicity. The construct was acidic, hydrophobic, and thermostable in nature. Secondary and tertiary structures of this construct were drawn using the PSIPRED and RaptorX servers, respectively. A Ramachandran plot showed a high percentage of residues in this construct in favorable, allowed, and general regions. Molecular docking studies suggested that the complex was stable and our construct could potentially be a good candidate for immunization trials. Furthermore, we successfully cloned it into the pET-28a plasmid and transformed it into the BL21 strain. A restriction analysis was performed to confirm the transformation of our plasmid. After expression and purification, recombinant protein of 49 kDa was confirmed by western blotting. An ELISA detected increased specific antibody levels in the sera of the immunized animals compared with the control group, and flow cytometric analysis showed a stronger cell-mediated immune response. We believe our multi-epitope recombinant protein has the potential for the large-scale application for disease prevention globally in the bovine population. This study will act as a model for similar parasitic challenges.

Marginal Contribution of Pathogenic RAD51D Germline Variants to Pakistani Early-Onset and Familial Breast/Ovarian Cancer Patients.

Introduction: RAD51D has been reported as a breast cancer (BC) and ovarian cancer (OC) predisposition gene, particularly among Caucasian populations. We studied the prevalence of RAD51D variants in Pakistani BC/OC patients. Materials and Methods: In total, 371 young or familial BC/OC patients were thoroughly analyzed for RAD51D sequence variants using denaturing high-performance liquid chromatography pursued by DNA sequencing of differentially eluted amplicons. We also assessed the pathogenic effects of novel variants using in-silico algorithms. All detected RAD51D variants were investigated in 400 unaffected controls. Results: No pathogenic RAD51D variant was detected. However, we identified nine unique heterozygous variants. Of these, two missense variants (p.Pro10Leu and p.Ile311Asn) and one intronic variant (c.481-26_23delGTTC) were classified as in silico-predicted variants of uncertain significance, with a frequency of 0.8% (3/371). The p.Pro10Leu variant was detected in a 28-year-old female BC patient of Punjabi ethnic background, whose mother and maternal cousin had BCs at ages 53 and 40, respectively. This variant was also detected in 1/400 (0.25%) healthy controls, where the control subject's daughter had acute lymphoblastic leukemia. The p.Ile311Asn variant was identified in a female BC patient at age 29 of Punjabi ethnicity and in 1/400 (0.25%) healthy controls, where the control subject's daughter had Hodgkin's disease at age 14. A novel intronic variant, c.481-26_-23delGTTC, was found in a 30-year-old Punjabi female BC patient but not in 400 healthy controls. Conclusion: No pathogenic RAD51D variant was identified in the current study. Our study data suggested a negligible association of RAD51D variants with BC/OC risk in Pakistani women.

Effects of betaine supplementation on dry matter intake, milk characteristics, plasma non-esterified fatty acids, and ß-hydroxybutyric acid in dairy cattle: a meta-analysis.

Betaine supplementation in dairy cattle has gained attention due to its potential benefits to production and health as a methyl donor, which can play a crucial role in the metabolism of dairy cows. The objective of the current meta-analysis was to quantify the effects of betaine supplementation on milk production, composition, ß-hydroxybutyric acid (BHBA), and non-esterified fatty acids (NEFA). A systematic literature search was carried out, all relevant studies were retrieved, and the meta-analysis was carried out. The mean difference (MD) for dry matter intake (DMI) using the random-effects model was 0.499 kg/d (P < 0.0001). The subgroup analysis indicated that supplementing betaine in heat-stressed cows increased DMI by 0.584 kg/d (P < 0.001), while in cows not exposed to heat stress, DMI was increased by 0.381 kg/d (P = 0.007). The energy-corrected milk (ECM) increased by 1.36 kg/d (P < 0.0001). The milk fat yield was significantly increased in betaine-supplemented cows (MD = 0.040 kg/d, 95% CI = 0.015 to 0.065). The milk protein yield (kg/d) (MD = 0.014, P = 0.138) was increased (MD = 0.035, P = 0.0005) by betaine supplementation. The lactose yield (kg/d) was also significantly higher (MD = 0.055, P = 0.020) in betaine-supplemented cows. The standardized mean difference (SMD) for NEFA (SMD = - 0.447, 95% CI = - 1.029 to 0.135, P = 0.114) and BHBA (SMD = - 0.130, 95% CI = - 0.491 to 0.234). In conclusion, the findings from this meta-analysis suggest that betaine supplementation positively influences DMI, ECM, milk fat yield, milk lactose yield, and milk protein yield. Subgroup analysis further indicated that the positive effects on DMI are greater in heat-stressed cows compared to those not exposed to heat stress. The analysis did not find significant effects on the levels of NEFA or BHBA, suggesting that betaine supplementation may not directly influence these metabolic parameters.

The aim of this meta-analysis was to examine the effects of dietary betaine supplementation on dairy cows' dry matter intake, milk production, milk composition, non-esterified fatty acids, and ß-hydroxybutyric acid. The results indicated that the supplementation of betaine increased dry matter intake (+0.584 kg/d/cow), energy-corrected milk (+1.36 kg/d), milk fat yield (+ 0.040 kg/d), milk protein yield (+ 0.014 kg/d), and lactose yield (+ 0.055 kg/d). ß-Hydroxybutyric acid and plasma non-esterified fatty acids were not influenced by betaine supplementation in dairy cattle.

Morphology of Four Strains of Phellinoid Agaricomycetes and Microstructural and Physiological Properties of Their Exudates.

To study and compare the morphology of the phellinoid Agaricomycetes strains and find other strategies to improve Phellinus spp. growth and metabolism. In this study, the morphological characteristics of four Phellinus igniarius strains (phellinoid Agaricomycetes) were observed under a light microscope. The exudates from these fungi were observed using light microscopy, scanning electron microscopy (SEM), and energy-dispersive spectrometry (EDS). The exudates were initially transparent with a water-like appearance, and became darker with time at neutral pH. Microscopy of air-dried exudates revealed regular shapes and crystals. Cl- (chloride) and K+ were the two key elements analyzed using EDS. Polyphenol oxidase (POD), catalase (CAT), and laccase activities were detected in mycelia from each of the four Phellinus strains. The K+ content of the three strains was higher than that of the wild strain. Cl- content correlated negatively with that of K+. Laccase activities associated with each mycelia and its corresponding media differed under cold and contaminated conditions.

Unusual acute right abdominal pain. Distal ileum mesenteric cystic lymphangioma in adult, a rare case and literature review.

Lymphangiomas in the peritoneal cavity are rare in adults, with most cases occurring in children. We present the case of a 49-year-old woman who was admitted with severe lower abdominal pain. The diagnostic assessment revealed a multiloculated cystic structure in the mesentery of the distal ileum, suggesting a lymphangioma. The patient underwent laparotomy and resection, with successful removal of the mass. Histopathological examination confirmed the diagnosis of intestinal lymphangioma, a rare benign vascular neoplasm of the small bowel. Postoperatively, the patient experienced resolution of postoperative ileus and mild back and abdominal pain, with no complaints during follow-up. Awareness of this uncommon condition is crucial for accurate diagnosis and appropriate treatment. Surgical resection, supported by radiological and histopathological investigations, is the primary treatment modality for symptomatic lymphangioma. Regular follow-up with imaging may be necessary to monitor recurrence.

Group B Streptococcus Persistently Colonizing the Adenosquamous Carcinoma of the Lung: A Blessing in Disguise?

Group B Streptococcus (GBS), also known as Streptococcus agalactiae, is a gram-negative, beta-hemolytic facultative anaerobe that causes neonatal pneumonia and sepsis. The neoplastic epithelial cells in adults, especially those of squamous origin, can show special adhesive properties toward GBS, which tends to reside within these tumors. There are some animal and human studies proving this association. Here, we present a 64-year-old female patient who had lung carcinoma of mixed adeno and squamous origin found to have persistent GBS every time the bronchoscopy was done for tumor ablation or cryotherapy. Subsequently, after starting her on chemo-radiotherapy, she also presented with multiple episodes of pneumonia caused by GBS and Pseudomonas aeruginosa. Moreover, many animal studies have shown the anti-tumor properties of GBS toxin that can prevent its metastasis and stop vascular growth surrounding the tumor. This property of GBS toxin can prove a blessing in disguise.

Impact of Preoperative Nutritional Support on Surgical Outcomes in Gastrointestinal Surgeries: A Systematic Review.

Malnutrition presents a significant risk to patients undergoing gastrointestinal surgery, with direct consequences on postoperative complication rates, recovery times, and mortality. Our systematic review, guided by PRISMA protocols, examined the impact of preoperative nutritional support on these surgical outcomes. We scrutinized publications from PubMed, Medline, Embase, and the Cochrane Library up to April 2023, including randomized controlled trials, cohort studies, and systematic reviews. The stringent selection process narrowed to 10 studies demonstrating the efficacy of preoperative nutritional support, from oral supplements to enteral and parenteral nutrition, in reducing postoperative complications and length of hospital stays while enhancing recovery rates. The benefits varied, indicating a pressing need for customized nutritional regimens based on patient demographics and surgical specifics. Our findings advocate incorporating individualized nutritional strategies into preoperative care, enhancing patient outcomes. Future research should aim to refine these strategies, focusing on the optimal timing, duration, and type of nutritional support.

Composition of Whole Grain Dietary Fiber and Phenolics and Their Impact on Markers of Inflammation.

Inflammation is an important biological response to any tissue injury. The immune system responds to any stimulus, such as irritation, damage, or infection, by releasing pro-inflammatory cytokines. The overproduction of pro-inflammatory cytokines can lead to several diseases, e.g., cardiovascular diseases, joint disorders, cancer, and allergies. Emerging science suggests that whole grains may lower the markers of inflammation. Whole grains are a significant source of dietary fiber and phenolic acids, which have an inverse association with the risk of inflammation. Both cereals and pseudo-cereals are rich in dietary fiber, e.g., arabinoxylan and ß-glucan, and phenolic acids, e.g., hydroxycinnamic acids and hydroxybenzoic acids, which are predominantly present in the bran layer. However, the biological mechanisms underlying the widely reported association between whole grain consumption and a lower risk of disease are not fully understood. The modulatory effects of whole grains on inflammation are likely to be influenced by several mechanisms including the effect of dietary fiber and phenolic acids. While some of these effects are direct, others involve the gut microbiota, which transforms important bioactive substances into more beneficial metabolites that modulate the inflammatory signaling pathways. Therefore, the purpose of this review is twofold: first, it discusses whole grain dietary fiber and phenolic acids and highlights their potential; second, it examines the health benefits of these components and their impacts on subclinical inflammation markers, including the role of the gut microbiota. Overall, while there is promising evidence for the anti-inflammatory properties of whole grains, further research is needed to understand their effects fully.

A large cheek lipoma misdiagnosed as a dental infection: a rare case report.

The most frequent benign tumor is lipoma. About 1-4% of people have intraoral lipomas. This uncommon case report shows a large cheek lipoma misinterpreted as dental infection. A 14-year-old girl with a right cheek tumor was diagnosed and treated for a dental infection. Multiple imaging examinations complete the diagnosis. A benign lipoma, common in subcutaneous tissues but unusual in the mouth, created the lesion. A histological investigation confirmed lipoma after extraoral excision under general anesthesia utilizing an external flap. The edema did not return after surgery, which restored face symmetry. This case study shows that diagnosing and treating oral and maxillofacial edema requires extensive clinical and radiographic testing. Lipomas should be evaluated in the differential diagnosis of mouth swelling even without usual risk markers to prevent excessive treatments and delays. Surgery is recommended for lipomas since it has a low recurrence and fewer risks.

Predominance of MGMT promoter methylation among Pakistani glioblastoma patients.

BACKGROUND: Glioblastoma multiforme (GBM), the most prevalent subgroup of neuroepithelial tumors, is characterized by dismal overall survival (OS). Several studies have linked O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation to OS in GBM patients. However, MGMT methylation frequencies vary geographically and across ethnicities, with limited data for South Asian populations, including Pakistan. This study aimed to analyze MGMT promoter methylation in Pakistani GBM patients. METHODS: Consecutive primary GBM patients diagnosed ≥ 18 years-of-age, with no prior chemotherapy or radiotherapy history, were retrospectively selected. DNA was isolated from formalin-fixed-paraffin-embedded tissues. MGMT promoter methylation was analyzed using methylation-specific PCR. Clinical, pathological, and treatment data were assessed using Fisher's exact/Chi-squared tests. OS was calculated using Kaplan-Meier analysis in SPSS 27.0.1. RESULTS: The study included 48 GBM patients, comprising 38 (79.2%) males and 10 (20.8%) females. The median diagnosis age was 49.5 years (range 18-70). MGMT methylation was observed in 87.5% (42/48) of all cases. Patients with MGMT methylation undergoing radiotherapy or radiotherapy plus chemotherapy exhibited significantly improved median OS of 7.2 months (95% CI, 3.7-10.7; P < 0.001) and 16.9 months (95% CI, 15.9-17.9; P < 0.001), respectively, compared to those undergoing surgical resection only (OS: 2.2 months, 95% CI, 0.8-3.6). CONCLUSION: This is the first comprehensive study highlighting a predominance of MGMT methylation in Pakistani GBM patients. Furthermore, our findings underscore the association of MGMT methylation with improved OS across diverse treatment modalities. Larger studies are imperative to validate our findings for better management of Pakistani GBM patients.

Heart Failure Readmission in Patients With ST-Segment Elevation Myocardial Infarction and Active Cancer.

Background: Although numerous studies have examined readmission with heart failure (HF) after acute myocardial infarction (AMI), limited data are available on HF readmission in cancer patients post-AMI. Objectives: This study aimed to assess the rates and factors associated with HF readmission in cancer patients presenting with ST-segment elevation myocardial infarction (STEMI). Methods: A nationally linked cohort of STEMI patients between January 2005 and March 2019 were obtained from the UK Myocardial Infarction National Audit Project registry and the UK national Hospital Episode Statistics Admitted Patient Care registry. Multivariable Fine-Gray competing risk models were used to evaluate HF readmission at 30 days and 1 year. Results: A total of 326,551 STEMI indexed admissions were included, with 7,090 (2.2%) patients having active cancer. The cancer group was less likely to be admitted under the care of a cardiologist (74.5% vs 81.9%) and had lower rates of invasive coronary angiography (62.2% vs 72.7%; P < 0.001) and percutaneous coronary intervention (58.4% vs. 69.5%). There was a significant prescription gap in the administration of post-AMI medications upon discharge such as an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (49.5% vs 71.1%) and beta-blockers (58.4% vs 68.0%) in cancer patients. The cancer group had a higher rate of HF readmission at 30 days (3.2% vs 2.3%) and 1 year (9.4% vs 7.3%). However, after adjustment, cancer was not independently associated with HF readmission at 30 days (subdistribution HR: 1.05; 95% CI: 0.86-1.28) or 1 year (subdistribution HR: 1.03; 95% CI: 0.92-1.16). The opportunity-based quality indicator was associated with higher rates of HF readmission independent of cancer diagnosis. Conclusions: Cancer patients receive care that differs in important ways from patients without cancer. Greater implementation of evidence-based care may reduce HF readmissions, including in cancer patients.

Decoding the Genetic and Structural Features of HPV16 E5 Oncogene in Cervical Cancer Isolates from Pakistan: A Pilot Study.

Background: Many anogenital cancers are caused by high-risk HPV. The most common subtype is HPV16, which is prevalent in the world, including Pakistan. Various amino acid residues in HPV16 E5 are associated with high cell cycle progression and proliferation. Lack of studies on HPV16E5 in Pakistan prompted the current study. This is the first report on the occurrence of pathogenic E5 variant of HPV16 in tissue sections obtained from invasive cervical cancerous patients in Pakistan. Methods: A subset of 11 samples from HPV-positive biopsies were subjected to E5 gene amplification using PCR and analyzed using bioinformatics programs. The bioinformatics analysis detected mutations causing structural variations, which potentially contribute to the oncogenic properties of proteins. Results: The two-point mutations, C3979A and G4042A, observed in isolate 11 caused the substitution of isoleucine for leucine and valine at positions 44 and 65 in E5 protein. The rest of the isolates had Leu44Val65 amino acids. Intratypic variations and phylogenetic analysis revealed that the majority of the isolates were closely clustered with European-Asian lineage. Moreover, C3979A and G4042A contributed to higher degree of interactions with host receptors, i.e. EGFR. Conclusion: This is the first study reporting HPV16 variants in a Pakistani population based on variations in the E5 region. Our findings indicate that isolate 11 has a strong interaction with the intracellular domain of EGFR, which may enhance the generation of downstream signals. Since this was a pilot study to explore E5 gene mutation, future studies with large samples are absolutely needed.

Prevalence of BRCA1 and BRCA2 germline variants in an unselected pancreatic cancer patient cohort in Pakistan.

BACKGROUND: BRCA1 and BRCA2 (BRCA1/2) are the most frequently investigated genes among Caucasian pancreatic cancer patients, whereas limited reports are available among Asians. We aimed to investigate the prevalence of BRCA1/2 germline variants in Pakistani pancreatic cancer patients. METHODS: One hundred and fifty unselected and prospectively enrolled pancreatic cancer patients were comprehensively screened for BRCA1/2 germline variants using denaturing high-performance liquid chromatography and high-resolution melting analyses, followed by DNA sequencing of the variant fragments. The novel variants were analyzed for their pathogenic effect using in-silico tools. Potentially functional variants were further screened in 200 cancer-free controls. RESULTS: Protein truncating variant was detected in BRCA2 only, with a prevalence of 0.7% (1/150). A frameshift BRCA2 variant (p.Asp946Ilefs*14) was identified in a 71-year-old male patient of Pathan ethnicity, with a family history of abdominal cancer. Additionally, we found a novel variant in BRCA2 (p.Glu2650Gln), two previously reported variants in BRCA1 (p.Thr293Ser) and BRCA2 (p.Ile2296Leu) and a recurrent nonsense variant in BRCA2 (p.Lys3326Ter). These variants were classified as variants of uncertain significance (VUS). It is noteworthy that none of these VUS carriers had a family history of pancreatic or other cancers. CONCLUSIONS: In this first study, BRCA1/2 pathogenic variant is identified with a low frequency in pancreatic cancer patients from Pakistan. Comprehensive multigene panel testing is recommended in the Pakistani pancreatic cancer patients to enhance genetic understanding in this population.

Functional and radiological outcome of non-operative treated clavicle fractures and its association with acromioclavicular joint arthrosis.

BACKGROUND: Clavicle fractures are traditionally treated non-operatively. This study determines the functional outcome of midshaft clavicle fractures treated non-operatively, the factors influencing it, and the incidence of acromioclavicular joint (ACJ) arthrosis. METHODS: Patients with midshaft clavicular fractures treated non-operatively between 16 and 50 years old with no prior AC joint problems were assessed. Demographics, hand dominance, type of occupation, and smoking status were documented. Functional scoring using DASH score, CM score, and radiological evaluation was done with special tests to diagnose AC joint arthrosis. Two or more positive special tests were considered significant for this study. RESULTS: 101 patients were recruited, 83 male and 18 female patients. The average age of 34.7 ± 13.93 years. The average follow-up was 32.7 months (range: 24-75; SD ± 9.9 months). 48.5% were blue-collar workers, and 60.4% involved the dominant upper limb. 44.6% were cigarette smokers. There was 20 mm and more shortening in 21.8% of subjects. 40.6% had a significant special test, and 36.6% had radiological changes of AC joint osteoarthritis. Positive two or more special tests were significantly associated with radiological evidence of arthrosis (p = .00). The mean DASH score was 28.28 ± 17.4, and the mean CM score was 27.58 ± 14.34. Most have satisfactory to excellent scores. Hand dominance, smoking, and blue-collar work were significantly associated with poorer CM scores, and hand dominance was significant for Dash scores. CONCLUSION: There is an equal distribution poor, satisfactory and excellent functional outcomes in patients with midshaft clavicle fractures treated non-operatively. The poor outcomes may be attributed to ACJ arthrosis. Hand dominance, smoking and blue-collar work affected the functional outcome. Shortening of the clavicle had no bearing on the clinical and radiological findings of osteoarthritis and functional scores. The presence of two or more positive special tests is an accurate predictor of AC joint arthritis.

Comorbidity clusters and in-hospital outcomes in patients admitted with acute myocardial infarction in the USA: A national population-based study.

BACKGROUND: The prevalence of multimorbidity in patients with acute myocardial infarction (AMI) is increasing. It is unclear whether comorbidities cluster into distinct phenogroups and whether are associated with clinical trajectories. METHODS: Survey-weighted analysis of the United States Nationwide Inpatient Sample (NIS) for patients admitted with a primary diagnosis of AMI in 2018. In-hospital outcomes included mortality, stroke, bleeding, and coronary revascularisation. Latent class analysis of 21 chronic conditions was used to identify comorbidity classes. Multivariable logistic and linear regressions were fitted for associations between comorbidity classes and outcomes. RESULTS: Among 416,655 AMI admissions included in the analysis, mean (±SD) age was 67 (±13) years, 38% were females, and 76% White ethnicity. Overall, hypertension, coronary heart disease (CHD), dyslipidaemia, and diabetes were common comorbidities, but each of the identified five classes (C) included ≥1 predominant comorbidities defining distinct phenogroups: cancer/coagulopathy/liver disease class (C1); least burdened (C2); CHD/dyslipidaemia (largest/referent group, (C3)); pulmonary/valvular/peripheral vascular disease (C4); diabetes/kidney disease/heart failure class (C5). Odds ratio (95% confidence interval [CI]) for mortality ranged between 2.11 (1.89-2.37) in C2 to 5.57 (4.99-6.21) in C1. For major bleeding, OR for C1 was 4.48 (3.78; 5.31); for acute stroke, ORs ranged between 0.75 (0.60; 0.94) in C2 to 2.76 (2.27; 3.35) in C1; for coronary revascularization, ORs ranged between 0.34 (0.32; 0.36) in C1 to 1.41 (1.30; 1.53) in C4. CONCLUSIONS: We identified distinct comorbidity phenogroups that predicted in-hospital outcomes in patients admitted with AMI. Some conditions overlapped across classes, driven by the high comorbidity burden. Our findings demonstrate the predictive value and potential clinical utility of identifying patients with AMI with specific comorbidity clustering.

In-silico prediction of TGF-ß1 non-synonymous variants and their impact on binding affinity to Fresolimumab.

TGF-ß1 is a potent immunoregulatory cytokine that plays diverse roles in development, bone healing, fibrosis, and cancer. However, characterizing TGF-ß1 gene variants is challenging because the structural and functional consequences of these variants are still undetermined. In this study, we aimed to perform an in-silico analysis of TGF-ß1 non-synonymous variants and their pathogenic effects on the TGF-ß1 protein. A total of 10,252 TGF-ß1 SNPs were collected from the NCBI dbSNP database and in-silico tools (SIFT, PROVEAN, Mutation Taster, ClinVar, PolyPhen-2, CScape, MutPred, and ConSurf) were used. The in-silico predicted potential variants were further investigated for their binding to the TGF-ß1 targeting drug "Fresolimumab". Molecular docking was performed using HADDOCK and confirmed by PRODIGY and PDBsum. The in-silico analysis predicted four potential TGF-ß1 nsSNPs: E47G in the LAP domain of the propeptide and I22T, L28F, and E35D in the mature TGF-ß1 peptide. HADDOCK and molecular dynamics simulations revealed that the I22T and E35D variants have higher binding affinity for Fresolimumab as compared to the wild type and L28F variants. Molecular dynamics simulations (100 ns) and principal component analysis showed that TGF-ß1 variants influenced the protein structure and caused variations in the internal dynamics of protein complexes with the antibody. Among them, the E35D variant significantly destabilized the TGF-ß1 protein structure, resulting in rearrangement in the binding site and affecting the interactions with the Fresolimumab. This study identified four variants that can affect the TGF-ß1 protein structure and result in functional consequences such as impaired response to Fresolimumab.Communicated by Ramaswamy H. Sarma.

Bilateral Endometriotic Cystic Ovaries and Huge Splenic Epithelial Cyst With Elevated CA-125, CA19-9: A Report of a Rare Case.

Histologically benign splenic cysts (SCs) resemble splenic sacs. SCs are rare. Here, we present and discuss a new case of bilateral endometriotic cystic ovaries with massive SCs. A 26-year-old single female visited the hospital with left lower quadrant discomfort and suprapubic pain for three months, accompanied by anorexia, weight loss for these three months, and persistent dysmenorrhea for two years. Splenic examination revealed a soft abdomen with left hypochondria, suprapubic tenderness, and a lump in the upper left quadrant. All laboratory results were normal, except for two cancer antigens (CA-125 and CA 19-9). Therefore, magnetic resonance imaging was used to make the definitive diagnosis, which revealed bilateral ovarian endometrioma with a left upper abdominal cystic mass of splenic origin. When CA-125 and CA-19-9 readings are high, physicians should investigate endometriotic and SCs. Imaging aids diagnosis. Histopathological results are essential. Tools and follow-up should rule out malignancy, and surgery is the best treatment option.

Complex high-risk percutaneous coronary intervention types, trends, and outcomes according to vascular access site.

BACKGROUND: Radial access is associated with improved outcomes following percutaneous coronary intervention (PCI); however, its role in complex, high-risk percutaneous coronary intervention (CHiP) remains poorly studied. METHODS: We studied retrospectively all registered patients's records from the British Cardiovascular Intervention Society dataset and compared the baseline characteristics, trends and outcomes of CHiP procedures performed electively between January 2006 and December 2017 according to the access site. RESULTS: Out of 137,785 CHiP procedures, 61,825 (44.9%) were undertaken via transradial access (TRA). TRA use increased over time (14.6% in 2006 to 67% in 2017). The TRA patients were older, with a greater prevalence of previous stroke, hypertension, peripheral vascular disease, and smokers. TRA was used more frequently in most CHiP procedures (elderly (51.6%), chronic renal failure (52.6%), poor left ventricular (LV) function (47.6%), left main PCI (48.0%), treatment for severe vascular calcification (50.3%); although transfemoral access (TFA) was used more commonly in those with prior history of coronary artery bypass graft surgery, and PCI to a chronic total occlusion and LV support patients. Following adjustment for differences in clinical and procedural characteristics, TFA was independently associated with higher odds for mortality [adjusted odds ratio (aOR): 1.3 (1.1-1.7)], major bleeding [aOR: 2.9 (2.3-3.4)], and MACCE (following propensity score matching) [aOR: 1.2 (1.1-1.4)]. The same was found with multiple accesses: mortality [aOR: 2.1 (1.5-2.8)], major bleeding [aOR: 5.5 (4.3-6.9)], and MACCE [aOR: 1.4 (1.2-1.7)]. CONCLUSION: TRA has become the predominant access site for CHiP procedures and is associated with significantly lower mortality, major bleeding and MACCE odds than TFA.