The complete anatomy of the lingual nerve: A meta-analysis with implications for oral and maxillofacial surgery.

Lingual nerve (LN) injury during surgical procedures in the third molar region warrants a detailed study of its common pathway and important variations. Therefore, the objective of this study was to analyze and compile the multiple anatomical variations of the LN for use in oral and maxillofacial surgery. It is anticipated that the results of the present meta-analysis may help to minimize the possible complications when performing procedures associated with this anatomical entity. Major online databases such as PubMed, Web of Science, Scopus, Embase were used to gather all relevant studies regarding the LN anatomy. The results were established based on a total of 1665 LNs. The pooled prevalence of the LN being located below the lingual/ alveolar crest was found to be 77.87% (95% CI: 0.00%-100.00%). The LN was located above the lingual/ alveolar crest in 8.21% (95% CI: 4.63%-12.89%) of examined nerves. The most common shape of the LN was established to be round with a prevalence of 40.96% (95% CI: 23.96%-59.06%), followed by oval at 37.98% (95% CI: 23.98%-53.02%) and flat at 25.16% (95% CI: 12.85%-39.77%). In conclusion, we believe that this is the most accurate and up-to-date study regarding the anatomy of the LN. The LN was found to be located below the lingual/alveolar crest in 77.87% of the cases. Furthermore, the LN was found to enter the tongue under the submandibular duct in 68.39% of the cases. Knowledge about the anatomy of the LN is crucial for numerous oral and maxillofacial procedures such as during the extraction of the third molar.

Good performance of the criteria of American College of Medical Genetics and Genomics/Association for Molecular Pathology in prediction of pathogenicity of genetic variants causing thoracic aortic aneurysms and dissections.

BACKGROUND: The identification of pathogenic variant in patients with thoracic aortic aneurysms and dissections (TAAD) was previously found to be a significant indicator pointing to earlier need for surgical intervention. In order to evaluate available methods for classifying identified genetic variants we have compared the event-free survival in a cohort of TAAD patients classified as genotype-positive versus genotype-negative by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) criteria or by ClinVar database. METHODS: We analyzed previously unreported cohort of 132 patients tested in the routine clinical setting for genetic variants in a custom panel of 30 genes associated with TAAD or the TruSight Cardio commercial panel of 174 genes associated with cardiac disease. The identified variants were classified using VarSome platform. Kaplan-Meier survival curves were constructed to compare the event-free survival between probands defined as 'genotype-positive' and 'genotype-negative' using different classifications in order to compare their performance. RESULTS: Out of 107 rare variants found, 12 were classified as pathogenic/likely pathogenic by ClinVar, 38 were predicted to be pathogenic/likely pathogenic by ACMG. Variant pathogenicity as assessed by ACMG criteria was a strong predictor of event free survival (event free survival at 50 years 83% vs. 50%, for genotype positive patients vs. reference, respectively, p = 0.00096). The performance of ACMG criteria was similar to that of ClinVar (event free survival at 50 years 87% vs. 50%, for genotype positive patients vs. reference, respectively p = 0.023) but independent from it as shown by analysing variants with no ClinVar record (event free survival at 50 years 80% vs. 50%, p = 0.0039). Variants classified as VUS by ACMG criteria or ClinVar did not affect event-free survival. TAAD specific custom gene panel performed similar to the larger universal cardiac panel. CONCLUSIONS: In our cohort of unrelated TAAD patients ACMG classification tool available at VarSome was useful in assessing pathogenicity of novel genetic variants. Gene panel containing the established genes associated with the highest risk of hereditary TAAD (ACTA1, COL3A1, FBN1, MYH11, SMAD3, TGFB2, TGFBR1, TGFBR2, MYLK) was sufficient to identify prevailing majority of variants most likely to be causative of the disease.

Blood vessels of the shin - anterior tibial artery - anatomy and embryology - own studies and review of the literature.

Injuries of the lower leg are rather frequent in every day orthopedic routine. Process of healing takes quite a long time and is commonly dependent on the proper vasculature. e study was carried out on 50 human lower legs obtained during autopsies. The anatomy of the vascular system of the leg was studied using classical anatomical dissection methods. Based also on literature we have reviewed the current knowledge on the vascularization of the lower leg and its embryological background.

Blood vessels of the shin - posterior tibial artery - anatomy - own studies and review of the literature.

Anatomy of the vascular system of the leg was studied using classical anatomical dissection methods. Based also on literature we have reviewed the current knowledge on the vascularization of the lower leg and its embryological background with special respect toward the posterior tibial artery and its branches.

A study in Polish patients with cardiomyopathy emphasizes pathogenicity of phospholamban (PLN) mutations at amino acid position 9 and low penetrance of heterozygous null PLN mutations.

BACKGROUND: In humans mutations in the PLN gene, encoding phospholamban - a regulator of sarcoplasmic reticulum calcium ATPase (SERCA), cause cardiomyopathy with prevalence depending on the population. Our purpose was to identify PLN mutations in Polish cardiomyopathy patients. METHODS: We studied 161 unrelated subjects referred for genetic testing for cardiomyopathies: 135 with dilated cardiomyopathy, 22 with hypertrophic cardiomyopathy and 4 with other cardiomyopathies. In 23 subjects multiple genes were sequenced by next generation sequencing and in all subjects PLN exons were analyzed by Sanger sequencing. Control group included 200 healthy subjects matched with patients for ethnicity, sex and age. Large deletions/insertions were screened by real time polymerase chain reaction. RESULTS: We detected three different heterozygous mutations in the PLN gene: a novel null c.9_10insA:(p.Val4Serfs*15) variant and two missense variants: c.25C > T:(p.Arg9Cys) and c.26G > T:(p.Arg9Leu). The (p.Val4Serfs*15) variant occurred in the patient with Wolff-Parkinson-White syndrome in whom the diagnosis of cardiomyopathy was not confirmed and his mother who had concentric left ventricular remodeling but normal left ventricular mass and function. We did not detect large deletions/insertions in PLN in cohort studied. CONCLUSIONS: In Poland, similar to most populations, PLN mutations rarely cause cardiomyopathy. The 9(th) PLN residue is apparently a mutation hot spot whereas a single dose of c.9_10insA, and likely other null PLN mutations, cause the disease only with low penetrance or are not pathogenic.

Inferior tibiofibular joint (tibiofibular syndesmosis) - own studies and review of the literature.

The study was carried out on 50 human lower legs obtained during autopsies. The anatomy of the joint was studied using classical anatomical description methods. Based also on literature we have reviewed the current knowledge on the inferior tibiofibular joint.

A MYH7 variant in a five-generation-family with hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic condition with a prevalence of 1:500-1:3 000. Variants in genes encoding sarcomeric proteins are mainly responsible for the disease. MYH7 gene encoding a myosin heavy chain beta, together with MYPBC3 gene are the two most commonly affected genes. The clinical presentation of this disease varies widely between individuals. This study aims to report a variant of MYH7 responsible for HCM in a five-generation family with a history of cardiac problems. Methods: The diagnosis was established according to the European Society of Cardiology HCM criteria based on two-dimensional Doppler echocardiography or cardiovascular magnetic resonance. Genetic analysis was performed using next-generation-sequencing and Sanger method. Results: The medical history of the presented family began with a prenatal diagnosis of HCM in the first child of a family with previously healthy parents. Five generations of the family had a long history of sudden cardiac death and cardiac problems. A NM_000257.4:c.2342T>A (p.Leu781Gln) variant was detected in the MYH7 gene. It was heterozygous in the proband and in all affected individuals in a large family. The variant was present in 10 affected members of the family, and was absent in 7 members. The clinical course of the disease was severe in several members of the family: three family members died of sudden cardiac death, one patient required heart transplantation, three underwent septal myectomy, and three required implantable cardioverter defibrillator (ICD) implantation. Conclusion: Herein, we report a MYH7 variant responsible for HCM. Familial HCM is inherited primarily in autosomal dominant mode, which is in accordance with our study. However, the presented family showed a broad clinical spectrum of HCM. Out of 10 family members with positive genetic testing 8 had severe presentation of the disease and 2 had a mild phenotype. This suggests that the severity of the disease may depend on other factors, most likely genetic.

Troponin T Assessment Allows for Identification of Mutation Carriers among Young Relatives of Patients with LMNA-Related Dilated Cardiomyopathy.

Background:LMNA-related dilated cardiomyopathy (LMNA-DCM) caused by mutations in the lamin A/C gene (LMNA) is one of the most common forms of hereditary DCM. Due to the high risk of mutation transmission to offspring and the high incidence of ventricular arrhythmia and sudden death even before the onset of heart failure symptoms, it is very important to identify LMNA-mutation carriers. However, many relatives of LMNA-DCM patients do not report to specialized centers for clinical or genetic screening. Therefore, an easily available tool to identify at-risk subjects is needed. Methods: We compared two cohorts of young, asymptomatic relatives of DCM patients who reported for screening: 29 LMNA mutation carriers and 43 individuals from the control group. Receiver operating characteristic (ROC) curves for potential indicators of mutation carriership status were analyzed. Results: PR interval, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity cardiac troponin T (hscTnT) serum levels were higher in the LMNA mutation carrier cohort. Neither group differed significantly with regard to creatinine concentration or left ventricular ejection fraction. The best mutation carriership discriminator was hscTnT level with an optimal cut-off value at 5.5 ng/L, for which sensitivity and specificity were 86% and 93%, respectively. The median hscTnT level was 11.0 ng/L in LMNA mutation carriers vs. <3.0 ng/L in the control group, p < 0.001. Conclusions: Wherever access to genetic testing is limited, LMNA mutation carriership status can be assessed reliably using the hscTnT assay. Among young symptomless relatives of LMNA-DCM patients, a hscTnT level >5.5 ng/L strongly suggests mutation carriers.

Clinical and genetic yield of familial screening after a sudden unexplained death at a young age.

BACKGROUND: In a population under 45 years of age, the predominant causes of sudden cardiac death (SCD) are inherited cardiac diseases. Determining the underlying cause may help identify relatives at risk and prevent further events but is more difficult if an autopsy has not been performed. AIMS: We aimed to assess the diagnostic value of clinical and genetic screening in relatives of young non-autopsied sudden unexplained death (SUD) victims. MATERIAL AND METHODS: Eighty-seven relatives of 65 young non-autopsied SUD victims from 39 families were evaluated from 2016 to 2019. The relatives underwent extensive noninvasive cardiac workup. Genetic examinations were performed in 39 families. RESULTS: The definite diagnoses were made in 17 of 39 (44%) families. Cardiomyopathies were identified in 10 families (5 hypertrophic, 4 dilated, and 1 arrhythmogenic), followed by long QT syndrome (5 families). In 3 families, probable diagnoses were made, whereas in 20 families no diagnosis was achieved. In total, definite and probable diagnoses were made in 18 and 5 patients, respectively. All affected relatives were offered medical management, one of them died of heart failure and one underwent transplantation during the median follow-up of 3 years. Disease-causing variants were found in 7 of 39 (18%) probands; all in families with a definite diagnosis. Variants of unknown significance were found in 2 probands. CONCLUSION: Screening of relatives of SUD victims is warranted and may save lives, even if it is not guided by autopsy results. Genetic testing in families without the disease phenotype has little effectiveness.

Pregnancy in women with dilated cardiomyopathy genetic variants.

INTRODUCTION AND OBJECTIVES: Limited information is available on the safety of pregnancy in patients with genetic dilated cardiomyopathy (DCM) and in carriers of DCM-causing genetic variants without the DCM phenotype. We assessed cardiac, obstetric, and fetal or neonatal outcomes in this group of patients. METHODS: We studied 48 women carrying pathogenic or likely pathogenic DCM-associated variants (30 with DCM and 18 without DCM) who had 83 pregnancies. Adverse cardiac events were defined as heart failure (HF), sustained ventricular tachycardia, ventricular assist device implantation, heart transplant, and/or maternal cardiac death during pregnancy, or labor and delivery, and up to the sixth postpartum month. RESULTS: A total of 15 patients, all with DCM (31% of the total cohort and 50% of women with DCM) experienced adverse cardiac events. Obstetric and fetal or neonatal complications were observed in 14% of pregnancies (10 in DCM patients and 2 in genetic carriers). We analyzed the 30 women who had been evaluated before their first pregnancy (12 with overt DCM and 18 without the phenotype). Five of the 12 (42%) women with DCM had adverse cardiac events despite showing NYHA class I or II before pregnancy. Most of these women had a history of cardiac events before pregnancy (80%). Among the 18 women without phenotype, 3 (17%) developed DCM toward the end of pregnancy. CONCLUSIONS: Cardiac complications during pregnancy and postpartum were common in patients with genetic DCM and were primarily related to HF. Despite apparently good tolerance of pregnancy in unaffected genetic carriers, pregnancy may act as a trigger for DCM onset in a subset of these women.

Clinical importance of the middle meningeal artery.

Middle meningeal artery (MMA)is an important branch which supplies among others cranial dura mater. It directly attaches to the cranial bones (is incorporated into periosteal layer of dura mater), favors common injuries in course of head trauma. This review describes available data on the MMA considering its varability, or treats specific diseases or injuries where the course of MMA may have clinical impact.

Trans-foramen magnum examination of the sella turcica region in the macerated human skulls.

This report presents a method of quick and accurate imaging of the sellar region by means of the laryngological mirror equipped with a light pipe and followed by taking digital photograph as the mirror image visible through the foramen magnum. A technique of the intracranial imaging of the osseous structures was tested on the macerated human skulls. Images of the sellar region were presented as the example of quality of the employed technique, which can be regarded as a simplified version of the endoscopic examination.

Blood supply of human uterine cervix - a SEM study.

AIM: The main goal of this study was assessment of vascular structure of human uterine cervix. MATERIALS AND METHODS: The study was carried out on 25 human uteri of females aged 25-45, collected upon autopsy. Vessels were injected with synthetic resin, next corroded and coated with gold, finally observed using scanning electron microscope. RESULTS: On a sagittal section we have distinguished several zones in the vascular picture of the uterine cervix consisted of differently arranged veins, arteries, arterioles and capillaries. Due to technical reasons we were unable to receive a picture of vascular composition of cervical uterine canal on transverse section. CONCLUSIONS: Scanning elector microscopy is a method which might be applied to study the structure of human uterine cervix.

Blood vessels of the intratumoral septa in uterine leiomyomata.

The angioarchitecture of fibroid intratumoral septa was studied using 32 uteri obtained during necropsies of the females aged between 35-57. The whole vascular bed of 16 uteri was injected with synthetic resin Mercox CL-2R and then the uteri were corroded in potassium hydroxide. Next 16 uteri were injected with acrylic emulsion, Liquitex R. Their vascular bed was studied using immunohistochemistry for von Willebrandt's factor. Immunohistochemistry allowed to visualize the vessels within the intratumoral septa, while SEM allowed to differentiate the vessels, which were mainly the venules and the veins. Apart from the veins the intratumoral septa were consisted of small arteries and capillaries.

Cardiovascular involvement and prognosis in Loeys-Dietz syndrome.

BACKGROUND: Loeys-Dietz syndrome (LDS) is an inherited connective tissue disorder associated with aortic root enlargement and risk of thoracic aortic dissection (AD). Genetic examination is essential for diagnosis. AIMS: The study aimed at analysis of clinical data on cardiovascular involvement and management of LDS patients. METHODS: The study included carriers of LDS-associated genetic variants, identified between 2012 and 2022. Assessment of cardiovascular involvement was based on echocardiography and computed tomography angiography with quantitative assessment of arterial tortuosity. Involvement of other systems was also evaluated. We noted major cardiovascular events, including aortic events, defined as AD, elective aortic surgery, or otherwise unexplained sudden death. RESULTS: Thirty-four patients from 15 families were included, and five identified variants were novel. Probands' mean age was 41 years. Cardiovascular abnormalities, aortic involvement, aortic tortuosity, and tortuosity of cervical arteries were present in 79%, 71%, 68%, and 100% of carriers, respectively. First aortic events (9 A-type AD, 6 elective thoracic aortic surgeries, and one sudden death) occurred in 16 (47%) patients at a median age of 35 years. The youngest age at AD was 16 years, and 7 years for elective aneurysm repair. Second and third aortic events occurred in 9 and 4 patients, respectively. Eight patients (24%) experienced other major cardiovascular events. Aortic event-free survival was shorter in the presence of skin striae (P = 0.03), tended to be shorter in the presence of Marfanoid features (P = 0.06), and longer with TGFB2 variants (P = 0.06). CONCLUSIONS: LDS is associated with high burden of cardiovascular complications at a young age.

Titin-Related Dilated Cardiomyopathy: The Clinical Trajectory and the Role of Circulating Biomarkers in the Clinical Assessment.

Titin truncating variants (TTNtv) are known as the leading cause of inherited dilated cardiomyopathy (DCM). Nevertheless, it is unclear whether circulating cardiac biomarkers are helpful in detection and risk assessment. We sought to assess 1) early indicators of cardiotitinopathy including the serum biomarkers high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in clinically stable patients, and 2) predictors of outcome among TTNtv carriers. Our single-center cohort consisted of 108 TTNtv carriers (including 70 DCM patients) from 43 families. Clinical, laboratory and follow-up data were analyzed. The earliest abnormality was left ventricular dysfunction, present in 8, 26 and 47% of patients in the second, third and fourth decade of life, respectively. It was followed by symptoms of heart failure, linked to NT-proBNP elevation and severe left ventricular systolic dysfunction, and later by arrhythmias. Hs-cTnT serum levels were increased in the late stage of the disease only. During the median follow-up of 5.2 years, both malignant ventricular arrhythmia (MVA) and end-stage heart failure (esHF) occurred in 12% of TTNtv carriers. In multivariable analysis, NT-proBNP level ≥650 pg/mL was the best predictor of both composite endpoints (MVA and esHF) and of MVA alone. In conclusion, echocardiographic abnormalities are the first detectable anomalies in the course of cardiotitinopathies. The assessment of circulating cardiac biomarkers is not useful in the detection of the disease onset but may be helpful in risk assessment.

A novel risk model for predicting potentially life-threatening arrhythmias in non-ischemic dilated cardiomyopathy (DCM-SVA risk).

BACKGROUND: Non-ischemic dilated cardiomyopathy (DCM) can be complicated by sustained ventricular arrhythmias (SVA) and sudden cardiac death (SCD). By now, left-ventricular ejection fraction (LV-EF) is the main guideline criterion for primary prophylactic ICD implantation, potentially leading either to overtreatment or failed detection of patients at risk without severely impaired LV-EF. The aim of the European multi-center study DETECTIN-HF was to establish a clinical risk calculator for individualized risk stratification of DCM patients. METHODS: 1393 patients (68% male, mean age 50.7 ± 14.3y) from four European countries were included. The outcome was occurrence of first potentially life-threatening ventricular arrhythmia. The model was developed using Cox proportional hazards, and internally validated using cross validation. The model included seven independent and easily accessible clinical parameters sex, history of non-sustained ventricular tachycardia, history of syncope, family history of cardiomyopathy, QRS duration, LV-EF, and history of atrial fibrillation. The model was also expanded to account for presence of LGE as the eight8h parameter for cases with available cMRI and scar information. RESULTS: During a mean follow-up period of 57.0 months, 193 (13.8%) patients experienced an arrhythmic event. The calibration slope of the developed model was 00.97 (95% CI 0.90-1.03) and the C-index was 0.72 (95% CI 0.71-0.73). Compared to current guidelines, the model was able to protect the same number of patients (5-year risk ≥8.5%) with 15% fewer ICD implantations. CONCLUSIONS: This DCM-SVA risk model could improve decision making in primary prevention of SCD in non-ischemic DCM using easily accessible clinical information and will likely reduce overtreatment.

A Novel DSP Truncating Variant in a Family with Episodic Myocardial Injury in the Course of Arrhythmogenic Cardiomyopathy-A Possible Role of a Low Penetrance NLRP3 Variant.

Mono-allelic dominant mutations in the desmoplakin gene (DSP) have been linked to known cardiac disorders, such as arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy. During the course of DSP cardiomyopathy, episodes of acute myocardial injury may occur. While their mechanisms remain unclear, myocarditis has been postulated as an underlying cause. We report on an adolescent girl with arrhythmogenic biventricular cardiomyopathy and three acute myocarditis-like episodes in whom we found a novel truncating DSP variant accompanied by a known low penetrance R490K variant in the NLRP3. Upon family screening, other carriers of the DSP variant have been identified in whom only mild cardiac abnormalities were found. We hypothesized that the uncommon course of cardiomyopathy in the proband as well as striking discrepancies in the phenotype observed in her family may be explained by the co-existence of her low penetrance genetic autoinflammatory predisposition.

Can Circulating Cardiac Biomarkers Be Helpful in the Assessment of LMNA Mutation Carriers?

Mutations in the lamin A/C gene are variably phenotypically expressed; however, it is unclear whether circulating cardiac biomarkers are helpful in the detection and risk assessment of cardiolaminopathies. We sought to assess (1) clinical characteristics including serum biomarkers: high sensitivity troponin T (hsTnT) and N-terminal prohormone brain natriuretic peptide (NT-proBNP) in clinically stable cardiolaminopathy patients, and (2) outcome among pathogenic/likely pathogenic lamin A/C gene (LMNA) mutation carriers. Our single-centre cohort included 53 patients from 21 families. Clinical, laboratory, follow-up data were analysed. Median follow-up was 1522 days. The earliest abnormality, emerging in the second and third decades of life, was elevated hsTnT (in 12% and in 27% of patients, respectively), followed by the presence of atrioventricular block, heart failure, and malignant ventricular arrhythmia (MVA). In patients with missense vs. other mutations, we found no difference in MVA occurrence and, surprisingly, worse transplant-free survival. Increased levels of both hsTnT and NT-proBNP were strongly associated with MVA occurrence (HR > 13, p ≤ 0.02 in both) in univariable analysis. In multivariable analysis, NT-proBNP level > 150 pg/mL was the only independent indicator of MVA. We conclude that assessment of circulating cardiac biomarkers may help in the detection and risk assessment of cardiolaminopathies.

Analysis of De Novo Mutations in Sporadic Cardiomyopathies Emphasizes Their Clinical Relevance and Points to Novel Candidate Genes.

The vast majority of cardiomyopathies have an autosomal dominant inheritance; hence, genetic testing is typically offered to patients with a positive family history. A de novo mutation is a new germline mutation not inherited from either parent. The purpose of our study was to search for de novo mutations in patients with cardiomyopathy and no evidence of the disease in the family. Using next-generation sequencing, we analyzed cardiomyopathy genes in 12 probands. In 8 (66.7%), we found de novo variants in known cardiomyopathy genes (TTN, DSP, SCN5A, TNNC1, TPM1, CRYAB, MYH7). In the remaining probands, the analysis was extended to whole exome sequencing in a trio (proband and parents). We found de novo variants in genes that, so far, were not associated with any disease (TRIB3, SLC2A6), a possible disease-causing biallelic genotype (APOBEC gene family), and a de novo mosaic variant without strong evidence of pathogenicity (UNC45A). The high prevalence of de novo mutations emphasizes that genetic screening is also indicated in cases of sporadic cardiomyopathy. Moreover, we have identified novel cardiomyopathy candidate genes that are likely to affect immunological function and/or reaction to stress that could be especially relevant in patients with disease onset associated with infection/infestation.