First Report of Inclisiran Utilization for Hypercholesterolemia Treatment in Real-world Clinical Settings in a Middle East Population.

PURPOSE: Inclisiran is the first small interfering RNA-based treatment approved for reducing pro-atherogenic lipoproteins in patients with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of low-density lipoprotein cholesterol (LDL-C). We report the first evaluation of the effects of inclisiran in a Middle East population. METHODS: We conducted a retrospective review of patients initiating inclisiran treatment at an outpatient diabetology, endocrinology, and cardiology center between May 2021 and December 2022. All patients followed up for 90 days or more, or with at least 1 lipid determination post initiation were included. Participants were categorized into primary prevention (n = 57) and secondary prevention (n = 89) groups according to previous atherosclerotic cardiovascular disease. FINDINGS: Inclisiran was initiated in 146 patients; mean (SD) age was 54.8 (12.12) years, 82 patients (56.2%) were male, 28 patients (19.2%) had received a diagnosis of familial hypercholesterolemia, 89 patients (61%) had received a diagnosis of diabetes mellitus, and 35 patients (23.9%) had a statin intolerance. Median (interquartile range) follow-up was 137 (90 to 193) days. At 90 days, median (interquartile range) reductions in serum LDL-C and triglycerides were -37.9% (-9.5% to -51.2%) and -12.0% (-9.8% to -40.5%), respectively, in primary prevention and -54.1% (-17.1% to -71.4%) and -15.3% (-14% to -38.8%), respectively, in secondary prevention (all, P < 0.001). LDL-C goals were attained in 110 patients (75.3%). Nonattainment of LDL-C goal was attributed to system effect in 26 patients (72.2%), biological effect in 5 patients (13.9%), and discontinuation of treatment in 5 patients (13.9%). Therapy was well tolerated. IMPLICATIONS: This study is the first from the Middle East and North Africa region that reported the real-world efficacy and safety profile of inclisiran in a mixed-risk population of patients with heterozygous familial hypercholesterolemia and other non-familial hypercholesterolemia indications. Clinically meaningful and sustained reductions in pro-atherogenic lipids with good tolerability were observed after inclisiran initiation. Fewer AEs were reported in this predominantly Arabic population, consistent with previous safety reports for inclisiran. It is important to note that no patient stopped inclisiran treatment due to AEs. Strengths of our study included an optimal cohort, patient heterogeneity, and high retention. In addition, we were able to report mean robust effects of inclisiran and good medication tolerability, quite like randomized studies and open-label extension periods. Despite this, our study had some limitations, including selection bias due to the retrospective design and the absence of a comparative group.

Early, Forme Fruste keratoconus and normal thin cornea, evaluation of sensitive parameters by combined Placido Scheimpflug topography.

PURPOSE: To determine the sensitive indices distinguishing forme-fruste keratoconus (FFKC) and early keratoconus (early KC) from thin normal corneas, and their cutoff values using Sirius topography. METHODS: 156 eyes with normal thin corneas < 500 um (group 1), 99 eyes with early KC (group 2) and 41 eyes with FFKC (group 3), were assessed retrospectively for: corneal keratometric indices, pachymetry indices, corneal aberrations, elevation indices; thinnest corneal point elevation, Q value, root mean square (RMS) withRMS/ area (RMS/A); and KC summary indices of front and back surfaces; surface asymmetry index (SIf, SIb), elevation at KC vertex (KVf, KVb), Baiocchi-Calossi-Versaci index (BCVf, BCVb) and summation of its vector (BCV). Cutoff values were calculated. RESULTS: Keratometry indices were significantly different between early KC and thin normal cases (apex front curvature had the highest area-under-the-ROC-curve (AUROC) (0.926) in early KC, while only apex curvature and coordinates were significant in FFKC cases. Pachymetry indices did not show any significance in differentiating either early KC or FFKC from normal thin corneas. KC summary indices were highly significant among the 3 groups. The highest AUROC was observed with KVb in early KC (0.987) and with KVf in FFKC (0.831). Vertical coma and vertical trefoil showed the highest significance of all aberration parameters differentiating the 3 groups. Thinnest point elevation, RMS and RMS/A showed the highest AUROC in differentiating early KC and FFKC cases from thin normal corneas. CONCLUSION: Comparing early KC and FFKC to thin normal corneas, Sirius provided high precision in prediction.

Conservative Treatment of Ruptured Abdominal Aortic Aneurysm.

Although nonsurgical management of ruptured abdominal aortic aneurysm (rAAA) is still used among a significant number of patients, survival after conservative treatment is extremely rare. We report a case of an 86-year-old female who presented with an rAAA that was confirmed clinically and radiologically via computed tomography angiography. Although the patient was not deemed a candidate for surgery owing to significant comorbidities and poor baseline function, she survived the episode with no surgical intervention. Given the growing aging and frail population, it is vital to explore this further, with the aim of improving both mortality and advanced care planning in the nonsurgical management of rAAA.

Synthesis, antiproliferative activity, and molecular modeling of novel 4-methylcoumarin derivatives and/or nitric oxide donor hybrids.

Two new 4-methylcoumarin derivatives (3a-f and 4a-f) were designed, synthesized, and evaluated for their cytotoxic activity. Different spectroscopic methods and elemental analyses confirmed all the synthesized derivatives' characterization. All the prepared compounds were biologically screened against four cancer cell lines (hepatocellular carcinoma HepG-2, colon cancer cell lines HCT-116, breast cancer cell lines MCF-7, and prostate cancer cell lines PC3). The in vitro antiproliferative activity of the target analogues 4b, 4c, 4f, 3b, and 3d against the MCF-7 cancer cell line was significant, with IC50 values of 3.98, 7.80, 10.94, 17.7, and 24.07 µM, respectively. Furthermore, the potent cytotoxic oxime derivative 4b was evaluated for cell cycle analysis showing a significant substantial disruption in cell cycle profile and cell cycle arrest at the S phase boundary with a time-dependent rise in a pre-G cell population, as well as a 22-fold increase in MCF-7 apoptosis compared to control cells. Accordingly, the Bax/Bcl-2 ratio, a critical ratio in controlling cell sensitivity to apoptosis, increased upon treatment with the oxime analog 4b. A docking investigation was conducted within the BcL-2 binding site to explore and anticipate the binding modes of the synthesized compounds. Thus, synthesizing these novel coumarin/nitric oxide hybrids may aid in developing promising antiproliferative agents.

The First Report of a Real-world Experience With a PCSK9 Inhibitor in a Large Familial Hyperlipidemia and Very-high-risk Middle Eastern Population.

PURPOSE: Evolocumab, a monoclonal inhibitor of proprotein convertase subtilisin/kexin 9, has been shown to reduce proatherogenic lipoproteins in patients with or without familial hypercholesterolemia (FH), diabetes mellitus, or atherosclerotic cardiovascular disease (ASCVD). We explored the safety profile and clinical effectiveness of evolocumab in an outpatient population of Emirati individuals with FH diagnosed per Dutch Lipid Clinic Network criteria, previous ASCVD, or statin intolerance. METHODS: This study was a retrospective review of patients initiating evolocumab treatment for any indication at Imperial College London Diabetes Centre between 2017 and 2020. All individuals followed up for at least 90 days or with at least one lipid panel postinitiation were included. Participants were subclassified into primary prevention (no previous ASCVD event, n = 81) and secondary prevention (any prior clinical ASCVD event, n = 102) groups. FINDINGS: Evolocumab was initiated in 183 individuals (mean [SD] age, 51.5 [12.4] years; 51% male); 108 (59%) had a clinical or genetic FH diagnosis, and 70.5% had diabetes mellitus. Statin intolerance was a treatment indication in 60 (32.8%) individuals. At 90 days, substantial reductions in serum LDL-C, triglycerides (TG), and total cholesterol:HDL-C (TC:HDL-C) were observed in both the primary and secondary prevention groups, and both FH and non-FH individuals. In the primary prevention group, median (interquartile range) reduction in LDL-C was 43.7% (10.8%; 63.0%); TG, 15.0% (7.2%; 35.3%); and TC:HDL-C, 31.5% (11.1%; 46.0%). In the secondary prevention group, median (interquartile range) reduction in LDL-C was 48.3% (22%; 70%); TG, 19.6% (1.2%; 32.5%); and TC:HDL-C, 32.6% (14.6%; 46.3%) (all, P < 0.0001). American College of Cardiology/American Heart Association LDL-C targets were consistently achieved in 114 (62.3%) patients during a follow-up of 359 (79-639) days. Nonattainment of the LDL-C target was attributed to nonadherence in 36 (52.2%) patients and discontinuation of treatment in 14 (20.3%) patients. Evolocumab was discontinued in 4 patients because of adverse events. IMPLICATIONS: This study is the first from the Middle East and North Africa region that reports the real-world efficacy of evolocumab in a mixed risk population of individuals with FH and other non-FH indications. Clinically meaningful and sustained reductions in LDL-C, TG, and cholesterol ratios were observed after evolocumab initiation. Few adverse events were reported in this predominantly Arabic population, consistent with previous safety reports for evolocumab. Notable strengths of this study include a relatively large cohort, patient heterogeneity and high retention, and a minimum follow-up of 1 year. Despite these strengths, the study has some limitations, including the selection bias due to the retrospective design and absence of comparative group.

Cryoballoon Pulmonary Vein Isolation and Roof and Posterior Wall Debulking Using Navik 3D™: A New Technique for Atrial Fibrillation Ablation.

The success rates of traditional endocardial ablation techniques for managing atrial fibrillation remain modest. Recently, the performance of posterior wall ablation in conjunction with pulmonary vein (PV) isolation (PVI) has been reported to increase the chance of success following endocardial ablation. We report a systematic approach for the isolation of the PVs and ablation of the left atrial roof and posterior wall using a cryoballoon guided by the novel Navik 3D™ mapping system (APN Health LLC, Waukesha, WI, USA) and offer preliminary data including procedure, fluoroscopy, and cryoablation times for review. Patients (n = 52) aged 63 years ± 10 years with paroxysmal (n = 42), persistent (n = 11), or chronic (n = 2) atrial fibrillation underwent cryoballoon ablation for PVI and/or the left atrial roof, posterior wall, anterior ganglion plexi (GP), or mitral isthmus line. Lesions were accurately delivered to the PVs, left atrial roof, posterior wall, anterior GP, or mitral isthmus line as appropriate. Acute PVI was achieved in 98% of all patients, and eight (15%) required direct current cardioversion to restore sinus rhythm at the end of the procedure. The mean ± standard deviation procedure, fluoroscopy, and cryoballoon ablation times were 149 minutes ± 39 minutes, 33 minutes ± 30 minutes, and 41 minutes ± 14 minutes, respectively. The Navik 3D™ mapping system is believed to be the only available mapping system that allows for the visualization and location of the cryoballoon in three dimensions, enabling the operator to deliver contiguous, overlapping lesions on the roof and posterior wall of the left atrium. It also facilitates precise measurement of the distance between the esophageal temperature probe and the cryoballoon, thereby helping to avoid freezing damage to the esophagus.

Multiple Linear Regression for Reconstruction of Gene Regulatory Networks in Solving Cascade Error Problems.

Gene regulatory network (GRN) reconstruction is the process of identifying regulatory gene interactions from experimental data through computational analysis. One of the main reasons for the reduced performance of previous GRN methods had been inaccurate prediction of cascade motifs. Cascade error is defined as the wrong prediction of cascade motifs, where an indirect interaction is misinterpreted as a direct interaction. Despite the active research on various GRN prediction methods, the discussion on specific methods to solve problems related to cascade errors is still lacking. In fact, the experiments conducted by the past studies were not specifically geared towards proving the ability of GRN prediction methods in avoiding the occurrences of cascade errors. Hence, this research aims to propose Multiple Linear Regression (MLR) to infer GRN from gene expression data and to avoid wrongly inferring of an indirect interaction (A → B → C) as a direct interaction (A → C). Since the number of observations of the real experiment datasets was far less than the number of predictors, some predictors were eliminated by extracting the random subnetworks from global interaction networks via an established extraction method. In addition, the experiment was extended to assess the effectiveness of MLR in dealing with cascade error by using a novel experimental procedure that had been proposed in this work. The experiment revealed that the number of cascade errors had been very minimal. Apart from that, the Belsley collinearity test proved that multicollinearity did affect the datasets used in this experiment greatly. All the tested subnetworks obtained satisfactory results, with AUROC values above 0.5.

Concurrent acute Vogt-Koyanagi-Harada disease in one eye and chronic disease in the fellow eye.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is a granulomatous panuveitis, usually involving both eyes at the same time or within a few days or weeks. Acute and chronic diseases are characterized by distinct clinical features, treatment modalities, and visual outcomes. We report an atypical case of probable VKH disease, with features of acute disease in one eye and chronic disease in the fellow eye. FINDINGS: A 53-year-old female presented with exudative retinal detachment associated with mild vitritis in the right eye and anterior uveitis, vitritis, and sunset-glow fundus in the left eye. Based on clinical findings and results of multimodal imaging including fundus photography, spectral-domain optical coherence tomography, fluorescein angiography, indocyanine green angiography, and B-scan ultrasonography, a diagnosis of acute VKH disease in the right eye and chronic VKH disease in the left eye was made. The patient received systemic corticosteroids and mycophenolate mofetil. After a 15-month follow-up, the right fundus eye was normal, and there was a sunset-glow fundus in the left eye. CONCLUSIONS: VKH disease may begin with asymptomatic unilateral ocular involvement. The patient may present only when the fellow eye is affected. A significant delay before involvement of the second eye leads to atypical features of acute disease in one eye and chronic disease in the other eye.

Diagnostic Utility of QuantiFERON-TB Gold (QFT-G) in Active Pulmonary Tuberculosis.

BACKGROUND: The utility of QuantiFERON-TB Gold In-Tube (QFT-G) test in the diagnosis of tuberculosis disease has been validated in high and low tuberculosis-prevalent (TB) countries. AIM: The aim of this study is to assess the performance of the QFT-G test in the diagnosis of tuberculosis disease among tuberculosis patients in an intermediate prevalent country. SETTING AND DESIGN: A retrospective study at the King Abdulaziz Medical City-Riyadh (KAMC-R). MATERIALS AND METHODS: We retrospectively reviewed all the patients with a diagnosis of pneumonia, including tuberculosis, admitted to KAMC-R between 1 January 2009 and 31 December 2013. We included only patients with an available result of the QFT-G test. A total of 142 tuberculosis cases and 226 pneumonia cases were studied, to assess the utility of the QFT-G test in diagnosing tuberculosis cases. RESULTS: Among the tuberculosis (n = 142) cases, the QFT-G tested positive in 68.3%, negative in 23.2%, and indeterminate in 12 cases (8.5%). Of the 226 pneumonia cases, the QFT-G tested positive in only 20.4%, while a majority of 66.4% tested negative, with 30 cases (13.3%) being indeterminate. When we excluded 42 patients with indeterminate results, the QFT-G test achieved a sensitivity of 74.6% [95% CI: 66.09 to 81.65%] and specificity of 76.53 % [95% CI: 69.85 to 82.15%] in the diagnosis of tuberculosis cases. CONCLUSIONS: This study concludes that the QFT-G test is a useful tool for detecting tuberculosis disease when used as an adjunct tool for the diagnosis of active TB cases. It certainly cannot be used solely and indiscriminately, separate from other clinical and radiological information, in the diagnosis of active tuberculosis cases.

Pythium rishiriense sp. nov. from water and P. alternatum sp. nov. from soil, two new species from Japan.

In an investigation of Pythium species in natural ecosystems of Rishiri Island in Northern Japan, two new species, Pythium rishiriense and P. alternatum, were identified based on morphological and molecular analyses. Pythium rishiriense differed morphologically from other Pythium species by its characteristic oogonial formation which occasionally arranged in chains. Pythium alternatum differed morphologically from other Pythium species by its distinguishing sexual organs where oogonia occasionally arranged alternately with antheridia in chains. Pythium rishiriense is a fast growing, high-temperature loving species, while P. alternatum is a slow growing species. Phylogenetic analyses based on the internal transcribed spacer region and cytochrome c oxidase 1 gene sequences showed that these two species are clearly separate from morphologically similar species.

Congenital circumflex coronary artery fistulae; presentation and diagnosis.

Small fistulae between coronary arteries and the pulmonary artery are common, but abnormal vascular communications between the coronary arteries and other cardiac structures are rare. They were first described by Krause in 1865. We report two cases of fistulous connexions between the circumflex coronary artery and the coronary sinus.

Endovascular management of ruptured infected popliteal artery aneurysm.

Infected popliteal aneurysm is a rare high-risk condition that can present as an emergency with acute rupture and sepsis. Management of acute ischemia in the presence of local and systemic sepsis is challenging. Open surgery is not always possible and carries a high risk of morbidity and death. An endovascular approach has been advocated in infected aneurysms elsewhere in the body, with good short-term and medium-term outcomes encouraging such approach in the popliteal artery. We report a case of successful endovascular treatment of an infected ruptured popliteal aneurysm with favorable outcome after 2-year follow-up and a related review of the literature.

Spinal cord ischemia following external iliac artery angioplasty: a case report.

Spinal cord ischemia (SCI) is a rare disease that leads to variable degrees of neurological deficit including permanent paraplegia. It has been reported after open and endovascular interventions of the thoracic and abdominal aorta, but it is extremely rare after interventions involving peripheral vessels. We present a case of permanent paraplegia after iliac angioplasty and stenting for critical limb ischemia and a related review of the literature.

[Hydatid cysts of the pancreas, report of two cases]. / Kyste hydatique du pancréas: propos de deux observations.

BACKGROUND: Hydatid cyst of the pancreas is a rare affection with a frequency less than one percent of the various sites of hydatid disease. AIM: We report two cases of hydatid cyst of the pancreas. CASE 1: A 49 year old woman with a history of laparotomy for liver and peritoneal hydatid cyst was admitted with recurrent liver and peritoneal hydatid disease associated with a head pancreatic cyst of 3 cm in size. Surgical treatment consisted in a resection of the protruding dome with uneventful postoperative course. CASE 2: A 45 year old man who underwent laparotomy four years ago for hepatic hydatid cyst was admitted with recurrent liver and peritoneal hydatid disease associated with a head pancreatic cyst of 4 cm in size. At laparotomy it was a head pancreatic hydatid cyst without duct pancreatic lesion. The treatment consisted in the resection of the protruding dome. The postoperative evolution was simple. CONCLUSION: Hydatid cyst of the pancreas is rare. If associated with another hydatid localization, the diagnosis is generally easy. It can however be more difficult if the pancreatic localization is isolated. In most cases, resection of the protruding dome is sufficient.

Squamous cell carcinoma arising in Verneuil's disease.

BACKGROUND: Verneuil's disease or hidradenitis suppurativa is a chronic suppurative, and cicatricial inflammatory disease, mainly affecting apocrine-bearing area of the skin. Squamous cell carcinoma is an uncommon but a frightening complication of hidradenitis suppurativa. AIM: To report a new case of squamous cell carcinoma arising in Verneuil's disease. CASE REPORT: We reported a case of 60 year old man with a 30 years history of hidradenitis suppurativa in which squamous cell carcinoma arise. A wide surgical excision removing the tumour and leaving a large defect was performed. The patient had a well recovery, wounds healed well by primary intention. No recurrence observed at 18 months of follow up. CONCLUSION: Squamous cell carcinoma is an uncommon complication of hidradenitis suppurativa. Surgical excision represents also the treatment of choice.

Stent fracture, an incidental finding or a significant marker of clinical in-stent restenosis?

BACKGROUND: The predictors and clinical significance for stent fracture (SF) in drug-eluting stents (DES) remain unknown. We identified procedural factors leading to SF and its clinical consequences in DES. METHODS: Percutaneous coronary interventions were performed on 3,920 patients with DES over 12 months. In-stent restenosis (ISR) of DES was observed in 188 cases with 121 cases (64.4%) receiving a sirolimus-eluting stent (SES) and 67 (35.6%) a paclitaxol-eluting stent (PES). RESULTS: SF was identified in 35 (18.6%) of the 188 cases. The 35 cases were then compared with 153 cases of ISR without angiographic evidence of SF. SF was identified in 29 (23.9%) SES compared with 6 (9.0%) in PES (P < 0.05). With univariate analysis, additional factors associated with SF included longer mean stented segment length, male gender, overlapping stents, vessel segment angulation >75 degrees , and more stents (all P < 0.05). With multivariate adjustment, three factors, i.e., stenting on a bend >75 degrees (OR = 13.8, 95%CI 3.7 to 51; P < 0.001), SES (OR = 4.1, 95%CI 1.3 to 13.4; P < 0.018) and overlapping stented segments (OR = 3.9, 95%CI 1.1 to 14.1; P < 0.041) were statistically significant independent predictors of SF while larger stent diameter was protective (OR = 0.14, 95%CI 0.04 to 0.70; P < 0.017). CONCLUSION: SF proved to be associated with angiographically-documented clinical ISR. Although the exact mechanism is unknown, factors that appear to play a negative role in SF include vessel tortuosity, use of SES and overlapping stents. Larger stent diameter was protective. Further studies are needed to better define the factors important in the mechanism of SF.