Endovascular Interventions for Peripheral Artery Disease: A Contemporary Review.

PURPOSE OF REVIEW: Peripheral artery disease (PAD) is an increasingly prevalent but frequently underdiagnosed condition that can be associated with high rates of morbidity and mortality. While an initial noninvasive approach is the cornerstone of management, revascularization is often pursued for patients with treatment-refractory claudication or chronic limb-threatening ischemia (CLTI). In this review, we discuss the current state of endovascular interventions for PAD and explore the many new emerging technologies. RECENT FINDINGS: The last decade has resulted in numerous advances in PAD interventions including the ongoing evolution of drug-coated devices, novel approaches to complex lesions, and contemporary evidence from large clinical trials for CLTI. Advances in endovascular management have allowed for increasingly complex lesions to be tackled percutaneously. Future directions for the field include the continued evolution in device technology, continued development of state-of-the-art techniques to revascularization of complex lesions, and increased collaboration between a largely multidisciplinary field.

Water-soluble organic aerosols over South Asia - Seasonal changes and source characteristics.

Water-soluble organic carbon (WSOC) has been identified as a key component in atmospheric aerosols due to its ability to act as cloud condensation nuclei (CCN) owing to their highly hygroscopic nature. This paper discusses about the spatio-temporal variability in WSOC mass concentration, sources (primary and secondary contributions), the role of long-range air-mass transport in modulating their abundance, at distinct sectors over South Asia. We found from our observations that, photochemical ageing of primary organic aerosols that are derived from biomass emissions, significantly contribute to the total WSOC budget over South Asia. The wide range of water-soluble compounds released by biomass burning can contribute directly to the WSOC fraction or undergo further atmospheric processing, such as oxidation or ageing, leading to the formation of additional WSOC. WSOC/OC (organic carbon) ratio and the correlation between the WSOC and secondary organic carbon (SOC) are used for assessing the contribution from secondary sources. The three different ratios are used to delineate different source processes; OC/EC (elemental carbon) for source identification, WSOC/OC for long-range atmospheric transport (ageing) and WSOC/SOC to understand the primary and secondary contribution of WSOC. The present investigation revealed that, the primary OC that have undergone significant chemical processing as a result of long-range transport have a substantial influence on WSOC formation over South Asia, especially in Indo Gangetic Plain outflow regions such as southern peninsular and adjacent marine regions. Overall, oxidation and ageing of primary organic aerosols emitted from biomass burning was found to serve as an important source of WSOC over South Asia.

Molecular docking study on europium nanoparticles and mussel adhesive protein for effective detection of latent fingerprints.

Background: Reflecting on the difficulty of finding the evidence of latent fingerprints on wet and rough surfaces, scientists need to visualise those fingermarks without any background interference and stable adhesion of visualising material over the fingermark residues.Objective: To stabilize the interaction with the fingermarks, the synthesized nanoparticles were conjugated with a highly adhesive biopolymer, Mussel Adhesive Protein (MAP) which can effectively interact with fingerprint deposits.Material and Methods: Rare earth metal, europium oxide and nanoparticles were used as a visualisation material to get high contrast and reduced background interference-based fingerprints. To stabilise the interaction with the fingermarks, the synthesised nanoparticles were conjugated with highly adhesive biopolymer, Mussel Adhesive Protein (MAP) which can effectively interacts with fingerprint deposits. A molecular docking study was done using Auto-Dock to find the binding affinity between the metal nanoparticle and the protein. Further, the stability of the bioconjugated with fingerprint residues was analysed by protein-protein interaction study through patch dock and PDB Sum.Results: The docking analysis between europium and nanoparticles with MAP was found to be -8.77 kcal/mol and -47.49 kcal/mol respectively. Protein-protein interaction studies showed a highest affinity for dermcidin and keratin with a binding affinity of -16.76 kcal/mol and -24.76 kcal/mol respectively.Conclusions: The docking studies showed an efficient interaction between the synthesised molecules and the fingermark residues. Results of these interaction studies proved that this bio-conjugated complex can be explored for efficient visualisation of low intensified fingermarks.

State-of-the-Art Endovascular Therapies for the Femoropopliteal Segment: Are We There Yet?

Peripheral arterial disease is an increasingly prevalent condition with significant associated morbidity, mortality, and health care expenditure. Endovascular interventions are appropriate for most patients with either ongoing symptoms of intermittent claudication despite lifestyle and medical optimization or chronic limb-threatening ischemia. The femoropopliteal segment is the most common arterial culprit responsible for claudication and the most commonly revascularized segment. Endovascular approaches to revascularization of the femoropopliteal segment are advancing with an evolving landscape of techniques for arterial access, device-based therapies, vessel preparation, and intraprocedural imaging. These advances have been marked by debate and controversy, notably related to the safety of paclitaxel-based devices and necessity of atherectomy. In this review, we provide a critical overview of the current evidence, practice patterns, emerging evidence, and technological advances for endovascular intervention of the femoropopliteal arterial segment.

Appropriate Use of Intravascular Ultrasound During Arterial and Venous Lower Extremity Interventions.

BACKGROUND: There has been growing use of intravascular ultrasound (IVUS) during lower extremity arterial and venous revascularization. Observational data suggest that the use of IVUS can improve periprocedural and long-term outcomes, but largescale prospective data remain limited. Consensus opinion regarding the appropriate use of IVUS during peripheral intervention is needed. OBJECTIVES: The purpose of this consensus document is to provide guidance on the appropriate use of IVUS in various phases of peripheral arterial and venous interventions. METHODS: A 12-member writing committee was convened to derive consensus regarding the appropriate clinical scenarios for use of peripheral IVUS. The group iteratively created a 72-question survey representing 12 lower extremity arterial interventional scenarios. Separately, a 40-question survey representing 8 iliofemoral venous interventional scenarios was constructed. Clinical scenarios were categorized by interventional phases: preintervention, intraprocedure, and postintervention optimization. Thirty international vascular experts (15 for each survey) anonymously completed the survey instrument. Results were categorized by appropriateness using the median value and disseminated to the voting panel to reevaluate for any disagreement. RESULTS: Consensus opinion concluded that IVUS use may be appropriate during the preintervention phase for evaluating the etiology of vessel occlusion and plaque morphology in the iliac and femoropopliteal arteries. IVUS was otherwise rated as appropriate during iliac and femoropopliteal revascularization in most other preintervention scenarios, as well as intraprocedural and postprocedural optimization phases. IVUS was rated appropriate in all interventional phases for the tibial arteries. For iliofemoral venous interventions, IVUS was rated as appropriate in all interventional phases. CONCLUSIONS: Expert consensus can help define clinical procedural scenarios in which peripheral IVUS may have value during lower extremity arterial and venous intervention while additional prospective data are collected.

Intravascular ultrasound in peripheral venous and arterial interventions: A contemporary systematic review and grading of the quality of evidence.

Although angiography has been the primary imaging modality used in peripheral vascular intervention, this technique has major limitations due to the evaluation of three-dimensional vessels in two dimensions. Intravascular ultrasound (IVUS) is an important adjunctive tool that can address some of these limitations. This systematic review assesses the appropriateness of IVUS as an imaging modality for guiding peripheral intervention through evidence collection and clinical appraisal of studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a cohort of 48 studies (29 arterial; 19 venous) detailing IVUS use in peripheral vascular intervention were extracted. Qualitative assessment of the studies evaluated pre- and postprocedure efficacy of IVUS and revealed that IVUS-guided peripheral intervention in arterial and venous diagnosis and treatment was superior to other imaging techniques alone. Each study in the cohort was further assessed for reliability and validity using the Oxford Centre for Evidence Based Medicine (CEBM) level of evidence scale. The majority of both arterial (79.3%) and venous (73.7%) studies received a 2b rating, the second highest level of evidence rating. The evidence to date indicates that IVUS results in better clinical outcomes overall and should be more widely adopted as an adjunctive imaging modality during peripheral intervention. (PROSPERO Registration No.: CRD42021232353).

Role of Neural Stem Cells and Vitamin D Receptor (VDR)-Mediated Cellular Signaling in the Mitigation of Neurological Diseases.

Specific stem cell-based therapies for treating Alzheimer's disease, Parkinson's disease, and schizophrenia are gaining importance in recent years. Accumulating data is providing further support by demonstrating the efficacy of neural stem cells in enhancing the neurogenesis in the aging brain. In addition to stem cells, recent studies have shown the efficacy of supplementing vitamin D in promoting neurogenesis and neuronal survival. Studies have also demonstrated the presence of mutational variants and single-nucleotide polymorphisms of the vitamin D receptor (VDR) in neurological disorders; however, implications of these mutations in the pathophysiology and response to drug treatment are yet to be explored. Hence, in this article, we have reviewed recent reports pertaining to the role of neural stem cells and VDR-mediated cellular signaling cascades that are involved in enhancing the neurogenesis through Wnt/ß-catenin and Sonic Hedgehog pathways. This review benefits neurobiologists and pharmaceutical industry experts to develop stem cell-based and vitamin D-based therapies to better treat the patients suffering from neurological diseases.

Outcomes Associated With Peripheral Artery Disease in Myocardial Infarction With Cardiogenic Shock.

BACKGROUND: Mortality rates for patients presenting with acute myocardial infarction (AMI) and cardiogenic shock (CS) remain high despite advances in revascularization strategies and mechanical circulatory support (MCS) devices. OBJECTIVES: This study sought to elucidate the association between comorbid lower extremity peripheral artery disease (PAD) and outcomes in CS and AMI. METHODS: PAD status was defined in Medicare beneficiaries hospitalized with CS and AMI from October 1, 2015 to June 30, 2018. Primary outcomes ascertained through December 31, 2018 included in- and out-of-hospital mortality. Secondary outcomes included bleeding, amputation, stroke, and lower extremity revascularization. Multivariable regression models with adjustment for confounders were used to estimate risk. Subgroup analyses included patients treated with MCS and those who underwent coronary revascularization. RESULTS: Among 71,690 patients, 5.9% (N = 4,259) had PAD. Mean age was 77.8 ± 7.9 years, 58.7% were male, and 84.3% were White. Cumulative in-hospital mortality was 47.2%, with greater risk among those with PAD (56.3% vs 46.6% without PAD; adjusted OR: 1.50; 95% CI: 1.40-1.59). PAD patients also had greater risk of in-hospital amputation (1.6% vs 0.2%; adjusted OR: 7.0; 95% CI: 5.26-9.37) and out-of-hospital mortality (67.9% vs 40.7%; adjusted HR: 1.78; 95% CI: 1.67-1.90). MCS was less frequently utilized in PAD patients (21.5% vs 38.6% without PAD; P < 0.001) and was associated with higher mortality, need for lower extremity revascularization, and amputation risk. Findings were consistent in patients who underwent coronary revascularization. CONCLUSIONS: Among patients presenting with AMI and CS, PAD was associated with worse limb outcomes and survival. In addition to lower MCS utilization rates, those with PAD who received MCS had increased mortality, lower extremity revascularization, and amputation rates.

Pre-Existing Autoimmune Disease Increases the Risk of Cardiovascular and Noncardiovascular Events After Immunotherapy.

Background: The use of immune checkpoint inhibitors (ICI) is associated with cardiovascular (CV) events, and patients with pre-existing autoimmune disease are at increased CV risk. Objectives: The aim of this study was to characterize the risk for CV events in patients with pre-existing autoimmune disease post-ICI. Methods: This was a retrospective study of 6,683 patients treated with ICIs within an academic network. Autoimmune disease prior to ICI was confirmed by chart review. Baseline characteristics and risk for CV and non-CV immune-related adverse events were compared with a matched control group (1:1 ratio) of ICI patients without autoimmune disease. Matching was based on age, sex, history of coronary artery disease, history of heart failure, and diabetes mellitus. CV events were a composite of myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, stroke, transient ischemic attack, deep venous thrombosis, pulmonary embolism, or myocarditis. Univariable and multivariable Cox proportional hazards models were used to determine the association between autoimmune disease and CV events. Results: Among 502 patients treated with ICIs, 251 patients with and 251 patients without autoimmune disease were studied. During a median follow-up period of 205 days, there were 45 CV events among patients with autoimmune disease and 22 CV events among control subjects (adjusted HR: 1.77; 95% CI: 1.04-3.03; P = 0.0364). Of the non-CV immune-related adverse events, there were increased rates of psoriasis (11.2% vs 0.4%; P < 0.001) and colitis (24.3% vs 16.7%; P = 0.045) in patients with autoimmune disease. Conclusions: Patients with autoimmune disease have an increased risk for CV and non-CV events post-ICI.

Evaluation of the Central Effects of Systemic Lentiviral-Mediated Leptin Delivery in Streptozotocin-Induced Diabetic Rats.

Type 1 diabetes (T1D) is characterized by hyperphagia, hyperglycemia and activation of the hypothalamic-pituitary-adrenal (HPA) axis. We have reported previously that daily leptin injections help to alleviate these symptoms. Therefore, we hypothesized that leptin gene therapy could help to normalize the neuroendocrine dysfunction seen in T1D. Adult male Sprague Dawley rats were injected i.v. with a lentiviral vector containing the leptin gene or green fluorescent protein. Ten days later, they were injected with the vehicle or streptozotocin (STZ). HPA function was assessed by measuring norepinephrine (NE) levels in the paraventricular nucleus (PVN) and serum corticosterone (CS). Treatment with the leptin lentiviral vector (Lepvv) increased leptin and insulin levels in non-diabetic rats, but not in diabetic animals. There was a significant reduction in blood glucose levels in diabetic rats due to Lepvv treatment. Both NE levels in the PVN and serum CS were reduced in diabetic rats treated with Lepvv. Results from this study provide evidence that leptin gene therapy in STZ-induced diabetic rats was able to partially normalize some of the neuroendocrine abnormalities, but studies with higher doses of the Lepvv are needed to develop this into a viable option for treating T1D.

Aortic Stiffness: Epidemiology, Risk Factors, and Relevant Biomarkers.

Aortic stiffness (AoS) is a maladaptive response to hemodynamic stress and both modifiable and non-modifiable risk factors, and elevated AoS increases afterload for the heart. AoS is a non-invasive marker of cardiovascular health and metabolic dysfunction. Implementing AoS as a diagnostic tool is challenging as it increases with age and varies amongst races. AoS is associated with lifestyle factors such as alcohol and smoking, as well as hypertension and comorbid conditions including metabolic syndrome and its components. Multiple studies have investigated various biomarkers associated with increased AoS, and this area is of particular interest given that these markers can highlight pathophysiologic pathways and specific therapeutic targets in the future. These biomarkers include those involved in the inflammatory cascade, anti-aging genes, and the renin-angiotensin aldosterone system. In the future, targeting AoS rather than blood pressure itself may be the key to improving vascular health and outcomes. In this review, we will discuss the current understanding of AoS, measurement of AoS and the challenges in interpretation, associated biomarkers, and possible therapeutic avenues for modulation of AoS.

Association between incidental statin use and skeletal myopathies in patients treated with immune checkpoint inhibitors.

OBJECTIVES: Skeletal myopathies are highly morbid, and in rare cases even fatal, immune-related adverse events (irAE) associated with immune checkpoint inhibitors (ICI). Skeletal myopathies are also a recognized statin-associated side effect. It is unknown whether concurrent use of statins and ICIs increases the risk of skeletal myopathies. METHODS: This was a retrospective cohort study of all patients who were treated with an ICI at a single academic institution (Massachusetts General Hospital, Boston, MA, USA). The primary outcome of interest was the development of a skeletal myopathy. The secondary outcome of interest was an elevated creatine kinase level (above the upper limit of normal). RESULTS: Among 2757 patients, 861 (31.2%) were treated with a statin at the time of ICI start. Statin users were older, more likely to be male and had a higher prevalence of cardiovascular and non-cardiovascular co-morbidities. During a median follow-up of 194 days (inter quartile range 65-410), a skeletal myopathy occurred in 33 patients (1.2%) and was more common among statin users (2.7 vs. 0.9%, P < 0.001). Creatine kinase (CK) elevation was present in 16.3% (114/699) and was higher among statin users (20.0 vs. 14.3%, P = 0.067). In a multivariable Cox model, statin therapy was associated with a >2-fold higher risk for skeletal myopathy (HR, 2.19; 95% confidence interval, 1.07-4.50; P = 0.033). CONCLUSION: In this large cohort of ICI-treated patients, a higher risk was observed for skeletal myopathies and elevation in CK levels in patients undergoing concurrent statin therapy. Prospective observational studies are warranted to further elucidate the potential association between statin use and ICI-associated myopathies.

Use of a Clinical Audit System in Implementing Surviving Sepsis Campaign Guidelines in Patients With Peritonitis.

Background Sepsis is the predominant cause of morbidity and mortality in patients with peritonitis. "Surviving Sepsis Campaign" (SSC) is an international effort in reducing mortality based on evidence-based guidelines. This study aims to assess the impact of audit-based feedback in a Plan-Do-Study-Act (PDSA) format on improving the implementation of the SSC guidelines in patients with generalized peritonitis at our center. Methods This prospective observational study was conducted in four audit cycles in PDSA format. Multi-departmental inputs were taken to suggest modifications in practice. A questionnaire-based analysis of reasons for non-compliance was performed to find out the opinions and reasons for non-compliance. Morbidity, mortality, and the length of ICU and hospital stay among these patients were also analyzed. Results Baseline compliance with intravenous (IV) bolus administration, central venous pressure (CVP)-guided fluids, and inotropes support when indicated were 100%. Over the course of the three audit cycles, statistically significant improvement in compliance was noted for obtaining blood cultures before antibiotics, antibiotic administration within three hours of presentation, and serum lactate measurement. Overall bundle compliance improved from 9.2% to 64.7% by the end of audit cycle III. Conclusions This study demonstrates that audit-based feedback is a dependable means of improving compliance with SSC guidelines. It brings about improvement by educating users, modifying their behavior through feedback, and enhances process improvement by identifying and correcting systemic deficiencies in the organization.

Dynamics of coupled modified Rössler oscillators: The role of nonisochronicity parameter.

The amplitude-dependent frequency of the oscillations, termed nonisochronicity, is one of the essential characteristics of nonlinear oscillators. In this paper, the dynamics of the Rössler oscillator in the presence of nonisochronicity is examined. In particular, we explore the appearance of a new fixed point and the emergence of a coexisting limit-cycle and quasiperiodic attractors. We also describe the sequence of bifurcations leading to synchronized, desynchronized attractors and oscillation death states in the coupled Rössler oscillators as a function of the strength of nonisochronicity and coupling parameters. Furthermore, we characterize the multistability of the coexisting attractors by plotting the basins of attraction. Our results open up the possibilities of understanding the emergence of coexisting attractors and into a qualitative change of the collective states in coupled nonlinear oscillators in the presence of nonisochronicity.

Hereditary Medullary Thyroid Carcinoma: Genotype, Phenotype and Outcomes in a North Indian Cohort.

BACKGROUND: Aggressiveness of hereditary medullary thyroid carcinoma (hMTC) has been conventionally described to correlate with American Thyroid Association (ATA) risk groups based on RET mutations. Recent evidence increasingly contradicts this notion. We studied the RET genotype and its correlation with disease phenotype and survival outcomes in a cohort of hMTC patients. METHODS: In a retrospective cohort of 55 hMTC patients from 23 families treated at a north Indian tertiary care institute over 15-years, RET genotype was correlated with disease phenotype (clinical, biochemical, and pathological attributes) and outcomes in terms of biochemical cure (normalization of serum calcitonin), structural cure, overall survival (OS) and disease specific survival (DSS). RESULTS: Forty-nine patients had Multiple Endocrine Neoplasia (MEN)-type 2A syndrome, 02 had MEN-2B, and 4 had familial MTC. Two patients belonged to highest ATA risk, 41 to high-risk, and 12 to moderate risk categories. Age of the patients or stage of disease at presentation did not differ significantly between the ATA risk groups. Though the baseline serum calcitonin was significantly higher in highest risk category, the biochemical cure rates were not significantly different. At a median follow up of 48 months (Inter-quartile range 18-84, range 12-192) structural cure rates in ATA moderate and high risk groups were significantly higher than highest risk group (p = 0.04). No significant difference in OS between the three ATA groups of hMTC among the patients who underwent surgical treatment was observed (p = 0.098). CONCLUSIONS: The ATA moderate and high risk groups have better structural cure rates compared to ATA highest risk group. The biochemical cure and overall survival rates did not significantly differ between ATA risk-groups, and were impacted by the disease stage at presentation. The current ATA risk-groups do not reliably predict the outcomes in terms of biochemical cure and survival in hMTC patients.

Experimental and Computational Investigations of the Tropospheric Photooxidation Reactions of 1,1,1,3,3,3-Hexafluoro-2-Methyl-2-Propanol Initiated by OH Radicals and Cl Atoms.

The gas-phase kinetics for the reactions of OH radicals and Cl atoms with 1,1,1,3,3,3-hexafluoro-2-methyl-2-propanol (HF2M2P) were measured at temperatures between 268 and 363 K using the relative rate experimental technique. Methane and acetonitrile were used as reference compounds to measure the rate coefficients of the title reactions. For the reactions of HF2M2P with OH radicals and Cl atoms, the rate coefficients were measured to be (7.07 ± 1.21) × 10-15 and (2.85 ± 0.54) × 10-14 cm3 molecule-1 s-1, respectively, at 298 K. The obtained Arrhenius expressions for the reactions of HF2M2P with OH radicals and Cl atoms are kHF2M2P + OHExp - (268 - 363 K) = (7.84 ± 0.75) × 10-14 exp [-(717 ± 59)/T] and kHF2M2P + ClExp - (268 - 363 K) = (3.21 ± 0.45) × 10-12 exp [-(1395 ± 83)/T] cm3 molecule-1 s-1. In addition to the experimental measurements, computational kinetic calculations were also performed for the title reactions at the M06-2X/MG3S//M06-2X/6-31 + G(d,p) level of theory using advanced methods such as the canonical variational transition-state theory coupled with small curvature tunneling corrections at temperatures between 200 and 400 K. Theoretical calculations reveal that the H-abstraction from the CH3 group is a more favorable reaction channel than that from the OH group. Thermochemistry, branching ratios, cumulative atmospheric lifetime, global warming potential, acidification potential, and photochemical ozone creation potential of HF2M2P were calculated in the present investigation.

Low-cost Fluorescein as an Alternative to Radio-colloid for Sentinel Lymph Node Biopsy-a Prospective Validation Study in Early Breast Cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) using radio-pharmaceutical (RP) and a blue dye is gold standard for axillary staging in clinically node-negative early breast cancer. High costs and limited availability of RP and/or gamma probe are major deterrents in performing SLNB in developing countries. Fluorescence-guided SLNB can obviate the need for RP and gamma probe. Fluorescein is an inexpensive fluorescent lymphatic tracer. In this study, we compared SLN identification rate (SLN-IR) and false negative rates (FNR) of fluorescein-guided SLNB and radio-guided SLNB using 99mTc-Sulfur-colloid, in isolation, or in combination with methylene blue dye (MBD). METHODS: Sixty-five cN0 early and large operable breast cancer patients underwent validation SLNB using fluorescein (and blue LED light), 99mTc-Sulfur-colloid (and gamma probe) and MBD. Inj Fluorescein 4% was injected, 1 ml each peri-tumoral and sub-areolar five minutes before axillary incision. Axillary dissection was performed irrespective of SLNB histology. The SLN-IR and FNR with various tracers and their combinations were compared. RESULTS: The mean number of SLNs identified was 3.5 ± 1.8 (range 1-6). The SLN-IR using RP alone was 94%, fluorescein alone was 92%, and MBD alone was 82%. The SLN-IR using fluorescein plus MBD combination was 95.4%, compared to 97% using MBD plus RP combination. FNR was 6.3% using fluorescein plus MBD, as well as RP plus MBD combinations. CONCLUSIONS: SLN-IR of > 90% and SLN-FNR of < 10% using fluorescein plus MBD combination are in acceptable range, and are comparable to that of RP plus MBD combination. Fluorescein can replace RP for performing SLNB, in combination with MBD.

Genetic Profile of Indian Pheochromocytoma and Paraganglioma Patients - A Single Institutional Study.

BACKGROUND AND AIMS: Pheochromocytomas (PCCs) and Paragangliomas (PGL) are rare catecholamine producing tumors that may present in sporadic or familial settings. Despite vast strides in understanding of PCC/PGL genetics in the last two decades, there is a dearth of information from India. The aim here is to study the prevalence of genetic mutations in Indian PCC/PGL patients. SETTINGS AND DESIGN: Tertiary care academic hospital; prospective study. METHODS: 50 histopathologically diagnosed PCC/PGL patients formed the study group. Clinical, biochemical, pathological attributes and outcomes were documented and the phenotype was compared to the genotype. Succinyl dehydrogenase (SDH), Re-Arranged during Transfection (RET), Von-Hippel-Lindau (VHL) and NeuroFibromatosis-1 (NF1) mutations were studied. Additionally, immunohistochemisty for SDHB was also done, and the results compared to mutational analysis of SDH by MLPA (Multiplex Ligation-dependent Probe Activation). STATISTICAL ANALYSIS: Independent samples t-test and Fisher's exact test were used as appropriate. P values ≤0.05 were considered statistically significant. RESULTS: The mean age was 34.3 years. Of the 50 patients, 27 were males and 23 females. 10 patients (20%) in all were detected to have a genetic mutation. 6 patients possessed a RET mutation, while two had VHL mutations. No patient presented with a NF1 mutation. 2 patients had a SDH mutation, and Immunohistochemistry for SDHB correlated with mutational analysis for these patients. CONCLUSIONS: The proportion of patients with a familial variant of PCC/PGL is more than what the historic "Rule of Ten" suggests. Our study found that one in five patients have a genetic mutation. PCC/PGL patients with genetic mutations not only require more stringent follow-up, but also screening of family members.