Blood Biomarkers in Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that affects millions of people worldwide. The characteristic pathological manifestation of AD includes the deposition of extracellular insoluble ß amyloid plaques and intracellular neurofibrillary tangles formed from hyperphosphorylated tau protein. Cost effective and minimally invasive peripheral blood-based biomarkers are critical for early AD diagnosis. Currently, the plasma based two fraction of ß amyloid peptide ratio (Aß42/40) and phosphorylated tau (p-tau) are considered as blood-based biomarkers for AD diagnosis. Recent research indicates that oxidative stress (OS) occurs prior to amyloid plaque (Aß) formation and abnormal tau phosphorylation in AD. The imbalance of the master antioxidant, glutathione (GSH), and prooxidants (iron, zinc, and copper)─plays a crucial role in AD neurodegeneration. We present peripheral blood-based OS related biomarkers that are mechanistically involved in the disease process and may serve as a novel screening tool for early detection of AD onset. This OS based approach may also provide a quick and cost efficient method to monitor the effects of disease-modifying therapies in AD clinical trials.

New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.

Cardiac rhythm regulated by micro-macroscopic structures of heart. Pacemaker abnormalities or disruptions in electrical conduction, lead to arrhythmic disorders may be benign, typical, threatening, ultimately fatal, occurs in clinical practice, patients on digitalis, anaesthesia or acute myocardial infarction. Both traditional and genetic animal models are: In-vitro: Isolated ventricular Myocytes, Guinea pig papillary muscles, Patch-Clamp Experiments, Porcine Atrial Myocytes, Guinea pig ventricular myocytes, Guinea pig papillary muscle: action potential and refractory period, Langendorff technique, Arrhythmia by acetylcholine or potassium. Acquired arrhythmia disorders: Transverse Aortic Constriction, Myocardial Ischemia, Complete Heart Block and AV Node Ablation, Chronic Tachypacing, Inflammation, Metabolic and Drug-Induced Arrhythmia. In-Vivo: Chemically induced arrhythmia: Aconitine antagonism, Digoxin-induced arrhythmia, Strophanthin/ouabain-induced arrhythmia, Adrenaline-induced arrhythmia, and Calcium-induced arrhythmia. Electrically induced arrhythmia: Ventricular fibrillation electrical threshold, Arrhythmia through programmed electrical stimulation, sudden coronary death in dogs, Exercise ventricular fibrillation. Genetic Arrhythmia: Channelopathies, Calcium Release Deficiency Syndrome, Long QT Syndrome, Short QT Syndrome, Brugada Syndrome. Genetic with Structural Heart Disease: Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia, Dilated Cardiomyopathy, Hypertrophic Cardiomyopathy, Atrial Fibrillation, Sick Sinus Syndrome, Atrioventricular Block, Preexcitation Syndrome. Arrhythmia in Pluripotent Stem Cell Cardiomyocytes. Conclusion: Both traditional and genetic, experimental models of cardiac arrhythmias' characteristics and significance help in development of new antiarrhythmic drugs.

Spontaneous Cerebral Air Embolism-An Unusual Scenario.

The introduction of air into cerebral venous or arterial circulation known as cerebral air embolism (CAE) is a rare clinical entity. CAE is commonly iatrogenic secondary to central venous catheter (CVC) placement or removal, various endoscopic procedures, or trauma or surgical scenarios. Here we report a case of spontaneous CAE in an unusual scenario. A 71-year-old male presented to emergency after developing giddiness following a yoga session. His MRI showed air embolism in the posterior fossa along cerebellar folia, prepontine, and suprasellar cisterns and tracking superiorly along the tentorium cerebelli. CAE is a rare clinical entity. Our case had CAE as a complication of cholesteatoma and possibly got triggered due to change in air pressor dynamics during yoga session.

Hippocampal glutathione depletion with enhanced iron level in patients with mild cognitive impairment and Alzheimer's disease compared with healthy elderly participants.

Oxidative stress has been implicated in Alzheimer's disease, and it is potentially driven by the depletion of primary antioxidant, glutathione, as well as elevation of the pro-oxidant, iron. Present study evaluates glutathione level by magnetic resonance spectroscopy, iron deposition by quantitative susceptibility mapping in left hippocampus, as well as the neuropsychological scores of healthy old participants (N = 25), mild cognitive impairment (N = 16) and Alzheimer's disease patients (N = 31). Glutathione was found to be significantly depleted in mild cognitive impaired (P < 0.05) and Alzheimer's disease patients (P < 0.001) as compared with healthy old participants. A significant higher level of iron was observed in left hippocampus region for Alzheimer's disease patients as compared with healthy old (P < 0.05) and mild cognitive impairment (P < 0.05). Multivariate receiver-operating curve analysis for combined glutathione and iron in left hippocampus region provided diagnostic accuracy of 82.1%, with 81.8% sensitivity and 82.4% specificity for diagnosing Alzheimer's disease patients from healthy old participants. We conclude that tandem glutathione and iron provides novel avenue to investigate further research in Alzheimer's disease.

Effect of socioeconomic, nutritional status, diet, and oral habits on the prevalence of different types of malocclusion in school-children.

OBJECTIVE: Although there have been many reports on the prevalence of malocclusion, there is paucity of data concerning factors associated with it. The present study aimed to study the effects of three environmental factors namely socio-economic status (SES), nutritional status, and oral habits on malocclusion. MATERIAL AND METHODS: A total number of 765 students [Low socio-economic status (LSS; 369 subjects) and High socio-economic status (HSS; 396 subjects)] based on Modified Kuppuswamy scale were examined within the age group of 13- 15 years amongst various government and private schools in Chandigarh, India. A questionnaire was filled up by the subjects, which was followed up with clinical examination using the Dental Aesthetic Index (DAI). Additionally, the provisional diagnosis, retained, transposed teeth, and overbite were estimated. RESULTS: The total prevalence of malocclusion in the population was 49.7%. The prevalence of malocclusion in LSS was found to be 42.90% and in HSS was 57.10% (P: 0.003). The mean DAI score in LSS was 26.011 and in HSS was 27.179. The mean DAI score in soft eaters was 29.527, average eaters was 26.369 and hard eaters was 26.410. CONCLUSION: The total prevalence of malocclusion in Chandigarh was 49.7%. Class I type 1 was the most prevalent type of malocclusion. Adolescents belonging to HSS had more malocclusion as compared to those belonging to LSS. Soft diet caused increased malocclusion. The present study highlighted the effect of diet pattern on the prevalence of malocclusion. (www.actabiomedica.it).

Participant-Directed Intervention Tailoring Is Associated With Improvements in Glycemic Control for South Asian Adults With Type 2 Diabetes.

OBJECTIVES: Our aim was to determine the impact of a 3-month diabetes self-management education and support (DSME/DSMS) intervention involving both professional and peer support on glycemic control and diabetes distress in South Asian adults with type 2 diabetes (T2D) living in Metro Vancouver. METHODS: We recruited 114 South Asian adults with T2D for a study conducted across 7 sites in Metro Vancouver. A previous DSME/DSMS intervention was modified using participant feedback. Participants attended the updated intervention involving 6 biweekly group-based DSME sessions co-led by a diabetes educator and peer leader and 6 biweekly DSMS sessions delivered by a peer leader. Assessments were conducted at baseline and 3 months. Primary outcomes were glycated hemoglobin (A1C) and diabetes distress. Secondary outcomes included apolipoprotein B, blood pressure (BP), height and weight, waist circumference, diabetes support and depressive symptoms. RESULTS: After the 3-month intervention, linear mixed-effects modelling demonstrated A1C decreased significantly from 8.2% (66 mmol/mol) to 7.8% (62 mmol/mol) (p<0.0001), as did body mass index (from 30.02 to 29.7 kg/m2; p=0.0005) and diastolic BP (from 75.86 to 70.78 mmHg; p<0.0001). These reductions persisted after adjusting for the fixed-effects of age, sex, intensification of diabetes and BP medication, as well as random effects for subject and location. CONCLUSIONS: Participation in a professional plus peer-led intervention tailored by South Asian adults with T2D is associated with improved glycemic control and other favourable health outcomes.

Vascular access complications in patients undergoing veno-arterial ecmo and their impact on survival in patients with refractory cardiogenic shock: A retrospective 8-year study.

Introduction: Veno-arterial extracorporeal membrane oxygenation (ECMO) is well-recognized treatment modality for patients with refractory cardiogenic shock. Uncomplicated cannulation is a prerequisite and basis for achieving a successful outcome in ECMO. Vascular access is obtained either by surgical cut-down. Common vascular access complications are bleeding and limb ischemia. Objective: To evaluate cannulation technique, the incidence of vascular complications, and their impact on the outcome. Methods: A retrospective data analysis conducted on 95 patients receiving ECMO from 2013 to 2020 was done. The patients were divided into two groups: no vascular access complications (non-VAC group) and vascular access complications (VAC group). The groups were compared related to the hospital and ICU stays and blood transfusion. Results: The patients in both groups were demographically and clinically comparable. The Non-VAC group had 75 patients, whereas the VAC group had a total of 20 patients. The main complication observed in the VAC group was bleeding from the cannulation site which required more blood transfusion than the non-VAC group (6.8 ± 1.02 vs 4.2 ± 1.26). Limb ischemia was another complication seen in the VAC group (4.2%, n = 4). Two patients had delayed bleeding after decannulation. The overall average length of stay in the hospital was statistically similar in both the groups (22 days in the VAC group vs 18 days in the non-VAC group), but the average ICU stay was more in the VAC group compared to the non-VAC group (18 days vs 12.06 days). Conclusion: Bleeding and limb ischemia are the important vascular access site complications, which increase blood transfusion requirements, ICU stay, and overall hospital stay.

Effect of anti-platelet therapy on peri-operative blood loss in patients undergoing off-pump coronary artery bypass grafting.

Purpose: The purpose of this study was to review the effect of the pre-operative use of clopidogrel and aspirin on peri-operative bleeding, blood product transfusion, and resource utilization after coronary artery bypass grafting (CABG). Materials and Methods: A total of 1200 patients who underwent off-pump CABG (OPCABG) between 2010 and 2012 were retrospectively studied. Patients were divided into three groups: group 1: discontinued aspirin and clopidogrel 6 days prior to surgery (n = 468), group 2: discontinued both drugs 3 to 5 days prior to surgery (n = 621), and group 3: discontinued both drugs 2 days prior to surgery (n = 111). The bleeding pattern and blood product transfusion were studied and compared between the groups. Patients having history of other drugs affecting the coagulation profile, other organ dysfunction, on-pump CABG, and the combined procedure were excluded from the study. Results: Group 2 patients had a higher rate of bleeding and a reduced mean value of hemoglobin (Hb) as compared to other groups. The same results were seen in blood and blood product transfusion. Patients of group 2 and group 3 were associated with higher blood loss in terms of drainage at 12 and 24 hours. Post-operatively, this was statistically significant. Re-exploration was statisitically significant in group 3 patients (9.01%) than in group 2 (2.58%) and group 1 (1.07%) patients. Conclusion: The pre-operative use of clopidogrel and aspirin in patients undergoing OPCABG showed limited clinical benefits; however, its use significantly increased the risk of bleeding and blood transfusion, thus increasing morbidity and resource utilization. Hence, clopidogrel and aspirin should be stopped at least 6 days prior to surgery.

Novel Protocols for the Production of Autologous Blood Concentrates With High Platelet Volume.

Autologous blood concentrates (ABCs), specifically platelet-rich plasma (PRP), were originally discussed in the literature more than 60 years ago. Since then, protocols to fabricate PRP from patient-derived blood have steadily evolved with the aim of creating better products with more effective clinical results. Key to the protocol evolution has been the development of ABCs with higher concentrates of platelets and other blood components that enhance soft- and hard-tissue healing and, hence, regeneration. The authors present a protocol for obtaining high-platelet-concentration PRP and autogenous thrombin. This fifth-generation protocol allows PRP to be attained with a platelet concentration six times higher than that which is present in the original clot. This double-centrifugation PRP protocol is relatively simple and inexpensive, as it does not require special equipment or advanced technical knowledge by the practitioner and can readily be conducted in a private dental clinical setting.

Analysis of anticoagulation therapy related complications in patients with prosthetic valves: Our experience.

PURPOSE: The aim of this study is to analyze anticoagulation-related complications in patients following mechanical valve replacement and factors influencing the outcome. MATERIALS AND METHODS: A total of 250 patients were analyzed during OPD follow-up for anticoagulation-related complications and various factors influencing outcome. Patients received prosthetic valve at mitral and/or aortic or both. RESULTS: Out of 250 patients, 48% were male and 52% were female. The mean age was 41.9 ± 14.4. A total of 139 had mitral valve replacement (MVR), 70 had aortic valve replacement (AVR), 40 had double valve replacement (DVR), and 1 patient had triple valve replacement. Valves implanted were mechanical bileaflet valve. The mean international normalization ratio (INR) in the study was 2.4 ± 0.56. A total of 49 events occurred during follow-up, of which 4.5% per patient years were anticoagulation-related hemorrhagic events and 4.8% per patient years were thromboembolic events. Among thromboembolic events, valve thrombosis occurred in 10 patients and cerebrovascular accidents occurred in 11 patients. Mean INR for thromboembolic events was 1.46 ± 0.25 and anticoagulation-related hemorrhagic events was 4.4 ± 1.03. Mortality rate was 1.6% in AVR, 4% in MVR, and 0.4% in DVR groups; about 34% of patients needed dose modification of Acenocoumarol and reason for derangement of INR was associated with infectious process and poor compliance; 85% of cases showed good compliance for daily anticoagulation therapy. CONCLUSION: Anticoagulation for mechanical valve replacement can be managed with INR range of 2.0 to 2.5 in MVR and 1.5 to 2.0 in AVR with acceptable hemorrhagic and thromboembolic events. We must educate and counsel the patients during follow-up for better compliance to optimal anticoagulation.

Landscape of Biomarkers and Actionable Gene Alterations in Adenocarcinoma of GEJ and Stomach-A Real World Data Analysis.

After several years of negative phase III trials in gastric and esophageal cancer, a significant breakthrough in the treatment of metastatic adenocarcinomas of the gastroesophageal junction (GEJ) and stomach (GC) is now becoming evident with the emerging of precision oncology and implementation of molecular targets in tumor treatment. In addition, new generation studies such as umbrella and basket trials are focused on these molecular targets, which makes an early molecular diagnosis based on IHC/ISH and NGS necessary. The required companion diagnostics of Her2neu overamplification or PD-L1 expression is based on immunohistochemistry (IHC) or additionally in situ hybridization (ISH) in case of an IHC Her2neu score of 2+. However, there are investigator-dependent differences in the assessment of Her2neu amplification and different PD-L1 scoring systems obtained by IHC/ISH. The use of high-throughput technologies such as next-generation sequencing (NGS) holds the potential to standardize the analysis and thus make them more comparable. In the presented study, real-world multigene sequencing data of 72 Caucasian patients diagnosed with metastatic adenocarcinomas of GEJ and stomach were analyzed. In the clinical companion diagnostics, we found ESCAT level I molecular targets in one-third of our patients, which directly determined the therapy. In addition, we found potential targets in 14/72 patients (19.4%) who potentially qualify for precision therapies in corresponding molecular studies. The study highlights the importance of comprehensive molecular profiling for precision treatment of GEJ/GC and indicates that a biomarker evaluation should be performed for all patients with metastatic adenocarcinomas before the initiation of first-line treatment and during second-line or subsequent treatment.

Comparison of closed incision negative pressure wound therapy with conventional dressing for reducing wound complications in emergency laparotomy.

OBJECTIVE: The aim of this study was to compare the post-operative effects of closed incision negative pressure wound therapy with conventional dressing in emergency laparotomy. METHODS: This study was conducted from 1st November 2018 to 31st March 2020 in ABVIMS & Dr. R.M.L. Hospital, New Delhi. The potential candidates for the study were patients of 18 years and above who were admitted in surgical emergency and underwent emergency laparotomy by a midline incision. Fifty random patients were alternatively allotted to group A (25 patients) and group B (25 patients). In the patients of group A, closed incision negative pressure wound therapy (ciNPWT) was applied on midline closed wound after an exploratory laparotomy procedure. The patients in group B, standard dry gauze dressing was done. RESULTS: The mean age of patients in group A and group B were 46.76±12.20 and 41.96±8.33 years, respectively (p-value-0.11). The wound infection was present in 12% of cases in group A and 32% in group B, but when we calculate the p-value, it was found to be statistically non-significant (p-value-0.08). Similarly, seroma formation and wound dehiscence were found less in group A as compared to group B but not reached up to a statistically significant limit (p-value 0.55 and 0.38 respectively). The frequency of dressing change was 1-2 per week in 92% of cases in group A while it was 3-4 per week in 68% of cases in group B. The mean time of the frequency of dressing change was 1.24±0.72 per week and 4.28±1.90 per week in both the groups respectively (p-value <0.001). There was no significant (p>0.05) difference in the duration of hospital stay between group A (mean hospital stay 8.20±2.34 days) and group B (mean hospital stay 8.21±3.37 days). CONCLUSION: Closed incision negative pressure wound therapy has no advantages over conventional dressing in terms of post-operative complications and hospital stay. However, it reduces the frequency of dressing change significantly, which reduces the mental stress of the patient and the burden of changing daily dressing.

Left Ventricular Thrombus and Cardioembolic Stroke in a Patient with Ulcerative Colitis: A Case Report.

Left ventricular (LV) thrombi usually occur in the setting of global or regional LV systolic dysfunction and are extremely rare in the absence of LV wall motion abnormalities. We report here a case of a 23-year-old female who presented with cardioembolic stroke due to ulcerative colitis. To determine the cause of stroke, several investigations and evaluations were carried out, but the results were mostly normal or unremarkable. Transthoracic echocardiography revealed an oscillating pedunculated globular mass, which was eventually resected due to recurrent transient ischemic attacks. The histopathology of the excised mass revealed it to be an organized thrombus with acute and chronic inflammatory cells and fibroblasts. The uncommon etiology combined with the unusual appearance of the thrombus presented a major diagnostic and therapeutic dilemma for this exceedingly rare cause for intracardiac thrombus formation. Therefore, it would be useful to have a low threshold for screening patients with active inflammatory bowel disease for possible ventricular thrombosis before discharge, especially if other risk factors are present.

Study on Evolution of Micropipes from Hexagonal Voids in 4H-SiC Crystals by Cathodoluminescence Imaging.

This paper presents an investigation on micropipe evolution from hexagonal voids in physical vapor transport-grown 4H-SiC single crystals using the cathodoluminescence (CL) imaging technique. Complementary techniques optical microscopy, scanning electron microscopy, and energy-dispersive spectroscopy (EDS) are also used to understand the formation mechanism of hexagonal voids along with the origin of pipes from these voids. The ability of CL to image variations along the depth of the sample provides new insights on how micropipes are attached to hexagonal voids that lie deep within the bulk single crystals. CL imaging confirms that multiple micropipes can originate from a single hexagonal void. EDS mapping shows that the inside of the micropipe walls exhibits higher levels of carbon. Investigation of the seed region by optical imaging shows that improper fixing of the seed to the crucible lid is the root cause for the formation of hexagonal voids that subsequently lead to micropipe formation.

Pathophysiological Mechanisms and Neurological Manifestations in COVID-19.

With increasing knowledge of the coronavirus disease-2019 (COVID-19), we now understand that COVID-19 presents with various extrapulmonary manifestations with multi-organ involvement. Involvement of the central nervous system (CNS) occurs probably via transsynaptic spread or transfer across the blood-brain barrier. Hypoxia, immune-mediated injury, and vascular damage are the potential mechanisms for the CNS manifestations. Headache, dizziness, chemosensory disturbances, such as loss of smell, taste, encephalopathy, stroke, etc., are among the commonly encountered neurological presentations. Headache is identified as one of the red flag symptoms for COVID-19. Sudden onset of loss of smell and/or taste in the absence of nasal congestion can help in COVID-19 case identification and testing prioritization. Both hemorrhagic and ischemic brain injury is common in patients developing stroke. Besides these, COVID-19-associated CNS involvement demands more careful attention toward patients with existing neurological disorders especially that are managed with immunosuppressant agents. In all, neurological involvement in COVID-19 is not uncommon and may precede, occur concomitantly or after the respiratory involvement. It may also be the sole presentation in some of the patients necessitating high vigilance for COVID-19. In this review, we briefly discussed the pathogenesis of CNS involvement and some important neurological manifestations in COVID-19. How to cite this article: Zirpe KG, Dixit S, Kulkarni AP, Sapra H, Kakkar G, Gupta R, et al. Pathophysiological Mechanisms and Neurological Manifestations in COVID-19. Indian J Crit Care Med 2020;24(10):975-980.

Tenecteplase-induced Nonaneurysmal Subarachnoid Hemorrhage in a Patient with Acute Ischemic Stroke: A Case Report and Literature Review.

Recently, tenecteplase (TNK) has been used for intravenous thrombolysis in acute ischemic stroke (AIS). Although spontaneous subarachnoid hemorrhage (SAH) following thrombolysis with tissue plasminogen activator has been reported, there is a lack of literature regarding TNK-induced nonaneurysmal spontaneous SAH. Our index case received intravenous TNK within an hour of symptom onset of AIS. Following deterioration of sensorium, repeat noncontrast computed tomography was performed, which showed diffuse SAH. Cerebral angiography did not reveal any aneurysm. Nonaneurysmal SAH can be a complication of TNK thrombolysis, which is not reported in literature. Knowledge of this possible adverse reaction is critical for appropriate counseling and management.

Outpatient ADE (cytarabine, daunorubicin, and etoposide) is feasible and effective for the first relapse of pediatric acute myeloid leukemia: A prospective, phase II study.

BACKGROUND: Approximately 40% children with acute myeloid leukemia (AML) invariably relapse, after attaining the first complete remission (CR), with dismal long-term outcome. There is little consensus regarding choice of optimal induction chemotherapy regimen for relapsed pediatric AML. PROCEDURE: A prospective single arm phase II study (CTRI/2017/02/007757) was carried out at our center to evaluate the safety and efficacy of outpatient cytarabine, daunorubicin, and etoposide (ADE) regimen in pediatric AML (≤18 years) at the first relapse. Response evaluation was done by bone marrow aspiration morphology along with minimal residual disease (MRD) assessment. All adverse events including need and duration of hospitalization, transfusion support, and antimicrobial use were recorded. RESULTS: Total 45 patients were included with median age of 12 years. The CR rate of the cohort was 66% and 54% of patients were MRD negative. The estimated 2-year event-free survival (EFS) and overall survival (OS) were 29% (±7%) and 34% (±7%), respectively. The presence of fever at relapse was associated with inferior CR rate (P = .001), positive MRD (P = .01), and inferior EFS (P = .02), while not achieving nadir absolute neutrophil count of zero during induction was associated with inferior CR rate (P = .03) and inferior OS (P = .04). Approximately all patients developed ≥Grade 3 cytopenia and febrile neutropenia. Twenty-six (59%) patients required hospitalization for management of toxicity and there were four (9%) deaths attributed to infection. CONCLUSION: ADE is an effective induction regimen for pediatric AML patients at the first relapse with reasonable toxicity profile. Outpatient administration of the regimen is feasible in the presence of proper support structure and rigorous follow up.

Real world data analysis of next generation sequencing and protein expression in metastatic breast cancer patients.

Next generation sequencing (NGS) together with protein expression analysis is back bone of molecularly targeted therapy in precision medicine. Our retrospective study shows our experience with NGS of 324 genes in combination with protein expression in patients with advanced breast cancer (aBC). The primary purpose was to analyze the prevalence of individual genetic alterations combined with protein expression to define potential targets for an individualized therapy. Between April 2018 and September 2019, 41 patients with aBC were offered a NGS test. The test was used to detect clinically relevant genomic alterations and to support further targeted therapy decisions. Hormone receptors, ERBB2 of tumors and PD-L1 was stained by immunohistochemistry. The data was recorded up to September 2019. After prior consent 41 results were available for further analysis. The most common BC subtypes were triple-negative (n = 16), HR+/ERBB2- (n = 15), and ERBB2+ (n = 9), with one missing data of the primary tumor. 27 patients had more than one genetic alteration. The most common alterations were PIK3CA (n = 14) and ERBB2 alterations (n = 11). Followed by ESR1 (n = 10), FGFR1 (n = 7) and PTEN (n = 7). 68% of the alterations were clinically relevant (tier I and II of ESCAT classification). The most common treatment recommendation was ERBB2-directed therapy (single or double blockade, trastuzumab emtansine and lapatinib) followed by alpelisib in combination with fulvestrant. Comprehensive genomic profiling combined with protein expression analysis in aBC allowed a guided personalized therapy for half of our patients. So far there are no well-defined tools allowing interpretations of genomic alterations detected by NGS in combination with protein expression and other factors.

Changes in Mandibular Third Molar Angulation in High-anchorage Extraction vs Non-extraction Orthodontic Treatment: A Prospective Study.

AIM AND OBJECTIVE: The study aimed to compare the prospective changes in mandibular third molar angulation in high anchorage cases treated with first premolar extractions vs non-extraction orthodontic treatment. MATERIALS AND METHODS: The sample consisted of 56 nongrowing patients: Group I had 26 patients with a high anchorage requirement who underwent first premolar extractions and group II had 30 patients who underwent non-extraction treatment. Pretreatment, mid-treatment, and posttreatment panoramic radiographs were obtained for group I and pretreatment and posttreatment for group II. Angle between M2 (second molar)-horizontal reference plane (HRP), M3 (third molar)-HRP, and M2-M3 were measured bilaterally. Data were analyzed using Student t test and ANOVA test (p value < 0.05). RESULTS: Statistically significant increase was found between the pretreatment, mid-treatment, and posttreatment values of M2-M3 in group I (p value = 0.02 R and p value = 0.049 L) and between pretreatment to posttreatment values of M2-HRP in group II bilaterally (p value = 0.001). Significant increase was found in the M2-M3 angulations in group II on the right side (p value = 0.036). M3-HRP decreased in group I without reaching statistical significance. No statistically significant intergroup differences were found between the two groups in relation to M2-HRP, M3-HRP, and M2-M3 angulations. CONCLUSION: M2-M3 angulations increased significantly bilaterally in group I and on the right side in group II, indicating worsening of third molar angulation. M3-HRP worsened in group I without reaching statistical significance. Extraction therapy in high anchorage cases does not lead to an improvement in third molar angulation. CLINICAL SIGNIFICANCE: The extraction of first premolars in high anchorage cases does not lead to an improvement in the angulation of mandibular third molars; moreover, the angulation worsened with extraction therapy. Prospective orthodontic patients need to be cautioned against any improvement in mesioangular impaction of mandibular third molars in high anchorage premolar extraction cases.

Primary orofacial granulomatous involvement of lip and gingiva only: A diagnostic challenge.

Wiesenfeld described orofacial granulomatosis (OFG) as a group of noncaseating granulomatous disorders affecting the different parts of the body including oral and maxillofacial region, which can have variable etiology. The involvement of oral and maxillofacial region can be exclusive or primary before the involvement of other organs. OFG is a multifactorial clinicopathologic disorder, and its clinical manifestation mimics the various systemic conditions making its diagnosis tough for a dentist. Delay in diagnosis and evaluation of OFG may cause indurated, swollen lips that may compromise cosmetic face value, speaking, and eating functions, and other possible systemic granulomatous disorders can be missed. Here, we present a case of OFG with tooth-associated infection without any recognizable systemic cause. This article presents the diagnostic challenges that a dentist may face in diagnosing such cases, and thus treatment planning should be of the multidisciplinary approach. Regular follow-up is very essential for proper care and management.