Lapland Central Hospital

Breast cancer is hallmarked by phenotypic transitions enabling abnormal cell proliferation and invasion. The stress-protective transcription factor heat shock factor 2 (HSF2) is associated with cancer, but its function in breast carcinogenesis remains poorly understood. Analysis of human breast tumor samples and mouse in vivo xenografts uncovered that HSF2 expression and activity undergo dynamic changes as a function of tumor progression. HSF2 expression, nuclear localization, and coexpression with the proliferation marker Ki67 are increased in ductal carcinoma in situ (DCIS), suggesting that HSF2 designates hyperplastic cells underlying tumor expansion. In mouse xenografts, HSF2 localization switches from nuclear to cytoplasmic upon DCIS-to-invasive transition. Using cell-based models, we identify canonical transforming growth factor–β (TGF-β) signaling as the molecular mechanism regulating HSF2. TGF-β–mediated down-regulation of HSF2 allowed acquisition of an invasive cell phenotype, which was counteracted by ectopic HSF2. Together, we propose that HSF2 acts as a stage-specific switch between proliferation and invasion in breast cancer.

BackgroundIn patients with some cardiovascular disease conditions, slightly elevated body mass index (BMI) is associated with a lower mortality risk (termed “obesity paradox”). It is uncertain, however, if this obesity paradox exists in patients who have had invasive cardiology procedures. We evaluated the association between BMI and mortality in patients who underwent coronary angiography.MethodsWe utilised the KARDIO registry, which comprised data on demographics, prevalent diseases, risk factors, coronary angiographies, and interventions on 42,636 patients. BMI was categorised based on WHO cut‐offs or transformed using P‐splines. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated for all‐cause mortality.ResultsDuring a median follow‐up of 4.9 years, 4688 all‐cause deaths occurred. BMI was nonlinearly associated with mortality risk: compared to normal weight category (18.5–25 kg/m2), the age‐adjusted HRs (95% CIs) for all‐cause mortality were 1.90 (1.49, 2.43), 0.96 (0.92, 1.01), 1.04 (0.99, 1.09), 1.08 (0.96, 1.20), and 1.45 (1.22, 1.72) for underweight (<18.5 kg/m2), preobesity (25 to <30 kg/m2), obesity class I (30 to <35 kg/m2), obesity class II (35 to <40 kg/m2), and obesity class III (>40 kg/m2), respectively. The corresponding multivariable adjusted HRs (95% CIs) were 2.00 (1.55, 2.58), 0.92 (0.88, 0.97) 1.01 (0.95, 1.06), 1.10 (0.98, 1.23), and 1.49 (1.26, 1,78), respectively.ConclusionsIn patients undergoing coronary angiography, underweight and obesity class III are associated with increased mortality risk, and the lowest mortality was observed in the preobesity class. It appears the obesity paradox may be present in patients who undergo invasive coronary procedures.

BackgroundDrugs with histone deacetylase inhibitory (HDACi) properties have shown to decrease prostate cancer (PCa) cell growth in vitro.MethodsA cohort of 9261 PCa cases from the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) was used to evaluate prostate cancer-specific mortality in men using anti-epileptic drugs (AEDs). A national subscription database was used to obtain information on medication use. Cox regression with AED use as a time-dependent variable was used to analyse prostate cancer mortality in men using AEDs compared to non-users, and in men using HDACi AEDs compared to users of other AEDs. The analysis was adjusted for age, screening trial arm, PCa risk group, primary treatment of PCa, Charlson co-morbidity score and concomitant use of other drugs.ResultsThe use of AEDs, in general, was associated with an increased risk of PCa death. The use of HDACi AEDs was not significantly associated with decreased PCa mortality compared to use of other AEDs (HR 0.61, 95% CI 0.31–1.23).ConclusionsAED usage is associated with elevated PCa mortality compared to non-users, likely reflecting the differences between men with epilepsy and those without. No benefit was observed from HDACi drugs compared to other AEDs.

ABSTRACT Chediak-Higashi syndrome (CHS) is a rare autosomal disorder characterized by immunodeficiency, albinism, and progressive neurologic abnormalities. While survivors of the childhood-onset disease are known to exhibit learning disabilities and neuropsychiatric disorders followed by middle-age dementia, we lack detailed data on the progression. We present the case of a young adult with records from infancy to the first signs of deterioration. An early neuropsychological and neuropsychiatric profiling is crucial to intervention selection as children with CHS may not benefit from regular special education. Our patient never showed neuropsychiatric symptoms but high levels of socioemotional adaptability.

Abstract Background Real-life long-term evidence on ustekinumab treatment in patients with Crohn’s disease (CD) is limited. We performed a retrospective non-interventional nation-wide chart review study of dosing and long-term clinical outcomes in Finnish CD patients treated with ustekinumab (FINUSTE2, EUPAS30920). Methods FINUSTE2 was carried out in 17 Finnish centres. Eligible patients were adults with CD, receiving an intravenous (IV) first dose of ustekinumab during 2017 or 2018. Data on disease activity, dosage, and concomitant medications were collected at baseline, 16 weeks, and 1 year from treatment initiation. All measurements on ustekinumab trough concentrations (TC) were recorded. Results The study included 155 patients (48% female) with a mean age of 44 and disease duration of 14 years. The disease was stricturing or penetrating in 69% of patients, 59% had prior CD-related surgeries, and 96% had a treatment history of at least one biologic agent. After one IV dose and one to two subcutaneous (SC) doses at 8 to 16 weeks, 140 patients (93%) continued to maintenance treatment with SC ustekinumab, of which nearly three-quarters with a dosage interval of 8 weeks (Figure 1). Of 93 patients with a follow-up of at least 1 year, 77 were still on ustekinumab. During follow-up, 55 patients (39%) had their ustekinumab dose adjusted, mostly (n = 44, 31.4%) as a shortening of the dosage interval. Forty-nine patients had in total 65 ustekinumab TC measurements performed, with a mean of 2.2 µg/ml at 16 weeks (n = 23) and 2.7 µg/ml at 1 year (n = 25). In 67% of cases, the reason for measuring TC was lack of or insufficient response. No anti-drug antibodies appeared at any time point. The proportion of patients on ustekinumab monotherapy increased significantly, from 34% (n = 52) at baseline to 54% (n = 79/146; p &amp;lt; 0.001) at 16 weeks and 64% (n = 49/77; p &amp;lt; 0.01) at 1 year. Correspondingly, corticosteroid use decreased significantly, and a trend towards reduced use of immunomodulators was observed (Figure 2). Conclusion In this nationwide real-life study, treatment with ustekinumab in patients with longstanding and complicated CD was persistent and allowed for significant corticosteroid tapering. A vast majority started the maintenance treatment with an 8-week dosage interval and nearly one-third of all patients required a dose increase, suggesting a highly refractory disease phenotype. The lack of detected antidrug antibodies during follow-up indicates low immunogenicity for ustekinumab.

The aim of this study was to evaluate the effect of increasing screening-to-labor interval on the performance of group B streptococcus (GBS) screening by late-pregnancy enriched culture compared with intrapartum real-time polymerase chain reaction (RT-PCR). Group B streptococcus colonization was determined in 2624 women with singleton pregnancies by culture at 35-37weeks of gestation and at the beginning of labor by culture and RT-PCR from recto-vaginal swab samples. Group B streptococcus colonization rates were 29.0% in late-pregnancy culture, 29.7% in intrapartum culture and 28.2% in intrapartum PCR. Intrapartum culture was used as a reference, the late-pregnancy culture had an overall sensitivity of 89.2% (95% CI 88.0%-90.4%) and specificity of 96.5% (95% CI 95.8%-97.2%), and intrapartum PCR had sensitivity of 91.5% (95% CI 90.4%-92.6%) and specificity of 98.5% (95% CI 98.0%-99.0%). However, up to 4weeks after screening, the sensitivity of late-pregnancy culture was equivalent to or higher than that of RT-PCR. The RT-PCR was invalid in 0.9% of the women. Between late-pregnancy screening and labor, GBS colonization changed from negative to positive in 3.2% and from positive to negative in 2.5% of the women. The late-pregnancy enriched culture and intrapartum RT-PCR have comparable sensitivities in the detection of GBS when culture screening is conducted no more than 4weeks before labor. Late-pregnancy culture sampling should be postponed to at least 37weeks of gestation.

Background: In general, nature relatedness is positively associated with physical activity, health, and subjective well-being. However, increased residence in urban areas, and the decrease in natural spaces, may affect the younger generation most adversely. The associated environmental changes can increase youths’ risk of spending most of their time indoors, and weaken their nature relatedness, making them less likely to enjoy nature’s health benefits. This is a serious public health issue, since inadequate physical activity, combined with minimum time spent in green space, can affect health across the whole lifespan. Thus, to develop effective interventions for physical activation and promote health and well-being among young men, further knowledge of the determinants of their nature relatedness is necessary. Aims: To explore factors related to nature relatedness, including physical activity, physical activity with parents, and residential environment. Methods: The study population consisted of all 914 young men (mean—17.8 years; SD—0.5) who participated in mandatory call-ups for military service and completed the study questionnaire in 2013. The questionnaire inquired about their nature relatedness, demographic characteristics, socioeconomic status, physical activity, health, and subjective well-being. A geographic information system (GIS) was used to assess the features of their residential environments. Multivariable linear regression was used to analyze the data. Results: Physical activity (p = 0.021) and physical activity with parents at primary school age (p = 0.007), and currently (p = 0.001) as well as good self-rated health (p = 0.001), and father’s higher socioeconomic status (p = 0.041), were positively connected to nature relatedness. Conclusions: Physical activity in general, physical activity with parents, and nature relatedness were positively related. This knowledge can be utilized in promoting physical activity and health among young men.

Over the past decades, laparoscopic colorectal surgery has become widely used for various indications. Large multicenter studies have demonstrated that laparoscopy has clear advantages over open surgery. Compared to open procedures, laparoscopy decreases perioperative blood loss, post-operative pain, and hospitalization time, but provides equivalent long-term oncological and surgical results. Most studies have been conducted in high-volume institutions with selected patients, which may have influenced the reported outcome of laparoscopy. Here, we investigated the primary outcome of all laparoscopic colorectal resections performed between 2005 and 2015 in a low-volume center. This retrospective study included bowel resections performed between 2005 and 2015 in the Lapland Central Hospital. Data were retrieved from electronic patient registries, and all operations that began as a laparoscopy were included. Patient records were investigated to determine the primary surgical outcome and possible complications within the first 30 days after surgery. During 2005-2015, 385 laparoscopic colorectal resections were performed. Indications included benign (n = 166 patients, 43.1%) and malignant lesions (n = 219 cases, 56.9%). The median patient age was 68 years, and 50.4% were male. The median American Society of Anesthesiologist score was III, and 48.5% of patients had an American Society of Anesthesiologist class of III or IV. The median hospital stay after surgery was 6 days (interquartile range: 3.8). The conversion rate to open surgery rate was 13%. The total surgical complication rate was 24.2%, and re-operation was required in 11.2% of patients. A total of 26 patients had anastomotic leakage, of which 16 required re-operations. The 30-day mortality was 0.8%. Our results showed that laparoscopic colorectal surgery in a peripheral hospital resulted in primary outcome rates within the range of those reported in previous multicenter trials. Therefore, the routine use of laparoscopic colorectal resections with high-quality outcome is feasible in small and peripheral surgical units.