Search

Meier–Gorlin syndrome (MGORS) is an autosomal recessive disorder characterized by short stature, microtia, and patellar hypoplasia, and is caused by pathogenic variants of cellular factors involved in the initiation of DNA replication. We previously reported that biallelic variants in GINS3 leading to amino acid changes at position 24 (p.Asp24) cause MGORS. Here, we describe the phenotype of a new individual homozygous for the Asp24Asn variant. We also report the clinical characteristics of an individual harboring a novel homozygous GINS3 variant (Ile25Phe) and features suggestive of MGORS. Modification of the corresponding residue in yeast Psf3 (Val9Phe) compromised S phase progression compared to a humanized Psf3 Val9Ile variant. Expression of Psf3 Val9Phe in yeast also caused sensitivity to elevated temperature and the replicative stress‐inducing drug hydroxyurea, confirming partial loss of function of this variant in vivo and allowing us to upgrade the classification of this variant. Taken together, these data validate the critical importance of the GINS DNA replication complex in the molecular etiology of MGORS. [ABSTRACT FROM AUTHOR]

Although a genetic evaluation can identify the etiology in 15-30% of individuals with autism spectrum disorder, several studies show an underuse of genetic services by affected families. We have explored the access to genetic services and perception of genetics and recurrence risk in parents of autistic children in Spain. Despite the high interest in genetics, our results show a remarkable underutilization of genetic services, with only 30% of families having visited a genetic service and 13% of patients having undergone the recommended genetic test. This poor service provision influenced recurrence risk perception and had a great impact on family planning. The National Health System should ensure their access to genetic services allowing them to take informed decisions with precise information.

Background: Consanguineous couples have an increased risk of severe diseases in offspring due to autosomal recessive disorders. Exome sequencing (ES) offers the possibility of extensive preconception carrier screening (PCS) in consanguineous couples who may be at risk of rare genetic disorders. Methods: We retrospectively analysed ES data from 65 probands affected with rare genetic disorders born from consanguineous couples. We explored diagnostic yield and carrier status for recessive disorders. Results: The overall diagnostic yield in a singleton approach was 53.8%, mostly recessive variants. In a hypothetical exome-based PCS, only 11.7% of these causative rare variants would have been missed in the filtering process. Carrier screening for recessive conditions allowed the identification of at least one additional pathogenic or likely pathogenic variant in 85.7% of the probands, being the majority with a gene carrier frequency <1 in 200. In addition, considering only clinically actionable conditions, we estimated that 12.3% of our close consanguineous couples may be at risk for an additional recessive disease. Conclusions: Our results demonstrate that ES outperforms panel-based screening in a PCS context in consanguineous couples and could potentially increase their reproductive autonomy and facilitate informed decision-making. [ABSTRACT FROM AUTHOR]

The molecular study of nuclear genes involved in the replication and maintenance of mtDNA identified the c.614A > G (p.Asp205Gly) homozygote variant in exon 6 of the I TOP3A i gene (NM 004618.5). We report two adult siblings with c.614A>G (p.Asp205Gly) homozygous missense variant in the TOP3A gene who had CPEO plus syndrome. Chronic progressive external ophthalmoplegia (CPEO) plus syndrome due to pathogenic biallelic variants in TOP3A gene has been described in only one single patient. [Extracted from the article]

Aim: Autologous platelet-rich plasma (PRP) therapy produces satisfactory results in chronic wounds. There is a lack of knowledge about the mechanism of action of PRP from patients with chronic wounds in stimulating cell activity and its correlation with clinical effectiveness. In this study, we determined the viability, migration, and differentiation activity in cell cultures treated with PRP. Method: PRP was obtained by centrifugation of blood from 5 patients receiving PRP therapy for chronic wounds. Platelet-released Factors (PRF) were prepared by activating platelets from PRP. Platelet-poor plasma (PPP) was used as an internal control for each patient. The effect of PRF and PPP were tested in vitro to assess viability and tube formation in human umbilical vein endothelial cells (HUVEC), and migration in human dermal fibroblast (HDF). Results / Discussion: The five samples included in the study showed variable results. Nonetheless, viability and differentiation to angiogenesis was different in HUVEC stimulated with PRF (1% and 5%), compared to PPP from the same patient. Wound closure assay in HDF was faster in cells incubated with PRF, compared to PPP. PRF did not increase in vitro the probability to wound closure at 24h post-incubation versus PPP. Conclusion: Platelet-released factors stimulate differentiation to angiogenesis in cultured HUVEC and reduce the wound healing time of HDF model. These results might reflect the new blood vessel formation observed in the early stages of clinical therapy application, and a decrease in healing time, that might reduce wound complication. [ABSTRACT FROM AUTHOR]

Introduction: Martorell hypertensive ulcers are considered to be a rare cause of leg ulcers. The diagnosis of these wounds' etiology is clinical, following in-depth exclusion criteria, and unfortunately mostly belated. The heals response to conventional treatment takes time and is often unsatisfactory. Case description: We present a case of an autonomous 82-year-old female that was referred for a 6,70cm² ulcer on the leg (wound age: 2 months). She reported intense pain that swiftly became severe requiring opioid treatment for its management. In addition, the ulcer had a fast progression increasing up to 346.88cm² in size affecting the Achilles tendon and rapidly turning into a necrotic lesion with purple-reddish edges. The ulcer was diagnosed as hypertensive etiology due to the normal kidney function, hypertension diagnosis, and the clinical picture. To promote wound healing, and reduce pain and opioid administration, the wound was treated with advanced therapy with autologous growth factors combined with punch skin grafting. Complete epithelialization was observed at 6 months. Discussion: Martorell hypertensive ulcer resolution required the combination of various advanced therapies emphasizing the therapeutic difficulty of these lesions. Autologous growth factors combined with punch grafting enhanced wound healing, and interestingly they alleviate ulcer pain by the release of growth factors and other mediators. Conclusions: Martorell hypertensive ulcers pose an important diagnostic and therapeutic challenge in clinical practice. An early prescription of advanced biological therapies for these ulcers is essential to mitigate the pain and cease the uncontrolled necrotic and the ulcer size increase. [ABSTRACT FROM AUTHOR]

Introduction: The complexity of diabetic foot ulcers demands rapid and personalized interventions to prevent major amputation and maintain patient autonomy. Case description: We present a case of a diabetic 85-year-old man with an infected plantar ulcer. During clinical admission in the complex wound care unit, the patient received an accurate assessment to detect the resources and specialists needed for the case, and a multidisciplinary approach was established. The vascular surgeon's evaluation prescribed to endure surgery for minor amputations of the 1st, 2nd, and 3rd toes and a stent insertion in the peroneal artery due to popliteal stenosis. These surgical interventions allowed recovering the vascular circulation around the ulcer. However, the wound bed kept showing abundant slough due to a slow debridement preventing the proper cicatrisation. The application of an hydrosurgical technique, by a nurse, achieved a successful debridement in one session. After hydrosurgery, autologous platelet-rich plasma (PRP) therapy was applied to promote complete wound closure. Finally, in order to prevent future lesions, the orthopaedist provided him with special shoes and insoles that allowed him to keep his autonomy to walk. Discussion: Diabetic foot ulcers are complex to treat, especially in patients with vascular pathology. Our results showed that rapid intervention, easy interdisciplinary coordination and communication, and the use of advanced interventions allow the achievement of the best results for the patient. Conclusion: Interdisciplinary teamwork and advanced therapies are crucial for treating diabetic foot ulcers to avoid major amputation, promoting cicatrisation, and maintaining patient autonomy. [ABSTRACT FROM AUTHOR]

Introduction: The manifestation of a perianal ulcer caused by a hemorrhoidal ointment has not been commonly described to date. However, an increasing number of cases has been reported during the COVID-19 pandemic and the resulting confinement in Spain. The case we are presenting is not isolated, as other cases have been documented after they used the same ointment containing the active ingredients triamcinolone acetonide, lidocaine, and pentosan polysulfate sodium. Case description: We present a case of an autonomous 82-year-old male affected by a 35,80cm² perianal ulcer with no condition or concomitant disease that could justify the ulcer's cause. The application of in-depth exclusion criteria, including a biopsy to refuse pyoderma gangrenosum, allowed the identification of a hemorrhoidal rectal ointment as the cause of the ulcer. We led a multidisciplinary therapeutic approach to treat this complex wound. The ulcer healed completely after three months when the application of the ointment was stopped and the autologous growth factors advanced therapy was applied. Discussion: The vasoconstrictor effect of corticosteroids and its risk of causing skin atrophy after continued use are well known. Before prescribing some hemorrhoidal ointment to elder patients, clinicians should consider the great potential harm of triamcinolone acetonide an ingredient of some hemorrhoidal ointments. Conclusions: This is an interesting case describing a condition barely reported in the literature although this hemorrhoidal ointment has been marketed for more than 40 years. It is relevant to show the damage that can be caused without a proper medical follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Elderly people undergo many changes on a multidimensional level and have a higher degree of fragility that increases their vulnerability. Moreover, aging produces a reduction of skin collagen and cell activity, changes in skin functionality, increased susceptibility to skin injury, and hampered wound healing. Consequently, minor trauma can unleash a complicated situation in the elder population. Case description: We present two clinical cases of upper extremity acute injuries caused by minor traumatic accidents. First case, a 93-year-old woman with initial fragility and a skin tear wound on the arm evoked by a door hit. Second case, a 77-year-old woman with initial fragility and skin tear on the hand caused by the pressure applied by a caregiver during mobilization. The patients reported severe pain affecting their quality of life. Both wounds were large (12,45 cm2 and 17 cm2) and deep, showing tendons and adjacent tissue. Taking into advantage that both wounds were clean, autologous platelet-rich plasma (PRP) therapy was applied resulting in pain reduction and in wound healing in one and two months each. Discussion: In elderly frail people, skin is susceptible to losing its continuity when a force is applied. In both clinical cases, wounds were painful and wound healing failed by using conventional treatment requiring an advanced therapy. Conclusion: Autologous PRP therapy is useful for soothing pain and accelerate wound healing in elder patients reducing the probability of infection, even when there is a full thickness loss of tissue. [ABSTRACT FROM AUTHOR]

Aim: Chronic wounds are difficult to heal with conventional treatments. The patients' profile who better benefit from autologous platelet-rich plasma (PRP) therapy is not clear. This study is focused on the identification of influential variables in the success of this therapy to analyze the personalized-therapeutical potential of PRP for treating chronic wounds. Method: Observational pilot study in patients with chronic wounds treated with autologous PRP. We analyzed socio-demographic data, etiology, clinical and analytical parameters, healing rate and healing time. Data were analyzed using descriptive statistics, principal component analysis (PCA), cluster analysis and survival analysis. Results/Discussion: The study included 56 patients (33 women, mean age 75.07±14.7), of whom 55% have mild and moderate frailty (VIG index: 0.16-0.35). Wound etiologies: 20% venous, 18% suture dehiscence, 12% pressure ulcers, 12% traumatic, 9% diabetics, 9% arterial, and 20% others. The mean wound size was 17.65 cm2. Higher healing rate was observed in patients with lower VIG and in wounds < 10 cm2. A total of 3 patients' clusters have been identified according to their analytical parameters. Cluster patients with high values of erythrocytes, hemoglobin, hematocrit, platelets, and albumin showed the highest healing rate. The survival analysis showed: a) 15% of ulcers healed at 5 weeks, 55% at 10 weeks, and 79% at 15 weeks; and b) patients with wound size < 4cm2 or VIG < 0.35 had the lowest healing time. Conclusion: PRP therapy success depends on wound size, patients' frailty, and analytical parameters, suggesting that personalization of PRP therapy might be recommended. [ABSTRACT FROM AUTHOR]