Pregnancy and neonatal outcomes among women with early-onset colorectal cancer: a nationwide case-control study.

Background: Early-onset colorectal cancer has risen worldwide, leaving more women with colorectal cancer at reproductive ages. We aimed to investigate the risk of adverse pregnancy and neonatal outcomes among women with early-onset colorectal cancer. Methods: We conducted a nationwide, matched case-control study of maternal/pregnancy outcomes including pre-eclampsia and Cesarean delivery (C-section) as well as neonatal outcomes including preterm birth among 207 births in women with early-onset colorectal cancer (ages 18-49) and 1019 births in women without colorectal cancer in Sweden (1992-2019). Early-onset colorectal cancer cases were identified through the Cancer Register, and outcome data were retrieved through linkage to Medical Birth Register and National Patient Register. Using conditional logistic regression, we estimated multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Findings: Between Jan 1, 1992, and Dec 31, 2019, women with early-onset colorectal cancer who gave birth had increased odds of pre-eclampsia (7.2% vs 3.2%; OR = 2.52, 95%CI = 1.25-5.08), any C-section (24.6% vs 19.4%; OR = 1.43, 95%CI = 1.00-2.06), particularly emergency C-section (17.4% vs 10.5%; OR = 1.79, 95%CI = 1.17-2.75), after adjustment for maternal education level, country of birth, body mass index and smoking in early pregnancy, and comorbidities. Maternal history of early-onset colorectal cancer was also associated with offspring preterm birth (12.1% vs 5.2%; OR = 2.31, 95%CI = 1.34-3.99), delineated as spontaneous (OR = 1.06, 95%CI = 0.47-2.39) or medically-indicated preterm birth (OR = 4.48, 95%CI = 2.05-9.79). There was no increased risk of congenital malformation or small for gestational age birth. Interpretation: In this population-based study, maternal history of early-onset colorectal cancer was associated with risk of both adverse pregnancy (pre-eclampsia, C-section) and neonatal outcomes (preterm birth). Funding: US National Institutes of Health, Swedish Society of Medicine, Swedish Cancer Foundation.

Mini-Review on Targeted Treatment of Desmoplastic Small Round Cell Tumor.

Desmoplastic small round cell tumor (DSRCT) is a devastating disease which most commonly affects adolescents, with a male predominance. Despite the best multimodality treatment efforts, most patients will ultimately not survive more than 3-5 years after diagnosis. Some research trials in soft-tissue sarcoma and Ewing sarcoma include DSRCT patients but few studies have been tailored to the specific clinical needs and underlying cytogenetic abnormalities characterizing this disease such as the typical EWSR1-WT1 gene fusion. Downstream activation of EWSR1-WT1 gene fusion includes signaling pathways of platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and insulin growth factor (IGF)-1. Other biological pathways that are activated and expressed in DSRCT cells include endothelial growth factor receptor (EGFR), androgen receptor pathway, c-KIT, MET, and transforming growth factor (TGF) beta. Investigation of somatic mutations, copy number alterations (CNA), and chromosomes in DSRCT samples suggests that deregulation of mesenchymal-epithelial reverse transition (MErT)/epithelial-mesenchymal transition (EMT) and DNA damage repair (DDR) may be important in DSRCT. This mini review looks at known druggable targets in DSRCT and existing clinical evidence for targeted treatments, particularly multityrosine kinase inhibitors such as pazopanib, imatinib, and sorafenib alone or in combination with other agents such as mTOR (mammalian target of rapamycin) inhibitors. The aim is to increase shared knowledge about current available treatments and identify gaps in research to further efforts toward clinical development of targeted agents.

The effect of gestational age on clinical and radiological presentation of necrotizing enterocolitis.

BACKGROUND/PURPOSE: To test the hypothesis that clinical and radiological features of necrotizing enterocolitis vary with gestational age in all neonates with NEC and in subgroup of surgically treated patients. METHODS: This was a retrospective study case series. NEC cases treated in Stockholm County from 2009 to 2014 were identified in the National Quality Register. Patients were included in the study if they had a verified NEC diagnosis and they were divided into 2 groups according to the gestational age. RESULTS: A total of 89 patients were included. Of these 60 (67.4%) neonates had a gestational age <28 and 29 (32.6%) infants ≥28weeks. Surgical NEC patients were 57 (64%). Pneumatosis intestinalis at the abdominal radiographs was noted significantly more often in neonates born at ≥28weeks of gestation (86.2%) compared to extremely preterm newborns (60.0%). Neonates born at ≥28weeks of gestation presented more often bloody stools (58.6%) compared to extremely preterm newborns (20.0%). In surgical NEC patients gasless abdomen was detected in 35.6% of the neonates born <28weeks compared to 6.7% of the more mature neonates. CONCLUSIONS: Extremely preterm neonates with NEC show less specific clinical and radiological signs of NEC compared to more mature neonates. This suggests that Bell's classification is not adequate for the diagnosis and staging of NEC in extremely preterm neonates. LEVEL OF EVIDENCE: III.

Angiotensin II receptor blockers and risk of acute pancreatitis - a population based case-control study in Sweden.

BACKGROUND: Acute pancreatitis is a potentially lethal disease, with a rising incidence in the Western world. Yet, no pharmacological prevention or specific treatment for acute pancreatitis exists. Also, the connection with severity of acute pancreatitis is unknown. Experimental and epidemiological research suggests a protective effect of angiotensin II receptor blockers. METHODS: During 2006 to 2008, we performed a nationwide case-control study on Swedish residents aged 40-84 years. First-time cases with acute pancreatitis were identified in the National Patient Register and data on dispensed prescriptions was retrieved from the Prescribed Drug Register. Controls were randomly selected from the general population in Sweden frequency-matched on sex, age, and calendar year. To estimate relative risk of acute pancreatitis, by degree of severity, among users of angiotensin II receptor blockers, as compared to non-users, we used multivariable logistic regression analysis to calculate odds ratios (OR) with 95% confidence interval (CI). RESULTS: Among 6,161 cases of acute pancreatitis and 61,637 controls, current use of angiotensin II receptor blockers was followed by a decreased risk of acute pancreatitis, compared to non-users, adjusted OR 0 · 77 (95% CI 0 · 69-0 · 86). No protective association, but an increased risk was found for users of angiotensin-converting enzyme inhibitors (adjusted OR 1 · 11, 95% CI: 1 · 01-1 · 21), analysed for comparison reasons. There was a significant decreased risk associated with both severe acute pancreatitis, (OR 0 · 71 (0 · 59-0 · 85), and mild acute pancreatitis; adjusted OR 0 · 81 (0 · 70-0 · 94). CONCLUSION: This population-based case-control study indicates that use of angiotensin II receptor blockers might be associated with a lesser risk of acute pancreatitis, and that the protective association was significant among cases of both severe and mild acute pancreatitis.

Medical students' experiences of their own professional development during three clinical terms: a prospective follow-up study.

BACKGROUND: A modern competency-based medical education is well implemented globally, but less is known about how the included learning activities contribute to medical students' professional development. The aim of this study was to explore Swedish medical students' perceptions of the offered learning activities and their experiences of how these activities were connected to their professional development as defined by the CanMEDS framework. METHODS: A prospective mixed method questionnaire study during three terms (internal medicine, scientific project, and surgery) in which data were collected by using contextual activity sampling system, i.e., the students were sent a questionnaire via their mobile phones every third week. All 136 medical students in the 6th of 11 terms in the autumn of 2012 were invited to participate. Seventy-four students (54%) filled in all of the required questionnaires (4 per term) for inclusion, the total number of questionnaires being 1335. The questionnaires focused on the students' experiences of learning activities, especially in relation to the CanMEDS Roles, collaboration with others and emotions (positive, negative, optimal experiences, i.e., "flow") related to the studies. The quantitative data was analysed statistically and, for the open-ended questions, manifest inductive content analysis was used. RESULTS: Three of the CanMEDs Roles, Medical Expert, Scholar, and Communicator, were most frequently reported while the four others, e.g., the role Health Advocate, were less common. Collaboration with students from other professions was most usual during the 8th term. Positive emotions and experience of "flow" were most often reported during clinical learning activities while the scientific project term was connected with more negative emotions. CONCLUSIONS: Our results showed that it is possible, even during clinical courses, to visualise the different areas of professional competence defined in the curriculum and connect these competences to the actual learning activities. Students halfway through their medical education considered the most important learning activities for their professional development to be connected with the Roles of Medical Expert, Scholar, and Communicator. Given that each of the CanMEDS Roles is at least moderately important during undergraduate medical education, the entire spectrum of the Roles should be emphasised and developed during the clinical years.

Association between personality traits and future choice of specialisation among Swedish doctors: a cross-sectional study.

BACKGROUND: Medical students' choice of their future specialty is influenced by several factors, including working conditions and type of patient relations. The aim of this study was to investigate the association between the choice of specialty and personality traits. METHODS: This is a cross-sectional questionnaire-based study of 399 alumni from Karolinska Institutet Medical School who were assumed to undergo specialty training at the time of the survey in 2013. The Big Five Inventory was used to assess the personality traits extraversion, agreeableness, conscientiousness, neuroticism and openness to experience. Medical specialties were categorised as primary care, psychiatry, internal medicine and surgical and hospital service specialties. Adjustments were made for demographic factors and the method of selection for medical school admission. RESULTS: The response rate was 72% (n=289, of which 262 were in training to become specialists). Among these, surgeons scored lower in agreeableness than physicians in primary care, internal medicine and hospital services. Psychiatrists and hospital service physicians showed lower conscientiousness compared with surgeons. CONCLUSIONS: We found distinctive differences in personality traits between medical specialties even after adjusting for other potential explanatory variables. Since there are differences between specialties, for example, surgeons and psychiatrists, this supports previous findings that personality may affect medical students' specialty choice also in a Swedish setting.

New-onset type 2 diabetes, elevated HbA1c, anti-diabetic medications, and risk of pancreatic cancer.

BACKGROUND: Associations between type 2 diabetes, anti-diabetic medications and pancreatic cancer are controversial. This study aims to clarify such associations with new-onset type 2 diabetes and repeated measurements of glycated haemoglobin (HbA1c) levels. METHODS: A nested case-control study was initiated from the Health Improvement Network (THIN) in UK from 1996 to 2010. Information of pancreatic cancer cases was retrieved electronically from the medical records and manually validated. Control subjects were randomly selected and frequency-matched to the cases on sex, age, and calendar years. Multivariable unconditional logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI), and adjusted for potential confounders. RESULTS: Among 1,574,768 person-years of follow-up, 529 pancreatic cancer cases and 5000 controls were identified. Type 2 diabetes, or changed HbA1c levels (rather than HbA1c levels at diabetes diagnosis) in diabetes patients (⩾4 mmol mol(-1) compared with <0 mmol mol(-1)) were followed by an increased OR of pancreatic cancer (OR, 2.16, 95% CI 1.72-2.72 and OR, 5.06, 95% CI 1.52-16.87, respectively). Among the anti-diabetic medications in diabetes patients, the OR for insulin users was 25.57 (95% CI 11.55-56.60), sulphonylureas 2.22 (95% CI 1.13, 4.40), and metformin users 1.46 (95% CI 0.85-2.52), compared with no use of any anti-diabetic medications. CONCLUSIONS: New-onset type 2 diabetes and, particularly, diabetes with rising HbA1c seem to be independent risk factors for pancreatic cancer. The relation between different anti-diabetic medications and pancreatic cancer seems to vary in strength, with the highest risk among users of insulin.

Antidopaminergic drugs and acute pancreatitis: a population-based study.

OBJECTIVES: To evaluate the suggested association between antidopaminergic drugs and acute pancreatitis. DESIGN: A large population-based nested case-control study. SETTING: Swedish nationwide study from 2006 to 2008. PARTICIPANTS: The Patient Register was used to identify 6161 cases of acute pancreatitis. The 61 637 control subjects were randomly selected from the Register of the Total Population by frequency-based density sampling, matched for age, sex and calendar year. EXPOSURE: Exposure data were extracted from the Prescribed Drug Register. Antidopaminergic drugs were grouped into antiemetic/anxiolytic and other antipsychotics. Current use of antidopaminergic drugs was defined as filling a prescription 1-114 days before index date, while previous use was 115 days to 3.5 years before index date. MAIN OUTCOME MEASURES: Cases were defined as being diagnosed as having acute pancreatitis. ORs and 95% CIs were calculated using unconditional logistic regression. RESULTS: The unadjusted OR indicated an increased risk of acute pancreatitis among current users of antiemetic/anxiolytics (OR 1.9, 95% CI 1.4 to 2.6), but not in the multivariable model adjusting for alcohol-related comorbidity, chronic obstructive lung disease, ischaemic heart disease, obesity, diabetes, opioid use, gallstone disease, educational level, marital status and number of concomitant medications (OR 0.9, 95% CI 0.6 to 1.2). Similarly, among current users of other antipsychotics, the unadjusted OR was 1.4 (95% CI 1.1 to 1.6), while the adjusted OR was 0.8 (95% CI 0.6 to 0.9). Results regarding previous use of antidopaminergic drugs followed a similar risk pattern as for current use. CONCLUSIONS: The lack of association between antidopaminergic drugs and acute pancreatitis after adjustment for confounding factors in this study suggests that the previously reported positive associations might be explained by confounding.

Increased risk of acute pancreatitis among tetracycline users in a Swedish population-based case-control study.

OBJECTIVE: To evaluate the suggested association between tetracycline and acute pancreatitis in a large pharmacoepidemiological study. DESIGN: The use of tetracycline in relation to the risk of acute pancreatitis was examined in a nationwide case-control study of people aged 40-84 years between 2006 and 2008 in Sweden. The Swedish Patient Register was used to identify 6161 cases of first-episode acute pancreatitis. The Register of the Total Population was used to randomly select 61,637 control subjects from the general population using frequency-based density sampling, matched for age, sex, and calendar year. Tetracycline use was defined as 'current', 'recent', 'past' or 'former' if the drug had been dispensed 0-30 days, 31-180 days, 181-365 days or 1-3½ years before the index date, respectively. The risk of acute pancreatitis was estimated by unconditional logistic regression, providing ORs with 95% CIs, adjusted for potential confounding factors. RESULTS: There was a 60% increased risk of acute pancreatitis among current users of tetracycline after adjustment for potential confounders (OR=1.6, 95% CI 1.2 to 2.1). There was no increased OR for any category of previous use. CONCLUSION: Current use of tetracycline is associated with an increased risk of acute pancreatitis, verifying previous case reports.