UNASSIGNED: This systematic review and meta-analysis aimed to examine the risk of second primary cancers (SPCs) among retinoblastoma (Rb) patients, both hereditary and nonhereditary. Previous studies have reported on the long-term risk of SPCs in these patient populations, but a comprehensive synthesis of the existing evidence is lacking.
UNASSIGNED: A systematic search was conducted in PubMed, EMBASE, and Cochrane Library from inception to 12 March 2023, supplemented by manual screening. Eligible studies were identified, and data were extracted. The primary outcome measure was the standardized incidence ratios (SIRs) of SPCs in Rb patients. Summary estimates were calculated using random or fixed effects models. The quality of included studies was assessed using the Newcastle-Ottawa Scale.
UNASSIGNED: Ten studies, including nine high-quality studies, were included in this review. The summary estimate of SIR for SPCs among hereditary Rb patients was 17.55 (95% CI=13.10-23.51), while the pooled estimate of SIR for SPCs among nonhereditary Rb patients was 1.36 (95% CI=0.90-2.04). Significant differences in SIRs for different SPC types were observed (P=0.028), including nasal cavity tumor (SIR=591.06, 95% CI=162.79-2146.01), bone tumor (SIR=442.91, 95% CI=191.63-1023.68), soft tissue sarcoma (SIR=202.93, 95% CI=114.10-360.93), CNS (SIR=12.84, 95% CI=8.80-18.74), and female breast cancer (SIR=3.68, 95% CI=2.52-5.37). Chemotherapy and radiation therapy were associated with an increased risk of SPCs among hereditary Rb patients.
UNASSIGNED: The findings of this review indicate that hereditary Rb patients have a significantly elevated risk of developing SPCs, whereas nonhereditary Rb patients do not show the same risk. Furthermore, significant differences were observed in the SIRs of different SPC types. Treatment techniques, specifically chemotherapy and radiation therapy, were associated with an increased risk of SPCs among hereditary Rb patients. These findings highlight the importance of radiation protection for Rb patients and the need for further research and tailored management strategies for this high-risk population.

UNASSIGNED: To provide a synthesis of the published evidence pertaining to the intergenerational health effects of parental preconceptional exposure to ionizing radiation in humans.
UNASSIGNED: The study populations are the descendants of those who were exposed to ionizing radiation prior to conception. A Boolean search identified publications for review in accordance with Office of Health Assessment and Translation guidelines. Initially, a risk of bias assessment was conducted for each published study and relevant data extracted. Information was organized into adverse health outcome groups and exposure situations. To make an assessment from the body of evidence within each group, an initial confidence rating was assigned, before factors including inconsistencies between studies, magnitude of effect, dose response and confounders were considered. From this, \'an effect\', \'no effect\' or whether the evidence remained \'inadequate\' to determine either effect or no effect, was ascertained. This assessment was based primarily upon the author\'s conclusions within that evidence-base and, by binomial probability testing of the direction of effect reported.
UNASSIGNED: 2441 publications were identified for review which after screening was reduced to 127. For the majority of the adverse health groups, we find there to be inadequate evidence from which to determine whether the health effect was, or was not, associated with parental preconceptional radiation exposure. This was largely due to heterogeneity between individual study\'s findings and conclusions within each group and, the limited number of studies within each group. We did observe one health grouping (congenital abnormalities) in occupationally exposed populations, where an increase in effect relative to their controls or large magnitude of effects, were reported, although it is noted that the authors of these studies interpreted their findings as most likely not to be associated with parental radiation exposure.
UNASSIGNED: We find there to be a lack of evidence to enable the formal assessment of radiation-related adverse effects in offspring of exposed humans. This is not the same as there being no clear evidence that effects may occur but does infer that if adverse health effects do arise in children of exposed parents, then these effects are small and difficult to reproducibly measure. Inconsistencies in designing studies are unavoidable, however we highlight the need for an element of standardization and, more sharing of primary datasets as part of open access initiatives, in order for future reviews to make reasonable conclusions. Overall, there is a need for future work to ensure comparable measures between studies where possible.

UNASSIGNED: The purpose of this paper was to conduct a review of the studies published between 2018 and 2022 to investigate radiation-related effects in the offspring of human individuals exposed to ionizing radiation.
UNASSIGNED: The search identified 807 publications, from which 9 studies were selected for detailed analysis to examine for effects in children whose parents were exposed to various types and doses of radiation.
UNASSIGNED: The review does not yield substantial evidence supporting intergenerational effects of radiation exposure in humans. However, caution is required when interpreting the results due to limitations in the majority of the published articles.
UNASSIGNED: This review, covering the period 2018-2022, serves as an extension of the previous systematic review conducted by Stephens et al. (2024), which encompassed the years 1988-2018. Together, these two papers offer a comprehensive overview of the available evidence regarding the intergenerational effects of parental pre-conceptional exposure to ionizing radiation. Overall, the findings do not provide strong evidence supporting a significant association between adverse (or other) outcomes in unexposed children and parental preconception radiation exposure.

Transthyretin amyloidosis (ATTR-amyloidosis) is a systemic disorder associated with extracellular deposition in the tissues and organs of amyloid fibrils, transthyretin-containing insoluble protein-polysaccharide complexes. The change in transthyretin conformation, leading to its destabilization and amyloidogenicity, can be acquired (wild type, ATTRwt) and hereditary due to mutations in the TTR gene (variant, ATTRv) [1, 2]. Hereditary ATTR-amyloidosis has an earlier onset and greater phenotypic diversity. The age of the manifestation, the predominant phenotype, and the prognosis are often determined by the genetic variant. To date, more than 140 variants in the TTR gene have been identified; however, most of them are described in single patients and do not have clear evidence of pathogenicity. The prospects of a new pathogenetic treatment of ATTR-amyloidosis [3], especially effective in the early stages of the disease, increases the relevance of timely diagnosis, which is challenging due to physicians\' lack of awareness. This article presents a clinical case of ATTRv-amyloidosis associated with a rare pathogenic variant in the TTR gene and a newly described skin symptom. This article is a literature review.
Транстиретиновый амилоидоз (ATTR-амилоидоз) – системное заболевание, связанное с внеклеточным отложением в тканях и органах амилоидных фибрилл – нерастворимых белково-полисахаридных комплексов, содержащих белок транстиретин. Изменение конформации транстиретина, приводящее к его дестабилизации и амилоидогенности, может быть приобретенным (wild type, ATTRwt) и наследственным по причине мутаций в гене TTR (variant, ATTRv) [1, 2]. Наследственный ATTR-амилоидоз имеет более ранний дебют и большее фенотипическое разнообразие. Возраст манифестации, преимущественный фенотип и прогноз зачастую определяются генетическим вариантом. На сегодняшний день выявлено более 140 вариантов в гене TTR, но большинство из них описаны у единичных больных и не имеют четких доказательств патогенности. Возможности нового патогенетического лечения ATTR-амилоидоза [3], особенно эффективного на ранних стадиях болезни, повышает актуальность своевременной диагностики заболевания, которая затруднена в большей степени из-за недостаточной осведомленности врачей. В данной статье представлен клинический случай ATTRv-амилоидоза, связанного с редким патогенным вариантом в гене TTR и впервые описанным кожным симптомом. Приводится обзор литературы.

UNASSIGNED: De Novo transplant amyloidosis denotes the condition when a patient develops amyloidosis after transplantation but had not been diagnosed with the disease prior to transplantation. The incidence of de novo amyloidosis in kidney transplants is rare, but few published case reports have described the occurrence of de novo Amyloid A protein (AA) and Light Chain (AL) amyloidosis. However, de novo hereditary fibrinogen A alpha chain (AFib) has not been previously reported.
UNASSIGNED: We present a 72-year-old man, a kidney transplant recipient, who developed progressive rise in his creatinine about 3 years after transplantation. He has long-standing diabetes mellitus type 2, obesity, and hypertension, so he did not have a kidney biopsy of his native kidneys prior to transplantation.
UNASSIGNED: A kidney transplant biopsy was done that showed amyloidosis. Mass spectrophotometry confirmed it as AFib amyloidosis. Genetic testing of the patient revealed that he has fibrinogen A alpha gene (FGA) point mutation with a p.E545V variant.
UNASSIGNED: Cardiac evaluation showed normal transthoracic echocardiogram. Cardiac magnetic resonance imaging (MRI) showed no involvement by amyloidosis. A peripheral nerve biopsy showed diabetic neuropathy. Thus, the kidney was the only organ involved by the disease. The kidney transplant was managed conservatively with blood pressure and diabetes control in addition to his usual immunosuppression regimen which was not altered. He is being treated with diuretics, angiotensin receptor inhibitors, and sodium glucose transport 2 inhibitors.
UNASSIGNED: Kidney transplant function exhibited only slow progression over 18 months since the diagnosis was confirmed. This slow progression is likely because the p.E545V point mutation variant is less aggressive than other gene deletion mutations and because our patient was judged to have been diagnosed early in the course of his disease.
UNASSIGNED: In this case report, we illustrate the findings and testing that confirmed the diagnosis of AFib amyloidosis. We summarize the clinical aspects, outcomes of the disease, and treatment options. We believe this case report is interesting because it is the first reported case of AFib amyloidosis in a kidney transplant recipient who was not known to have the disease prior to kidney transplantation.
UNASSIGNED: L’amyloïdose de novo de la transplantation désigne l’état d’un patient qui développe une amylose après une transplantation alors que la maladie n’avait pas été diagnostiquée avant l’intervention. L’incidence de l’amyloïdose de novo est rare en contexte de transplantation rénale, bien que la survenue d’amyloses AA et al de novo ait été décrite dans quelques rapports de cas publiés. L’amyloïdose de novo héréditaire de la chaîne alpha du fibrinogène A (FibA) n’a cependant jamais été rapportée.
UNASSIGNED: Nous présentons le cas d’un homme de 72 ans, receveur d’une greffe rénale, dont le taux de créatinine a augmenté progressivement environ trois ans après la transplantation. Le patient souffrait depuis longtemps de diabète de type 2, d’obésité et d’hypertension, de sorte qu’il n’avait pas subi de biopsie de ses reins d’origine avant la transplantation.
UNASSIGNED: Une biopsie du greffon rénal a montré une amyloïdose, laquelle a ultérieurement été typée par spectrophotométrie de masse comme étant une amyloïdose FibA. Des tests génétiques ont révélé que le patient présentait une mutation ponctuelle du gène alpha du fibrinogène (FGA) avec le variant p.E545V.
UNASSIGNED: L’échocardiogramme transthoracique du bilan cardiaque était normal. L’IRM cardiaque n’a montré aucune implication par amyloïdose, et une biopsie des nerfs périphériques a révélé une neuropathie diabétique. Ainsi, le rein était le seul organe touché par la maladie. La greffe rénale a été gérée de manière conservatrice, soit par le contrôle de la pression artérielle et du diabète en plus du schéma habituel d’immunosuppression, lequel n’a pas été modifié. Le patient est traité avec des diurétiques, des inhibiteurs des récepteurs de l’angiotensine et des inhibiteurs du cotransport sodium-glucose de type 2.
UNASSIGNED: La fonction du greffon n’a montré qu’une lente progression sur 18 mois depuis la confirmation du diagnostic. Cette lente progression est probablement due au fait que la mutation ponctuelle p.E545V est moins agressive que d’autres mutations de délétion du gène, et parce que notre patient a été jugé comme ayant reçu son diagnostic tôt dans l’évolution de sa maladie.
UNASSIGNED: Dans ce rapport de cas, nous mettons en évidence les résultats et tests qui ont confirmé le diagnostic d’amyloïdose FibA. Nous résumons les aspects cliniques, le pronostic de la maladie et les options de traitement. Ce rapport de cas est intéressant, car il s’agit du premier cas rapporté d’amyloïdose FibA chez un receveur d’une greffe rénale sans diagnostic connu de la maladie avant la transplantation.

Cerebral small vessel disease (cSVD) refers to a group of pathological processes with various etiologies affecting the small vessels of the brain. Most cases are sporadic, with age-related and hypertension-related sSVD and cerebral amyloid angiopathy being the most prevalent forms. Monogenic cSVD accounts for up to 5% of causes of stroke. Several causative genes have been identified. Sporadic cSVD has been widely studied whereas monogenic cSVD is still poorly characterized and understood. The majority of cases of both the sporadic and monogenic types, including cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), typically have their onset in adulthood. Types of cSVD with infantile and childhood onset are rare, and their diagnosis is often challenging. The present review discusses the clinical and neuroimaging findings of monogenic cSVD from the prenatal to adolescent period of development. Early diagnosis is crucial to enabling timely interventions and family counseling.

UNASSIGNED: This study aimed to report the genotypes and phenotypes of hereditary transthyretin cardiac amyloidosis (hATTR-CA) in a Western Chinese cohort and review the genetic profiles of this disorder in the Chinese population.
UNASSIGNED: Transthyretin (TTR) gene sequencing of probands diagnosed with TTR cardiac amyloidosis and their relatives was performed at West China Hospital of Sichuan University from January 2018 to December 2021. All patients underwent endomyocardial biopsy for light and electron microscopy examinations. Clinical and essential examination materials were retrospectively collected and analysed.
UNASSIGNED: TTR gene alteration was demonstrated in five probands and their two relatives. Three TTR variants were identified, namely, Ser23Asn, Glu54Leu and Thr60Ala. This study is the first to report Glu54Leu as pathogenic mutations in Chinese hATTR-CA patients. The Ser23Asn mutation was the most common mutation in this cohort. Five probands, including two males and three females, were all ethnic Han-Chinese. The median age at diagnosis and delay in diagnosis (interval from onset to diagnosis) was 56 years (range, 54-69 years) and 8 years (range, from 1 to 30 years), respectively. Three cases showed a defined family history of amyloidosis. Endomyocardial biopsies and TTR immunohistochemistry showed positive results in all patients. Two probands died 17.0 months and 21.0 months after diagnosis.
UNASSIGNED: We identified one novel TTR variants causing hATTR-CA in the West Han Chinese population. To avoid misdiagnosis or delayed diagnosis of hATTR-CA, TTR genotypic screening and endomyocardial biopsy should be performed as soon as possible in cases with heightened clinical suspicion.

Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide. Although most prevalent among older people, its incidence above 50 years old has been decreasing globally in the last decades, probably as a result of better screening. Paradoxically, its incidence in patients below 50 years old [early-onset CRC (EO-CRC)] has been increasing, for reasons not yet fully understood. EO-CRC\'s increasing incidence is genre independent but shows racial disparities and has been described to occur worldwide. It follows a birth-cohort effect which probably reflects a change in exposure to CRC risk factors. Its incidence is predicted to double until 2030, which makes EO-CRC a serious public health issue. Both modifiable and non-modifiable risk factors have been identified - some are potential targets for preventive measures. EO-CRC is often diagnosed at advanced stages and histological features associated with poor prognosis have been described. EO-CRC presents some distinctive features: Microsatellite in-stability is common, but another subtype of tumours, both microsatellite and chromosome stable also seems relevant. There are no age-specific treatment protocols and studies on EO-CRC survival rates have shown conflicting data. Due to the higher germline pathological mutations found in EO-CRC patients, an accurate genetic risk evaluation should be performed. In this review, we summarize the current evidence on epidemiological, clinical, histopathological and molecular features of EO-CRC and discuss the contribution of genetics and lifestyle risk factors. We further comment on screening strategies and specific dimensions to consider when dealing with a younger cancer patient.

The diagnosis of hereditary or familial breast cancers influences the locoregional approach to breast cancer, with most patients undergoing mastectomy to avoid or minimize the use of adjuvant radiation therapy. We evaluated the current literature about known high- and moderate-penetrance genes and studied their impact on local control, toxicities, and contralateral breast cancers after adjuvant radiation therapy. The aim is to encourage the safe use of adjuvant radiation therapy when indicated in concordance with the updated guidelines.

Hereditary fructose intolerance (HFI) is a rare autosomal recessive inherited disorder that occurs due to the mutation of enzyme aldolase B located on chromosome 9q22.3. A fructose load leads to the rapid accumulation of fructose 1-phosphate and manifests with its downstream effects. Most commonly children are affected with gastrointestinal symptoms, feeding issues, aversion to sweets and hypoglycemia. Liver manifestations include an asymptomatic increase of transaminases, steatohepatitis and rarely liver failure. Renal involvement usually occurs in the form of proximal renal tubular acidosis and may lead to chronic renal insufficiency. For confirmation, a genetic test is favored over the measurement of aldolase B activity in the liver biopsy specimen. The crux of HFI management lies in the absolute avoidance of foods containing fructose, sucrose, and sorbitol (FSS). There are many dilemmas regarding tolerance, dietary restriction and occurrence of steatohepatitis. Patients with HFI who adhere strictly to FSS free diet have an excellent prognosis with a normal lifespan. This review attempts to increase awareness and provide a comprehensive review of this rare but treatable disorder.