Standardized Duplex Ultrasound-Based Protocol for Early Diagnosis of Transplant Renal Artery Stenosis: Results of a Single-Institution Retrospective Cohort Study

Transplant renal artery stenosis (TRAS) is the most frequent vascular complication after kidney transplantation (KT) and has been associated with potentially reversible refractory hypertension, graft dysfunction, and reduced patient survival. The aim of the study is to describe the outcomes of a standardized Duplex Ultrasound- (DU-) based screening protocol for early diagnosis of TRAS and for selection of patients potentially requiring endovascular intervention. We retrospectively reviewed our prospectively collected database of KT from January 1998 to select patients diagnosed with TRAS. The follow-up protocol was based on a risk-adapted, dynamic subdivision of eligible KT patients in different risk categories (RC) with different protocol strategies (PS). Of 598 patients included in the study, 52 (9%) patients had hemodynamically significant TRAS and underwent percutaneous angioplasty (PTA) and stent placement. Technical and clinical success rates were 97% and 90%, respectively. 7 cases of restenosis were recorded at follow-up and treated with re-PTA plus stenting. Both DU imaging and clinical parameters improved after stent placement. Prospective high-quality studies are needed to test the efficacy and safety of our protocol in larger series. Accurate trial design and standardized reporting of patient outcomes will be key to address the current clinical needs

Give the planet a chance if we want our patients to have a future

Climate changes have never been as dramatically apparent in our everyday life as now. It is urgent to reduce greenhouse gas emissions and mitigate the consequences of climate changes both on the planet and on human health. The indiscriminate exploitation of natural resources and the lack of shared rules are among the major causes. Recently, some economists have called for a radical change in the present economic model towards a 'social solidarity economy' model. G.Giraud, a French economist, called for an ecological and social transition in order to reduce the ecological footprint and deal concretely with the problem of global warming. The good news is that the solutions are there and do not have to be punitive. Health consequences of climate changes have already caused serious draw backs on public health. Doctors and scientific institutions can and must contribute to help mitigate the effects of climate change through increasing commitment and support to goodenvironmental policies. Climate emergency requires the extension of ethics and medical practice beyond their traditional mission to involve the relationship between patients, doctors and society. We propose that medical scientific institutions quickly promote the birth of task forces dedicated to addressing this problem

Health-related quality of life and functional changes in DMD: A 12-month longitudinal cohort study

In Duchenne muscular dystrophy (DMD) little has been reported on the association between clinical outcome measures and patient health-related quality of life (HRQOL) tools. Our study evaluated the relationship between 12 month changes on the Generic Core Scales (GCS), the Multidimensional Fatigue Scale and the Neuromuscular Module of the PedsQL\u2122 with several outcome measures (6 minute walk test, North Star Ambulatory Assessment and timed items) in ambulatory DMD. Ninety-eight ambulatory DMD in a multicentric setting were included in the study. At baseline, the PedsQL\u2122 inventories correlated with almost all the functional measures On the Child Self-Report there was a significant decrease between baseline and 12 months on the PedsQL\u2122 GCS and its first domain, in parallel with the decrement in the functional outcome measures. Correlation between the 12 month changes on the PedsQL\u2122 inventories and functional measures were almost all negligible. Similar results were obtained on the Parent Proxy-Report.In conclusion, PedsQL\u2122 correlates with the level of impairment at baseline, but this does not hold true when 12 month changes are considered. Further studies comparing different tools are needed to better elucidate the complexity of the relationship between HRQOL and functional performances

Congenital myopathies: Clinical phenotypes and new diagnostic tools

Congenital myopathies are a group of genetic muscle disorders characterized clinically by hypotonia and weakness, usually from birth, and a static or slowly progressive clinical course. Historically, congenital myopathies have been classified on the basis of major morphological features seen on muscle biopsy. However, different genes have now been identified as associated with the various phenotypic and histological expressions of these disorders, and in recent years, because of their unexpectedly wide genetic and clinical heterogeneity, next-generation sequencing has increasingly been used for their diagnosis. We reviewed clinical and genetic forms of congenital myopathy and defined possible strategies to improve cost-effectiveness in histological and imaging diagnosis

Standardized Duplex Ultrasound-Based Protocol for Early Diagnosis of Transplant Renal Artery Stenosis: Results of a Single-Institution Retrospective Cohort Study

Transplant renal artery stenosis (TRAS) is the most frequent vascular complication after kidney transplantation (KT) and has been associated with potentially reversible refractory hypertension, graft dysfunction, and reduced patient survival. The aim of the study is to describe the outcomes of a standardized Duplex Ultrasound- (DU-) based screening protocol for early diagnosis of TRAS and for selection of patients potentially requiring endovascular intervention. We retrospectively reviewed our prospectively collected database of KT from January 1998 to select patients diagnosed with TRAS. The follow-up protocol was based on a risk-adapted, dynamic subdivision of eligible KT patients in different risk categories (RC) with different protocol strategies (PS). Of 598 patients included in the study, 52 (9%) patients had hemodynamically significant TRAS and underwent percutaneous angioplasty (PTA) and stent placement. Technical and clinical success rates were 97% and 90%, respectively. 7 cases of restenosis were recorded at follow-up and treated with re-PTA plus stenting. Both DU imaging and clinical parameters improved after stent placement. Prospective high-quality studies are needed to test the efficacy and safety of our protocol in larger series. Accurate trial design and standardized reporting of patient outcomes will be key to address the current clinical needs

Copy Number Variants Account for a Tiny Fraction of Undiagnosed Myopathic Patients

Next-generation sequencing (NGS) technologies have led to an increase in the diagnosis of heterogeneous genetic conditions. However, over 50% of patients with a genetically inherited disease are still without a diagnosis. In these cases, different hypotheses are usually postulated, including variants in novel genes or elusive mutations. Although the impact of copy number variants (CNVs) in neuromuscular disorders has been largely ignored to date, missed CNVs are predicted to have a major role in disease causation as some very large genes, such as the dystrophin gene, have prone-to-deletion regions. Since muscle tissues express several large disease genes, the presence of elusive CNVs needs to be comprehensively assessed following an accurate and systematic approach. In this multicenter cohort study, we analyzed 234 undiagnosed myopathy patients using a custom array comparative genomic hybridization (CGH) that covers all muscle disease genes at high resolution. Twenty-two patients (9.4%) showed non-polymorphic CNVs. In 12 patients (5.1%), the identified CNVs were considered responsible for the observed phenotype. An additional ten patients (4.3%) presented candidate CNVs not yet proven to be causative. Our study indicates that deletions and duplications may account for 5–9% of genetically unsolved patients. This strongly suggests that other mechanisms of disease are yet to be discovered.Next-generation sequencing (NGS) technologies have led to an increase in the diagnosis of heterogeneous genetic conditions. However, over 50% of patients with a genetically inherited disease are still without a diagnosis. In these cases, different hypotheses are usually postulated, including variants in novel genes or elusive mutations. Although the impact of copy number variants (CNVs) in neuromuscular disorders has been largely ignored to date, missed CNVs are predicted to have a major role in disease causation as some very large genes, such as the dystrophin gene, have prone-to-deletion regions. Since muscle tissues express several large disease genes, the presence of elusive CNVs needs to be comprehensively assessed following an accurate and systematic approach. In this multicenter cohort study, we analyzed 234 undiagnosed myopathy patients using a custom array comparative genomic hybridization (CGH) that covers all muscle disease genes at high resolution. Twenty-two patients (9.4%) showed non-polymorphic CNVs. In 12 patients (5.1%), the identified CNVs were considered responsible for the observed phenotype. An additional ten patients (4.3%) presented candidate CNVs not yet proven to be causative. Our study indicates that deletions and duplications may account for 5–9% of genetically unsolved patients. This strongly suggests that other mechanisms of disease are yet to be discovered.Peer reviewe

Prevalence of congenital muscular dystrophy in Italy: a population study

We provide a nationwide population study of patients with congenital muscular dystrophy in Italy

Copy Number Variants Account for a Tiny Fraction of Undiagnosed Myopathic Patients

Next-generation sequencing (NGS) technologies have led to an increase in the diagnosis of heterogeneous genetic conditions. However, over 50% of patients with a genetically inherited disease are still without a diagnosis. In these cases, different hypotheses are usually postulated, including variants in novel genes or elusive mutations. Although the impact of copy number variants (CNVs) in neuromuscular disorders has been largely ignored to date, missed CNVs are predicted to have a major role in disease causation as some very large genes, such as the dystrophin gene, have prone-to-deletion regions. Since muscle tissues express several large disease genes, the presence of elusive CNVs needs to be comprehensively assessed following an accurate and systematic approach. In this multicenter cohort study, we analyzed 234 undiagnosed myopathy patients using a custom array comparative genomic hybridization (CGH) that covers all muscle disease genes at high resolution. Twenty-two patients (9.4%) showed non-polymorphic CNVs. In 12 patients (5.1%), the identified CNVs were considered responsible for the observed phenotype. An additional ten patients (4.3%) presented candidate CNVs not yet proven to be causative. Our study indicates that deletions and duplications may account for 5⁻9% of genetically unsolved patients. This strongly suggests that other mechanisms of disease are yet to be discovered