Upsala journal of medical sciences最新文献

Background: The heterogeneous features of enamel renal syndrome (ERS) make diagnosis and treatment challenging. The main symptoms are disturbed amelogenesis and nephrocalcinosis. Bi-allelic likely pathogenic (LP) or pathogenic (P) variants in FAM20A have been associated with the syndrome since 2012. Affected patients often receive extensive dental treatment because of deviant orofacial morphology. However, knowledge about long-term prognosis and treatment guidelines are still lacking. The complex nature of ERS might endanger both dental and general health. The purpose of this article is to highlight the risks of overlooking the symptoms of the syndrome, and to discuss management strategies, surveillance and prognosis.

Case presentation: We report the management of a case with suspected ERS after initial dental treatment elsewhere with no adjustment for the syndrome. Dental treatment was revised and followed for 8 years. Complementary medical examinations were conducted, and ERS was genetically confirmed, revealing homozygosity for a LP c.755_757del, p.(Phe252del) variant in FAM20A. The nephrological investigation revealed medullary calcium deposits, normal renal function and hypophosphatemia. Urine analysis revealed hypocitraturia and hypocalciuria. Accordingly, the patient now medicates with potassium citrate to decrease the risk of progressive renal stone formation.

Conclusion: We herein describe a patient with confirmed ERS with an 8-year follow-up. Diagnostic delay until adulthood led to complicated dental treatment. The results of nephrological investigations are presented. The importance of dental and medical multidisciplinary management in syndromic disorders affecting the formation of the enamel is also exemplified. The dental prognosis after rehabilitation is likely affected by anatomical variations and patient cooperation. The prognosis for renal function seems to be good. However, lifelong surveillance of renal function is recommended.

Registration: The ethics committee in Uppsala, Sweden, determined that ethical approval was not necessary in this case (2019-04835). Informed consent was obtained from the participant in writing and is documented in the medical records.

Background: Trigger finger, or stenosing tendovaginitis, is one of the most common causes of hand disability, where a finger or thumb painfully snaps and locks due to a tendon-sheath size mismatch at the A1 pulley. The exact aetiology of trigger finger is unknown, though it is associated with factors like diabetes, rheumatic disease and carpal tunnel syndrome. The main purpose of this prospective study was to explore clinical characteristics and comorbidities in a cohort of 139 patients who underwent surgery for trigger finger and find factors of importance for the outcome 1 year postoperatively.

Methods: Pain, range of motion, hand function evaluated by the Disabilities of the Arm Shoulder and Hand questionnaire as well as Quinnell grade of triggering were examined preoperatively. Symptom duration, working status, medical history and comorbidities at baseline were also noted. Further, range of motion was evaluated 3 months after surgery, pain and hand function were evaluated 3 and 12 months after surgery. An outcome scale with three levels was defined. The development of any new comorbidities was monitored during an extended postoperative observation period, with a mean duration of 70 months (range: 56-88 months).

Results: Poor outcome was strongly associated with younger age (P = 0.0009), a high level of preoperative pain in the operated hand (P = 0.0027), psoriatic arthritis (P = 0.021) and atopic disease (P = 0.028; odds ratio [OR]: 3.87, 95% confidence interval [CI]: 1.15-13.04). A low range of motion preoperatively did not affect the outcome. Carpal tunnel syndrome was the most common comorbidity but did not affect the outcome. A good preoperative range of motion, good hand function and less pain were associated with better outcomes.

Conclusion: Younger age, a high level of preoperative pain, psoriatic arthritis and atopic disease were factors associated with a worse outcome of trigger finger surgery. Pain and disability decreased 3 months postoperatively and continued to decrease between 3 and 12 months.

Background: Infertility along with fertility treatments has been reported to have a devastating effect on the well-being of the individuals involved as well as their relationship. So far, the studies exploring the impact on the relationship have mainly focused on heterosexual couples facing infertility and undergoing treatment. There is, therefore, a lack of data on the potential role of sexual orientation, gamete origin, as well as treatment success on the risk of separation after fertility treatment. The purpose of this study was, thus, to explore whether sexual orientation, donation treatment, and fertility success affected the relationship well-being and to explore various separation-related aspects.

Methods: We have performed a prospective cohort study of heterosexual and homosexual couples undergoing fertility treatment with autologous and donated gametes in Sweden and followed them for up to 10 years after receiving fertility treatment. In the current follow-up study, 660 individuals have been included.

Results: Almost 39% of lesbian couples participating reported having separated as opposed to 11-17% of heterosexual couples undergoing treatment with own or donated gametes. Neither background factors nor treatment success protected against separation. By using the relationship satisfaction ENRICH tool, we were able to demonstrate that dissatisfaction of one of the lesbian spouses or heterosexual spouses undergoing oocyte donation increased significantly the risk of separation 8-10 years after treatment commencement.

Conclusion: The findings can be used by fertility clinics to provide relationship tools to the treated couples in order to help them nurture their relationship and decrease the risk of separation in the long run.

Background: Diffuse astrocytomas preferentially infiltrate eloquent areas affecting the outcome. A preoperative understanding of isocitrate dehydrogenase (IDH) status may offer opportunities for specific targeted therapies impacting treatment management. The aim of this study was to analyze clinical, topographical, radiological in WHO 2 astrocytomas with different IDH status and the long-term patient's outcome.

Methods: A series of confirmed WHO 2 astrocytoma patients (between 2005 and 2015) were retrospectively analyzed. MRI sequences (FLAIR) were used for tumor volume segmentation and to create a frequency map of their locations into the Montreal Neurological Institute (MNI) space. The Brain-Grid (BG) system (standardized radiological tool of intersected lines according to anatomical landmarks) was used as an overlay for infiltration analysis of each tumor. Long-term follow-up was used to perform a survival analysis.

Results: Forty patients with confirmed IDH status (26 IDH-mutant, IDHm/14 IDH-wild type, IDHwt) according to WHO 2021 classification were included with a mean follow-up of 7.8 years. IDHm astrocytomas displayed a lower number of BG-voxels (P < 0.05) and were preferentially located in the anterior insular region. IDHwt group displayed a posterior insular and peritrigonal location. IDHwt group displayed a shorter OS compared with IDHm (P < 0.05), with the infiltration of 7 or more BG-voxels as an independent factor predicting a shorter OS.

Conclusions: IDHm and IDHwt astrocytomas differed in preferential location, number of BG-voxels and OS at long follow-up time. The number of BG-voxels affected the OS in IDHwt was possibly reflecting higher tumor invasiveness. We encourage the systematic use of alternative observational tools, such as gradient maps and the Brain-Grid analysis, to better detect differences of tumor invasiveness in diffuse low-grade gliomas subtypes.

Background and aim: As the spleen plays a significant role in immunity, the aim was to investigate the associations of different body composition markers derived from various sources with spleen volume in a general population sample.

Materials and methods: Cross-sectional data of 1095 individuals (570 women; 52%) aged between 30 and 90 years were collected in the Study of Health in Pomerania (SHIP-START-2). We measured spleen volume by magnetic resonance imaging (MRI).Body composition markers were derived from classic anthropometry, bioelectrical impedance analysis, including absolute fat mass (FM) and fat-free mass (FFM), as well as from MRI, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and liver fat content. Sex-stratified-adjusted linear regression models were used to analyze the associations of body composition markers with spleen volumes.

Results: We observed positive associations of body mass index, body weight, waist circumference, hip circumference, waist-to-height ratio, absolute FM, absolute FFM, and VAT and SAT with spleen volume in men and women. An 8.12 kg higher absolute FFM was associated with a 38.4 mL (95% confidence interval [CI]: 26.7-50.1) higher spleen volume in men and a 5.21 kg higher absolute FFM with a 42.6 mL (95% CI: 26.2-59.0) higher spleen volume in women.

Conclusion: Our findings indicate that obesity-related body composition markers and FFM are associated with a higher spleen volume. Particularly, higher absolute FFM showed a strong association with a larger spleen volume in both men and women. Further studies are warranted to understand the clinical significance of body composition markers on large spleen volume.

Mutations in the TP53 tumor suppressor gene occur with high prevalence in a wide range of human tumors. A significant fraction of these mutations (around 10%) are nonsense mutations, creating a premature termination codon (PTC) that leads to the expression of truncated inactive p53 protein. Induction of translational readthrough across a PTC in nonsense mutant TP53 allows the production of full-length protein and potentially restoration of normal p53 function. Aminoglycoside antibiotics and a number of novel compounds have been shown to induce full-length p53 in tumor cells carrying various TP53 nonsense mutations. Full-length p53 protein generated by translational readthrough retains the capacity to transactivate p53 target genes and trigger tumor cell death. These findings raise hopes for efficient therapy of TP53 nonsense mutant tumors in the future.

Cancer-associated fibroblasts (CAFs) are a heterogeneous cell population recognized as a key component of the tumour microenvironment (TME). Cancer-associated fibroblasts are known to play an important role in maintaining and remodelling the extracellular matrix (ECM) in the tumour stroma, supporting cancer progression and inhibiting the immune system's response against cancer cells. This review aims to summarize the immunomodulatory roles of CAFs, particularly focussing on their T-cell suppressive effects. Cancer-associated fibroblasts have several ways by which they can affect the tumour's immune microenvironment (TIME). For example, their interactions with macrophages and dendritic cells (DCs) create an immunosuppressive milieu that can indirectly affect T-cell anticancer immunity and enable immune evasion. In addition, a number of recent studies have confirmed CAF-mediated direct suppressive effects on T-cell anticancer capacity through ECM remodelling, promoting the expression of immune checkpoints, cytokine secretion and the release of extracellular vesicles. The consequential impact of CAFs on T-cell function is then reflected in affecting T-cell proliferation and apoptosis, migration and infiltration, differentiation and exhaustion. Emerging evidence highlights the existence of specific CAF subsets with distinct capabilities to modulate the immune landscape of TME in various cancers, suggesting the possibility of their exploitation as possible prognostic biomarkers and therapeutic targets.

Background: Staging and treatment of rectal cancer have evolved over several decades with considerably fewer locoregional recurrences but no marked improved survival since systemic recurrence risks remain virtually unchanged. This development will briefly be summarised followed by a thorough discussion of two recent developments.

Methods: A systematic approach towards the literature is aimed at focusing on organ preservation and the delivery of all non-surgical treatments prior to surgery or total neoadjuvant treatment (TNT).

Results: Organ preservation, that is to defer surgery if the tumour happens to disappear completely after any pre-treatment given to locally advanced tumours to decrease recurrence risks has increased in popularity and is, if not universally, widely accepted. To give neo-adjuvant treatment to intentionally obtain a clinically complete remission to avoid surgery is practised in some environments but is mostly still experimental. TNT, that is to provide both radiotherapy and chemotherapy aimed at killing microscopic disease in the pelvis or elsewhere has been subject to several trials. Collectively, they show that the chance of achieving a complete response, pathologically or clinically, has approximately doubled, increasing the chance for organ preservation, and the risk of distant metastasis has decreased at least in some trials. The best schedule remains to be established.

Conclusions: To obtain substantial progress and also improve survival, the systemic treatments need to be improved even if preoperative delivery is more effective and better tolerated than postoperative. The locoregional treatment may be further optimised through better risk prediction.

Background: Treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduces low-density lipoprotein cholesterol (LDL-C) levels and decreases the incidence of major ischaemic events in clinical trials. However, less is known about the efficacy of PCSK9 inhibition in clinical practice. This study aimed to describe the change in LDL-C levels over time and LDL-C goal achievement in patients with/without atherosclerotic cardiovascular disease (ASCVD), who were prescribed evolocumab in clinical practice, and to describe adherence to and persistence with treatment.

Methods: Patients in Sweden with at least one evolocumab prescription filled between July 2015 and May 2020 were included. Medical history and lipid-lowering therapy (LLT) were sourced from national registries. LDL-C levels before and after treatment initiation were assessed using medical records. Persistence with and adherence to evolocumab and oral LLT were assessed up to 12 months after treatment initiation using the refill-gap method and proportion of days covered, respectively.

Results: Of the 2,360 patients with at least one prescription for evolocumab, 2,341 were included; 1,858 had ASCVD. Persistence with (76%) and adherence to (86%) evolocumab were high throughout the 12 months following initiation. Mean LDL-C levels decreased by 53% (95% confidence interval [CI]: 51-55%) in patients adherent to evolocumab (n = 567) and 59% (95% CI: 55-63%) in patients adherent to evolocumab and oral LLT (n = 186). Similar reductions in LDL-C were observed in patients with/without ASCVD. Reduced LDL-C levels remained stable during follow-up. Amongst patients adherent to evolocumab and those adherent to evolocumab and oral LLT, 23 and 55% achieved the LDL-C goal of <1.4 mmol/L, respectively.

Conclusions: The evolocumab LDL-C-lowering effect observed in clinical trials was confirmed in clinical practice in Sweden, particularly in patients also treated with oral LLT. During follow-up, adherence to and persistence with evolocumab were high, with stable reduced levels of LDL-C during observation.