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Interleukin 10 rs1800896 and interleukin 1B rs16944 polymorphisms and the risk of cervical cancer
No full textBackground The purpose of this study was to evaluate the relationships between interleukin 10 (IL10) (rs1800896) and interleukin 1B (IL1B) (rs16944) genetic polymorphisms and the risk for cervical cancer in a cohort of women from Croatia.
Methods A case–control study of 81 patients with cervical cancer and 80 age-matched healthy controls was performed. We collected peripheral blood samples, extracted deoxiribonucleic acid (DNA), and analyzed two single-nucleotide polymorphisms (SNPs) rs1800896 and rs16944 using TaqMan assays (Fa. Thermo Fisher Scientific, Waltham, MA, USA) and real-time polymerase chain reaction (PCR). We investigated a possible association between two cytokine genetic polymorphisms and the occurrence of cervical cancer.
Results Our results showed no significant difference in the frequency of IL10 (rs1800896) and IL1B (rs16944) genotypes between the patients and the controls (χ2 test, P< 0.05).
Conclusion In this study, no association was found between IL10 rs1800896 and IL1B rs16944 polymorphisms and cervical cancer development
Real-world operation of multiple sclerosis centres in Central-Eastern European countries covering 107 million inhabitants
No full textBackground: In 2018 multiple sclerosis (MS) care unit (MSCU) recommendations were defined. Nevertheless, the information on MS care, and whether MS centres fulfil the international recommendation is limited. Thus our objectives were to assess whether centres meet the MSCU recommendations and gain a comprehensive overview of MS care in Central-Eastern European countries.
Methods: A self-report questionnaire assessing aspects of the MSCU recommendations, disease-modifying therapy (DMT) and registry use and the patient number was assembled and sent to nine Central-Eastern European countries. Furthermore, one Danish and one German centre were contacted as a reference.
Results: In 9/9 countries, MS care was pursued in centres by MS neurologists and MS nurses. In Austria and the Czech Republic, management of MS was conducted under strict regulations displaying a referral centre system, fundamentally similar to but independent of the MSCU criteria. Several centres fulfilled all aspects of the MSCU criteria, while others had similar insufficiencies consisting of a speech therapist, continence, pain and spasticity specialist, neuro-ophthalmologist, and oto-neurologist. In 9/9 countries, DMTs were reimbursed. However, some centres did not provide every available DMT. A national registry was available in 4/9 countries with mandatory registry use only in Austria and the Czech Republic.
Conclusion: In countries where MSCU recommendations are not fulfilled, a strictly regulated centre system similar to the Austrian and Czech model with a registry-based quality control might ensure appropriate care for people with MS
Brain Infarction in the Artery of Percheron Supply Area due to Reversible Cerebral Vasoconstriction Syndrome
No full textAn ischemic stroke caused by the occlusion of the artery of Percheron encompasses both posterior thalami, and the resulting clinical presentation can mask the clinical presentation of a stroke. We present the case report of a 62-year-old female patient who was admitted to our emergency department in a soporous state after initial headache and dizziness. A neurological exam found left-sided spasticity and a flexor response to pain. Systemic thrombolysis was administered after an urgent computerized tomography (CT) of the brain with angiography. The interventional radiologist proposed a digital subtraction angiography which found a vasospasm in the right medial cerebral artery from the M2 seg- ment reaching distally, and a balloon dilation was done. Following the endovascular procedure, a CT scan showed ischemia in both posterior thalami. Additionally, the patient’s neurological impairment improved at that moment showing Parinaud syndrome, drowsiness, and left-sided palsy. The patient experienced a possible reversible cerebral vasoconstriction syndrome, the cause of which is still unknown, which resulted in an ischemic stroke. The typical clinical presentation of that syndrome was lacking, probably due to the presence of the artery of Percheron ipsilateral to the vasospasm. Our goal in presenting this case study is to draw attention to the artery of Percheron syndrome as a potential clinical sign of an acute ischemic stroke that can easily lead us to be misled
Corroborating evidence for the correlation between the MTHFR C677T single nucleotide variant and smoking in Croatian subjects independent of ischemic stroke
No full textHyperhomocysteinaemia is a risk factor for ischemic stroke development. Single nucleotide variation in the methylenetetrahydrofolate reductase gene (MTHFR, C677T polymorphism, T allele) causes a Ala222Val mutation that is associated with hyperhomocysteinemia, cardiovascular disease and stroke. The homozygous TT genotype of MTHFR may also be linked to tobacco smoking in patients from distinct demographic groups. This study evaluated the association of T allele with smoking in a cohort of 301 Croatian adults, including 187 healthy controls and 114 patients with ischemic stroke (IS) and proven ischemic cerebral infarction based on Computed Tomography (CT). Exclusion criteria were hemorrhagic cerebral infarction on CT scan, medical history of diabetes mellitus, and age (>60 years). Cholesterol, triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and C-reactive protein (CRP) were biochemically analyzed. A positive correlation between the TT genotype of MTHFR and smoking was observed within our entire study cohort (p = 0.011). In the control group, the relative frequency of the TT genotype in smokers is complemented by the prevalence of the CC genotype among non-smokers. Hence, our study with Croatian subjects corroborates previous studies indicating that the TT MTHFR variant is linked to smoking. This positive correlation between the TT genotype and smoking represents a confounding parameter that must be accounted for to permit evaluation of statistical associations with stroke and biochemical markers in blood and single nucleotide variations in the MTHFR gene
Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up
No full textBackground and Objectives: Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).
Methods: We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.
Results: There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1–6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1–4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4–5.8]; p < 0.0001). Larger declines were observed
at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6–0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31–1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82–2.97], 5,656/195,539) of all stroke hospitalizations.
Discussion: There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year
Systematic review on gene–sun exposure interactions in skin cancer
No full textBackground: The risk of skin cancer is determined by environmental factors like ultraviolet radiation (UVR), personal habits like time spent outdoors and genetic factors. This review aimed to survey existing studies in gene–environment (GxE) interaction on skin cancer risk, and report on GxE effect estimates.
Methods: We searched Embase, Medline (Ovid) and Web of Science (Core Collection) and included only primary research that reported on GxE on the risk of the three most common types of skin cancer: basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and melanoma. Quality assessment followed the Newcastle–Ottawa Scale. Meta-analysis was not possible because no two studies examined the same interaction. This review was registered on PROSPERO (CRD42021238064).
Results: In total 260 records were identified after exclusion of duplicates. Fifteen studies were included in the final synthesis—12 used candidate gene approach. We found some evidence of GxE interactions with sun exposure, notably, with MC1R, CAT and NOS1 genes in melanoma, HAL and IL23A in BCC and HAL and XRCC1 in SCC.
Conclusion: Sun exposure seems to interact with genes involved in pigmentation, oxidative stress and immunosuppression, indicating that excessive UV exposure might exhaust oxidative defence and repair systems differentially, dependent on genetic make-up. Further research is warranted to better understand skin cancer epidemiology and develop sun exposure recommendations. A genome-wide approach is recommended as it might uncover unknown disease pathways dependent on UV radiation
Zračenje može koristiti pacijentima s karcinomom želuca s visoko izraženom mikrosatelitnom nestabilnosti
No full textGastric cancer remains one of the deadliest types of cancer despite the improvements in therapy regimens. The knowledge about specific molecular and histopathologic features of gastric tumors leads toward targeted therapy protocols. Patients with microsatellite instability-high cancer exhibit special characteristics regarding the response to therapy. These patients benefit from specific immunotherapy regimens and respond poorly to conventional therapy. Our study aimed to evaluate the effect of chemotherapy and chemoradiotherapy on the survival of patients with microsatellite instability gastric cancer in our institution. The results of our study show an increase in survival in the microsatellite instability-high group of patients who received radiotherapy (p=0.04). Since all the recent studies recommend radiotherapy only in patients with incompletely resected disease or those with less than D2 lymphadenectomy, our study offers a novelty suggestion in consideration of therapeutic options. If the benefit of radiotherapy can be confirmed in a larger sample of patients, radiotherapy could be a part of tailored therapy for microsatellite instability-high (MSI-H) gastric cancer.Karcinom želuca jedan je od najsmrtonosnijih karcinoma usprkos napretku u njegovom liječenju. Spoznaje o specifičnim molekularnim i histopatološkim značajkama tumora želuca vode nas prema ciljanim terapijskim protokolima. Pacijenti s karcinomom želuca s visoko izraženom mikrosatelitnom nestabilnosti pokazuju posebne značajke u odgovoru na terapiju. Ovi pacijenti dobro reagiraju na specifične imunoterapijske režime, ali imaju loš odgovor na konvencionalnu terapiju. Cilj našeg istraživanja je bila procjena učinka kemoterapije i kemoradioterapije na preživljenje pacijenta s karcinomom želuca s izraženom mikrosatelitnom nestabilnošću u našoj ustanovi. Rezultati naše studije pokazuju produljenje preživljenja u skupini pacijenata s visoko izraženom mikrosatelitnom nestabilnošću koji u primili radioterapiju (p=0.04). S obzirom da sva recentna istraživanja preporučuju zračenje samo pacijentima s nepotpuno reseciranim tumorom ili onima kod kojih je učinjeno manje od D2 limfadenektomije, naše istraživanje donosi moguću novost u razmatranju terapijskih opcija. U slučaju potvrde pozitivnog učinka zračenja u studijama s većim brojem pacijenata, radioterapija bi mogla postati dio ciljane terapije za karcinome želuca s visoko izraženom mikrosatelitnom nestabilnšću
Molecular classification of muscle-invasive bladder cancer based on a simplified immunohistochemical panel using GATA3, CK5/6, and p16
No full textThe choice of therapy for muscle-invasive bladder cancer (MIBC) could be influenced by the tumor’s molecular subtype. Currently, well-defined consensus subtypes are based on tumor microarray mRNA data. Clearly defined and easy-to-use surrogate molecular subtypes, based on immunohistochemistry (IHC) performed on whole slides, are needed to make subtyping cost-effective and useful in routine work and future research. To aid in the development of a simple immunohistochemical classifier, a retrospective single-center series of 92 cases of localized bladder cancer was identified. Routine IHC for GATA 3 transcription factor (GATA3), cytokeratins 5 and 6 (CK5/6), and p16 was performed on whole tissue blocks containing muscle-invasive disease. Electronic medical records were retrieved and searched for clinical variables, treatment, and survival data. The mean age was 69.6 years, and 73% were males. Conservative treatment was used in 55% of cases, while cystectomy with chemotherapy was used in 45%. GATA3 and CK5/6 expression divided cases into broad luminal and basal subtypes, respectively, while p16 expression was used to subclassify luminal cases into luminal papillary and luminal unstable types according to the consensus molecular classification. When subtyped in this way, GATA3 and CK5/6 negative cases showed worse overall survival. Molecular subtyping of MIBC on whole slides containing muscle-invasive tumor using only three commonly used consensus-based antibodies is a feasible and cost-effective method for detecting subtypes of invasive bladder cancer. Future work combining morphological analysis and IHC is needed to fully translate the consensus molecular classification into a comprehensive, cost-effective subtyping strategy
Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation: a post-hoc analysis from the GLORIA-AF Registry
No full textBackground: Previous studies suggested potential ethnic differences in the management and outcomes of atrial fibrillation (AF). We aim to analyse oral anticoagulant (OAC) prescription, discontinuation, and risk of adverse outcomes in Asian patients with AF, using data from a global prospective cohort study.
Methods: From the GLORIA-AF Registry Phase II–III (November 2011–December 2014 for Phase II, and January 2014–December 2016 for Phase III), we analysed patients according to their self-reported ethnicity (Asian vs. non-Asian), as well as according to Asian subgroups (Chinese, Japanese, Korean and other Asian). Logistic regression was used to analyse OAC prescription, while the risk of OAC discontinuation and adverse outcomes were analysed through Cox-regression model. Our primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). The original studies were registered with ClinicalTrials.gov, NCT01468701, NCT01671007, and NCT01937377.
Findings: 34,421 patients were included (70.0 ± 10.5 years, 45.1% females, 6900 (20.0%) Asian: 3829 (55.5%) Chinese, 814 (11.8%) Japanese, 1964 (28.5%) Korean and 293 (4.2%) other Asian). Most of the Asian patients were recruited in Asia (n = 6701, 97.1%), while non-Asian patients were mainly recruited in Europe (n = 15,449, 56.1%) and North America (n = 8378, 30.4%). Compared to non-Asian individuals, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian patients (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22–0.25] and 0.66 [0.61–0.71], respectively), but higher in the Japanese subgroup. Asian ethnicity was also associated with higher risk of OAC discontinuation (Hazard Ratio [HR] and [95% CI]: 1.79 [1.67–1.92]), and lower risk of the primary composite outcome (HR [95% CI]: 0.86 [0.76–0.96]). Among the exploratory secondary outcomes, Asian ethnicity was associated with higher risks of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding.
Interpretation: Our results showed that Asian patients with AF showed suboptimal thromboembolic risk management and a specific risk profile of adverse outcomes; these differences may also reflect differences in country-specific factors. Ensuring integrated and appropriate treatment of these patients is crucial to improve their prognosis
Surgical Considerations in Addressing Cholesterol Granuloma of the Petrous Apex through an Infracochlear Approach
No full textCholesterol granuloma of the petrous bone is a foreign body giant cell reaction to cholesterol deposits with symptoms including hearing loss, vestibular dysfunction, and cranial nerve deficit as a result of cystic mass compression. Surgical treatment is often difficult to plan due to limited access to the lesion and possible injury to surrounding structures. We report on a case of petrous apex cholesterol granuloma drainage through an infracochlear approach. A 27-year-old female patient presented with acute diplopia due to leftsided abducens paralysis. Multislice computed tomography (MSCT) and magnetic resonance (MR) imaging described a 3.5-cm well-marginated lesion in petrous bone apex, compressing the left abducens nerve at the point of entry into
the cavernous sinus, corresponding to cholesterol granuloma. The patients was surgically treated through a transcanal infracochlear approach, since preserving the external and middle ear conduction mechanisms was paramount for the patient. The patient was discharged on the second postoperative day and diplopia resolved within 5 days postoperatively. Six months after the surgery, her hearing on the left side is normal, and she remains symptom-free. This case underpins the value of preoperative planning when approaching the petrous apex, an anatomically complex area due to abundance of important neurovascular structures crowded in a narrow and confined region