[Evaluation of Psychological Distress in Obstetric Patients during the Visit Ban in Hospitals in the SARS-CoV-2 Pandemic: A Prospective, Multicentre, Controlled Study]. / Evaluation der psychischen Belastung geburtshilflicher Patientinnen während des Besuchsverbots der Kliniken im Rahmen der SARS-CoV-2-Pandemie: Eine prospektive, multizentrische, kontrollierte Studie.

INTRODUCTION: Risk factors for postpartum depression include a lack of social support and perceived social isolation. We would like to determine whether the isolation of inpatients on the maternity wards during Covid-19 leads to increased psychological stress. METHODS: This is a multicentre, controlled study of obstetric patients who gave birth during an inpatient stay. Patients were included during the visitation ban (study group) and after the visitation ban (control group). Psychological stress was evaluated with the Edinburgh Postnatal Depression Scale (EPDS) during the inpatient stay and six to eight weeks postpartum. RESULTS: A total of 194 women were included, 107 in the study group and 87 in the control group. The overall result of the first EPDS shows a higher score in the study group compared to the control group (7.0 vs. 4.9 points). Primipara show a higher score in the first EPDS compared to multipara (7.28 vs. 4.82). Caesarean section, regardless of isolation, shows a higher score in the first EPDS than vaginal birth (8.42 vs. 5.11). Comparison of vaginal birth shows a higher score only in the study group (5.97 vs. 4.07). CONCLUSION: In the context of Covid-19, women giving birth and new mothers, especially primipara, are exposed to increased psychological stress in the clinics. Caesarean section leads to increased psychological stress.

The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With at Least Two Tyrosine Kinase Inhibitors.

Asciminib is an allosteric high-affinity tyrosine kinase inhibitor (TKI) of the BCR-ABL1 protein kinase. This kinase is translated from the Philadelphia chromosome in chronic myeloid leukemia (CML). Marketing authorization for asciminib was granted on August 25, 2022 by the European Commission. The approved indication was for patients with Philadelphia chromosome-positive CML in the chronic phase which have previously been treated with at least 2 TKIs. Clinical efficacy and safety of asciminib were evaluated in the open-label, randomized, phase III ASCEMBL study. The primary endpoint of this trial was major molecular response (MMR) rate at 24 weeks. A significant difference in MRR rate was shown between the asciminib treated population and the bosutinib control group (25.5% vs. 13.2%, respectively, P = .029). In the asciminib cohort, adverse reactions of at least grade 3 with an incidence ≥ 5% were thrombocytopenia, neutropenia, increased pancreatic enzymes, hypertension, and anemia. The aim of this article is to summarize the scientific review of the application which led to the positive opinion by the European Medicines Agency's Committee for Medicinal Products for Human Use.

1-year outcome after treatment of uterovaginal prolapse with a 6-point fixation mesh.

INTRODUCTION: The aim of this study was to describe the safety and anatomical results of a surgical approach with a single-incision 6-point fixation vaginal mesh for the treatment of pelvic organ prolapse at perioperatively and at 1-year follow-up. MATERIALS AND METHODS: This was a prospective observational study of patients who underwent operation receiving an InGYNious anterior transvaginal mesh. All patients with symptomatic stage II prolapse or higher were included in the study. Exclusion criteria were the unwillingness or inability to give written informed consent, neuromuscular disorders, malignant diseases, previous radiation in the pelvis, or chronic pain syndrome. Every patient completed a structured questionnaire and a full physical examination according to the IUGA-ICS POP-Q staging system before the operation and at 1-year follow-up. RESULTS: Two hundred fifty-four patients (91%) were included in the study. The intraoperative complication rate was 7% with hemorrhage being the most common complication. Six patients (2.4%) had undergone reoperation for prolapse (four out of the six patients had reoperation in the posterior compartment) and were excluded from the objective outcome analysis. In the remaining 248 patients all POP-Q measurements were significantly improved in the anterior and apical compartments. Similarly, urge urinary incontinence and voiding dysfunction improved significantly. CONCLUSIONS: In this series, the objective outcome one year after the InGYNious mesh was good with low numbers of mesh-related problems or reoperation for prolapse.

Risk markers for later cardiovascular diseases in liver-transplanted children and adolescents.

BACKGROUND: Increased risk of cardiovascular diseases is well described after adult liver transplantation, whereas the risk in the pediatric population still is discussed. The aim of this study was to investigate the prevalence of metabolic syndrome in pediatric liver transplant recipients and whether measurements of carotid intima media thickness and pulse wave velocity were increased compared to healthy controls. METHODS: We included 42 pediatric liver transplantation recipients and examined them for markers of metabolic syndrome, liver fibrosis measured by shear wave velocity, body fat measured by DXA scans and carotid intima-media thickness, and pulse wave velocity (n = 41 for the carotid scans). The ultrasound measurements of carotid intima-media thickness and pulse wave velocity were also conducted on 82 healthy children and adolescents matched on height and age, respectively. RESULTS: Participants had a median age of 13.03 years, and median time since transplantation was 8.54 years. Compared to healthy controls, liver-transplanted patients had significantly increased intima-media thickness measurements in both control groups whereas there was no significant difference with regard to pulse wave velocity. Two patients (6.25%) were diagnosed with metabolic syndrome. Within the group of liver-transplanted pediatric patients, only elevated body mass index was associated with elevated carotid intima-media thickness measurement. Elevated pulse wave velocity was only associated with abdominal obesity. Factors not significantly correlated with either were age, sex, metabolic syndrome, hyperglycemia, triglycerides, years since transplantation, fibrosis of the liver, body fat content, smoking habits, HDL cholesterol levels, hypertension, and mono-drug versus multi-drug therapies. CONCLUSION: Pediatric liver transplant recipients do have an increased risk of increased carotid intima-media thickness.

Regulatory issues with multiplicity in drug approval: Principles and controversies in a changing landscape.

Recently, new draft guidelines on multiplicity issues in clinical trials have been issued by European Medicine Agency (EMA) and Food and Drug Administration (FDA), respectively. Multiplicity is an issue in clinical trials, if the probability of a false-positive decision is increased by insufficiently accounting for testing multiple hypotheses. We outline the regulatory principles related to multiplicity issues in confirmatory clinical trials intended to support a marketing authorization application in the EU, describe the reasons for an increasing complexity regarding multiple hypotheses testing and discuss the specific multiplicity issues emerging within the regulatory context and being relevant for drug approval.

Disentangling estimands and the intention-to-treat principle.

Randomized controlled trials (RCTs) aim at providing reliable estimates of treatment benefit. Missing data and nonadherence to treatment are distinct problems that can substantially impede this task. In practice, the fact that the handling of missing data due to nonadherence affects the question that is addressed is often ignored. Estimands allow precisely predefining the question of interest. Estimands are definitions of that which is being estimated with regard to population, endpoint, and handling of postrandomization events (eg, nonadherence). Depending on the situation, different estimands are of relevance. Therefore, it is important that the intention-to-treat (ITT) principle, which is considered the gold standard for analyzing RCTs, does not restrict an RCT's primary objective to only one of several relevant estimands. Although much ambiguity is involved around what is considered to constitute the ITT principle, many associate ITT with completely following up all patients and including all data of all randomized patients as allocated into the analysis. This would restrict primary objectives to estimating the effect of treatment policy and is certainly not warranted in all situations. To maintain the advantage of having the clear recommendation to follow the ITT principle while allowing for various relevant estimands as primary objective, we argue that the appropriate way forward is to define ITT as including all randomized patients into the analysis set and each patient is to be allocated to his or her randomized treatment. This definition comprises the actual intent of ITT and can be fully implemented also in settings where complete follow-up is impossible.

Outcome and safety of mechanical thrombectomy in patients with acute ischemic stroke due to internal carotid artery dissection.

BACKGROUND: Mechanical thrombectomy (MT) in patients with symptoms of acute ischemic stroke (AIS) due to internal carotid artery dissection (ICAD) remains controversial. In this study, we present clinical outcome and safety of MT in acute ICAD compared to other acute carotid artery pathology. METHODS: Patients with symptoms of AIS due to internal carotid artery pathology, treated with MT from 2017-2021, were categorized as ICAD or non-ICAD. Baseline and procedural characteristics, complications, and functional outcome at 90 days were compared between the two groups. Factors associated with a favorable outcome (modified Rankin Scale 0-2) were analyzed using multivariate logistic regression. Safety analyses included in-stent thrombosis, perforation, intracranial hemorrhage, and mortality. RESULTS: Sixty-seven ICAD patients (14.8%) and 387 non-ICAD patients (85.2%) were enrolled. ICAD patients were younger, median age 53 years (interquartile range (IQR) 47-61) vs. non-ICAD 72 years (IQR 64-79), p < 0.001. Favorable outcome was more common in ICAD patients, 49 ICAD patients (76.6%) vs. 158 non-ICAD patients (42.4%), p < 0.001. Post-procedural symptomatic intracranial hemorrhage occurred in 41 patients, 5 (7.5%) ICAD patients vs. 36 (9.3%) non-ICAD patients, p = 0.6. Mortality differed significantly, 6 (9%) ICAD patients vs. 94 (24.3%) non-ICAD patients, p = 0.01. ICAD was not associated with functional outcome in multivariate analysis, OR = 1.25 [95%confidence interval:0.55-2.86]. CONCLUSION: ICAD patients achieved a better 90-day functional outcome compared with non-ICAD patients. ICAD patients did not perform worse in safety measures than non-ICAD patients. Our data provide indirect evidence that MT is of clinical benefit in ICAD patients with symptoms of AIS.

Trials of endovascular thrombectomy of basilar-artery occlusion compared to real-life data.

BACKGROUND: Two recent clinical trials showed mechanical thrombectomy (MT) of basilar-artery occlusions (BAO) in stroke to be safe and effective: Endovascular Treatment for Acute BAO (ATTENTION) and BAO Chinese Endovascular (BAOCHE). The trials restricted patient inclusion on both age and pre-stroke mRS, and with both trials conducted in China, population differences may affect generalisability of the trial results. METHODS: Consecutive patients with BAO undergoing MT were registered from 2017 to 2021 with retrospective data collection at a single centre with a predominantly Caucasian catchment population of 2.7 million. Age and pre-stroke modified Rankin Scale (mRS) were not absolute contraindications for MT. We present functional outcome as mRS at 90 days, patient characteristics and procedural safety compared to the trial intervention groups. RESULTS: Of the 108 included patients, 50 % achieved mRS 0-3 at 90 days and mortality was 32 %, which was no different from ATTENTION (46 %, p = 0.40, 37 %, p = 0.31, respectively) and BAOCHE (46 %, p = 0.50, 31 %, p = 0.93). Pre-stroke mRS 0 was seen in 62 %, 89 %, and 77 % of the study patients, ATTENTION, and BAOCHE, respectively. Proximal segment BAO was less common (22 % vs. 31 %, p = 0.04, and 65 %, p < 0.01) and intracranial stenting less frequently used (9 % vs. 40 % and 55 %, p < 0.01) in study patients compared to ATTENTION and BAOCHE, respectively. CONCLUSION: Outcome of MT in BAO stroke in a clinical patient cohort was similar to recent trials, despite broader patient inclusion and differences in both occluded BAO segment and use of stenting. Our study suggest that MT is safe and effective in a Caucasian population.

Criteria for brain death in Denmark.

In 1990, the Danish brain death legislation was adopted by the Danish Parliament. Each year, around 100 patients in Denmark fulfil criteria for brain death/death by neurological criteria (BD/DNC). In this review of current Danish criteria including the indication for ancillary investigation, which in Denmark is digital subtraction angiography (DSA), we conclude that the time has come to revise the national BD/DNC criteria. We propose that visible anoxic-ischaemic encephalopathy on brain CT after cardiac arrest does not require evaluation by ancillary testing, and that CT-angiography can be used instead of DSA.

Identification of gene expression biomarkers to predict clinical response to methotrexate in patients with rheumatoid arthritis.

OBJECTIVES: To identify biomarkers at the gene expression level to predict response to methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: MTX-naïve patients with RA were started on MTX and followed up over three months. The disease activity score 28 (DAS28) was used to classify patients into responders and non-responders. Genome-wide gene expression analysis was performed in CD4 + and CD14 + mononuclear cells sampled from whole blood at baseline to identify differentially expressed genes in responders versus non-responders. Gene selection methods and prediction modelling obtained the most relevant differentially expressed genes. A logistic regression prediction model was subsequently constructed and validated via bootstrapping. The area under the receiver operating characteristic (AUC) curve was calculated to judge model quality. RESULTS: Seventy-nine patients with RA (53.4 ± 13.9 years, 74.7% females) were enrolled, and 70 finished the study with a documented treatment EULAR response (77.1% responders). Forty-six differentially expressed genes were found. The most promising genes were KRTAP4-11, LOC101927584, and PECAM1 in CD4 + cells and PSMD5 and ID1 in CD14 + cells. The final prediction model using these genes reached an AUC of 90%; the validation set's AUC was 82%. CONCLUSIONS: Our prediction model constructed via genome-wide gene expression analysis in CD4 + and CD14 + mononuclear cells yielded excellent predictions. Our findings necessitate confirmation in other cohorts of MTX-naïve RA patients. Especially if used in conjunction with previously identified clinical and laboratory (bio)markers, our results could help predict response to MTX in RA to guide treatment decisions. Key Points • Patients with rheumatoid arthritis may or may not respond to treatment with methotrexate, which is the recommended first-line drug in guidelines around the world. • In non-responders, valuable time is lost until second-line treatments are started. • This study aimed at predicting response to methotrexate by identifying differentially expressed genes from peripheral blood samples. • The final prediction model yielded excellent prognostic values, but validation in other cohorts is necessary to corroborate these findings.

Prostate cancer risk assessment model: a scoring model based on the Swedish Family-Cancer Database.

BACKGROUND: Many prostate cancer (PC) risk assessment models have been developed, however almost none include familial history. AIM: To produce a risk assessment model for PC based on familial background of related cancers. METHOD: 976 859 independent index men aged ≥30 in year 1998 and their family members in the Swedish Family-Cancer Database (FCD2010) were randomly divided into development (60%) and validation (40%) datasets (follow-up=10 years). The HR from Cox model was used to extrapolate risk scores. Results Specified scores were: for PC in situ at age <60 years in index man, 5; for PC at age <60 years in each first-degree relative (FDR), 15; for PC at age ≥60 years in each FDR, 10; for PC at age <60 years in each second-degree relative, 5; for breast cancer in each FDR, 2; for oesophageal carcinoma in situ in index man, 2; and for oesophagus cancer in each FDR, 2. Based on the findings, if the milestone age for a PC screening programme was 60 years or more, the recommended starting age for the men with the score-group 6-10 would be 54 years; score-group 11-15, 52 years; score-group 16-20, 50 years; score-group 21-25, 44 years; and for the score-group 26+ it should start before age 40. The concordance index in development and validation sets was 0.885 (95% CI 0.883 to 0.888). No significant difference was found between curves from development and validation datasets (internally validated using twofold validation and bootstrapping). CONCLUSION: Familial history of relevant malignancies can be used as risk factors to estimate a man's prior risk of developing PC. The prostate cancer risk assessment model could satisfactorily assess risk of developing prostate cancer.

Multimodality Imaging in Cranial Giant Cell Arteritis: First Experience with High-Resolution T1-Weighted 3D Black Blood without Contrast Enhancement Magnetic Resonance Imaging.

In order to support or refute the clinical suspicion of cranial giant cell arteritis (GCA), a supplemental imaging modality is often required. High-resolution black blood Magnetic Resonance Imaging (BB MRI) techniques with contrast enhancement can visualize artery wall inflammation in GCA. We compared findings on BB MRI without contrast enhancement with findings on 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/low-dose computed tomography (2-[18F]FDG PET/CT) in ten patients suspected of having GCA and in five control subjects who had a 2-[18F]FDG PET/CT performed as a routine control for malignant melanoma. BB MRI was consistent with 2-[18F]FDG PET/CT in 10 out of 10 cases in the group with suspected GCA. In four out of five cases in the control group, the BB MRI was consistent with 2-[18F]FDG PET/CT. In this small population, BB MRI without contrast enhancement shows promising performance in the diagnosis of GCA, and might be an applicable imaging modality in patients.

Integrin genes and susceptibility to human melanoma.

Integrins are transmembrane adhesion molecules that mediate cell-cell and cell-extracellular matrix attachment. Integrins regulate cell growth, proliferation, migration and apoptosis and as a consequence, can have a potential role in tumour progression and metastasis. In this study, we investigated 19 non-synonymous variants in the coding region of the human integrin genes representing 3 beta subunits and 13 alpha subunits, for their potential role in melanoma susceptibility and survival. The variants were selected on the basis of probable functional relevance and theoretical predictions. Our data showed that no genetic variant was significantly associated with survival. However, the variants in ITGA10 and ITGA6 genes showed association with decreased risk, and variants in ITGA2, ITGAE and ITGAM were associated with increased risk of melanoma. The haplotype analysis revealed association of CA haplotype of ITGAE and TAC haplotype of ITGAX with the risk modulation. A prediction analysis of functional effect, homology modelling and multiple sequence alignments of integrin sequences from different species supported our data for linkage of variants in the ITGA2 and ITGAE genes with susceptibility. The amino acid changes in each of these integrin proteins could affect intramolecularly and/or the interaction of the heterodimers. Our experimental data indicated a possible role for some of the variant alleles and/or haplotypes of the integrin genes in melanoma susceptibility, which is augmented by the theoretical analysis performed.

Comparison of six statistics of genetic association regarding their ability to discriminate between causal variants and genetically linked markers.

OBJECTIVES: Genome-wide association (GWA) studies still rely on the common-disease common-variant hypothesis since the assumption is associated with increased power. In GWA studies, polymorphisms are genotyped and their association with disease is investigated. Most of the identified associations are indirect and reflect a shared inheritance of the genotyped markers and genetically linked causal variants. We have compared six statistics of genetic association regarding their ability to discriminate between markers and causal susceptibility variants, including a probability value (Pval) and a Bayes Factor (BF) based on logistic regression, and the attributable familial relative risk (FRR). METHODS: We carried out a simulation-based sensitivity analysis to explore several conceivable scenarios. Theoretical results were illustrated by established causal associations with age-related macular degeneration and by using imputed data based on HapMap for a case-control study of breast cancer. RESULTS: Our data indicate that a representation of genetic association by FRRs and BFs generally facilitates the distinction of causal variants. The FRR showed the best discriminative power under most investigated scenarios, but no single statistic outperformed the others in all situations. For example, rare moderate- to low-penetrance variants (allele frequency: 1%, dominant odds ratio: ≤2.0) seem to be best discriminated by BFs. CONCLUSIONS: Present results may help to fully utilize the data generated in association studies that take advantage of next generation sequencing and/or multiple imputation based on the 1000 Genomes Project.

Non-intubated Uniportal Subxiphoid Video-Assisted Thoracoscopic Surgery for Extended Thymectomy in Myasthenia Gravis Patients: A Case Series.

Minimally invasive strategies are increasingly popular in patients with myasthenia gravis (MG)-associated thymomas. Within the context of video-assisted thoracoscopic surgery (VATS) as a widely known minimally invasive option, the most recent achievement is uniportal subxiphoid VATS. In MG patients, it is mandatory (1) to minimize perioperative interference with administered anesthetics to avoid complications and (2) to achieve a complete surgical resection, as the prognosis essentially depends on radical tumor resection. In order to fulfill these criteria, we merged this surgical technique with its anesthesiologic counterpart: regional anesthesia with the maintenance of spontaneous ventilation via a laryngeal mask. Non-intubated uniportal subxiphoid VATS for extended thymectomy allowed radical thymectomy in all MG patients with both rapid symptom control and fast recovery.

Lanthanum Carbonate Opacities-A Systematic Review.

BACKGROUND: Lanthanum carbonate is a phosphate binder used in advanced kidney disease. Its radiopaque appearance has been described in many case studies and case series. Misinterpretation of this phenomenon leads to unnecessary diagnostic tests and procedures. The objectives of this study were to summarize the literature on lanthanum carbonate opacities and present a visual overview. METHODS: A systematic search was conducted using MEDLINE, Embase, and Web of Science. We included all types of studies, including case reports/studies, describing radiological findings of lanthanum carbonate opacities in patients with chronic kidney disease. No filter for time was set. RESULTS: A total of 36 articles were eligible for data extraction, and 33 articles were included in the narrative synthesis. Lanthanum carbonate opacities were most commonly reported in the intestines (26 studies, 73%), stomach (8 studies, 21%), and the aerodigestive tract (2 studies, 6%). The opacities in the intestine were most frequently described as multiple, scattered radiopaque densities, compared with the aerodigestive tract, where the opacities were described as a single, round foreign body. Suspicion of contrast medium or foreign bodies was the most common differential diagnosis. LC opacities in patients with CKD are commonly misinterpreted as foreign bodies or suspect contrast media. CONCLUSIONS: CKD patients treated with LC may have opacities throughout the digestive tract that can vary in appearance. Stopping LC treatment or changing to an alternative phosphate binder prior to planned image studies can avoid diagnostic confusion. If this is not an option, knowledge of the presentation of LC opacities is important.

Mechanical thrombectomy in stroke patients of advanced age with score-based prediction of outcome.

BACKGROUND: Stroke patients ≥80 years constituted only 15% in randomised trials on mechanical thrombectomy (MT), but is a considerable higher proportion in clinical practice. Association of clinical variables collected before MT with functional outcome has not been independently described in these patients, while being important in the decision of patient eligibility for MT. METHODS: We included patients consecutively at a single centre (2017-2021) categorised as octogenarians (age: 80-89 years) or nonagenarians (age: 90-99 years). Functional outcome at 90 days was defined as fair (modified Rankin Scale (mRS) 0-3) or poor (mRS 4-6). Clinical variables collected before MT were analysed for association with shift of mRS in a poor direction. Significant predictors were used to produce a risk score of fair outcome. Significance was set at the p < 0.05 level. RESULTS: Nonagenarians (n = 43, 15.5%) compared to octogenarians (n = 235, 84.5%) less likely achieved fair outcome (20.9% vs. 46.0%, p < 0.01) with higher mortality (65.1% vs. 31.9%, p < 0.01). Significant predictors of outcome were: age, adjusted odds ratio (aOR) = 0.91 (95% confidence interval (CI): 0.86-0.97); pre-stroke mRS, aOR = 0.57 (95% CI: 0.44-0.73); National Institute of Health Stroke Scale at admission, aOR = 0.91 (95% CI: 0.87-0.95); Alberta Stroke Program Early Computed Tomography, aOR = 1.23 (95% CI: 1.05-1.45). After bootstrap validation, the area under the curve of the risk score was 0.74 and the optimal cut-off for fair outcome was a score of >7 points. CONCLUSIONS: One in two octogenarians achieved fair outcome, however, only one in five nonagenarians had fair outcome. The clinical risk score could be considered as guidance when deciding patient eligibility for MT.

Risks of papillary and follicular thyroid cancer among immigrants to Sweden.

Previous studies have indicated that ionizing radiation, particularly during childhood, is the main established risk factor for thyroid cancer. History of benign nodules/adenoma, goiter, iodine deficiency or high-iodine intake might be other associated factors. We wanted to define the histology-specific thyroid cancer risk in the first-generation immigrants to Sweden. We used the 2010 update of the nation-wide Swedish Family-Cancer Database (>12 million individuals; 1.8 million immigrants; histology code in force since 1958) to calculate standardized incidence ratios (SIRs) for histology-specific thyroid cancer among immigrants compared to the native Swedes. The patient series covered 2,604 male and 6,406 female Swedes, and 247 and 863 immigrants. The median age at immigration was 29 years, and the median age at thyroid cancer diagnosis was 46 years. Increased risks for female papillary carcinoma were observed for Finns (SIR = 1.63), former Yugoslavians (2.36), Russians (2.34), other East Europeans (2.14), Turks (3.16), Iranians (2.68), Iraqis (2.77), East and Southeast Asians (2.92), other Asians (1.69) and South Americans (2.23). Male Iranians (2.85), East and Southeast Asians (3.57) and other Asians (2.26) had an increased risk for papillary carcinoma. Only male East and Southeast Asians (2.93) had an increased risk for follicular carcinoma. The data might suggest that immigrant populations in Sweden from areas of low or high-iodine intake are at risk of papillary carcinoma, implicating iodine imbalance as a contributing factor to our findings. The increased risk of thyroid cancer among Asian immigrants may confirm the role of childhood-ionizing radiation on thyroid cancer risk.

Incidence and mortality in epithelial ovarian cancer by family history of any cancer.

BACKGROUND: Practically all data on familial risk in ovarian and other cancers are based on incident cancer, whereas familiality in cancer mortality is largely unknown. If fatal forms of cancer are a highly familial subtype, then familial risk for mortality may exceed that of incidence, which is relevant for clinical decision making and counseling. METHODS: Ovarian cancer patients in the nationwide Swedish Family Cancer Database were classified according to fatal and nonfatal (incident) family history. Familial risks for incident and fatal ovarian cancer were calculated for offspring based on their parental or sibling family history of any cancer using standardized incidence ratios (SIRs) for incidence and standardized mortality ratios (SMRs) for mortality. Offspring without family history were referents. RESULTS: The database included 24,757 mothers and 8138 daughters with ovarian cancer. When a mother had ovarian cancer, the SIR for incident ovarian cancer in daughters was 2.69, and when a sister had ovarian cancer it was 3.49. The SMRs for fatal cancer by fatal cancer in probands were 3.39 and 5.80, respectively. For fatal serous cancers among siblings, the SMR was 6.16, compared with 10.01 for the endometrioid type. Ovarian cancer was associated with maternal (SIR, 1.22; SMR, 1.56) and sororal breast cancer (SIR, 1.27). Another discordant association was between ovarian and paternal prostate cancer (SIR, 1.12; SMR, 1.66). CONCLUSIONS: Fatal familial risks were higher for concordant ovarian, ovarian-breast, and ovarian-prostate cancers than the corresponding incident risks. This may suggest that highly fatal subtypes exist for these cancers, calling for genetic dissection.