Gender differences in outcomes following endoscopic sinus surgery: a systematic review and meta-analysis.

BACKGROUND: The extent to which gender affects outcomes in chronic rhinosinusitis (CRS) is unclear. The objective of this study was to examine differential outcomes between genders following endoscopic sinus surgery (ESS) among CRS patients. METHODS: PubMed/Ovid, Embase and Cochrane databases were queried. Outcomes included disease burden on imaging and endoscopy, patient-reported outcome measures (PROMs) including the Sinonasal Outcome Test (SNOT-22), revision rates, and olfactory outcomes. Meta-analysis was performed using the Mantel-Haenszel method with random effects model. RESULTS: Of 4,656 articles screened, 32 (n=103,499) were included for qualitative analysis and four (n=2,602) for meta-analysis. On qualitative analysis, 19 of the 32 studies noted a significant gender difference in post-operative outcomes, with five studies favoring women and 14 favoring men. Nine of 18 studies with PROMs noted a difference between genders, all favoring men. Olfactory outcomes were mixed with studies divided on favoring men vs women. No studies noted significant gender differences of disease burden on imaging or endoscopy. Across four studies included in the meta-analysis, women had higher preoperative and post-operative SNOT-22 scores. CONCLUSION: Meta-analysis shows that women patients have worse pre and postoperative SNOT-22 scores. Postoperative gender differences are most apparent in studies that examined PROMs. Further research is needed to investigate the underlying causes and to mitigate disparities between genders.

Recruiting refugees and migrants as potential hematopoietic stem cell donors to serve patients of comparable ethnicities with rare human leucocyte antigen patterns - The BluStar.NRW project in North Western Germany.

Currently, approximately 19 million people with a migration background live in Germany. The majority of those descend from regions where the population has a genetically different distribution of HLA antigens when compared to the HLA frequencies usually found in North Western Europe. In case of severe haematological disorders of these individuals, allogeneic stem cell transplantation may be the treatment of choice. However, finding appropriate histocompatible hematopoietic stem cell donors continues to be a major challenge. If no matching sibling donors are available, there are only few suitable donors with a similar genetic background available in international blood stem cell donor registries. The "BluStar.NRW" project aimed to recruit new blood and hematopoietic stem cell donors with a migration background and to noticeably increase the number of suitable donors for patients within this group. Since December 2017, a total number of 9100 blood and stem cell donors with a migration background were recruited and typed for this project. HLA typing for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 was performed by Next Generation Sequencing. We assessed the proportion of rare alleles according to HLA frequency tables, as defined by a frequency of <1:1000. The rare HLA allele frequencies according to HLA frequency tables of the BluStar.NRW cohort were compared with a matched control donor cohort: Rare HLA-A, -B, -C, -DRB1 and -DQB1 alleles occurred three times more frequent than in the control group, but rare HLA-DPB1 alleles occurred more frequently in the control cohort. This difference was highly significant for all HLA alleles (p < 0.0001 for HLA-A, -B, -C, -DRB1, -DPB1; p = 0.0002 for HLA-DQB1). In addition, the distribution of rare alleles differed between the two groups. To date, 29 work-ups were initiated, 12 PBSC, one BM and three DLI were collected so far out of the BluStar.NRW cohort. The apheresis probability is twofold higher (0.18% vs. 0.07%) compared to the control group which clearly shows a serious medical need. However, 13 work-ups were cancelled in the BluStar.NRW donor cohort which represents an almost twice as higher cancellation rate (45% vs. 25%). This single registry analysis with a large sample cohort clearly indicates that hematopoietic stem cell donors with a migration background represent an adequate donor pool to serve patients of comparable ethnicity.

The enigma of incisional hernia prediction unraveled: external validation of a prognostic model in colorectal cancer patients.

PURPOSE: Accurate prediction of hernia occurrence is vital for surgical decision-making and patient management, particularly in colorectal surgery patients. While a hernia prediction model has been developed, its performance in external populations remain to be investigated. This study aims to validate the existing model on an external dataset of patients who underwent colorectal surgery. METHODS: The "Penn Hernia Calculator" model was externally validated using the Hughes Abdominal Repair Trial (HART) data, a randomized trial comparing colorectal cancer surgery closure techniques. The data encompassed demographics, comorbidities, and surgical specifics. Patients without complete follow-up were omitted. Model performance was assessed using key metrics, including area under the curve (AUC-ROC and AUC-PR) and Brier score. Reporting followed the TRIPOD consensus. RESULTS: An external international dataset consisting of 802 colorectal surgery patients were identified, of which 674 patients with up to 2 years follow-up were included. Average patient age was 68 years, with 63.8% male. The average BMI was 28.1. Prevalence of diabetes, hypertension, and smoking were 15.7%, 16.3%, and 36.5%, respectively. Additionally, 7.9% of patients had a previous hernia. The most common operation types were low anterior resection (35.3%) and right hemicolectomy (34.4%). Hernia were observed in 24% of cases by 2-year follow-up. The external validation model revealed an AUC-ROC of 0.66, AUC-PR of 0.72, and a Brier score of 0.2. CONCLUSION: The hernia prediction model demonstrated moderate performance in the external validation. Its potential generalizability, specifically in those undergoing colorectal surgery, may suggest utility in identifying and managing high-risk hernia candidates.

Optimal computed tomography-based biomarkers for prediction of incisional hernia formation.

PURPOSE: Unstructured data are an untapped source for surgical prediction. Modern image analysis and machine learning (ML) can harness unstructured data in medical imaging. Incisional hernia (IH) is a pervasive surgical disease, well-suited for prediction using image analysis. Our objective was to identify optimal biomarkers (OBMs) from preoperative abdominopelvic computed tomography (CT) imaging which are most predictive of IH development. METHODS: Two hundred and twelve rigorously matched colorectal surgery patients at our institution were included. Preoperative abdominopelvic CT scans were segmented to derive linear, volumetric, intensity-based, and textural features. These features were analyzed to find a small subset of OBMs, which are maximally predictive of IH. Three ML classifiers (Ensemble Boosting, Random Forest, SVM) trained on these OBMs were used for prediction of IH. RESULTS: Altogether, 279 features were extracted from each CT scan. The most predictive OBMs found were: (1) abdominopelvic visceral adipose tissue (VAT) volume, normalized for height; (2) abdominopelvic skeletal muscle tissue volume, normalized for height; and (3) pelvic VAT volume to pelvic outer aspect of body wall skeletal musculature (OAM) volume ratio. Among ML prediction models, Ensemble Boosting produced the best performance with an AUC of 0.85, accuracy of 0.83, sensitivity of 0.86, and specificity of 0.81. CONCLUSION: These OBMs suggest increased intra-abdominopelvic volume/pressure as the salient pathophysiologic driver and likely mechanism for IH formation. ML models using these OBMs are highly predictive for IH development. The next generation of surgical prediction will maximize the utility of unstructured data using advanced image analysis and ML.

Transversus abdominis release with biosynthetic mesh for large ventral hernia repair: a 5-year analysis of clinical outcomes and quality of life.

INTRODUCTION: Transversus abdominis release (TAR) may provide an optimal plane for mesh placement for large ventral hernias requiring medial myofascial flap advancement. Long-term outcomes of TAR for large ventral hernia repair (VHR) remains under-studied. This study aims to assess longitudinal clinical outcomes and quality of life (QoL) following large VHR with TAR and resorbable biosynthetic mesh. METHODS: Retrospective review of clinical outcomes and prospective QoL was performed for patients undergoing VHR with poly-4-hydroxybutyrate mesh and TAR from 2016 to 2021. Patients with ≤ 24 months of follow-up, defects ≤ 150 cm2, and parastomal hernias were excluded. Cost-related data was collected for each patient's hospital course. QoL was compared using paired Wilcoxon signed-rank tests. RESULTS: Twenty-nine patients met inclusion criteria. Median age and BMI were 61 years (53.2-68.1 years) and 31.4 kg/m2 (26.1-35.3 kg/m2). Average hernia defect was 390cm2 ± 152.9 cm2. All patients underwent previous abdominal surgery and were primarily Ventral Hernia Working Group 2 (58.6%). Two hernia recurrences (6.9%) occurred over the median follow-up period of 63.1 months (IQR 43.7-71.3 months), with no cases of mesh infection or explantation. Delayed healing and seroma occurred in 27 and 10.3% of patients, respectively. QoL analysis identified a significant improvement in postoperative QoL (p < 0.005), that continued throughout the 5-year follow-up period, with a 41% overall improvement. Cost analysis identified the hospital revenue generated was approximately equal to the direct costs of patient care. Higher costs were associated with ASA class and length of stay (p < 0.05). CONCLUSION: Large VHR with resorbable biosynthetic mesh and TAR can be performed safely, with a low recurrence and complication rate, acceptable hospital costs, and significant improvement in disease-specific QoL at long-term follow-up.

[Eosinophilic dermatoses]. / Eosinophile Dermatosen.

Eosinophilic dermatoses are a heterogeneous group of rare diseases that histopathologically display the defining pattern of an eosinophil-rich dermal infiltrate. In these eosinophilic dermatoses, a histopathologic pattern called flame figures, which result from degranulation of eosinophils in the tissue, can be observed. Although eosinophil granulocytes can also be detected in other dermatoses such as atopic dermatitis, urticaria, prurigo and bullous pemphigoid, the eosinophil-rich infiltrate is decisive for classic eosinophilic dermatoses. Accordingly, eosinophilic dermatoses include hypereosinophilic syndrome, eosinophilic fasciitis, granuloma faciale, pustular sterile eosinophilia, and angiolymphoid hyperplasia with eosinophilia. These eosinophilic dermatoses display clinical different patterns and are discussed in this article, as well as the interesting eosinophils and novel therapeutic options.

National epidemiologic trends (2008-2018) in the United States for the incidence and expenditures associated with incisional hernia in relation to abdominal surgery.

PURPOSE: It is unknown whether the trend of rising incisional hernia (IH) repair (IHR) incidence and costs until 2011 currently persists. We aimed to evaluate how the IHR procedure incidence, cost and patient risk-profile have changed over the last decade relative to all abdominal surgeries (AS). METHODS: Repeated cross-sectional analysis of 38,512,737 patients undergoing inpatient 4AS including IHR within the 2008-2018 National Inpatient Sample. Yearly incidence (procedures/1,000,000 people [PMP]), hospital costs, surgical and patient characteristics were compared between IHR and AS using generalized linear and multinomial regression. RESULTS: Between 2008-2018, 3.1% of AS were IHR (1,200,568/38,512,737). There was a steeper decrease in the incidence of AS (356.5 PMP/year) compared to IHR procedures (12.0 PMP/year) which resulted in the IHR burden relative to AS (2008-2018: 12,576.3 to 9,113.4 PMP; trend difference P < 0.01). National costs averaged $47.9 and 1.7 billion/year for AS and IHR, respectively. From 2008-2018, procedure costs increased significantly for AS (68.2%) and IHR (74.6%; trends P < 0.01). Open IHR downtrended (42.2%), whereas laparoscopic (511.1%) and robotic (19,301%) uptrended significantly (trends P < 0.01). For both AS and IHR, the proportion of older (65-85y), Black and Hispanic, publicly-insured, and low-income patients, with higher comorbidity burden, undergoing elective procedures at small- and medium-sized hospitals uptrended significantly (all P < 0.01). CONCLUSION: IH persists as a healthcare burden as demonstrated by the increased proportion of IHR relative to all AS, disproportionate presence of high-risk patients that undergo these procedures, and increased costs. Targeted efforts for IH prevention have the potential of decreasing $17 M/year in costs for every 1% reduction.

Comprehensive cancer predisposition testing within the prospective MASTER trial identifies hereditary cancer patients and supports treatment decisions for rare cancers.

BACKGROUND: Germline variant evaluation in precision oncology opens new paths toward the identification of patients with genetic tumor risk syndromes and the exploration of therapeutic relevance. Here, we present the results of germline variant analysis and their clinical implications in a precision oncology study for patients with predominantly rare cancers. PATIENTS AND METHODS: Matched tumor and control genome/exome and RNA sequencing was carried out for 1485 patients with rare cancers (79%) and/or young adults (77% younger than 51 years) in the National Center for Tumor Diseases/German Cancer Consortium (NCT/DKTK) Molecularly Aided Stratification for Tumor Eradication Research (MASTER) trial, a German multicenter, prospective, observational precision oncology study. Clinical and therapeutic relevance of prospective pathogenic germline variant (PGV) evaluation was analyzed and compared to other precision oncology studies. RESULTS: Ten percent of patients (n = 157) harbored PGVs in 35 genes associated with autosomal dominant cancer predisposition, whereof up to 75% were unknown before study participation. Another 5% of patients (n = 75) were heterozygous carriers for recessive genetic tumor risk syndromes. Particularly, high PGV yields were found in patients with gastrointestinal stromal tumors (GISTs) (28%, n = 11/40), and more specifically in wild-type GISTs (50%, n = 10/20), leiomyosarcomas (21%, n = 19/89), and hepatopancreaticobiliary cancers (16%, n = 16/97). Forty-five percent of PGVs (n = 100/221) supported treatment recommendations, and its implementation led to a clinical benefit in 40% of patients (n = 10/25). A comparison of different precision oncology studies revealed variable PGV yields and considerable differences in germline variant analysis workflows. We therefore propose a detailed workflow for germline variant evaluation. CONCLUSIONS: Genetic germline testing in patients with rare cancers can identify the very first patient in a hereditary cancer family and can lead to clinical benefit in a broad range of entities. Its routine implementation in precision oncology accompanied by the harmonization of germline variant evaluation workflows will increase clinical benefit and boost research.

[Internal medical emergencies in the pregnant patient : Peripartum sepsis, metabolic derailment, endocrinological emergencies and pulmonary edema]. / Internistische Notfälle bei der schwangeren Patientin : Peripartale Sepsis, Stoffwechselentgleisungen, endokrinologische Notfälle und Lungenödem.

Peripartum emergencies that require intensive medical care represent a major challenge for the interdisciplinary treatment team. Due to physiological changes in pregnant women symptoms can be masked and the initiation of treatment is delayed. Peripartum sepsis has a relatively high incidence. The anti-infective treatment depends on the spectrum of pathogens to be expected. Endocrinological emergencies are rare but can be fulminant and fatal. The development of ketoacidosis is favored by decreased bicarbonate buffer and placental hormones. In the case of thyrotoxicosis, propylthiouracil and thiamazole are available for treatment depending on the stage of gestation. Sheehan's syndrome is an infarction of the anterior lobe of the pituitary gland during a hemorrhage. Due to the loss of production of vital hormones, this can be fatal. The development of pulmonary edema is just as acute. This is favored by physiological changes during pregnancy. The differentiation between hypertensive and hypotensive pulmonary edema is important for the causal treatment.

Characterizing hernia centers in the United States: what defines a hernia center?

PURPOSE: A universal definition for what constitutes a hernia center does not exist. The purpose of this study was to characterize hernia centers in the United States by analyzing hernia centers and their non-hernia center counterparts. METHODS: A web-based search was conducted to identify defining features of hernia centers including faculty demographics and composition, research output, research funding, clinical trials, and website content. Hernia centers and non-hernia centers were compared. RESULTS: Most hernia centers (n = 36) are in urban areas (89%) and distributed evenly across regions of the United States. Hernia centers are associated with University program types (p = 0.001) while non-hernia centers are associated with University-Affiliate (p = 0.001) and Community (p = 0.02) program types. Hernia centers are associated with Abdominal Core Health Quality Collaborative participation (p = 0.01) and Center of Excellence by the Surgical Review Corporation certification (p = 0.005). Hernia centers are associated with presence of active clinical trials (p < 0.001) and number of clinical trials (p < 0.001). Hernia centers are associated with industry-sponsored trials (p < 0.001) but are not associated with NIH-sponsored trials. Fifty percent of hernia centers have PRS faculty. The vast majority of hernia center websites describe hernias treated (92%) and repair techniques (89%). The majority of hernia center mission statements emphasize an individualized care plan (61%) and multidisciplinary care (57%). Only 39% of websites and 17% of mission statements mention research. CONCLUSION: In the United States, hernia centers are clinically oriented, multidisciplinary surgical teams at predominantly urban, University programs that may use this title to attract patient referrals and industry sponsorship of clinical trials.

The Abdominal Hernia-Q: a critical analysis of the components that impact quality-of-life.

PURPOSE: Ventral hernias (VH) are a common surgical problem associated with significant morbidity. While assessment tools have examined quality-of-life (QoL), the relative change in specific domains of hernia-related QoL measures from pre- to post-operative period has yet to be comprehensively examined. Using the Abdominal Hernia-Q (AHQ), this study aims to assess the impact of ventral hernia repair (VHR) on key components of QoL. METHODS: A retrospective chart review was conducted of patients undergoing VHR between September 2017 and September 2019 who had completed at least one pre- and post-operative AHQ. Post-operative intervals were created to capture AHQ responses around standard follow-up visits (< 1.5 months, 1.5-4.5 months, 4.5-11 months, and 11 + months) and scores were statistically analyzed. RESULTS: A total of 136 patients were included, with an average age of 54.8 years at the time of VHR. Compared to the pre-operative period, the appearance score increased significantly (p < 0.05). The physical domain score increased from < 1.5 month to the 1.5-4.5 month period (p = 0.03) and remained significantly higher in later time period. The appearance score decreased from the 1.5-4.5 month to 4.5-11 month period (p = 0.05). CONCLUSIONS: VHR leads to a sustained multi-dimensional increase in hernia-specific QoL measures during the post-operative course driven by early positive changes in appearance and sustained physical functioning. The initial increase in QoL is mainly driven by an improvement in appearance, while the sustained increase may be due to restored physical function.

An evaluation of clinical and quality of life outcomes after ventral hernia repair with poly-4-hydroxybutyrate mesh.

PURPOSE: Despite continued efforts, recurrence after ventral hernia repair (VHR) remains a common problem. Biosynthetic Phasix™ (Poly-4-Hydroxybutyrate, P4HB) mesh combines the durability of synthetic mesh with the bio-resistance of biologics. P4HB has shown promising early outcomes, but long-term data are lacking. We examine patients following VHR with P4HB with at least 3 years of follow-up to assess clinical and patient reported outcomes (PROs). METHODS: Adult patients (≥ 18 years old) undergoing VHR with P4HB mesh between 10/2015 and 01/2018 by a single surgeon were retrospectively identified. Patients with < 36 months of follow-up were excluded unless they had a documented recurrence. Clinical outcomes and quality of life using the Hernia-Related Quality of Life Survey (HerQLes) were assessed. RESULTS: Seventy-one patients were included with a median age and body mass index of 61.2 and 31 kg/m2, respectively. Mesh was placed in the retromuscular (79%) and onlay (21%) planes with 1/3 of patients having hernias repaired in contaminated fields. There were no mesh infections, enterocutaneous fistulas, or mesh explantations. Nine patients (12.7%) developed recurrence at a median follow-up of 43.1 months [38.2-49.1]. Mesh plane, fixation technique, and Ventral Hernia Working Group were not associated with recurrence. Significant improvement in disease-specific PROs was observed and maintained at 3-year follow-up. CONCLUSION: Longitudinal clinical and quality of life outcomes after clean and contaminated VHR with P4HB are limited. Here, we conclude that P4HB is an effective and versatile mesh option for use in abdominal wall reinforcement.

The incisional hernia epidemic: evaluation of outcomes, recurrence, and expenses using the healthcare cost and utilization project (HCUP) datasets.

BACKGROUND: Incisional hernias (IH) following abdominal surgery persist as morbid, costly, and multi-disciplinary surgical challenges. Using longitudinal, multi-state, administrative claims data (HCUP State Inpatient Databases (SID)); (HCUP State Ambulatory Surgery and Services Databases (SASD)), we aimed to characterize the epidemiology, outcomes, recurrence, and costs of IH. STUDY DESIGN: 529,108 patients undergoing abdominal surgery in 2010 across six specialties (colorectal, general/bariatric, hepatobiliary, obstetrics/gynecology, urology, and vascular) were identified within inpatient and ambulatory databases for Florida (FL), Iowa (IA), Nebraska (NE), New York (NY), and Utah (UT). IH repairs, complications, and expenditures were assessed through 2014. Predictive regression modeling was validated using a training set of 1000 bootstrapped repetitions. RESULTS: 16,169 (3.1%) patients developed hernias requiring repair (4.3-year mean follow-up), 3176 (20%) underwent recurrent repair, and 731 (23%) underwent re-recurrent repair. Patients with IH had increased readmissions (6.6 vs. 2.4), morbidity (39 vs. 8% surgical and 22 vs. 7% medical), and costs ($46,000 vs. $25,000) when compared to patients without IH (p < 0.001). IH expenditures totaled $875 million: initial ($687 million), recurrent ($155 million), and re-recurrent hernias ($33 million). IH predominated in colorectal (10%), hepatobiliary (8%), and vascular (5%) procedures. Of 31 significant independent IH risk factors (p < 0.001), obesity, age, smoking, open surgery, and prior surgery were pervasive across surgical specialties. CONCLUSION: IH represents an unremitting surgical epidemic associated with considerable morbidity, costs, and features consistent with a chronic disease state. We define critical pervasive risk factors (obesity, age, smoking open surgery, and prior surgery) independently associated with IH across surgical disciplines. With failed repairs, subsequent success becomes less likely, increasing morbidity and costs-underscoring the critical importance of optimal treatment and prevention.

Risk factors, outcomes, and complications associated with combined ventral hernia and enterocutaneous fistula single-staged abdominal wall reconstruction.

PURPOSE: To compare two cohorts of patients; those with isolated ventral hernias (VH) and those with VH and enterocutaneous fistulas (ECF). Risk factors for surgical complications (including recurrent ECF) and outcomes during single-stage VH with ECF surgical reconstruction were analyzed. METHODS: A retrospective review was performed from 2008 to 2019. We compared two cohorts of patients with single-stage VH repairs: (1) ventral hernia repair alone (hernia alone), and (2) combined VH repair and ECF repair (hernia plus ECF). Inclusion criteria were patients ≥ 18 years of age with pre-operative VH either with or without an ECF, who underwent open hernia repair and ECF repair in a single-stage operation, with a minimum follow-up of 12 months. Patient risk factors, operative characteristics, outcomes and surgical-site complications were compared using univariate and multivariate analyses. RESULTS: We included 442 patients (hernia alone = 401; hernia plus ECF = 41) with a median follow-up of 22 months (12-96). Hernia plus ECF patients were more likely to have inflammatory bowel disease (IBD)(OR 4.4, 95% CI 1.1-17.5, p = 0.037), a history of abdominal wound infections (OR 3.4, 95% CI 1.5-7.9, p = 0.004), reoperations (OR 4.9, 95% CI 1.6-15.4, p = 0.006), superficial soft tissue infections (OR 2.5, 95% CI 1.1-6.1, p = 0.044) and hematomas (OR 8.4, 95% CI 1.2-58.8, p = 0.031), compared to hernia alone patients. ECF recurrence was associated with diabetes mellitus (DM) (n = 8, 73% vs. n = 6, 20%; p = 0.003) and surgical-site complications (n = 10, 91% vs. n = 16, 53%; p = 0.048), compared to ECF resolution. CONCLUSION: Risk factors for developing ECF were IBD and history of abdominal wound infections. Single-staged combined ECF reconstruction was associated with reoperations, soft tissue infections and hematomas. DM and surgical-site complications were associated with ECF recurrence.

Ventral hernia repair with synthetic mesh in a contaminated field: a systematic review and meta-analysis.

PURPOSE: The use of mesh in ventral hernia repair becomes especially challenging when associated with a contaminated field. Permanent synthetic mesh use in this setting is currently debated and this discussion is yet to be resolved clinically or in the literature. We aim to systematically assess postoperative outcomes of non-absorbable synthetic mesh (NASM) used in ventral hernia repair in the setting of contamination. METHODS: A literature search of PubMed, Embase, Scopus, Cinahl, and Cochrane Library identified all articles from 2000-2020 that examined the use of NASM for ventral hernia repair in a contaminated field. Postoperative outcomes were assessed by means of pooled analysis and meta-analysis. Qualitative analysis was completed for all included studies using a modified Newcastle-Ottawa scale. RESULTS: Of 630 distinct publications and 104 requiring full review, this study included 17 articles published between 2007 and 2020. Meta-analysis demonstrated absorbable mesh was associated with more HR (OR 1.89, 1.15-3.12, p = 0.008), SSO (OR 1.43, 0.96-2.11, p = 0.087), SSI (OR 2.84, 1.85-4.35, p < 0.001), and unplanned reoperation (OR 1.99, 1.19-3.32, p = 0.009) compared to NASM. CONCLUSION: The use of NASM for ventral hernia repair in a contaminated field may be a safe alternative to absorbable mesh, as evidenced by lower rates of postoperative complications. This review counters the current clinical paradigm, and additional prospective randomized controlled trials are warranted.

Sensitivity of C-Reactive Protein and Procalcitonin Measured by Point-of-Care Tests to Diagnose Urinary Tract Infections in Nursing Home Residents: A Cross-Sectional Study.

BACKGROUND: Diagnosing urinary tract infections (UTIs) in nursing home residents is complex, as specific urinary symptoms are often absent and asymptomatic bacteriuria (ASB) is prevalent. The aim of this study was to assess the sensitivity of blood C-reactive protein (CRP) and procalcitonin (PCT), measured by point-of-care tests (PoCTs), to diagnose UTIs in this setting. METHODS: Elderly residents (≥65 years old) with a suspected UTI were recruited from psychogeriatric, somatic, or rehabilitation wards across 13 participating nursing homes. CRP and PCT were tested simultaneously in the same study participants. To assess the tests' sensitivities, a stringent definition of "true" UTI was used that included the presence of symptoms, urinary leucocytes, a positive urine culture, and symptom resolution during antibiotic treatment covering isolated uropathogen(s). The original sample size was 440 suspected UTI episodes, in order to detect a clinically relevant sensitivity of at least 65% when calculated using the matched analysis approach to compare both PoCTs. RESULTS: After enrollment of 302 episodes (68.6% of the planned sample size), an unplanned and funder-mandated interim analysis was done, resulting in premature discontinuation of the study for futility. For 247 of 266 eligible episodes, all mandatory items required for the true UTI definition (92.9%) were available. In total, 49 episodes fulfilled our stringent UTI definition (19.8%). The sensitivities of CRP (cut-off, 6.5 mg/L) and PCT (cut-off, 0.025 ng/mL) were 52.3% (95% confidence interval [CI], 36.7-67.5%) and 37.0% (95% CI, 23.2-52.5%), respectively. CONCLUSIONS: Our results indicate that CRP and PCT are not suitable tests for distinguishing UTI and ASB in nursing home residents. CLINICAL TRIALS REGISTRATION: Netherlands Trial Registry NL6293.

ICF-based multidisciplinary rehabilitation program for complex regional pain syndrome of the hand: efficacy, long-term outcomes, and impact of therapy duration.

BACKGROUND: Complex regional pain syndrome (CRPS) is a rare but feared complication in hand surgery. Although multimodal therapy concepts are recommended, there is only low evidence on efficacy of such approaches. Furthermore, recommendations regarding therapy duration are lacking. Aim of this study was to validate the efficacy of an International Classification of Functioning, Disability and Health (ICF)-based multidisciplinary rehabilitation concept for treatment of CRPS of the hand and to find correlations between therapy duration and outcome measures. METHODS: Patients with CRPS of the hand after occupational trauma that underwent an ICF-based rehabilitation program between 2010 and 2014 were included in this retrospective study. Besides demographic data, outcomes included pain (VAS), range of motion assessed by fingertip-to-palm-distance (PTPD) and fingernail-to-table-distance (FTTD) as well as strength in grip, 3-point pinch and lateral pinch. All measures were gathered at admission to and discharge from inpatient rehabilitation therapy as well as at follow-up. Statistical analysis included paired t-test, ANOVA and Pearson's correlation analysis. RESULTS: Eighty-nine patients with a mean age of 45 years were included in this study. Duration of rehabilitation therapy was 53 days on average. All outcomes improved significantly during rehabilitation therapy. Pain decreased from 6.4 to 2.2. PTPD of digit 2 to 5 improved from 2.5, 2.8, 2.6, and 2.3 cm to 1.3, 1.4, 1.2, and 1.1 cm, respectively. FTTD of digit 2 to 5 decreased from 1.5, 1.7, 1.5, and 1.6 cm to 0.6, 0.8, 0.7, and 0.7 cm, respectively. Strength ameliorated from 9.5, 3.7, 2.7 kg to 17.9, 5.6, 5.0 kg in grip, lateral pinch, and 3-point pinch, respectively. Improvement in range of motion significantly correlated with therapy duration. 54% of patients participated at follow-up after a mean of 7.5 months. Outcome measures at follow-up remained stable compared to discharge values without significant differences. CONCLUSION: The ICF-based rehabilitation concept is a reliable and durable treatment option for CRPS of the hand. Range of motion improved continuously with therapy duration and thus may serve as an indicator for optimum length of therapy.

International validation of a risk prediction algorithm for patients with malignant colorectal polyps.

AIM: The optimal management strategy for patients with endoscopically resected malignant colorectal polyps (MCP) has yet to be defined. The aim of this study was to validate a published decision-making tool, termed the Scottish Polyp Cancer Study (SPOCS) algorithm, on a large international population. METHODS: The SPOCS algorithm allocates patients to risk groups based on just two variables: the polyp resection margin and the presence of lymphovascular invasion (LVI). The risk groups are termed low (clear margin, LVI absent), medium (clear margin, LVI present) or high (involved/non-assessable margin). The International Polyp Cancer Collaborative was formed to validate the algorithm on data from Australia, Denmark, UK and New Zealand. RESULTS: In total, 1423 patients were included in the final dataset. 680/1423 (47.8%) underwent surgical resection and 108/680 (15.9%) had residual disease (luminal disease 8.8%, lymph node metastases 8.8%). The SPOCS algorithm classified 602 patients as low risk (in which 1.5% had residual disease), 198 patients as medium risk (in which 7.1% had residual disease) and 484 as high risk (in which 14.5% had residual disease) (P < 0.001, χ2 test). Receiver operating characteristic curve analysis demonstrated good accuracy of the algorithm in predicting residual disease (area under the curve 0.732, 95% CI 0.687-0.778, P < 0.001). When patients were designated as low risk, the negative predictive value was 98.5%. CONCLUSION: The SPOCS algorithm can be used to predict the risk of residual disease in patients with endoscopically resected MCPs. Surgery can be safely avoided in patients who have a clear margin of excision and no evidence of LVI.

Risk stratification of EGFR+ lung cancer diagnosed with panel-based next-generation sequencing.

OBJECTIVE: Panel-based next-generation sequencing (NGS) is increasingly used for the diagnosis of EGFR-mutated non-small-cell lung cancer (NSCLC) and could improve risk assessment in combination with clinical parameters. MATERIALS AND METHODS: To this end, we retrospectively analyzed the outcome of 400 tyrosine kinase inhibitor (TKI)-treated EGFR+ NSCLC patients with validation of results in an independent cohort (n = 130). RESULTS: EGFR alterations other than exon 19 deletions (non-del19), TP53 co-mutations, and brain metastases at baseline showed independent associations of similar strengths with progression-free (PFS hazard ratios [HR] 2.1-2.3) and overall survival (OS HR 1.7-2.2), in combination defining patient subgroups with distinct outcome (EGFR+NSCLC risk Score, "ENS", p < 0.001). Co-mutations beyond TP53 were rarely detected by our multigene panel (<5%) and not associated with clinical endpoints. Smoking did not affect outcome independently, but was associated with non-del19 EGFR mutations (p < 0.05) and comorbidities (p < 0.001). Laboratory parameters, like the blood lymphocyte-to-neutrophil ratio and serum LDH, correlated with the metastatic pattern (p < 0.01), but had no independent prognostic value. Reduced ECOG performance status (PS) was associated with comorbidities (p < 0.05) and shorter OS (p < 0.05), but preserved TKI efficacy. Non-adenocarcinoma histology was also associated with shorter OS (p < 0.05), but rare (2-3 %). The ECOG PS and non-adenocarcinoma histology could not be validated in our independent cohort, and did not increase the range of prognostication alongside the ENS. CONCLUSIONS: EGFR variant, TP53 status and brain metastases predict TKI efficacy and survival in EGFR+ NSCLC irrespective of other currently available parameters ("ENS"). Together, they constitute a practical and reproducible approach for risk stratification of newly diagnosed metastatic EGFR+ NSCLC.