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Background Laparoscopic major hepatectomy (LMH) for hepatocellular carcinoma (HCC) is currently perceived a complex and challenging laparoscopic procedure and is limited to a few expert teams. This study analyzed the short- and long-term outcomes of LMH for HCC compared with open hepatectomy. Methods From January 2006 to May 2014, 38 patients underwent LMH for HCC (10 left and 28 right hepatectomy). They were matched and compared to 38 patients (10 left and 28 right hepatectomy) who underwent a conventional open approach. Short-term operative and postoperative outcomes as well as long-term outcomes, including disease-free survival and overall survival rates, were evaluated. Results Patients were well matched for several preoperative factors. Overall complication rates were significantly higher for the open group. No significant difference was seen in 3-year overall survival between the open and laparoscopic groups (69.2 vs. 73.4 %; p  = 0.951). A trend toward better 3-year disease-free survival after laparoscopy was observed (29.7 vs. 50.3 %; p  = 0.219), even though the difference did not reach statistical significance. The same trend was seen in subgroup analyses of right and left hepatectomy. Conclusions This study shows the feasibility of LMH for HCC compared to open hepatectomy in regard to both short- and long-term outcomes. LMH offers many advantages commonly attributed to laparoscopy and is well suited for HCC with cirrhosis when performed by experienced surgeons.

Purpose Customised individually made (CIM) total knee arthroplasty (TKA) was introduced to potentially improve patient satisfaction and other patient-reported outcome measures (PROMs). The purpose of this study was to compare PROMs, especially patient satisfaction, of patients with CIM and OTS TKA in a matched-pair analysis with a 2-year follow-up. Methods This is a prospective cohort study with a propensity score matching of 85 CIM and 85 off-the-shelf (OTS) TKA. Follow-up was at 4 months, 1 year and 2 years. The primary outcome was patient satisfaction. Secondary outcomes were as follows: overall improvement, willingness to undergo the surgery again, Knee injury and Osteoarthritis Outcome Score (KOOS), Forgotten Joint Score (FJS-12), High-Activity Arthroplasty Score (HAAS), EQ-5D-3L, EQ-VAS, Knee Society Score (KSS) and surgeon satisfaction. Results Patient satisfaction ranged from 86 to 90% and did not differ between CIM and OTS TKA. The EQ-VAS after 4 months and the HAAS after 1 year and 2 years were higher for CIM TKA. KOOS, FJS-12 and EQ-5D-3L were not different at follow-up. The changes in KOOS symptoms, pain and daily living were higher for OTS TKA. The KSS was higher for patients with CIM TKA. Surgeon satisfaction was high throughout both groups. Patients who were satisfied after 2 years did not differ preoperatively from those who were not satisfied. Postoperatively, all PROMs were better for satisfied patients. Patient satisfaction was not correlated with patient characteristics, implant or preoperative PROMs, and medium to strongly correlated with postoperative PROMs. Conclusion Patient satisfaction was high with no differences between patients with CIM and OTS TKA. Both implant systems improved function, pain and health-related quality of life. Patients with CIM TKA showed superior results in demanding activities as measured by the HAAS. Level of evidence II, prospective cohort study.

Purpose The rarity of cerebellar glioblastoma presents a significant challenge in clinical practice due to the lack of extensive prognostic data on long-term survival rates, rendering it an underrepresented entity compared to its supratentorial counterpart. This study aims to analyze potential differences in survival outcome between patients with cerebellar and supratentorial glioblastomas. Methods From 2009 to 2020, 8 patients underwent surgical treatment for cerebellar glioblastoma at the authors’ institution. These patients were individually matched with a cohort of 205 consecutive patients from our institutional database with supratentorial glioblastoma, taking into account key prognostic parameters. Progression-free survival (PFS) and overall survival (OS) rates were compared. Additionally, we performed a systematic literature review to compile further survival data on cerebellar glioblastoma patients. Results The median OS for cerebellar glioblastoma patients was 18 months (95% CI 11–25). The balanced matched-pair analysis showed no significant difference in survival when compared to patients with supratentorial glioblastoma, exhibiting a median OS of 23 months (95% CI 0–62) ( p  = 0.63). Respective values for PFS were 8 months (95% CI 4–12) for cerebellar and 7 months (95% CI 0–16) for supratentorial glioblastoma ( p  = 0.2). The systematic review revealed that median OS for cerebellar glioblastoma in current literature ranges from 7 to 21 months. Conclusions The present findings indicate that patients with supra- and infratentorial glioblastoma do not significantly differ in regard to survival outcome parameters. This similarity in prognosis might encourage clinicians to consider surgical interventions for both supra- and infratentorial glioblastoma in a similar manner.

Abstract Aims Pulmonary arterial hypertension (PAH) is often diagnosed in elderly patients with comorbidities. Although initial monotherapy is recommended for these patients, the value of combination therapy remains unclear. Here, we compare the efficacy of initial monotherapy and combination therapy in PAH patients with cardiovascular comorbidities. Methods and results Data from adult patients with incident pre-capillary PAH and cardiovascular comorbidities from the COMPERA database (European registry for PH) were analysed. A matched-pair analysis of patients treated with monotherapy versus combination therapy based on age, sex, WHO functional class (FC) and 4-strata risk at baseline was performed. The matching strategy identified 216 pairs of PAH patients with cardiovascular comorbidities, who differed considerably from the enrolled patient population (n = 1871), especially in terms of mean age (mono: matched pairs 62.9 ± 13.5 years vs. 70.6 ± 11.4 years, combination: matched pairs 62.0 ± 13.6 years vs. 60.5 ± 14.9 years). In the matched-pair analysis, the initial combination therapy group showed more pronounced improvements in WHO-FC, N-terminal pro–B-type natriuretic peptide (BNP/NT-proBNP) and risk status than patients treated with initial monotherapy, with no significant differences in 6-min walk distance (6MWD), PAH-related hospitalisations, survival and drug discontinuation. Conclusions This analysis suggests that PAH patients with comorbidities may benefit more pronounced from combination therapy regarding WHO-FC, BNP/NT-pro-BNP and risk status without a significant difference in survival. Good tolerability is indicated. However, given the relatively younger patient matched subgroup, these findings may not necessarily apply to older patients with a wider range of comorbidities. AIM This analysis provides a comparison of the efficacy of initial mono and combination therapy in patients with PAH and cardiovascular comorbidities or with risk factors of HFpEF (heart failure with preserved ejection fractioin).METHOD Data from the European COMPERA registry were used for a matched pair analysis. Changes in clinical parameters, risk status and PAH-related hospitalizations, survival and continuation of PAH treatment from baseline to follow-up were assessed.FINDINGS 216 matched pairs of patients were identified. This cohort differed from the original one, especially in terms of age. At follow-up patients with initial combination therapy showed greater improvements e.g. in risk status (fig.). No significant differences in survival were observed.Figure: Risk stratification at first follow-up among patients with at least one cardiovascular comorbidity.

Purpose The perioperative and oncological outcomes of laparoscopic radical nephrectomy (LRN) for T1–T2 renal cell carcinoma (RCC) are well established. We aim to determine whether LRN is a comparable alternative to open radical nephrectomy (ORN) in the treatment of T3 RCC using a matched pair analysis study design. Methods A review of a prospectively collected database at the Western General Hospital, Edinburgh, between 2000 and 2011 was conducted. Patient pairs were matched based on age at operation, gender, histological subgroup, maximal tumour diameter, TNM stage and grade. Patient demographics, operative and post-operative outcomes were compared. Overall, cancer-specific and progression-free survival [overall survival, cancer-specific survival (CSS) and progression-free survival (PFS)] were estimated using the Kaplan–Meier method. Results From 252 patients with T3 disease, 25 pairs were matched. Patients were of median age 66.2 years, 64 % male. Tumours were all clear cell RCC, were stage pT3a (32 %) or pT3b and had maximal tumour diameters of 8.7 cm for LRN and 10.0 cm for ORN. Estimated blood loss (100 ml LRN; 650 ml ORN, p  < 0.001) and length of post-operative hospital stay (4 days LRN: 9 days ORN, p  < 0.001) were lower in the LRN group. Operation time and post-operative complication rates were comparable. CSS and PFS were comparable with a mean CSS of 91.3 months for LRN and 88.7 months for ORN. Conclusion This study reports the longest median follow-up in a T3 LRN cohort. In matched patients, LRN has been shown to have a superior perioperative profile to ORN for the treatment of pT3a/b RCC, with no adverse effect on midterm oncological outcomes.

Background Research shows disparities in cancer outcomes by ethnicity or socio-economic status. Therefore, it is the aim of our study to perform a matched-pair analysis which compares the outcome of German and non-German (in the following described as ‘foreign’) cancer patients being treated at the Center for Integrated Oncology (CIO) Köln Bonn at the University Hospital of Bonn between January 2010 and June 2016. Methods During this time, 6314 well-documented patients received a diagnosis of cancer. Out of these patients, 219 patients with foreign nationality could be matched to German patients based on diagnostic and demographic criteria and were included in the study. All of these 438 patients were well characterized concerning survival data (Overall survival, Progression-free survival and Time to progression) and response to treatment. Results No significant differences regarding the patients’ survival and response rates were seen when all German and foreign patients were compared. A subgroup analysis of German and foreign patients with head and neck cancer revealed a significantly longer progression-free survival for the German patients. Differences in response to treatment could not be found in this subgroup analysis. Conclusions In summary, no major differences in survival and response rates of German and foreign cancer patients were revealed in this study. Nevertheless, the differences in progression-free survival, which could be found in the subgroup analysis of patients with head and neck cancer, should lead to further research, especially evaluating the role of infectious diseases like human papillomavirus (HPV) and Epstein-Barr virus (EBV) on carcinogenesis and disease progression.

Background Statistical methods that use the mid- p approach are useful tools to analyze categorical data, particularly for small and moderate sample sizes. Mid- p tests strike a balance between overly conservative exact methods and asymptotic methods that frequently violate the nominal level. Here, we examine a mid- p version of the McNemar exact conditional test for the analysis of paired binomial proportions. Methods We compare the type I error rates and power of the mid- p test with those of the asymptotic McNemar test (with and without continuity correction), the McNemar exact conditional test, and an exact unconditional test using complete enumeration. We show how the mid- p test can be calculated using eight standard software packages, including Excel. Results The mid- p test performs well compared with the asymptotic, asymptotic with continuity correction, and exact conditional tests, and almost as good as the vastly more complex exact unconditional test. Even though the mid- p test does not guarantee preservation of the significance level, it did not violate the nominal level in any of the 9595 scenarios considered in this article. It was almost as powerful as the asymptotic test. The exact conditional test and the asymptotic test with continuity correction did not perform well for any of the considered scenarios. Conclusions The easy-to-calculate mid- p test is an excellent alternative to the complex exact unconditional test. Both can be recommended for use in any situation. We also recommend the asymptotic test if small but frequent violations of the nominal level is acceptable.

To study the association between bilateral oophorectomy and the rate of accumulation of multimorbidity. In this historical cohort study, the Rochester Epidemiology Project records-linkage system was used to identify all premenopausal women who underwent bilateral oophorectomy before age 50 years between January 1, 1988, and December 31, 2007, in Olmsted County, Minnesota. Each woman was randomly matched to a referent woman born in the same year (±1 year) who had not undergone bilateral oophorectomy. We studied the rate of accumulation of 18 common chronic conditions over a median of approximately 14 years of follow-up. Although women who underwent bilateral oophorectomy already had a higher multimorbidity burden at the time of oophorectomy, they also experienced an increased risk of subsequent multimorbidity. After adjustments for 18 chronic conditions present at baseline, race/ethnicity, education, body mass index, smoking, age at baseline, and calendar year at baseline, women who underwent oophorectomy before age 46 years experienced an increased risk of depression, hyperlipidemia, cardiac arrhythmias, coronary artery disease, arthritis, asthma, chronic obstructive pulmonary disease, and osteoporosis. In addition, they experienced an accelerated rate of accumulation of the 18 chronic conditions considered together (hazard ratio, 1.22; 95% CI, 1.14-1.31; P<.001). Several of these associations were reduced in women who received estrogen therapy. Bilateral oophorectomy is associated with a higher risk of multimorbidity, even after adjustment for conditions present at baseline and for several possible confounders. However, several of these associations were reduced in women who received estrogen therapy.

Twins, full siblings, and half-siblings are increasingly used as comparison groups in matched cohort and matched case-control studies. The “within-pair” estimates acquired through these comparisons are free from confounding from all factors that are shared by the siblings. This has made sibling comparisons popular in studying associations thought likely to suffer confounding from socioeconomic or genetic factors. Despite the wide application of these designs in epidemiology, they have received little scrutiny from a statistical or methodological standpoint. In this paper we show, analytically and through a series of simulations, that the standard interpretation of the models is subject to several limitations that are rarely acknowledged.Although within-pair estimates will not be confounded by factors shared by the siblings, such estimates are more severely biased by non-shared confounders than the unpaired estimate. If siblings are less similar with regard to confounders than to the exposure under study, the within-pair estimate will always be more biased than the ordinary unpaired estimate. Attenuation of associations due to random measurement error in exposure will also be higher in the within-pair estimate, leading within-pair associations to be weaker than corresponding unpaired associations, even in the absence of confounding. Implications for the interpretation of sibling comparison results are discussed.

Protein and genetic interaction maps can reveal the overall physical and functional landscape of a biological system. To date, these interaction maps have typically been generated under a single condition, even though biological systems undergo differential change that is dependent on environment, tissue type, disease state, development or speciation. Several recent interaction mapping studies have demonstrated the power of differential analysis for elucidating fundamental biological responses, revealing that the architecture of an interactome can be massively re‐wired during a cellular or adaptive response. Here, we review the technological developments and experimental designs that have enabled differential network mapping at very large scales and highlight biological insight that has been derived from this type of analysis. We argue that differential network mapping, which allows for the interrogation of previously unexplored interaction spaces, will become a standard mode of network analysis in the future, just as differential gene expression and protein phosphorylation studies are already pervasive in genomic and proteomic analysis. Protein and genetic interaction maps have typically been generated under a single condition, providing a static view of the interactome. Recent studies employing differential analysis, however, have revealed that widespread re‐wiring of the interactome underlies key biological responses.