Anatomy of the pudendal nerve in clinically important areas: a pictorial essay and narrative review.

PURPOSE: The pudendal nerve is an anatomical structure arising from the ventral branches of the spinal roots S2-S4. Its complex course may be affected by surrounding structures. This may result in irritation or entrapment of the nerve with subsequent clinical symptoms. Aim of this study is to review the anatomy of the pudendal nerve and to provide detailed photographic documentation of the areas with most frequent clinical impact which are essential for surgical approach. METHODS: Major medical databases were searched to identify all anatomical studies investigating pudendal nerve and its variability, and possible clinical outcome of these variants. Extracted data consisted of morphometric parameters, arrangement of the pudendal nerve at the level of roots, formation of pudendal nerve, position according to sacrospinal and sacrotuberal ligaments and its terminal branches. One female cadaver hemipelvis was dissected with common variability of separate course of inferior rectal nerve. During dissection photodocumentation was made to record course of pudendal nerve with focus on areas with recorded pathologies and areas exposed to iatrogenic damage during surgical procedures. RESULTS: Narrative review was done to provide background for photodocumentation. Unique photos of course of the pudendal nerve was made in areas with great clinical significance. CONCLUSION: Knowledge of anatomical variations and course of the pudendal nerve is important for examinations and surgical interventions. Surgically exposed areas may become a site for iatrogenic damage of pudendal nerve; therefore, unique picture was made to clarify topographic relations.

Human papillomavirus infection (HPV) and pregnancy.

Human papillomavirus (HPV) is the most common sexually transmitted viral infection worldwide, which may result in the development in benign lesions or malignant tumors. The prevalence of HPV infection is twice as high in pregnancy as in non-pregnant women. Additionally, there is a risk of vertical transmission of HPV from mother to fetus during pregnancy or childbirth. Various studies have reported an increased risk of adverse pregnancy outcomes in HPV-positive women, including miscarriage, preterm birth, premature rupture of membranes, preeclampsia, fetal growth restriction, and fetal death. HPV vaccination is not currently recommended during pregnancy. On the other hand, there is no evidence linking HPV vaccination during pregnancy with adverse pregnancy outcomes and termination of pregnancy is not justified in this case.

Staging for endometrial carcinoma FIGO 2023 and its relevance for clinical practice.

BACKGROUND: International Federation of Gynaecology and Obstetrics (Fédération Internationale de Gynécologie et d'Obstétrique - FIGO) introduced a new staging system for endometrial carcinoma - FIGO 2023 - in June 2023. OBJECTIVE: The new staging system differs significantly from previous versions. The new system represents a significant departure from the traditional staging systems for other gynaecological cancers, as the definition of individual stages includes not only the traditional anatomical extent of the tumour, but also the molecular profile of the tumour and other histopathological parameters - histological type of tumour, tumour grade and the presence of substantial lymphovascular invasion. The new system defines stages I and II in a completely different way and expands the definition of stages III and IV, allowing for different types of tumour spread outside the uterus. The introduction of molecular testing is the main change in the new staging system. When certain molecular markers are detected, stage I or II is completely changed. By including these non-anatomical parameters, the FIGO 2023 staging system improves the accuracy of a patient's prognosis at a specific stage with better options for individualized treatment, including the use of immunotherapy. Another goal was to synchronise staging as much as possible with the recommendations of three professional societies: the European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP). The staging system for carcinosarcoma remains identical to the staging system for endometrial cancer. CONCLUSION: This article presents an overview of the new FIGO 2023 endometrial cancer staging system and discusses its advantages and disadvantages for clinical practice.

Characterization of degradation kinetics of additively manufactured PLGA under variable mechanical loading paradigms.

Controlled degradation of biodegradable poly-lactic-co-glycolic acid (PLGA) trauma implants may increase interfragmentary loading which is known to accelerate fracture healing. Additive manufacturing allows us to tune the mechanical properties of PLGA scaffolds; however, little is known about this novel approach. The purpose of this study was to use in vitro and in vivo models to determine the degradative kinetics of additively manufactured test coupons fabricated with PLGA. We hypothesized that 1) increases in infill density would lead to improved initial mechanical properties, and 2) loss of mechanical properties would be constant as a function of time, regardless of implant design. Porous and solid test coupons were fabricated using 85:15 PLGA filament. Coupons were either incubated in serum or implanted subcutaneously in rats for up to 16 weeks. Samples were tested in tension, compression, torsion, and bending on a universal test frame. Variables of interest included, but were not limited to: stiffness, and ultimate force for each unique test. Infill density was the driving factor in test coupon mechanical properties, whereas differences in lattice architecture led to minimal changes. We observed moderate levels of degradation after 8 weeks, and significant decreases for all specimens after 16 weeks. Results from this study suggest substantial degradation of 3-D printed PLGA implants occurs during the 8- to 16-week window, which may be desirable for bone fracture repair applications. This study represents initial findings that will help us better understand the complicated interactions between overall implant design, porosity, and implant biodegradation.

Erratum: iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells.

[This corrects the article DOI: 10.1016/j.isci.2023.107059.].

Discovering novel germline genetic variants linked to severe fluoropyrimidine-related toxicity in- and outside DPYD.

BACKGROUND: The Alpe-DPD study (NCT02324452) demonstrated that prospective genotyping and dose-individualization using four alleles in DPYD (DPYD*2A/rs3918290, c.1236G > A/rs75017182, c.2846A > T/rs67376798 and c.1679 T > G/rs56038477) can mitigate the risk of severe fluoropyrimidine toxicity. However, this could not prevent all toxicities. The goal of this study was to identify additional genetic variants, both inside and outside DPYD, that may contribute to fluoropyrimidine toxicity. METHODS: Biospecimens and data from the Alpe-DPD study were used. Exon sequencing was performed to identify risk variants inside DPYD. In silico and in vitro analyses were used to classify DPYD variants. A genome-wide association study (GWAS) with severe fluoropyrimidine-related toxicity was performed to identify variants outside DPYD. Association with severe toxicity was assessed using matched-pair analyses for the exon sequencing and logistic, Cox, and ordinal regression analyses for GWAS. RESULTS: Twenty-four non-synonymous, frameshift, and splice site DPYD variants were detected in ten of 986 patients. Seven of these variants (c.1670C > T, c.1913 T > C, c.1925 T > C, c.506delC, c.731A > C, c.1740 + 1G > T, c.763 - 2A > G) were predicted to be deleterious. The carriers of either of these variants showed a trend towards a 2.14-fold (95% CI, 0.41-11.3, P = 0.388) increased risk of severe toxicity compared to matched controls (N = 30). After GWAS of 942 patients, no individual single nucleotide polymorphisms achieved genome-wide significance (P ≤ 5 × 10-8), however, five variants were suggestive of association (P < 5 × 10-6) with severe toxicity. CONCLUSIONS: Results from DPYD exon sequencing and GWAS analysis did not identify additional genetic variants associated with severe toxicity, which suggests that testing for single markers at a population level currently has limited clinical value. Identifying additional variants on an individual level is still promising to explain fluoropyrimidine-related severe toxicity. In addition, studies with larger samples sizes, in more diverse cohorts are needed to identify potential clinically relevant genetic variants related to severe fluoropyrimidine toxicity.

Doença celíaca é super-representada em pacientes com constipação / Celiac disease is overrepresented in patients with constipation

OBJETIVO: Tem sido sugerido que pacientes com constipação sejam triados para doença celíaca. Da mesma forma, recomenda-se a investigação desses pacientes para hipotiroidismo e hipercalcemia. Contudo, nenhuma evidência para essas recomendações está disponível até o momento. Assim, propusemos-nos determinar a prevalência de doença celíaca, hipotiroidismo e hipercalcemia em crianças com constipação. MÉTODOS: Estudo de coorte prospectivo com 370 pacientes consecutivos que preencheram os critérios de Roma III para constipação. Esses pacientes foram encaminhados por um clínico geral a um pediatra devido ao fracasso no tratamento com laxantes. RESULTADOS: A biópsia comprovou doença celíaca em sete desses pacientes. Isso é significativamente mais alto (p < 0,001) do que a prevalência de 1:198 de doença celíaca nos Países Baixos. Dois pacientes tinham tiroidite autoimune. Nenhum paciente tinha hipercalcemia. CONCLUSÕES: Conclui-se que a doença celíaca é significativamente super-representada em pacientes com constipação encaminhados por um clínico geral a um pediatra devido ao fracasso no tratamento com laxantes. Todos esses pacientes devem, portanto, ser triados para doença celíaca.

OBJECTIVE: It is suggested that patients with constipation should be screened for celiac disease. Similarly, it is recommended to investigate these patients for hypothyroidism and hypercalcemia. However, no evidence for these recommendations is available so far. We therefore set out to determine the prevalence of celiac disease, hypothyroidism, and hypercalcemia in children with constipation. METHODS: Prospective cohort study of 370 consecutive patients who met the Rome III criteria for constipation. These patients were referred by a general practitioner to a pediatrician because of failure of laxative treatment. RESULTS: Seven of these patients had biopsy-proven celiac disease. This is significantly higher (p < 0.001) than the 1:198 prevalence of celiac disease in the Netherlands. Two patients had auto-immune thyroiditis. No patient had hypercalcemia. CONCLUSIONS: We conclude that celiac disease is significantly overrepresented in patients with constipation who are referred by a general practitioner to a pediatrician because of failure of laxative treatment. All such patients should, therefore, be screened for celiac disease.