Large Cohort Of Patients Research Articles

Combined simultaneous transsphenoidal and transcranial regimen improves surgical outcomes in complex giant pituitary adenomas: A longitudinal retrospective cohort study.

Surgical treatment of complex giant pituitary adenomas (GPAs) presents significant challenges. The efficacy and safety of combining transsphenoidal and transcranial approaches for these tumors remain controversial. In this largest cohort of patients with complex GPAs, we compared the surgical outcomes between those undergoing a combined regimen and a non-combined regimen. We also examined the differences in risks of complications, costs, and logistics between the two groups, which might offer valuable information for the appropriate management of these patients. This was a multicenter retrospective cohort study conducted at 13 neurosurgical centers. Consecutive patients who received a combined or non-combined regimen for complex GPAs were enrolled. The primary outcome was gross total resection, while secondary outcomes included complications, surgical duration, and relapse. A propensity score-based weighting method was used to account for differences between the groups. Out of 647 patients (298 [46.1%] women, mean age: 48.5 ± 14.0 years) with complex GPAs, 91 were in the combined group and 556 were in the non-combined group. Compared with the non-combined regimen, the combined regimen was associated with a higher probability of gross total resection (50.5% vs. 40.6%, odds ratio [OR]: 2.18, 95% confidence interval [CI]: 1.30-3.63, P = 0.003). The proportion of patients with life-threatening complications was lower in the combined group than in the non-combined group (4.4% vs. 11.2%, OR: 0.25, 95% CI: 0.08-0.78, P = 0.017). No marked differences were found between the groups in terms of other surgical or endocrine-related complications. However, the combined regimen exhibited a longer average surgery duration of 1.3 h (P < 0.001) and higher surgical costs of 22,000 CNY (approximate 3,000 USD, P = 0.022) compared with the non-combined approach. The combined regimen offered increased rates of total resection and decreased incidence of life-threatening complications, which might be recommended as the first-line choice for these patients.

O79: Adjuvant chemotherapy following surgery for adenocarcinoma arising from intraductal papillary mucinous neoplasia and impact on recurrence and survival: ADENO-IPMN study

Abstract Background The clinical impact of giving adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia (IPMN) is unclear. The present study aims to identify factors related to receipt of adjuvant chemotherapy, the type and its impact on recurrence, site specific recurrence and survival in a large international cohort of patients. Method Patients undergoing pancreatic resection for adenocarcinoma arising from IPMN between 2010-2020 at 18 pancreatic centres were identified. Propensity score matching (PSM) and survival analyses were performed to identify the impact of adjuvant chemotherapy on recurrence and survival. Results A total of 459 patients underwent pancreatic resection and 275 patients (59.9%) received adjuvant chemotherapy (Gemcitabine,51.3%; Gemcitabine-capecitabine,21.8%; Folfirinox,8.0%; and other,18.9%). In multivariate analysis, poor differentiation (30.2%vs.19.0%; p=0.007) was associated with adjuvant chemotherapy use. Adjuvant chemotherapy was not associated with all, locoregional, systemic or site-specific recurrence compared to no adjuvant chemotherapy on Kaplan-Meier analysis (median time to recurrence 26 versus 50 months; p=0.14), multivariate analysis (HR 0.79, p=0.175), and on propensity score matching (HR 0.76, p=0.111). No particular subgroup had lower rates of recurrence with adjuvant chemotherapy. No particular chemotherapy regime resulted in lower recurrence rates or longer survival. The overall or disease-free survival rates were not significantly different in multivariate analysis. Conclusion Based on the contemporary data, adjuvant chemotherapy after pancreatic resection for adenocarcinoma arising from IPMN does not appear to impact on recurrence rates, recurrence patterns and long term survival. However, data on the most potent chemotherapy (Folfirinox) is limited and warrants further studies

A Comparison of Prognostic Factors in a Large Cohort of In-Hospital and Out-of-Hospital Cardiac Arrest Patients.

We investigated independent factors predicting neurological outcome and death, comparing in-hospital (IHCA) and out-of-hospital cardiac arrest (OHCA) patients. The study was conducted in the mixed 34-bed Intensive Care Department at the Hôpital Universitaire de Bruxelles (HUB), Belgium. All adult consecutive cardiac arrest (CA) survivors were included between 2004 and 2022. For all patients, demographic data, medical comorbidities, CA baseline characteristics, treatments received during Intensive Care Unit stay, in-hospital major complications, and neurological outcome at three months after CA, using the Cerebral Performance Category (CPC) scale, were collected. In the multivariable analysis, in the IHCA group (n = 540), time to return of spontaneous circulation (ROSC), older age, unwitnessed CA, higher lactate on admission, asystole as initial rhythm, a non-cardiac cause of CA, the occurrence of shock, the occurrence of acute kidney injury (AKI), and the presence of previous neurological disease and of liver cirrhosis were independent predictors of an unfavorable neurological outcome. Among patients with OHCA (n = 567), time to ROSC, older age, higher lactate level on admission, unwitnessed CA, asystole or pulseless electrical activity (PEA) as initial rhythm, the occurrence of shock, a non-cardiac cause of CA, and a previous neurological disease were independent predictors of an unfavorable neurological outcome. To conclude, in our large cohort of mixed IHCA and OHCA patients, we observed numerous factors independently associated with a poor neurological outcome, with minimal differences between the two groups, reflecting the greater vulnerability of hospitalized patients.

Cardiac defects of hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders: a retrospective cohort study.

Defective connective tissue structure may cause individuals with hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorders (HSD) to develop cardiac defects. We conducted a retrospective chart review of adult patients treated in the EDS Clinic from November 1, 2019, to June 20, 2022 to identify those with cardiac defects. Echocardiogram data were collected using a data collection service. All EDS Clinic patients were evaluated by a single physician and diagnosed according to the 2017 EDS diagnostic criteria. Patient demographic, family and cardiac history were extracted from self-reported responses from a REDCap clinical intake questionnaire. Patients with at least 1 available echocardiogram (ECHO) were selected for the study (n = 568). The prevalence of aortic root dilation in patients with hEDS was 2.7% and for HSD was 0.6%, with larger measurements for males than females and with age. Based on self-reported cardiac history that was verified from the medical record, patients with hEDS with bradycardia (p = 0.034) or brain aneurysm (p = 0.015) had a significantly larger average adult aortic root z-score. In contrast, patients with HSD that self-reported dysautonomia (p = 0.019) had a significantly larger average aortic root z-score. The prevalence of diagnosed mitral valve prolapse in patients with hEDS was 3.5% and HSD was 1.8%. Variants of uncertain significance were identified in 16 of 84 patients that received genetic testing based on family history. These data reveal a low prevalence of cardiac defects in a large cohort of well-characterized hEDS and HSD patients. Differences in cardiovascular issues were not observed between patients with hEDS vs. HSD; and our findings suggest that cardiac defects in patients with hEDS or HSD are similar to the general population.

Ventricular Tachycardia in Patients With Peripartum Cardiomyopathy: Prevalence, Predictors, and Associated In-Hospital Adverse Events.

Introduction The purpose of this study was to determine the prevalence of ventricular tachycardia (VT) among patients admitted with peripartum cardiomyopathy (PPCM) as well as to analyze the independent association of VT with in-hospital outcomes among PPCM patients. Methods Data were obtained from the National Inpatient Sample from January 2016 to December 2019. We assessed predictors of VT in patients admitted with PPCM. We also assessed the independent association of VT with clinical outcomes among patients admitted with PPCM. Results From 2016 to 2019, 4730 patients with PPCM were reported to the national inpatient sample database, 309 of which developed VT (6.5%). Using multivariate analysis, we found predictors of VT to include patient characteristics and factors such as age (adjusted OR (aOR)=1.020, p=0.023), chronic kidney disease (aOR=1.440, p=0.048), coagulopathy (aOR=1.964, p=0.006), and atrial fibrillation (aOR=3.965,p<0.001). Conversely, pre-eclampsia was significantly associated with a decreased risk of VT in PPCM patients (aOR=0.218,p=0.001). Conclusion In a large cohort of patients admitted with peripartum cardiomyopathy, we found the prevalence of VT to be 6.5%. Risk factors for VT in this patient population included conditions such as coagulopathy and atrial fibrillation.

The Impact of Congestive Heart Failure on Outcomes in Patients Hospitalized With Preeclampsia.

The purpose of this study was to determine the prevalence of congestive heart failure (CHF) among patients admitted with preeclampsia as well as to analyze the independent association of CHF with in-hospital outcomes among women with preeclampsia. Data were obtained from the National (Nationwide) Inpatient Sample (NIS) from January 2016 to December 2019. We assessed the independent association of CHF with outcomes in patients admitted with preeclampsia. Predictors of mortality in patients admitted with preeclampsia were also analyzed. Women with preeclampsia in the United States between 2016 and 2019 were included in our analysis. A total of 256,010 cases were isolated, comprising 1150 patients with preeclampsia andCHF (0.45%). Multivariate analysis demonstrated that CHF in patients with preeclampsia was independently associated with several outcomes, among them cardiac arrest (adjusted OR (aOR) 4.635, p=0.004), ventricular tachycardia (aOR 17.487, p<0.001), pulmonary embolism (aOR 6.987, p<0.001), and eclampsia (aOR 2.503, p=0.011). Conversely, we found CHF to be protective against postpartum hemorrhage (aOR 0.665, p=0.003). Among the predictors of mortality in preeclampsia are age (aOR 1.062, p=0.022), Asian or Pacific Islander race (aOR 4.695, p=0.001), and CHF (aOR 25.457, p<0.001). Conclusions: In a large cohort of patients admitted with preeclampsia, we found the prevalence of CHF to be 0.45%. CHF was associated with several adverse outcomes as well as increased length of stay.

Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5’-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.

Attachment Loss Attributable to Third Molar Malposition/Extraction: The Case for Classification

Background: The 2017 World Workshop on the Classification of Periodontal and Peri-implant Diseases and Conditions established a periodontitis staging and grading scheme that—for the first time—integrates an assessment of disease severity with an appraisal of therapeutic complexity and risk for disease progression. Individuals exhibiting attachment loss attributable to third molar malposition or extraction represent a large cohort of non-periodontitis patients highly likely to respond favorably to treatment. The purpose of this clinical report is to illustrate the value in formally categorizing this common periodontal condition. Case Description: Two male patients were referred to the Department of Periodontics, Army Postgraduate Dental School, for evaluation of bone and attachment loss limited to distal surfaces of mandibular second molars. Each patient was treated using a combination of guided tissue regeneration and bone replacement grafts. Favorable clinical and radiographic outcomes were observed over follow-up periods ranging from 4 months to 4 years. Practical Implications: Many patients experiencing bone and attachment loss attributable to third molar malposition or extraction lack periodontitis risk factors/indicators, have low susceptibility to the disease, and are highly likely to respond favorably to treatment. Future classification systems of periodontal diseases and conditions should formally categorize this commonly encountered periodontal condition.

Postoperative Bisphosphonates Use is Associated with Reduced Adverse Outcomes After Primary Total Joint Arthroplasty of Hip and Knee: A Nationwide Population-Based Cohort Study.

Bisphosphonates have been associated with a decreased risk of revision surgery after total joint arthroplasty of the hip or knee (TJA) because of their effects on decreased periprosthetic bone loss and prosthetic migration. However, the results in the early literature are inconsistent, and the influence of bisphosphonates on associated complications and subsequent TJA remains unknown. This study investigated the association between the use of bisphosphonates and the risk of adverse outcomes after primary TJA. This matched cohort study utilized the National Health Insurance Research Database in Taiwan to identify patients who underwent primary TJA over a 15-year period (January 2000-December 2015 inclusive). Study participants were further categorized into two groups, bisphosphonate users and nonusers, using propensity score matching. The Kaplan-Meier curve analysis and adjusted hazard ratios (aHRs) of revision surgery, adverse outcomes of primary surgery and subsequent TJA were calculated using Cox regression analysis. This study analyzed data from 6485 patients who underwent total hip arthroplasty (THA) and 20,920 patients who underwent total knee arthroplasty (TKA). The risk of revision hip and knee arthroplasty was significantly lower in the bisphosphonate users than in the nonusers (aHR, 0.54 and 0.53, respectively). Furthermore, the risk of a subsequent total joint arthroplasty, adverse events and all-cause mortality were also significantly reduced in the bisphosphonate users. This study, involving a large cohort of patients who underwent primary arthroplasties, revealed that bisphosphonate treatment may potentially reduce the risk of revision surgery and associated adverse outcomes. Furthermore, the use of bisphosphonates after TJA is also associated with a reduced need for subsequent arthroplasty.Research Registration Unique Identifying Number (UIN): ClinicalTrials.gov Identifier-NCT05623540 ( https://clinicaltrials.gov/show/NCT05623540 ).

Transcatheter Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy: A Multicenter Propensity Score-Based Analysis

BackgroundThe prognostic impact of catheter ablation (CA) of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients has not yet been satisfactorily elucidated. ObjectivesThe aim of the study was to assess the impact of CA of AF on clinical outcomes in a large cohort of HCM patients. MethodsIn this retrospective multicenter study, 555 HCM patients with AF were enrolled, 140 undergoing CA and 415 receiving medical therapy. 1:1 propensity score matching led to the inclusion of 226 patients (113 medical group, 113 intervention group) in the final analysis. The primary outcome was a composite of all-cause mortality, heart transplant and acute heart failure exacerbations. Secondary outcomes included AF recurrence and transition to permanent AF. Additionally, an inverse probability weighted (IPW) model was examined. ResultsAt propensity score matching analysis, after a median follow-up of 58.1 months, the primary endpoint occurred in 29 (25.7%) patients in intervention group vs 42 (37.2%) in medical group (P = 0.9). Thromboembolic strokes and major arrhythmic events in intervention vs medical group were 9.7% vs 7.1% (P = 0.144) and 4.4 vs 8.0% (P = 0.779), respectively. Fewer patients in intervention vs medical group experienced AF recurrences (63.7% vs 84.1%, P = 0.001) and transition to permanent AF pattern (20.4% vs 33.6%, P = 0.026). IPW analysis showed consistent results. Severe complications related to CA were uncommon (0.7%). ConclusionsAfter 5 years of follow-up, CA did not improve major adverse cardiac outcomes in a large cohort of patients with HCM and AF. Nevertheless, CA seems to facilitate the maintenance of sinus rhythm and slow the progression to permanent AF, without significant safety concerns.

Offloading systems for the treatment of neuropathic foot ulcers in patients with diabetes mellitus: a meta-analysis of randomized controlled trials for the development of the Italian guidelines for the treatment of diabetic foot syndrome.

To compare the effectiveness of commonly used offloading devices for the treatment of neuropathic foot ulcers in patients with diabetes mellitus. This meta-analysis (MA) has been performed for giving an answer to clinical questions on this topic of the Italian guideline on diabetic foot syndrome. The present MA includes randomized controlled studies (duration > 12weeks) comparing, in patients with diabetes mellitus and non-infected neuropathic foot ulcer: any offloading device vs either no offloading device or conventional footwear; removable versus non-removable offloading devices; surgical procedure vs other offloading approaches. The primary endpoint was ulcer healing. A total of 184 studies were identified, and 18 were considered eligible for the analysis. We found that: any plantar off-loading, when compared to the absence of plantar offloading device, is associated with a higher ulcer healing (MH-OR: 3.13 [1.08, 9.11], p = 0.04, I2 = 0%); total contact cast or nonremovable knee-high walker, compared to other offloading devices, had a higher ulcer healing rate (MH-OR: 2.64 [1.43, 4.89], p = 0.002, I2 = 51%); surgical offloading for active ulcers in combination with post-surgery offloading achieves higher ulcer healing rate when compared to offloading devices alone (MH-OR: 6.77 [1.64, 27.93], p = 0.008, I2 = 0%). Any plantar offloading, compared to the absence of plantar offloading device, is associated with a higher ulcer healing rate. Total contact cast or nonremovable knee-high walker, compared to other offloading devices, is preferable. Surgical offloading for active ulcers, in combination with post-surgery offloading devices, achieves a higher ulcer healing rate when compared to other offloading devices alone. Further studies with a larger cohort of patients with diabetic neuropathic foot ulcers and extended follow-up periods are necessary.

Thorough assessment of the effectiveness of belimumab in a large Spanish multicenter cohort of systemic lupus erythematosus patients.

To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles. A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed. A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC. Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.

Intraoperative Techniques That Define the Mucosal Margins of Oral Cancer In-Vivo: A Systematic Review.

This systematic review investigates techniques for determining adequate mucosal margins during the resection of oral squamous cell carcinoma (SCC). The primary treatment involves surgical removal with ≥5 mm margins, highlighting the importance of accurate differentiation between SCC and dysplasia during surgery. A comprehensive Embase and PubMed literature search was performed. Studies underwent quality assessment using QUADAS-2. After the full-text screening and exclusion of studies exhibiting high bias, eight studies were included, focusing on three margin visualization techniques: autofluorescence, iodine staining, and narrow-band imaging (NBI). Negative predictive value (NPV) was calculable across the studies, though reference standards varied. Results indicated NPVs for autofluorescence, iodine, and NBI ranging from 61% to 100%, 92% to 99%, and 86% to 100%, respectively. Autofluorescence did not significantly enhance margins compared to white light-guided surgery, while iodine staining demonstrated improvement for mild or moderate dysplasia. NBI lacked comparison with a white light-guided surgery cohort. We recommend studying and comparing the diagnostic accuracy of iodine staining and NBI in larger cohorts of patients with oral SCC, focusing on discriminating between SCC and (severe) dysplasia. Furthermore, we advise reporting the diagnostic accuracy alongside the treatment effects to improve the assessment of these techniques.

Can Internal Carotid Arteries Be Used for Noninvasive Quantification of Brain PET Studies?

Because of the limited axial field of view of conventional PET scanners, the internal carotid arteries are commonly used to obtain an image-derived input function (IDIF) in quantitative brain PET. However, time-activity curves extracted from the internal carotids are prone to partial-volume effects due to the limited PET resolution. This study aimed to assess the use of the internal carotids for quantifying brain glucose metabolism before and after partial-volume correction. Methods: Dynamic [18F]FDG images were acquired on a 106-cm-long PET scanner, and quantification was performed with a 2-tissue-compartment model and Patlak analysis using an IDIF extracted from the internal carotids. An IDIF extracted from the ascending aorta was used as ground truth. Results: The internal carotid IDIF underestimated the area under the curve by 37% compared with the ascending aorta IDIF, leading to Ki values approximately 17% higher. After partial-volume correction, the mean relative Ki differences calculated with the ascending aorta and internal carotid IDIFs dropped to 7.5% and 0.05%, when using a 2-tissue-compartment model and Patlak analysis, respectively. However, microparameters (K 1, k 2, k 3) derived from the corrected internal carotid curve differed significantly from those obtained using the ascending aorta. Conclusion: These results suggest that partial-volume-corrected internal carotids may be used to estimate Ki but not kinetic microparameters. Further validation in a larger patient cohort with more variable kinetics is needed for more definitive conclusions.

Diagnostic performance of photon-counting detector CT for differentiation between adrenal adenomas and metastases.

Aim of this study was to assess the value of virtual non-contrast (VNC) reconstructions in differentiating between adrenal adenomas and metastases on a photon-counting detector CT (PCD-CT). Patients with adrenal masses and contrast-enhanced CT scans in portal venous phase were included. Image reconstructions were performed, including conventional VNC (VNCConv) and PureCalcium VNC (VNCPC), as well as virtual monochromatic images (VMI, 40-90keV) and iodine maps. We analyzed images using semi-automatic segmentation of adrenal lesions and extracted quantitative data. Logistic regression models, non-parametric tests, Bland-Altman plots, and a random forest classifier were used for statistical analyses. The final study cohort consisted of 90 patients (36 female, mean age 67.8years [range 39-87]) with adrenal lesions (45 adenomas, 45 metastases). Compared to metastases, adrenal adenomas showed significantly lower CT-values in VNCConv and VNCPC (p = 0.007). Mean difference between VNC and true non-contrast (TNC) was 17.67 for VNCConv and 14.85 for VNCPC. Random forest classifier and logistic regression models both identified VNCConv and VNCPC as the best discriminators. When using 26 HU as the threshold in VNCConv reconstructions, adenomas could be discriminated from metastases with a sensitivity of 86.7% and a specificity of 75.6%. VNC algorithms overestimate CT values compared to TNC in the assessment of adrenal lesions. However, they allow a reliable discrimination between adrenal adenomas and metastases and could be used in clinical routine in near future with an increased threshold (e.g., 26 HU). Further (multi-center) studies with larger patient cohorts and standardized protocols are required. VNC reconstructions overestimate CT values compared to TNC. Using a different threshold (e.g., 26 HU compared to the established 10 HU), VNC has a high diagnostic accuracy for the discrimination between adrenal adenomas and metastases. • Virtual non-contrast reconstructions may be promising tools to differentiate adrenal lesions and might save further diagnostic tests. • The conventional and a new calcium-preserving virtual non-contrast algorithm tend to systematically overestimate CT-values compared to true non-contrast images. • Therefore, increasing the established threshold for true non-contrast images (e.g., 10HU) may help to differentiate between adrenal adenomas and metastases on contrast-enhanced CT.

Nailfold capillaroscopy findings of a multicentric multi-ethnic cohort of patients with idiopathic inflammatory myopathies.

To assess nailfold video capillaroscopic (NVC) abnormalities and their association with clinical features, myositis-specific autoantibodies (MSA), and myositis-associated antibodies (MAA) in a large multi-ethnic cohort of patients with idiopathic inflammatory myopathies (IIM). We recruited 155 IIM patients from three centres in Mexico, Spain, and the USA. We evaluated the clinical and laboratory features of the patients and performed semiquantitative and quantitative analyses of the NVC. Each NVC study was defined as having a normal, non-specific, early systemic sclerosis (SSc), active SSc, or late SSc pattern. Twenty-three patients had at least one follow-up NVC when disease control was achieved. Quantitative variables were expressed as medians and interquartile range (IQR) and were compared with the Kruskal-Wallis, the Mann-Whitney U-test, and the Wilcoxon test for paired medians. Associations between qualitative variables were assessed with the χ2 test. Most patients were women (68.3%), Hispanic (73.5%), and had dermatomyositis (DM) (61.2%). Fourteen patients (9%) had a normal NVC. A non-specific abnormality pattern was the most frequent (53.9%), and was associated with joint involvement, interstitial lung disease, Jo1 autoantibodies, anti-synthetase syndrome, and immune-mediated necrotising myopathy. The SSc pattern was observed mostly in DM and overlap myositis and was associated with cutaneous features and anti-TIF-1g autoantibodies. After treatment, there was a decrease in the capillaroscopic score, the capillary diameter, and the number of avascular areas, and an increase in capillary density and bushy capillary number. NVC abnormalities are related to the diagnosis, clinical features, disease activity, and autoantibodies of patients with IIM.

Heart and Lung Dose as Predictors of Overall Survival in Patients With Locally Advanced Lung Cancer. A National Multicenter Study

IntroductionIt is an ongoing debate how much lung and heart irradiation impact overall survival (OS) after definitive radiotherapy for lung cancer. This study uses a large national cohort of patients with locally advanced NSCLC to investigate the association between OS and irradiation of lung and heart. MethodsTreatment plans were acquired from six Danish radiotherapy centers, and patient characteristics were obtained from national registries. A hybrid segmentation tool automatically delineated the heart and substructures. Dose-volume histograms for all structures were extracted and analyzed using principal component analyses (PCAs). Parameter selection for a multivariable Cox model for OS prediction was performed using cross-validation based on bootstrapping. ResultsThe population consisted of 644 patients with a median survival of 26 months (95% confidence interval [CI]: 24–29). The cross-validation selected two PCA variables to be included in the multivariable model. PCA1 represented irradiation of the heart and affected OS negatively (hazard ratio, 1.14; 95% CI: 1.04–1.26). PCA2 characterized the left-right balance (right atrium and left ventricle) irradiation, showing better survival for tumors near the right side (hazard ratio, 0.92; 95% CI: 0.84–1.00). Besides the two PCA variables, the multivariable model included age, sex, body-mass index, performance status, tumor dose, and tumor volume. ConclusionsBesides the classic noncardiac risk factors, lung and heart doses had a negative impact on survival, while it is suggested that the left side of the heart is a more radiation dose–sensitive region. The data indicate that overall heart irradiation should be reduced to improve the OS if possible.

New Genetic Markers of Skin T-Cell Lymphoma Treatment.

Cutaneous T-cell lymphomas (CTCL) can be described as chronic skin inflammation lesions with the content of malignant T cells and they are considered to be T-cell-mediated skin diseases. CD147 is recognized as a 58-kDa cell surface glycoprotein of the immunoglobulin superfamily; it can induce the synthesis of MMPs (matrix metalloproteinases) on the surface of tumor cells where it was originally identified. It can also function in adjacent tumor fibroblasts using CD147-CD147 interactions. The polymorphism rs8259 T/A is situated in the untranslated region (3'UTR) of the CD147 gene. HLA DRB1*1501 takes part in the process of presentation and recognition of different antigens to T cells. It can be expressed by antigen-presenting cells-macrophages, dendritic cells, and B cells. The aim of the study is to test genotype-phenotype associations of both polymorphisms including therapy in a large cohort of CTCL patients. A final total of 104 CTCL patients were enrolled in the study. For the first remission at the clinic department, they were treated by means of local skin-directed therapy, phototherapy, and systemic therapy. Genomic DNA was isolated from peripheral blood leukocytes. A standard technique using proteinase K was applied. The polymorphisms rs8259 T/A (CD147 gene) and rs3135388 (HLA DRB1*1501) were detected through standard PCR-restriction fragment length polymorphism methods. The severity of the disease (patients with parapsoriasis, stages IA and IB, vs patients with stages IIB, IIIA, and IIIB) was associated with the CD147 genotype: the AA variant was 3.38 times more frequent in more severe cases, which reflects the decision on systemic therapy (p = 0.02, specificity 0.965). The AA genotype in the CD147 polymorphism was 12 times more frequent in patients who underwent systemic therapy of CTCL compared to those not treated with this therapy (p = 0.009, specificity 0.976). The same genotype was also associated with radiotherapy-it was observed 14 times more frequently in patients treated with radiotherapy (p = 0.009, specificity 0.959). In patients treated with interferon α therapy, the AA genotype was observed to be 5.85 times more frequent compared to the patients not treated with interferon therapy (p = 0.03, specificity 0.963). The HLA DRB1*1501 polymorphism was associated with local skin-directed therapy of CTCL. The CC genotype of the polymorphism was observed to be 3.57 times more frequent in patients treated with local therapy (p = 0.008, specificity 0.948). When both polymorphisms had been calculated together, even better results were obtained: the AACC double genotype was 11 times more frequent in patients with severe CTCL (p = 0.009, specificity 0.977). The TACT double genotype was associated with local skin-directed therapy (0.09 times lower frequency, p = 0.007, sensitivity 0.982). The AACC genotype was 8.9 times more frequent in patients treated by means of systemic therapy (p = 0.02, specificity 0.976) and as many as 18.8 times more frequent in patients treated with radiotherapy (p = 0.005, specificity 0.969). Thus, the AACC double genotype of CD147 and DRB1*1501 polymorphisms seems to be a clinically highly specific marker of severity, systemic therapy and radiotherapy of patients with T-cell lymphoma. Although genotyping results were not known during the treatment decision and could not modify it, the clinical decision on severity and therapy reflected some aspects of the genetic background of this complicated T-cell-associated disease very well.

Gender-specific prolactin thresholds to determine prolactinoma size: a novel Bayesian approach and its clinical utility.

In clinical practice, the size of adenomas is crucial for guiding prolactinoma patients towards the most suitable initial treatment. Consequently, establishing guidelines for serum prolactin level thresholds to assess prolactinoma size is essential. However, the potential impact of gender differences in prolactin levels on estimating adenoma size (micro- vs. macroadenoma) is not yet fully comprehended. To introduce a novel statistical method for deriving gender-specific prolactin thresholds to discriminate between micro- and macroadenomas and to assess their clinical utility. We present a novel, multilevel Bayesian logistic regression approach to compute observationally constrained gender-specific prolactin thresholds in a large cohort of prolactinoma patients (N = 133) with respect to dichotomized adenoma size. The robustness of the approach is examined with an ensemble machine learning approach (a so-called super learner), where the observed differences in prolactin and adenoma size between female and male patients are preserved and the initial sample size is artificially increased tenfold. The framework results in a global prolactin threshold of 239.4 μg/L (95% credible interval: 44.0-451.2 μg/L) to discriminate between micro- and macroadenomas. We find evidence of gender-specific prolactin thresholds of 211.6 μg/L (95% credible interval: 29.0-426.2 μg/L) for women and 1,046.1 μg/L (95% credible interval: 582.2-2,325.9 μg/L) for men. Global (that is, gender-independent) thresholds result in a high sensitivity (0.97) and low specificity (0.57) when evaluated among men as most prolactin values are above the global threshold. Applying male-specific thresholds results in a slightly different scenario, with a high specificity (0.99) and moderate sensitivity (0.74). The male-dependent prolactin threshold shows large uncertainty and features some dependency on the choice of priors, in particular for small sample sizes. The augmented datasets demonstrate that future, larger cohorts are likely able to reduce the uncertainty range of the prolactin thresholds. The proposed framework represents a significant advancement in patient-centered care for treating prolactinoma patients by introducing gender-specific thresholds. These thresholds enable tailored treatment strategies by distinguishing between micro- and macroadenomas based on gender. Specifically, in men, a negative diagnosis using a universal prolactin threshold can effectively rule out a macroadenoma, while a positive diagnosis using a male-specific prolactin threshold can indicate its presence. However, the clinical utility of a female-specific prolactin threshold in our cohort is limited. This framework can be easily adapted to various biomedical settings with two subgroups having imbalanced average biomarkers and outcomes of interest. Using machine learning techniques to expand the dataset while preserving significant observed imbalances presents a valuable method for assessing the reliability of gender-specific threshold estimates. However, external cohorts are necessary to thoroughly validate our thresholds.

Prevalence and Patient Characteristics of Ectodermal Dysplasias in Denmark

Ectodermal dysplasias constitute a group of rare genetic disorders of the skin and skin appendages with hypodontia, hypotrichosis, and hypohidrosis as cardinal features. There is a lack of population-based research into the epidemiology of ectodermal dysplasias. To establish a validated population-based cohort of patients with ectodermal dysplasia in Denmark and to assess the disease prevalence and patient characteristics. This nationwide cohort study used individual-level registry data recorded across the Danish universal health care system to identify patients with ectodermal dysplasias from January 1, 1995, to August 25, 2021. A 3-level search of the Danish National Patient Registry and the Danish National Child Odontology Registry was conducted to identify patients with diagnosis codes indicative of ectodermal dysplasias; patients registered in the Danish RAREDIS Database, the Danish Database of Genodermatoses, and local databases were also added. The search results underwent diagnosis validation and review of clinical data using medical records. Of 844 patient records suggestive of ectodermal dysplasias, 791 patients (93.7%) had medical records available for review. Positive predictive values of the diagnosis coding were computed, birth prevalence was estimated, and patient characteristics were identified. Data analysis was performed from May 4 to December 22, 2023. The identified and validated study cohort included 396 patients (median [IQR] age at diagnosis, 13 [4-30] years, 246 females [62.1%]), of whom 319 had confirmed ectodermal dysplasias and 77 were likely cases. The combined positive predictive value (PPV) for ectodermal dysplasia-specific diagnosis codes was 67.0% (95% CI, 62.7%-71.0%). From 1995 to 2011, the estimated minimum birth prevalence per 100 000 live births was 14.5 (95% CI, 12.2-16.7) for all ectodermal dysplasias and 2.8 (95% CI, 1.8-3.8) for X-linked hypohidrotic ectodermal dysplasias. A molecular genetic diagnosis was available for 241 patients (61%), including EDA (n = 100), IKBKG (n = 55), WNT10A (n = 21), TRPS1 (n = 18), EDAR (n = 10), P63 (n = 9), GJB6 (n = 9), PORCN (n = 7), and other rare genetic variants. The findings of this nationwide cohort study indicate that the prevalence of ectodermal dysplasias was lower than previously reported. Furthermore, PPVs of the search algorithms emphasized the importance of diagnosis validation. The establishment of a large nationwide cohort of patients with ectodermal dysplasias, including detailed clinical and molecular data, is a unique resource for future research in ectodermal dysplasias.