Synthetic data as an investigative tool in hypertension and renal diseases research

There is a growing body of clinical research on the utility of synthetic data derivatives,an emerging research tool in medicine.In nephrology,clinicians can use machine learning and artificial intelligence as powerful aids in their clinical decision-making while also preserving patient privacy.This is especially important given the epidemiology of chronic kidney disease,renal oncology,and hypertension worldwide.However,there remains a need to create a framework for guidance regarding how to better utilize synthetic data as a practical application in this research.

A new perspective on intervertebral disc calcification—from bench to bedside

Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.Moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

Optimal timing and route of nutritional support after esophagectomy: A review of the literature

Some controversy surrounds the postoperative feeding regimen utilized in patients who undergo esophagectomy.Variation in practices during the perioperative period exists including the type of nutrition started,the delivery route,and its timing.Adequate nutrition is essential for this patient population as these patients often present with weight loss and have altered eating patterns after surgery,which can affect their ability to regain or maintain weight.Methods of feeding after an esophagectomy include total parenteral nutrition,nasoduodenal/nasojejunal tube feeding,jejunostomy tube feeding,and oral feeding.Recent evidence suggests that early oral feeding is associated with shorter LOS,faster return of bowel function,and improved quality of life.Enhanced recovery pathways after surgery pathways after esophagectomy with a component of early oral feeding also seem to be safe,feasible,and cost-effective,albeit with limited data.However,data on anastomotic leaks is mixed,and some studies suggest that the incidence of leaks may be higher with early oral feeding.This risk of anastomotic leak with early feeding may be heavily modulated by surgical approach.No definitive data is currently available to definitively answer this question,and further studies should look at how these early feeding regimens vary by surgical technique.This review aims to discuss the existing literature on the optimal route and timing of feeding after esophagectomy.

Transplantation of stem cell-derived astrocytes for the treatment of amyotrophic lateral sclerosis and spinal cord injury

Neglected for years, astrocytes are now recognized to fulfill and support many, if not all, homeostatic functionsof the healthy central nervous system(CNS). During neurodegenerative diseases such as amyotrophic lateral sclerosis(ALS) and spinal cord injury(SCI), astrocytes in the vicinity of degenerating areas undergo both morphological and functional changes that might compromise their intrinsic properties. Evidence from human and animal studies show that deficient astrocyte functions or loss-of-astrocytes largely contribute to increased susceptibility to cell death for neurons, oligodendrocytes and axons during ALS and SCI disease progression. Despite exciting advances in experimental CNS repair, most of current approaches that are translated into clinical trials focus on the replacement or support of spinal neurons through stem cell transplantation, while none focus on the specific replacement of astroglial populations. Knowing the important functions carried out by astrocytes in the CNS, astrocyte replacement-based therapies might be a promising approach to alleviate overall astrocyte dysfunction, deliver neurotrophic support to degenerating spinal tissue and stimulate endogenous CNS repair abilities. Enclosed in this review, we gathered experimental evidence that argue in favor of astrocyte transplantation during ALS and SCI. Based on their intrinsic properties and according to the cell type transplanted, astrocyte precursors or stem cell-derived astrocytes promote axonal growth, support mechanisms and cells involved in myelination, are able to modulate the host immune response, deliver neurotrophic factors and provide protective molecules against oxidative or excitotoxic insults, amongst many possible benefits. Embryonic or adult stem cells can even be genetically engineered in order to deliver missing gene products and therefore maximize the chance of neuroprotection and functional recovery. However, before broad clinical translation, further preclinical data on safety, reliability and therapeutic efficiency should be collected. Although several technical challenges need to be overcome, we discuss the major hurdles that have already been met or solved by targeting the astrocyte populationin experimental ALS and SCI models and we discuss avenues for future directions based on latest molecular findings regarding astrocyte biology.

Postoperative delirium after major orthopedic surgery

BACKGROUND Postoperative delirium(POD)is one of the most common complications in older adult patients undergoing elective surgery.Few studies have compared,within the same institution,the type of surgery,risk factors and type of anesthesia and analgesia associated with the development of POD.AIM To investigate the following three questions:(1)What is the incidence of POD after non-ambulatory orthopedic surgery at a high-volume orthopedic specialty hospital?(2)Does surgical procedure influence incidence of POD after nonambulatory orthopedic surgery?And(3)For POD after non-ambulatory orthopedic surgery,what are modifiable risk factors?METHODS A retrospective cohort study was conducted of all non-ambulatory orthopedic surgeries at a single orthopedic specialty hospital between 2009 and 2014.Patients under 18 years were excluded from the cohort.Patient characteristics and medical history were obtained from electronic medical records.Patients with POD were identified using International Classification of Diseases,9^th Revision(ICD-9)codes that were not present on admission.For incidence analyses,the cohort was grouped into total hip arthroplasty(THA),bilateral THA,total knee arthroplasty(TKA),bilateral TKA,spine fusion,other spine procedures,femur/pelvic fracture,and other procedures using ICD-9 codes.For descriptive and regression analyses,the cohort was grouped,using ICD-9 codes,into THA,TKA,spinal fusions,and all procedures.RESULTS Of 78492 surgical inpatient surgeries,the incidence from 2009 to 2014 was 1.2%with 959 diagnosed with POD.The incidence of POD was higher in patients undergoing spinal fusions(3.3%)than for patients undergoing THA(0.8%);THA patients had the lowest incidence.Also,urgent and/or emergent procedures,defined by femoral and pelvic fractures,had the highest incidence of POD(7.2%)than all other procedures.General anesthesia was not seen as a significant risk factor for POD for any procedure type;however,IV patient-controlled analgesia was a significant risk factor for patients undergoing THA[Odds ratio(OR)=1.98,95%confidence interval(CI):1.19 to 3.28,P=0.008].Significant risk factors for POD included advanced age(for THA,OR=4.9,95%CI:3.0-7.9,P<0.001;for TKA,OR=2.16,95%CI:1.58-2.94,P<0.001),American Society of Anesthesiologists score of 3 or higher(for THA,OR=2.01,95%CI:1.33-3.05,P<0.001),multiple medical comorbidities,hyponatremia(for THA,OR=2.36,95%CI:1.54 to 3.64,P<0.001),parenteral diazepam(for THA,OR=5.05,95%CI:1.5-16.97,P=0.009;for TKA,OR=4.40,95%CI:1.52-12.75,P=0.007;for spine fusion,OR=2.17,95%CI:1.19-3.97,P=0.01),chronic opioid dependence(for THA,OR=7.11,95%CI:3.26-15.51,P<0.001;for TKA,OR=2.98,95%CI:1.38-6.41,P=0.005)and alcohol dependence(for THA,OR=5.05,95%CI:2.72-9.37,P<0.001;for TKA,OR=6.40,95%CI:4.00-10.26,P<0.001;for spine fusion,OR=6.64,95%CI:3.72-11.85,P<0.001).CONCLUSION POD is lower(1.2%)than previously reported;likely due to the use of multimodal regional anesthesia and early ambulation.Both fixed and modifiable factors are identified.

Surgeon's perspective on short bowel syndrome: Where are we?

Short bowel syndrome(SBS) is due to a massive loss of small bowel: the reduction of gut function is below the minimum necessary to maintain health(in adults) and growth(in children) so intravenous supplementation is required. Parenteral nutrition represents the milestone of treatment and surgical attempts should be limited only when the residual bowel is sufficient to increase absorption, reducing diarrhea and slowing the transit time of nutrients, water and electrolytes. The surgical techniques lengthen the bowel(tapering it) or reverse a segment of it: developed in children, nowadays are popular also among adults. The issue is mainly represented by the residual length of the small bowel where ileum has shown increased adaptive function than jejunum, but colon should be considered because of its importance in the digestive process. These concepts have been translated also in intestinal transplantation, where a colonic graft is nowadays widely used and the terminal ileum is the selected segment for a livingrelated donation. The whole replacement by a bowel or multivisceral transplant is still affected by poor long term outcome and must be reserved to a select population of SBS patients, affected by intestinal failure associated with irreversible complications of parenteral nutrition.

Multicenter,randomized study to optimize bowel for colon capsule endoscopy

AIM To assess the cleansing efficacy and safety of a new Colon capsule endoscopy(CCE) bowel preparation regimen.METHODS This was a multicenter,prospective,randomized,controlled study comparing two CCE regimens. Subjects were asymptomatic and average risk for colorectal cancer. The second generation CCE system(Pill Cam? COLON 2;Medtronic,Yoqneam,Israel) was utilized. Preparation regimens differed in the 1 st and 2 nd boosts with the Study regimen using oral sulfate solution(89 m L) with diatrizoate meglumine and diatrizoate sodium solution("diatrizoate solution")(boost 1 = 60 m L,boost 2 = 30 m L) and the Control regimen oral sulfate solution(89 m L) alone. The primary outcome was overall and segmental colon cleansing. Secondary outcomes included safety,polyp detection,colonic transit,CCE completion and capsule excretion ≤ 12 h. RESULTS Both regimens had similar cleansing efficacy for the whole colon(Adequate: Study = 75.9%,Control = 77.3%;P = 0.88) and individual segments. In the Study group,CCE completion was superior(Study = 90.9%,Control = 76.9%;P = 0.048) and colonic transit was more often < 40 min(Study = 21.8%,Control = 4%;P = 0.0073). More Study regimen subjects experienced adverse events(Study = 19.4%,Control = 3.4%;P = 0.0061),and this difference did not appear related to diatrizoate solution. Adverse events were primarily gastrointestinal in nature and no serious adverse events related either to the bowel preparation regimen or the capsule were observed. There was a trend toward higher polyp detection with the Study regimen,but this did not achieve statistical significance for any size category. Mean transit time through the entire gastrointestinal tract,from ingestion to excretion,was shorter with the Study regimen while mean colonic transit times were similar for both study groups.CONCLUSION A CCE bowel preparation regimen using oral sulfate solution and diatrizoate solution as a boost agent is effective,safe,and achieved superior CCE completion.

COVID-19 related biliary injury:A review of recent literature

Since its emergence in 2019,it has become apparent that coronavirus 2019(COVID-19)infection can result in multi systemic involvement.In addition to pulmonary symptoms,hepatobiliary involvement has been widely reported.Extent of hepatic involvement ranges from minor elevation in liver function tests(LFTs)to significant hepatocellular or cholestatic injury.In majority of cases,resolution of hepatic injury or improvement in LFTs is noted as patients recover from COVID-19 infection.However,severe biliary tract injury progressing to liver failure has been reported in patients requiring prolonged intensive care unit stay or mechanical ventilation.Due to the timing of its presentation,this form of progressive cholestatic injury has been referred to as COVID-19 cholangiopathy or post-COVID-19 cholangiopathy,and can result in devastating consequences for patients.COVID-19 cholangiopathy is recognized by dramatic elevation in serum alkaline phosphatase and bilirubin and radiologic evidence of bile duct injury.Cholangiopathy in COVID-19 occurs weeks to months after the initial infection and during the recovery phase.Imaging findings and pathology often resemble bile duct injury associated with primary or secondary sclerosing cholangitis.Etiology of COVID-19 cholangiopathy is unclear.Several mechanisms have been proposed,including direct cholangiocyte injury,vascular compromise,and cytokine release syndromes.This review summarizes existing data on COVID-19 cholangiopathy,including reported cases in the literature,proposed pathophysiology,diagnostic testing,and long-term implications.

The nucleoside antiviral prodrug remdesivir in treating COVID-19 and beyond with interspecies significance

Infectious pandemics result in hundreds and millions of deaths,notable examples of the Spanish Flu,the Black Death and smallpox.The current pandemic,caused by SARS-CoV-2(severe acute respiratory syndrome coronavirus 2),is unprecedented even in the historical term of pandemics.The unprecedentedness is featured by multiple surges,rapid identification of therapeutic options and accelerated development of vaccines.Remdesivir,originally developed for Ebola viral disease,is the first treatment of COVID-19(Coronavirus disease 2019)approved by the United States Food and Drug Administration.As demonstrated by in vitro and preclinical studies,this therapeutic agent is highly potent with a broad spectrum activity against viruses from as many as seven families even cross species.However,randomized controlled trials have failed to confirm the efficacy and safety.Remdesivir improves some clinical signs but not critical parameters such as mortality.This antiviral agent is an ester/phosphorylation prodrug and excessive hydrolysis which increases cellular toxicity.Remdesivir is given intravenously,leading to concentration spikes and likely increasing the potential of hydrolysis-based toxicity.This review has proposed a conceptual framework for improving its efficacy and minimizing toxicity not only for the COVID-19 pandemic but also for future ones caused by remdesivir-sensitive viruses.

Outcomes of Extracorporeal Membrane Oxygenation in Blood Culture Positive Septic Patients

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is commonly used for refractory cardiac or respiratory failure. There are reported cases of successful use of ECMO in patients with septic shock;however, there is a lack of evidence to prove its overall efficacy. Thus, we conducted this study to analyze the relationship between sepsis and ECMO in our own patients. METHODS: 305 patients who were placed on ECMO between 2010 and 2020 were identified within an IRB-approved database. Their clinical outcomes were analyzed with a specific focus on patients who were septic before or during ECMO, defined as a positive blood culture. Group S was composed of patients with a positive blood culture before or during ECMO, while Group N was composed of all patients without a positive blood culture before or during ECMO. The primary outcome compared between groups was ECMO survival rate. RESULTS: Among the 305 patients on ECMO, 58 (19%) were in Group S and 247 (81%) were in Group N. ECMO survival rates were 45% in Group S and 62% in Group N (p = 0.017). CONCLUSION: Of our 305 patients, patients who were septic upon ECMO placement or those who developed sepsis during ECMO had worse ECMO survival rates than non-septic patients. Ultimately, patients who are septic or have a high probability of becoming septic may not be indicated for ECMO placement, and cautious administration of ECMO to these patients may be necessary.

Narrative review-drug delivery in age-related macular degeneration

This narrative review highlights routes of ocular drug delivery for age-related macular degeneration(AMD).AMD is the leading cause of irreversible blindness in industrialized countries and accounts for 8.7%of blindness worldwide.Advanced AMD can be classified into two subtypes:late-stage dry AMD[known as geographic atrophy(GA)]and neovascular AMD(nAMD).GA is often bilateral and results from progressive and irreversible loss of photoreceptors and areas of the retinal pigment epithelium.Wet AMD is characterized by angiogenesis from the choroid to the normally avascular regions underneath the retinal pigment epithelium(RPE)or retina,a process known as choroidal neovascularization(CNV).Various targeted therapeutic options are currently available to reduce the progression rate and maintain vision in patients with nAMD.Intravitreal delivery of anti-VEGF protein treatments to halt CNV is currently the gold-standard of care for nAMD.Subretinal and suprachoroidal delivery approaches are also being explored for gene and molecular therapies.Advancements in nanotechnology and biomaterials have also led to the development of microscopic drug delivery systems,including hydrogels,microparticles,nanoparticles,implants,and liposomes.Gene therapy and stem cell therapy has recently emerged as a potential candidate treatment modality for AMD and other retinal degenerations.New drug targets and modalities have stimulated exciting developments in ocular drug delivery with the promise of greater efficacy and durability of AMD treatment.

Discussing menstrual health in family medicine

MENSTRUAL HEALTH Menstrual health is a general biological marker for many cisgender women,transgender men and non-binary people.Despite more than half of the population being people who menstruate,stigma,lack of conversation and pressing social needs around menstrual health persists throughout medicine.1 Discussions around menstruation and menstrual management can be difficult for individuals,whether it is with friends or family,or in the healthcare setting.1 Patients who have never discussed menstruation with a clinician may not know what is healthy,assume that an abnormal experience is normal and may endure periods that negatively affect their life,career or well-being.2–5 Menstruation plays a vital role in overall well-being and contributes significantly to an individual’s quality of life.Given their scope of care,family medicine clinicians are poised to identify red-flag menstrual symptoms in their routine visits with patients,reducing time to diagnosis of menstrual disorders.We urge family medicine clinicians to have renewed conversations surrounding menstrual health with their patients.The purpose of this report is to supply a brief overview of the importance of menstrual communication in primary care and serve as a resource to enhance menstrual communication between patient and clinician,with the ultimate goal of decreasing menstrual stigma and promoting improved menstrual health and experiences for patients.

Transjugular Intrahepatic Portosystemic Shunt Linked to Increased Risk of Hepatocellular Carcinoma:A VA Matched Cohort Study

Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and often evolves from regenerating nodules in liver cirrhosis.While there have been significant advances in the treatment of HCC,the overall prognosis in patients with a large tumor burden,vascular invasion,or extrahepatic spread remains poor.1 The magnitude of liver stiffness in cirrhosis has been consistently associated with an increased risk of development of HCC.

A comparison of the relative efficiency of ICSI and extended culture with epididymal sperm versus testicular sperm in patients with obstructive azoospermia

This is a retrospective cohort study comparing blastocyst transfer outcomes following intracytoplasmic sperm injection utilizing epididymal versus testicular sperm for men with obstructive azoospermia.All cases at a single center between 2012 and 2016 were included.Operative approach was selected at the surgeon’s discretion and included microepididymal sperm aspiration or testicular sperm extraction.Blastocyst culture was exclusively utilized prior to transfer.The primary outcome was live birth rate.Secondary outcomes included fertilization rate,blastulation rate,euploidy rate,and implantation rate.A mixed effects model was performed.Seventy-six microepididymal sperm aspiration cases and 93 testicular sperm extraction cases were analyzed.The live birth rate was equivalent(48.6%vs 50.5%,P=0.77).However,on mixed effects model,epididymal sperm resulted in a greater likelihood of fertilization(adjusted OR:1.37,95%CI:1.05–1.81,P=0.02)and produced a higher blastulation rate(adjusted OR:1.41,95%CI:1.1–1.85,P=0.01).As a result,the epididymal sperm group had more supernumerary blastocysts available(4.3 vs 3,P<0.05).The euploidy rate was no different.Pregnancy rates were no different through the first transfer cycle.However,intracytoplasmic sperm injection following microepididymal sperm aspiration resulted in a greater number of usable blastocysts per patient.Thus,the true benefit of epididymal sperm may only be demonstrated via a comparison of cumulative pregnancy rates after multiple transfers from one cohort.

Apoptotic vesicles ameliorate lupus and arthritis via phosphatidylserine-mediated modulation of T cell receptor signaling

Mesenchymal stem cells(MSCs)influence T cells in health,disease and therapy through messengers of intercellular communication including extracellular vesicles(EVs).Apoptosis is a mode of cell death that tends to promote immune tolerance,and a large number of apoptotic vesicles(apoVs)are generated from MSCs during apoptosis.In an effort to characterize these apoVs and explore their immunomodulatory potential,here we show that after replenishing them systemically,the apoV deficiency in Fas mutant mice and pathological lymphoproliferation were rescued,leading to the amelioration of inflammation and lupus activity.ApoVs directly interacted with CD4^(+)T cells and inhibited CD25 expression and IL-2 production in a dose-dependent manner.A broad range of Th1/2/17 subsets and cytokines including IFNγ,IL17A and IL-10 were suppressed while Foxp3^(+)cells were maintained.Mechanistically,exposed phosphatidylserine(PtdSer/PS)on apoVs mediated the interaction with T cells to disrupt proximal T cell receptor signaling transduction.Remarkably,administration of apoVs prevented Th17 differentiation and memory formation,and ameliorated inflammation and joint erosion in murine arthritis.Collectively,our findings unveil a previously unrecognized crosstalk between MSC apoVs and CD4^(+)T cells and suggest a promising therapeutic use of apoVs for autoimmune diseases.

Autozygosity Mapping by Genome-wide Single Nucleotide Polymorphism Array Identifies a Novel Homozygous HR Mutation in a Consanguineous Family with Universal Hereditary Hair Loss

Objective:Isolated hereditary hypotrichosis is caused by mutations in as many as 11 different genes.The conventional mutation detection strategy consists of sequencing of individual candidate genes separately,a time consuming and costly approach.In this study,we perform genome-wide single nucleotide polymorphism(SNP)array to identify candidate genes of hereditary hypotrichosis.Methods:A consanguineous family with two patients with hereditary hypotrichosis was enrolled,and autozygosity mapping by genome-wide SNP array was utilized to identify candidate genes.Results:Autozygosity mapping delineated runs of homozygosity,and alignment of the 11 genes identified the hairless(HR)gene as the candidate gene.Nucleotide sequencing revealed a novel homozygous mutation c.381delT,p.Ser127ArgfsTer40.Conclusion:This study illustrates how autozygosity mapping by a high-density SNP array streamlines mutation detection in heritable skin diseases.

Genetic Predisposition to Numerous Large Ulcerating Basal Cell Carcinomas and Response to Immune Therapy

Objective:Well-defined germ-line mutations in thePTCH1 gene are associated with syndromic multiple basal cell carcinomas(BCCs).Here,we used whole exome sequencing(WES)to identify the role of patched-1 in patients with multiple,unusually large BCCs.Methods:A 72-year old patient presenting with numerous BCCs progressing to large ulcerating lesions was enrolled.WES was used to identify the pathogenic gene locus.Results:Genetic work-up by WES identified a homozygousPTCH1 nonsense mutation in the tumor tissue but not present in her blood cells or in non-lesional skin.In addition,heterozygous missense mutations were identified in three cancer-associated genes(EPHB2,RET,andGALNT12)in blood cells as well as in lesional and non-lesional skin.We also tested systemic immune therapy as a potentially beneficial approach to treat patients with numerous large BCCs on scatted areas of involvement.A rapid and sustained response to nivolumab was noted,suggesting that it is an efficacious drug for long-term therapeutic outcome.Conclusion:PTCH1,EPHB2,RET,andGALNT12 may potentially contribute to the synergistic oncogene driven malignant transformation manifesting as multiple,unusually large BCCs.

Immunological aspect of the liver and metastatic uveal melanoma

Uveal(eye)melanoma is the most common primary eye malignancy in adults.Despite optimal treatments for primary uveal melanoma,up to 50%of patients subsequently develop systemic metastasis,often in the liver.Once hepatic metastasis develops,the survival of patients is generally short and currently available treatments fail to show meaningful improvement of survival.Recent development of immune checkpoint blockades revolutionized immunotherapy for metastatic cutaneous(skin)melanoma.Unfortunately,metastatic uveal melanoma is unresponsive to this approach,thus there is an unmet need to improve the treatment of metastatic uveal melanoma.One unique characteristic of uveal melanoma is that the majority of metastases first develop in the liver.The liver is highly specialized in development of immune tolerance to food-derived antigens and consequently serves a unique function in the immune system.Understanding the mechanisms by which the liver orchestrates immune-related responses is important to the development of an effective immunotherapy for hepatic metastases such as metastatic uveal melanoma.In this review article,the authors overview the immunological aspects of the liver and discuss approaches to improve immunotherapy for metastatic uveal melanoma.

Dynamics and Emerging Trends in Genodermatology: A Scientometric Analysis

With the improved power and precision with genome sequencing,the body of relevant literature on genodermatology has grown rapidly in recent years.In this study,we used CiteSpace,a scientometric software,to delineate the structure and dynamics of genodermatology and to further understand the emerging trends in this field.CiteSpace integrates individual citations and forms a cocitation network that demonstrates the evolution of a scientific field over time.Each reference cited by multiple articles is represented by a node in the network.The size of a node indicates how many times the reference has been cited.The nature of the connectivity between the nodes represents a dual relationship between the cited references and their citing articles.

The Power of Molecular Genetics in Understanding Heritable Skin Disorders: Introduction to the Special Theme on Genodermatosis

Among the over 7,000 heritable disorders,at least 1,000 of them have cutaneous manifestations.Some of these conditions are exclusively limited to the skin,thus being non-syndromic,while some of them are associated with a number of extracutaneous manifestations,that is,they are syndromic,with protean manifestations.These conditions,heritable skin diseases,display a tremendous collection of phenotypes as well as a broad spectrum of severity and the overall outcome.In most severe forms,some of these conditions are lethal at the early stages of life,while at the other end of the spectrum they may present with a relatively minor skin involvement primarily of cosmetic concern,with no effect on the longevity of the affected individuals.Considering the plethora of clinical manifestations,frequently with overlapping clinical features and complex classification schemes often riddled with eponyms,the heritable skin disorders frequently pose a diagnostic challenge for practicing dermatologists.