Helsinki University Research Articles

Notes on Contributors

Notes on Contributors

340.4: Accessibility to the Kidney Transplantation Beyond Immunology

Background: Kidney transplantation (KT) has proven to be the preferable kidney replacement therapy (KRT) as it provides a better survival and quality of life. Well-known patient-related factors influencing patients’ access to KT are blood type, age, comorbidities, and pre-sensitization to HLA antigens. Research on home dialysis modalities´ effect on this matter is scarce. Methods: We included all adult patients who started kidney replacement therapy (KRT) between 2004 and 2017 in the Helsinki University Hospital treated with home dialysis modalities (N=536), including home hemodialysis (HHD) and peritoneal dialysis; both CAPD and APD. A control group of in-center HD (ICHD) patients was randomly selected (N=200). The patients were followed-up until kidney transplantation, death, or end of follow-up in December 2020. We retrieved from registries variables with a potential effect on access to transplantation, of special interest we considered dialysis modality at 90 days after initiating KRT. Results: In all, 481 out of 736 patients were waitlisted for kidney transplantation, of whom 423 were transplanted (88%), 23 patients (5%) died on the waitlist (WL), 24 were permanently removed from the WL (5%) and 11 were still on the WL at the end of FU. The probability of waitlisting was 2.1 as high in CAPD patients (p=0.004), and 7.9 times as high in both APD and HHD patients (p<0.001) compared to ICHD. Cardiovascular morbidity did not affect waitlisting. Of those who were waitlisted, both ICHD (N=74) and CAPD (N=80) patients were older than APD (N=199) and HHD (N=128) patients (mean age 54; 56; 48 and 49 YO respectively). Mean (95% CI) time elapsed from KRT initiation to WL inclusion was 307 days (251-362), time from WL to KT was 458 days (542-636) and time off the WL due to an intercurrence was 96 days (80-112). There were no differences between dialysis modalities in terms of time from WL to KT (p=0.176), but time to WL was significantly longer in ICHD patients (p=0.014) (Figure 1) The time off the WL equally delayed KT irrespective of the dialysis mode. (p=0.141) Dialysis modalities had an impact on the time elapsed from WL to KT (log rank p=0.028). (Figure 2) By Cox regression analysis the variables that were significantly related with the outcome were panel reactive antibodies type 1 (p=0.033), and time off the WL (p<0.001), while cardiovascular comorbidity (p=0.246), dialysis modality (p=0.208), malignancy (p=0.675), panel reactive antibodies type 2 (p=0.679) and age (p=0.054) did not reach the level of significance. Altogether 732 episodes resulted in the patients being temporarily removed from the WL, and the most common reasons were PD-peritonitis (20%), other infections (26%), and surgery/dental treatment (10%). On the other hand, both vascular access complications (1%) and cardiovascular intercurrences (4.9%) were uncommon. Conclusions: Dialysis modality significantly influences patients’ access to transplantation. APD and HHD modalities provided a benefit in terms of accessing the WL. In patients wait listed, intercurrent complications during dialysis, mainly infections, significantly prolonged the waiting time for KT in all patients beyond immunological reasons.

Eye Injuries Caused by Wooden Projectiles in Finland.

Eye injuries can cause decreased vision or even blindness, and predispose to future complications. Wood as an independent cause of eye injuries has infrequently been the focus of the studies. The aim of this study is to report the current population-based epidemiology, treatment, use of resources and outcomes of eye injuries caused by sticks, branches, and other wooden projectiles in Finland. The study included all patients injured by wooden projectiles with ocular or orbital traumas over a 1-y period. Patients were treated at the Helsinki University eye hospital, which covers a population of 1.5 million. The follow-up time was 3 mo. Wooden projectiles caused 67 eye injuries and compromised 6% of all eye traumas during 1 y. Of the patients, males predominated (76%) and 22% were children under 17 y. Injury was most likely in spring (36%) and in males aged 51 to 67 y. The most common activity to cause injury was playing (27%), but in relation to time spent in each activity, the highest risk for eye injury was in gardening. Diagnoses were mild superficial trauma (54%), blunt ocular trauma (37%), eyelid wound (4%), orbital fracture (3%), and open globe trauma (1%). Permanent disability was estimated for 10% and a need for lifelong follow-up was estimated for 37%. Eleven patients needed major surgeries. Wooden projectiles often cause serious eye injuries, permanent disability, and a need for lifelong follow-up. Caution is required to protect the eyes when playing with sticks and during gardening, forest work, and woodwork.

Quantitative Fecal Microbiota Profiles Relate to Therapy Response During Induction With Tumor Necrosis Factor α Antagonist Infliximab in Pediatric Inflammatory Bowel Disease.

The role of intestinal microbiota in inflammatory bowel diseases is intensively researched. Pediatric studies on the relation between microbiota and treatment response are sparse. We aimed to determine whether absolute abundances of gut microbes characterize the response to infliximab induction in pediatric inflammatory bowel disease. We recruited pediatric patients with inflammatory bowel disease introduced to infliximab at Children's Hospital, University of Helsinki. Stool samples were collected at 0, 2, and 6 weeks for microbiota and calprotectin analyses. We defined treatment response as fecal calprotectin value <100 µg/g at week 6. Intestinal microbiota were analyzed by 16S ribosomal RNA gene amplicon sequencing using the Illumina MiSeq platform. We analyzed total bacterial counts using quantitative polymerase chain reaction and transformed the relative abundances into absolute abundances based on the total counts. At baseline, the intestinal microbiota in the treatment responsive group (n = 10) showed a higher absolute abundance of Bifidobacteriales and a lower absolute abundance of Actinomycetales than nonresponders (n = 19). The level of inflammation according to fecal calprotectin showed no statistically significant association with the absolute abundances of fecal microbiota. The results on relative abundances differed from the absolute abundances. At the genus level, the responders had an increased relative abundance of Anaerosporobacter but a reduced relative abundance of Parasutterella at baseline. High absolute abundance of Bifidobacteriales in the gut microbiota of pediatric patients reflects anti-inflammatory characteristics associated with rapid response to therapy. This warrants further studies on whether modification of pretreatment microbiota might improve the outcomes.

End-of-life care of patients with esophageal or gastric cancer: decision making and the goal of care

Background Overall survival (OS) with advanced esophageal or gastric cancer is poor. To avoid overly aggressive treatments at the end-of-life and assure adequate end-of-life quality, the decision to focus on symptom-centered palliative care (PC) and terminate anticancer treatments, i.e., the PC decision, should be made in time. Material and methods We reviewed the charts of patients (N = 160) with esophageal or gastric cancer treated at the Department of Oncology at Helsinki University Central Hospital in 2013 and deceased by December 2014. The use of acute services (Emergency department (ED) visits and hospitalizations) and places of death were compared according to the timing of the PC decision. Reasons for ED visits and hospitalizations were collected. Results The median OS from diagnosis of advanced cancer was 6 months. Anti-cancer treatments were never started for 34% of the patients. The PC decision was made early (>30 days before death) for 54% of the patients and late (≤30 days before death) or not at all for 46%. Patients with late or no PC decision died more often in tertiary/secondary hospital (29 versus 7%, p = 0.001) and had more ED visits (49 versus 29%, p < 0.001) and hospitalizations (53 versus 28%, p = 0.001) in their last month, and visited the PC unit less often (18 versus 69%, p < 0.001), than the patients with early PC decision. The ED visits were most commonly related to cancer progression, and clinical deterioration (17%), fever (16%), and dysphagia (15%) were the most common symptoms. Conclusion The decision to focus on PC and terminate anticancer treatments, i.e., the PC decision, was made late or not at all in every other patient, leading to increased tertiary/secondary hospital service use and deaths at tertiary/secondary hospital. Early decision-making increased end-of-life care at specialized PC services or at home, implying better end-of-life care.

Risk factors for evaluating early mortality after microvascular reconstruction of head and neck cancers.

Free tissue transfer reconstruction carries significant complication rates in surgical head and neck oncology. A registry-based approach offers a possibility to investigate the factors affecting increased morbidity and early mortality, that is, death within 6 months of treatment. A retrospective registry review was conducted on a series of 317 consecutive microvascular free tissue transfers in head and neck cancer patients performed during 2013-2017 at the Helsinki University Hospital (Helsinki, Finland). All surviving patients had a minimum follow-up of 2 years (range 24-84 months). Overall, 36 (11.4%) early deaths occurred in this series. In multivariable logistic regression analysis, patients aged 75 years and older (p = 0.019), Adult Comorbidity Evaluation-27 (ACE-27) score of 3 (p = 0.048), tumor class T3 (p = 0.005), lymph node class N2 (p = 0.014), or thrombocyte count of 360 (× 109 L) or more (p = 0.001) were more likely to die within 6 months of surgery. Of these 36 patients, 27 (75%) had a complication warranting hospital care and most (n = 22, 61%) had several complications. Early postoperative mortality most frequently affects patients aged 75 years and above, with a high ACE-27 score, advanced tumor stage, or high thrombocyte count. Therefore, preoperative assessment and patient selection should have a crucial role in this patient population.

Development and external validation of DISPAIR fistula risk score for clinically relevant postoperative pancreatic fistula risk after distal pancreatectomy.

Highly utilized risk scores for clinically relevant postoperative pancreatic fistula (CR-POPF) have guided clinical decision-making in pancreatoduodenectomy. However, none has been successfully developed for distal pancreatectomy. This study aimed to develop and validate a new fistula risk score for distal pancreatectomy. Patients undergoing distal pancreatectomy at Helsinki University Hospital, Finland from 2013 to 2021, and at Karolinska University Hospital, Sweden, from 2010 to 2020, were included retrospectively. The outcome was CR-POPF, according to the 2016 International Study Group of Pancreatic Surgery definition. Preoperative clinical demographics and radiological parameters such as pancreatic thickness and duct diameter were measured. A logistic regression model was developed, internally validated with bootstrapping, and the performance assessed in an external validation cohort. Of 668 patients from Helsinki (266) and Stockholm (402), 173 (25.9 per cent) developed CR-POPF. The final model consisted of three variables assessed before surgery: transection site (neck versus body/tail), pancreatic thickness at transection site, and diabetes. The model had an area under the receiver operating characteristic curve (AUROC) of 0.904 (95 per cent c.i. 0.855 to 0.949) after internal validation, and 0.798 (0.748 to 0.848) after external validation. The calibration slope and intercept on external validation were 0.719 and 0.192 respectively. Four risk groups were defined in the validation cohort for clinical applicability: low (below 5 per cent), moderate (at least 5 but below 30 per cent), high (at least 30 but below 75 per cent), and extreme (75 per cent or more). The incidences in these groups were 8.7 per cent (11 of 126), 22.0 per cent (36 of 164), 63 per cent (57 of 91), and 81 per cent (17 of 21) respectively. The DISPAIR score after distal pancreatectomy may guide decision-making and allow a risk-adjusted outcome comparison for CR-POPF.

Decrease in paediatric emergency room visits during the COVID-19 pandemic restrictions: A population-based study.

AimTo investigate paediatric emergency room (ER) visits to evaluate the immediate health effects of COVID‐19 pandemic restrictions on children.MethodsWe retrospectively examined paediatric ER visits in the Helsinki University Hospital (HUH) district during the first wave of the pandemic (1 March to 31 May 2020), and a 2‐month period immediately before and after. These periods were compared to the corresponding time periods in 2015–2019 (“reference period”).ResultsThe total number of ER visits decreased by 23.4% (mean 6474 during the reference period, to 4960 during the pandemic period (incidence rate ratio [IRR] 0.75, 95% confidence interval 0.72 to 0.77; p < 0.001). This was due to a decrease in visits related to infectious diseases; visits due to surgical reasons did not decrease. The amount or proportion of patients triaged to the most urgent class (Emergency Severity Index 1) did not increase. Paediatric ER visits returned to baseline after lifting of restrictions.ConclusionsAlthough paediatric ER visits substantially decreased during the pandemic restrictions, children seen at the ER were not more severely ill. Our results do not indicate immediate detrimental health effects of pandemic control measures on children.

Comparison of primiparous women's childbirth experience in labor induction with cervical ripening by balloon catheter or oral misoprostol - a prospective study using a validated childbirth experience questionnaire (CEQ) and visual analogue scale (VAS).

Primiparity and labor induction, especially when cervical ripening is required, are risk factors for a negative childbirth experience. Our aim was to compare childbirth experience in primiparous women with cervical ripening by balloon catheter or oral misoprostol using the validated Childbirth Experience Questionnaire (CEQ). We also wanted to compare assessment of a negative childbirth experience by visual analogue scale (VAS) and CEQ. This is a prospective study of 362 primiparous women undergoing cervical ripening and labor induction by balloon catheter (67.4%) or oral misoprostol (32.6%) at Helsinki University Hospital, Finland, between January 1, 2019 and January 31, 2020. After delivery, the women assessed their childbirth experience using the CEQ, and patient records provided the patient characteristics, delivery outcomes and VAS ratings. We analyzed the results using IBM SPSS Statistics. Overall, the women experienced their labor and delivery rather positively, with a mean CEQ score of 2.9 (SD 0.6) (scale 1-4), and no differences were detectable when comparing women with cervical ripening by balloon catheter or misoprostol. However, women with balloon catheter were more often satisfied with the method chosen for them and would choose the same method in a future pregnancy. Compared with CEQ, VAS seems mainly to reflect the women's perception of their own capacity to give birth and the safety of the hospital setting, not the level of professional support or participation in decision-making. According to our results, CEQ and VAS are comparable, but the usability of the CEQ is limited by its inability to distinguish the most negative and the most positive experiences, and the VAS is limited by its simplicity. Women with cervical ripening by balloon catheter or oral misoprostol experienced their childbirth rather positively, results being similar in both groups. However, women with cervical ripening by balloon catheter were more content with their labor induction. The CEQ and VAS can both be used to assess the childbirth experience of primiparous women undergoing labor induction, but both methods have limitations.

Long-Term Follow-Up After Cervical Laminectomy without Fusion for Cervical Spondylotic Myelopathy

The objectives were to study the effect of cervical laminectomy without fusion on the incidence of further cervical surgeries, the risk for cervical misalignment, and current functional status. We retrospectively analyzed the clinical data of 340 patients who had undergone simple laminectomy for cervical spondylotic myelopathy (CSM) at Helsinki University Hospital between 2000 and2011. Forty-one patients (12.1%) had later undergone another cervical surgery during the follow-up of a mean of 8.5 years (maximum, 17.5 years). The most common indication for further surgery was residual stenosis at adjacent or other cervical levels (34%). Five patients (1%) required further surgery for correction of a sagittal balance problem. The mean Neck Disability Index was 28% at a median of 9.0 years after laminectomy. The mean EQ-5D (EuroQol 5 Dimension 3 Level) index score was 58.8 for patients and 77.2 for age-matched and gender-matched general population controls (P= 0.000), indicating patients' reduced health-related quality of life. Worse preoperative condition in the Nurick score was related to a lower (i.e., worse) EQ-5D score. In an additional arm of the study with radiographic imaging (40 patients), the mean change in sagittal alignment was 4.0° toward lordotic, and a newly developed kyphosis was found in 7.5% of patients. Because CSM is a serious degenerative progressive condition resulting in decreased health-related quality of life even after surgical treatment, the low rate of corrective surgery needed for alignment issues per se indicates that simple laminectomy can be a viable treatment option in treating multilevel CSM.

Effectiveness of mobile-delivered, therapist-assisted cognitive behavioral therapy for insomnia in nationwide routine clinical care in Finland.

Internet-delivered cognitive behavioral therapies (iCBTs) are efficacious for insomnia. Few studies have as yet reported their effectiveness in routine care. The objective of this study was to examine the effectiveness of the new Finnish 7-session HUS Helsinki University Hospital-iCBT for Insomnia (HUS-iCBTI) program in nationwide routine care. We studied 2,464 physician-referred patients in therapist-supported iCBTI. Treatment was free of charge for patients. The primary measure was the Insomnia Severity Index (ISI); the Patient Health Questionnaire, 4-item version (PHQ-4), and the Alcohol Use Disorders Identification Test (AUDIT-C) were also administered. As many as 75.4% completed the treatment, with the ISI scores declining, on average, by -7.04 points during treatment. Altogether, 91.1% of the completers improved in terms of having a lower ISI score in phase 7 than in phase 1 and 34.0% of the completers achieved remission by phase 7 (ISI score < 8); 46.0% responded to treatment (ISI-score reduction of ≥ 8 points from phase 1). The Cohen's effect size (ISI-score decline) was d = -1.449, showing a large effect. We observed large benefits for this publicly funded therapist-supported treatment in its naturalistic setting as a part of routine care. Effect sizes were comparable to randomized controlled trials reported earlier. HUS-iCBTI appears to be effective as a treatment for insomnia and may also reduce the risk of other adverse health consequences associated with poor sleep. Stenberg J-H, Ritola V, Joffe G, Saarni S, Rosenström T. Effectiveness of mobile-delivered, therapist-assisted cognitive behavioral therapy for insomnia in nationwide routine clinical care in Finland. J Clin Sleep Med. 2022;18(11):2643-2651.

First person – Venkatram Yellapragada

ABSTRACTFirst Person is a series of interviews with the first authors of a selection of papers published in Disease Models & Mechanisms, helping early-career researchers promote themselves alongside their papers. Venkatram Yellapragada is first author on ‘ FGF8–FGFR1 signaling regulates human GnRH neuron differentiation in a time- and dose-dependent manner’, published in DMM. He is a doctoral candidate in the lab of Taneli Raivio at the University of Helsinki, and investigates the modeling of human diseases in vitro in order to identify their underlying pathophysiology.

C-reactive protein and immune-related adverse events as prognostic biomarkers in immune checkpoint inhibitor treated metastatic renal cell carcinoma patients

ABSTARCT Background There is an ongoing need to identify biomarkers for correct patient selection for immune-oncology treatments in metastatic renal cell carcinoma (mRCC). The aim of our study was to evaluate the prognostic role of elevated C-reactive protein (CRP) values and immune-related adverse events (irAEs) to indicate immune checkpoint inhibitors’ (ICIs) efficacy in nivolumab-treated mRCC patients. Materials and methods Data from 96 mRCC patients treated with nivolumab at Comprehensive Cancer Center, Helsinki University Hospital in a real-life setting were collected between 2006 and 2020 retrospectively. Patients’ baseline CRP, on-treatment (<12 weeks) CRP, and reported irAE association to median survival and outcome were analyzed using Kaplan–Meier and Cox regression. Results Patients with elevated baseline CRP were associated with worse overall survival (OS) and progression-free survival (PFS) when compared with normal baseline CRP. This significant correlation was also observed with patients with elevated on-treatment CRP. In multivariate survival analyses both elevated baseline and on-treatment CRP had shorter OS and PFS than patients with normal CRP: hazard ratio (HR) 2.84 (95% CI 1.48–5.42), HR 3.68 (95% CI 1.92–7.03) and PFS: HR 1.77 (95% CI 1.06–2.97), HR 2.88 (95% CI 1.75–4.73), respectively. A significant difference in OS was also seen between patients without irAE and with irAE during treatment. In multivariate survival analyses, patients without irAE had shorter OS HR 1.93 (95% CI 1.03–3.62) compared with patients with reported irAE. Conclusions Elevated baseline CRP, on-treatment CRP, and absence of irAE correlate with poor outcome in nivolumb-treated mRCC patients. These results suggest that monitoring CRP values as well as potential irAEs during treatment may be of use in clinical decision making.

ACUTE PANCREATITIS in HELSINKI in 2016−2018: INCIDENCE, ETIOLOGY and RISK FACTORS - analysis of 1378 acute pancreatitis episodes in a Finnish normal population

Objectives Updated population-based studies on acute pancreatitis (AP) in Finland are lacking. Our aim was to evaluate the current data for AP in Helsinki. Materials and methods We performed an electronic health care records (EHRs) search on AP patients treated at Helsinki University Hospital between the years 2016 − 2018. Incidence was calculated, etiological and potential risk factors, as well as severity of AP were documented and analyzed. Results Between 2016 and 2018 we found 1378 AP episodes on 1084 patients, 35% of the patients had several AP episodes, i.e., recurrent AP (RAP). The domicile-adjusted incidence was 42.2/100 000. 47% of the patients had alcohol etiology (59% men, 27% women) and 23% had biliary etiology, 21% were idiopathic and 2.9% were post-ERCP pancreatitis. 13.1% of the patients had passed at the end of September 2021. 45% of the patients were currently smoking, 11% were ex-smokers, and the highest percentage of smokers was in the group of alcohol-caused AP with 74% ever-smokers. Biliary AP had the highest amount of overweight patients. 24% of the patients used anticoagulation (AC) medication, and the percentage was significantly higher with idiopathic AP (48%). RAP, female sex and normal BMI associated with a mild form of AP. Conclusions Incidence of AP and the percentage of alcohol etiology are lower than earlier reported for Finland although still higher than in other Nordic countries. Smoking and the use of AC medication associate with AP.

Health-Related Quality of Life After Breast Reconstruction: Comparing Outcomes Between Reconstruction Techniques Using the BREAST-Q

BackgroundReconstruction of the breast following mastectomy can improve patients’ health-related quality of life (HRQL). We aimed to assess HRQL in women after mastectomy and breast reconstruction and to identify differences in HRQL related to the reconstruction method used.MethodsA cross-sectional study was performed on patients who had undergone breast reconstruction in Helsinki University Hospital between 08/2017 and 7/2019. The postoperative HRQL was assessed using the BREAST-Q (2.0) Reconstruction Module. The results were compared between patients with different reconstruction methods using the Kruskal–Wallis test.ResultsA total of 146 patients were identified. Microvascular flaps (n = 77) were the most common method for primary breast reconstruction, followed by latissimus dorsi (LD) flaps (n = 45), fat grafting (n = 18) and implant reconstruction (n = 6). The satisfaction with breasts was high in all groups (median 61, IQR 49–71). The physical well-being of the chest was high regardless of the reconstructive method (median 100, IQR 80–100). However, women with fat grafting reported more adverse effects of radiation (median 17, IQR 14–17 vs. 18, IQR 17–18 for other groups, p = 0.02). Donor site morbidity was low, and patients reported high satisfaction with the back (median 66/100, IQR57-90) and abdomen (median 9/12, IQR 8–10), and physical well-being of the back (median 61/100, IQR 53–70) and abdomen (median 65/100, IQR 60–86).ConclusionsThe patient-reported HRQL after breast reconstruction is high. Most women report being satisfied with the reconstruction, irrespective of the reconstruction method used. The reconstruction method can thus be chosen individually in cooperation between the patient and the surgeon.

Long-term cognitive functioning is impaired in ICU-treated COVID-19 patients: a comprehensive controlled neuropsychological study

BackgroundCognitive impairment has emerged as a common post-acute sequela of coronavirus disease 2019 (COVID-19). We hypothesised that cognitive impairment exists in patients after COVID-19 and that it is most severe in patients admitted to the intensive care unit (ICU).MethodsThis prospective controlled cohort study of 213 participants performed at the Helsinki University Hospital and the University of Helsinki, Finland, comprised three groups of patients—ICU-treated (n = 72), ward-treated (n = 49), and home-isolated (n = 44)—with confirmed COVID-19 between March 13 and December 31, 2020, participating in a comprehensive neuropsychological evaluation six months after the acute phase. Our study included a control group with no history of COVID-19 (n = 48). Medical and demographic data were collected from electronic patient records and interviews carried out four months after the acute phase. Questionnaires filled six months after the acute phase provided information about change in cognitive functioning observed by a close informant, as well as the presence of self-reported depressive and post-traumatic symptoms.ResultsThe groups differed (effect size η2p = 0.065, p = 0.004) in the total cognitive score, calculated from neuropsychological measures in three domains (attention, executive functions, and memory). Both ICU-treated (p = 0.011) and ward-treated patients (p = 0.005) performed worse than home-isolated patients. Among those with more than 12 years of education, ICU-treated patients performed worse in the attention domain than ward-treated patients (p = 0.021) or non-COVID controls (p = 0.045); ICU-treated male patients, in particular, were impaired in executive functions (p = 0.037).ConclusionsICU-treated COVID-19 patients, compared to patients with less severe acute COVID-19 or non-COVID controls, showed more severe long-term cognitive impairment. Among those with more than 12 years of education, impairment existed particularly in the domains of attention and for men, of executive functions.Trial registration number: ClinicalTrials.gov NCT04864938, retrospectively registered February 9, 2021

Craniofacial structures, occlusal features, and TMD symptoms in juvenile idiopathic arthritis patients: a retrospective study.

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory disease in which temporomandibular joint (TMJ) arthritis commonly occurs. It may be asymptomatic and could cause problems in the growing joints. Our aim was to evaluate the craniofacial structures, occlusal features and temporomandibular dysfunction (TMD) symptoms of patients with JIA. The study consisted of 195 JIA patients treated at the Department of Oral and Maxillofacial Diseases, Helsinki University Hospital (HUH), Finland between 2015 and 2019. We retrospectively screened their medical and dental records and classified them according to age at JIA diagnosis (<7 and ≥7 years). Most of the patients had Angle Class I occlusion in both sides. Among all the patients, the mean overjet, and overbite were 3.3 mm and 2.4 mm, respectively. There were more open bite patients in the ≥7 years old group than in the <7 years old group (P = 0.010). Of all patients, 47% reported at least one TMD symptom. The TMD symptoms were more common in participants ≥7 years old than those <7 years old (P = 0.005). Occlusal features and the incidence of malocclusions seem to have similar tendency among the JIA patients with systematic visits in rheumatologist and orthodontist as in the healthy population, except for open bite that is more common with JIA patients. While treating JIA patients, a well-functioning collaboration between paediatric rheumatologists and orthodontists is essential, as well as a clear screening protocol to detect potentially asymptomatic TMJ arthritis. Particular attention should be paid to children with JIA under school age.

Presentation and diagnosis of childhood-onset combined pituitary hormone deficiency: A single center experience from over 30 years.

SummaryBackgroundChildhood-onset combined pituitary hormone deficiency (CPHD) has a wide spectrum of etiologies and genetic causes for congenital disease. We aimed to describe the clinical spectrum and genetic etiologies of CPHD in a single tertiary center and estimate the population-level incidence of congenital CPHD.MethodsThe retrospective clinical cohort comprised 124 CPHD patients (48 with congenital CPHD) treated at the Helsinki University Hospital (HUH) Children's Hospital between 1985 and 2018. Clinical data were collected from the patient charts. Whole exome sequencing was performed in 21 patients with congenital CPHD of unknown etiology.FindingsThe majority (61%;76/124) of the patients had acquired CPHD, most frequently due to craniopharyngiomas and gliomas. The estimated incidence of congenital CPHD was 1/16 000 (95%CI, 1/11 000-1/24 000). The clinical presentation of congenital CPHD in infancy included prolonged/severe neonatal hypoglycaemia, prolonged jaundice, and/or micropenis/bilateral cryptorchidism in 23 (66%) patients; despite these clinical cues, only 76% of them were referred to endocrine investigations during the first year of life. The median delay between the first violation of the growth screening rules and the initiation of GH Rx treatment among all congenital CPHD patients was 2·2 years, interquartile range 1·2–3·7 years. Seven patients harbored pathogenic variants in PROP1, SOX3, TBC1D32, OTX2, and SOX2, and one patient carried a likely pathogenic variant in SHH (c.676G>A, p.(Ala226Thr)).InterpretationOur study suggests that congenital CPHD can occur in 1/16 000 children, and that patients frequently exhibit neonatal cues of hypopituitarism and early height growth deflection. These results need to be corroborated in future studies and might inform clinical practice.FundingPäivikki and Sakari Sohlberg Foundation, Biomedicum Helsinki Foundation, and Emil Aaltonen Foundation research grants.

Examination performance of dentistry students during the COVID-19 pandemic

Objective The global COVID-19 pandemic has led to an increase in remote teaching and online assessment in higher education. The examination performance of undergraduate students of dentistry was evaluated to assess any possible association between the altered learning environment and learners’ performance. Materials and methods Using administrative data from the University of Helsinki, the examination performance during the years 2018 and 2019 was compared with that of 2020. Results In 16 out of 22 courses (73%) taught remotely during the pandemic, a statistically significant difference (p < .05) between the awarded grades was observed, as compared to the two previous years. Annual variation in examination grades was common even before the onset of remote teaching, but more so after it. The grade variation during the pandemic was nearly as prevalent towards falling grades (26%) as towards rising grades (36%), implying a multifactorial cause possibly unrelated to remote teaching. Conclusions Our results imply that online teaching did not systematically improve or worsen the examination performance of undergraduate students of dentistry. Our findings have important policy implications for educational practices in the future. The observed annual grade variation might reflect the effectiveness of remote teaching, changes in students’ performance, or non-systematic grading.

Delay in the initiation of adjuvant chemotherapy in patients with breast cancer with mastectomy with or without immediate breast reconstruction.

BackgroundPatients with breast cancer undergoing mastectomy should be offered the option of immediate breast reconstruction (IBR). The aim of this retrospective study was to assess whether there is a delay in the initiation of adjuvant chemotherapy in patients undergoing mastectomy with or without IBR.MethodThe study included patients aged 70 years or younger with clinically node-negative breast cancer who underwent unilateral mastectomy with IBR (IBR group) or mastectomy alone (no-IBR group) followed by adjuvant chemotherapy at the Helsinki University Hospital between January 2012 to July 2018.ResultsA total of 645 patients were included; 186 in the IBR group and 459 in the no-IBR group. Sixty-six (35.5 per cent) patients in the IBR group and 102 (22.2 per cent) patients in the no-IBR group received their first chemotherapy cycle later than 6 weeks after surgery (P < 0.001). The respective numbers for later than 8 weeks were 17 (9.1 per cent) and 14 (3.1 per cent) (P = 0.001). Among all 645 patients, postoperative complications were a significant risk factor for a delay in the initiation of chemotherapy. Sixty-seven (39.9 per cent) patients with and 101 (21.2 per cent) patients without complications had a delay in chemotherapy (P < 0.001). The delay in chemotherapy was due to complications in 39 (59.1 per cent) in the IBR group and in 28 (27.5 per cent) in the no-IBR group (P < 0.001).ConclusionPatients undergoing mastectomy alone were more likely to receive adjuvant chemotherapy within 6 weeks after surgery compared with the IBR patients. IBR significantly increased the risk of postoperative complications in comparison with mastectomy alone. The complications, in turn, were a significant risk factor for delay in adjuvant chemotherapy.