Impact of the preoperative cylinder on astigmatism correction in femtosecond lenticule extraction (FLEX): a prospective observational study.

PURPOSE: To explore the impact of the preoperative manifest cylinder on astigmatism correction via femtosecond lenticule extraction (FLEX), or small incision lenticule extraction (SMILE). METHODS: This was a prospective observational study. Eyes were categorized into mild (n = 88), moderate (n = 46), and severe (n = 53) astigmatism groups, based on the preoperative manifest cylinder. Vector analysis was conducted with the back vertex distance set at 12 mm. The primary outcome was the correction index (CI), with secondary outcomes including the safety, efficacy, predictability, and vectoral alterations related to FLEX. RESULTS: The average target-induced astigmatism was 0.45 ± 0.20 D, 0.95 ± 0.17 D, and 1.99 ± 0.65 D in the three groups (P < 0.001), and the average CI was 1.12± 0.05, 1.01 ± 0.03, and 0.95 ± 0.02 (P = 0.020), with the severe astigmatism group displaying a notably lower CI. The efficacy, safety, predictability, or stability of FLEX did not demonstrate any significant differences among the three groups. The CIs exhibited a significant difference in eyes with with-the-rule (WTR) astigmatism and against-the-rule (ATR) astigmatism from the mild to severe astigmatism group. In eyes with oblique astigmatism, the average CI exceeded one. CONCLUSION: Patients with manifest cylinder exceeding 1.25 D have a heightened risk of under-correction in WTR and ATR astigmatism compared to those with mild astigmatism, and mild over-correction may occur in cases of oblique astigmatism.

Identification of risk factors for acute exacerbation of idiopathic pulmonary fibrosis based on baseline high-resolution computed tomography: a prospective observational study.

BACKGROUND: This study aimed to investigate risk factors for acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) based on baseline high-resolution computed tomography (HRCT). METHODS: This prospective observational study enrolled patients with IPF treated at the General Hospital of Ningxia Medical University between January 2019 and January 2021. HRCT-derived quantitative parameters at baseline were analyzed. RESULTS: A total of 102 patients [92 (90.2%) males with a mean age of 67 years] with IPF were included, with a median follow-up of 32 (24-40.5) months. AE occurred in 30 (29.4%) IPF patients. Multivariable logistic regression analysis identified Doppler transthoracic echocardiography suggestive of pulmonary hypertension (PH) (13.43; 95% CI: 4.18-41.09; P < 0.001), honeycombing (OR 1.08; 95% CI: 1.02-1.14; P = 0.013), and whole lung volume (OR 0.99; 95% CI: 0.99-1.00; P = 0.037) as independent risk factors for AE-IPF. The combination of PH, honeycombing, whole lung volume, and the percentage of predicted forced vital capacity (FVC% pred) showed a high area under the curve from receiver operating characteristic curves of 0.888, with a sensitivity of 90% and specificity of 78%. CONCLUSIONS: This study emphasizes that quantitative CT parameters (honeycombing, whole lung volume) may serve as risk factors for AE-IPF. The combination of honeycombing, whole lung volume, FVC% pred, and PH may aid in predicting AE-IPF.

Patient reported quality of life and medication adherence in Fabry disease patients treated with migalastat: A prospective, multicenter study.

AIMS: Chaperone therapy with migalastat is a novel therapy option in Fabry disease (FD). In contrast to biweekly intravenous enzyme-replacement-therapy in a healthcare setting, oral delivery of migalastat every other day relies on the patient self-administration. Therapy adherence to migalastat and patient reported outcomes have not yet been studied in a real-world scenario. METHODS AND RESULTS: Prospective multicenter 'MigALastat Therapy Adherence among FABRY patients' (MALTA-FABRY) study examined therapy adherence and patient-reported outcomes including quality of life in FD-patients receiving migalastat. Outcome measurements were elicited by the 'Medication Adherence Questionnaire (MAQ)', 'SF-36' and 'Fabry Pain Questionnaire' over a follow-up period of 24 months. Therapy adherence was graded as high (MAQ score of 4), medium (score of 2-3) or low (score 0-1). Within the recruitment period between 2017 and 2021, 40 patients (19 females) from 3 German FD-centers were included in the study. Nearly all patients (n = 37, 92.5%) showed good therapy adherence (MAQ6Mmean:3.93, MAQ12Mmean:3.71 and MAQ24Mmean:3.7). Only one patient fulfilled criteria for low adherence. Patient reported outcomes with completed SF-36 questionnaires were available in 28 patients (14 females). Over 24 months, significant improvement of pain and life role limitations due to physical activity was reported (Pain: change from baseline: 8.57 points, 95%-CI: 1.32-15.82, p = 0.022; role limitations physical: change from baseline: 13.39 points, 95%-CI: 0.61-23.2, p = 0.048). CONCLUSION: Migalastat therapy adherence in FD-patients was high and remained high over a follow-up period of 2 years. Patient reported quality of life remained mostly stable, while pain and physical limitations improved over time.

Anti-Xa level monitoring of low-molecular-weight heparin during intermittent venovenous hemofiltration.

Low-molecular-weight heparin (LMWH) is an anticoagulant used to prevent clotting during blood purification treatments. This study aimed to evaluate the clinical use of the anti-factor Xa level (anti-Xa) for monitoring LMWH anticoagulant levels during intermittent venovenous hemofiltration (IVVHF). This prospective observational study enrolled patients who required IVVHF for renal failure in Beijing Hospital between May 2019 and February 2021. The LMWH anticoagulation was assessed by the coagulation grade of the filter and line. One hundred and ten participants were included. There were 90 patients with a filter and line coagulation grade of ≤ 1 and 20 patients with grade > 1. The anti-Xa level of 0.2 IU/mL was a critical value. The multivariable logistic regression analysis showed that anti-Xa level > 0.2 IU/mL (odd ratio [OR] = 2.263; 95% CI: 1.290-4.871, P = 0.034) and cardiovascular disease (OR = 10.028; 95% CI: 1.204-83.488; P = 0.033) were independently associated with the coagulation grade of the filter and line. Anti-Xa level could monitor LMWH anticoagulation during IVVHF.

Safety of troclosene sodium solution in decontamination of wounds: A prospective clinical and laboratory study.

Debate persists regarding the safety of hypochlorite-containing solutions in the decontamination of infected wounds. In 2006, the Israeli Ministry of Health withdrew licensing approval for troclosene sodium as a wound irrigation solution. The aim of this prospective clinical and laboratory study was to investigate the safety of troclosene sodium solution for decontamination of infected wounds. Troclosene sodium solution was used to treat 30 patients with 35 infected skin wounds of various etiologies and body areas, over a treatment period of 8 days. Data were gathered according to a prospectively designed protocol including general findings, wound-specific observations on Day 1 and Day 8 and laboratory parameters on Day 1 and Day 8. Wound swabs and tissue biopsy for culture were taken on Day 1 and Day 8. Statistical analysis was executed. Tests were 2-sided and p values of <0.05 were considered statistically significant. Eighteen males and 12 females, with 35 infected skin wounds were enrolled. There were no adverse clinical events. No significant changes were observed in general clinical observations. Statistically significant improvements were observed in: pain (p < 0.0001); edema (p < 0.0001); area of wound covered by granulation tissue (p < 0.0001); exudate (p < 0.0001); and erythema (p = 0.002). Prior to treatment, bacteria were demonstrated on microscopy or on culture in 90% of wound samples. On Day 8, this frequency reduced to 40%. There were no abnormal laboratory tests. Serum sodium concentration increased significantly between Day 1 and Day 8, whilst serum concentration of urea and concentrations of thrombocytes, leucocytes and neutrophils showed statistically significant reductions, but all values remained within normal laboratory ranges throughout the study period. Troclosene sodium solution is clinically safe in the management of infected wounds. These findings were presented to the Israel Ministry of Health and as a result, troclosene sodium was re-approved and licensed for decontamination of infected wounds in Israel.

Efficacy and Safety of Cold Snare Polypectomy of Colorectal Polyps 10-15 mm with a Hybrid Snare: A Prospective Observational Pilot Study.

INTRODUCTION: Cold snare polypectomy (CSP) is a safe and effective procedure for small colorectal polyps ≤9 mm. There are only limited data regarding CSP of larger neoplastic lesions. This study evaluated the efficacy and safety of CSP for polyps between 10 and 15 mm in size. METHODS: In this prospective single-arm observational pilot study, patients with a least one polyp 10-15 mm were included. These polyps were preferably removed by CSP using a dedicated hybrid snare. The primary outcome was the histological complete resection rate (CRR) determined by pathologically negative margins of the specimen and no neoplastic tissue obtained from biopsies of the resection site margin. Secondary outcomes were en bloc resection rate, failure of CSP, and incidence of adverse events. RESULTS: A total of 61 neoplastic polyps were removed from 39 patients. Overall CRR was 80.3% (49/61). CSP was feasible in 78.7% (48/61) of polyps and the CRR in this group was 85.4% (41/48). When CSP failed (13/61; 21.3%), lesions were successfully resected by immediate HSP using the same snare with a CRR of 61.5% (8/13) in this group. One patient presented delayed hemorrhage after HSP of a polyp but successful hemostasis was achieved with two hemoclips. No other adverse events occurred. No recurrence was seen on follow-up colonoscopy in cases with incomplete resected polyps. CONCLUSION: CSP seems to be efficient and safe in removing colorectal polyps up to 15 mm. A hybrid snare seems to be particularly advantageous for these polyps as it allows immediate conversion to HSP if CSP might fail in larger polyps. This trial is registered at ClinicalTrials.gov (NCT04464837).

HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol.

BACKGROUND: Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization's goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan. METHODS: This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection. CONCLUSION: The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan. STUDY REGISTRATION: This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.

Predictors of poor outcome following lumbar spinal fusion surgery: a prospective observational study to derive two clinical prediction rules using British Spine Registry data.

PURPOSE: Lumbar spinal fusion surgery (LSFS) is common for lumbar degenerative disorders. The objective was to develop clinical prediction rules to identify which patients are likely to have a favourable outcome to inform decisions regarding surgery and rehabilitation. METHODS: A prospective observational study recruited 600 (derivation) and 600 (internal validation) consecutive adult patients undergoing LSFS for degenerative lumbar disorder through the British Spine Registry. Definition of good outcome (6 weeks, 12 months) was reduction in pain intensity (Numerical Rating Scale, 0-10) and disability (Oswestry Disability Index, ODI 0-50) > 1.7 and 14.3, respectively. Linear and logistic regression models were fitted and regression coefficients, Odds ratios and 95% CIs reported. RESULTS: Lower BMI, higher ODI and higher leg pain pre-operatively were predictive of good disability outcome, higher back pain was predictive of good back pain outcome, and no previous surgery and higher leg pain were predictive of good leg pain outcome; all at 6 weeks. Working and higher leg pain were predictive of good ODI and leg pain outcomes, higher back pain was predictive of good back pain outcome, and higher leg pain was predictive of good leg pain outcome at 12 months. Model performance demonstrated reasonable to good calibration and adequate/very good discrimination. CONCLUSIONS: BMI, ODI, leg and back pain and previous surgery are important considerations pre-operatively to inform decisions for surgery. Pre-operative leg and back pain and work status are important considerations to inform decisions for management following surgery. Findings may inform clinical decision making regarding LSFS and associated rehabilitation.

Predictive factors of exclusive breastfeeding attrition at Week 6 post-partum among mothers of preterm infants based on the theory of planned behaviour.

Breastfeeding plays an important role in the growth and development of preterm infants, and exclusive breastfeeding (EBF) in the first 6 weeks post-partum is the key to continuous breastfeeding. This study was designed to explore the influencing factors that contribute to breastfeeding attrition among mothers of preterm infants at Week 6 post-partum based on the theory of planned behaviour (TPB). We herein adopted a prospective observational study design in which 97 mothers who exclusively breastfed at Week 6 post-partum at a tertiary specialised hospital in Shanghai from June 2021 to February 2022 were taken as the EBF group, and 179 mothers without EBF were assigned to the EBF attrition group. Through an extensive literature review and expert consultation, we determined the possible factors influencing EBF attrition, analysed those factors that showed statistical significance in our univariate analysis by applying binary logistic regression, and constructed a nomogram model for predicting EBF attrition. The results revealed that negative breastfeeding sentiment (odds ratio [OR] = 1.006; 95% confidence interval [CI], 1.000-1.011) generated a greater risk of breastfeeding attrition. However, positive breastfeeding sentiment (OR = 0.991; 95% CI, 0.983-0.999), social and professional support (OR = 0.993; 95% CI, 0.987-0.999), breastfeeding control (OR = 0.945; 95% CI, 0.896-0.996), knowledge (OR = 0.893; 95% CI, 0.799-0.998), and intention to EBF at Week 6 post-partum (OR = 0.522; 95% CI, 0.276-0.988) were the protective factors and facilitated the development of our nomogram model. The Hosmer-Lemeshow goodness-of-fit test generated a χ2 value of 11.344 (p = 0.183) and an area under the curve of 0.822 (95% CI, 0.771-0.873). The C-index was 0.800 in the internal bootstrap validation, indicating that the nomogram model possessed favourable predictive accuracy and discrimination.

Feasibility and applicability of locomotive syndrome risk test in elderly patients who underwent total knee arthroplasty.

OBJECTIVES: The concept of locomotive syndrome (LS) and its evaluation method, the LS risk test, have been applied in an integrated manner to capture the decline in mobility resulting from musculoskeletal disorders. The purpose of this study was to evaluate the impact of total knee arthroplasty (TKA) in the elderly with knee osteoarthritis, a common disorder found in LS. METHODS: A total of 111 patients were registered prior to TKA and postoperatively followed up for 1 year. Three components of the LS risk test (the two-step test, stand-up test, and Geriatric Locomotive Function Scale-25) were assessed pre- and postoperatively. RESULTS: After surgery, all three components of the test showed significant improvements from the baseline. The ratio of Stage 3 LS patients (progressed stage of decrease in mobility) reduced from 82.3% to 33.9% postoperatively. There was no significant difference in the degree of change in the scores between the younger (60-74 years) and older (≥75 years) age groups. CONCLUSIONS: We found that TKA has a major impact in preventing the progression of LS in patients with knee osteoarthritis. The LS risk test is a feasible tool for the longitudinal evaluation of patients with musculoskeletal diseases of varying severity and with multiple symptoms.

Association of SOFA Score with Severity of Muscle Wasting in Critically Ill Patients: A Prospective Observational Study.

Background: Muscle wasting is a frequent complication in critically ill patients. This study aimed to evaluate whether muscle wasting occurs in these patients and its association with the severity of the disease. Materials and methods: This was a prospective, observational study including 50 patients admitted to the multidisciplinary ICU of a tertiary care hospital. Using a linear ultrasound probe, the thickness of the rectus femoris was measured on day 1 of admission and repeated at the same point on day 7. Sequential organ failure assessment (SOFA) scores were calculated daily during the study period. The highest SOFA score during this period was recorded. The mean difference in the thickness of the rectus femoris between day 1 and day 7 was used to predict the occurrence of muscle wasting and the correlation between this difference and the highest SOFA score was analyzed. Results: The mean thickness of the rectus femoris on day 1 was 1.32 + 0.06 cm and on day 7 was 1.16 + 0.08 cm. The mean difference was found to be 0.16 cm (p < 0.01). There was a statistically significant difference in the thickness of the rectus femoris between day 1 and day 7. It was found to have a positive correlation with the highest SOFA score r = 0.886 (p < 0.01). Conclusion: This study demonstrates that there is significant muscle wasting in critically ill patients and this positively correlates with the severity of illness. Our study also highlights the role of bedside ultrasound in detecting muscle wasting. How to cite this article: Rajagopal K, Vijayan D, Thomas SM. Association of SOFA Score with Severity of Muscle Wasting in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2023;27(10):743-747.

Role of diet in stroke incidence: an umbrella review of meta-analyses of prospective observational studies.

BACKGROUND: Stroke is one of the major challenges for the global healthcare system, which makes it necessary to explore the relationship between various modifiable factors and stroke risk. Recently, numerous meta-analyses of prospective observational studies have reported that dietary factors played a key role in the occurrence of stroke. However, the conclusions of previous studies have remained controversial and unclear. Accordingly, we conducted an umbrella review synthesizing and recalculating available evidence to assess the certainty of the associations between dietary factors and stroke. METHODS: Relevant meta-analyses examining the associations between dietary factors and stroke were searched in PubMed and Embase databases up to September 1, 2021. For each eligible meta-analysis, two independent reviewers appraised the methodologic quality using the AMSTAR 2 criteria and estimated the summary effect size, 95% confidence intervals, 95% prediction intervals, heterogeneity between studies, and small-study effects. Moreover, we further assessed the associations between dietary factors and ischemic stroke as well as hemorrhagic stroke. Lastly, a set of pre-specified criteria was applied to qualitatively evaluate the epidemiological credibility of each dietary factor. RESULTS: Overall, our umbrella review included 122 qualified meta-analyses for qualitative synthesis, involving 71 dietary factors related to food groups, foods, macronutrients, and micronutrients. Using the AMSTAR 2 criteria, 5 studies were assessed as high quality, 4 studies as moderate quality, and 113 studies as low or critically low quality. We identified 34 dietary factors associated with stroke occurrence, 25 dietary factors related to ischemic stroke, and 11 factors related to hemorrhagic stroke. Among them, high/moderate certainty epidemiological evidence demonstrated an inverse association between intake of fruits (RR: 0.90) and vegetables (RR: 0.92) and stroke incidence, but a detrimental association between red meat (RR: 1.12), especially processed red meat consumption (RR:1.17), and stroke incidence. Besides, the evidence of high/moderate certainty suggested that the intake of processed meat, fruits, coffee, tea, magnesium, and dietary fiber was associated with ischemic stroke risk, while consumption of tea, fruits, and vegetables was relevant to hemorrhagic stroke susceptibility. CONCLUSIONS: Our study has reported that several dietary factors have a significant impact on stroke risk and offered a new insight into the relationship between dietary modification and stroke occurrence. Our results may provide an effective strategy for stroke prevention.

Berlin Registry of Neuroimmunological entities (BERLimmun): protocol of a prospective observational study.

BACKGROUND: Large-scale disease overarching longitudinal data are rare in the field of neuroimmunology. However, such data could aid early disease stratification, understanding disease etiology and ultimately improve treatment decisions. The Berlin Registry of Neuroimmunological Entities (BERLimmun) is a longitudinal prospective observational study, which aims to identify diagnostic, disease activity and prognostic markers and to elucidate the underlying pathobiology of neuroimmunological diseases. METHODS: BERLimmun is a single-center prospective observational study of planned 650 patients with neuroimmunological disease entity (e.g. but not confined to: multiple sclerosis, isolated syndromes, neuromyelitis optica spectrum disorders) and 85 healthy participants with 15 years of follow-up. The protocol comprises annual in-person visits with multimodal standardized assessments of medical history, rater-based disability staging, patient-report of lifestyle, diet, general health and disease specific symptoms, tests of motor, cognitive and visual functions, structural imaging of the neuroaxis and retina and extensive sampling of biological specimen. DISCUSSION: The BERLimmun database allows to investigate multiple key aspects of neuroimmunological diseases, such as immunological differences between diagnoses or compared to healthy participants, interrelations between findings of functional impairment and structural change, trajectories of change for different biomarkers over time and, importantly, to study determinants of the long-term disease course. BERLimmun opens an opportunity to a better understanding and distinction of neuroimmunological diseases.

Treatment response after palliative radiotherapy for bleeding gastric cancer: a multicenter prospective observational study (JROSG 17-3).

BACKGROUND: Palliative radiotherapy seems to be rarely performed for incurable gastric cancer. In this first multicenter study, we examined the effectiveness of palliative radiotherapy and investigated whether biologically effective dose (BED) is associated with survival, response, or re-bleeding. METHODS: Eligibility criteria included blood transfusion or hemoglobin levels < 8.0 g/dL. The primary endpoint was the intention-to-treat (ITT) bleeding response rate at 4 weeks. Response entailed all of the following criteria: (i) hemoglobin levels ≥ 8.0 g/dL; (ii) 7 consecutive days without blood transfusion anytime between enrollment and blood sampling; and (iii) no salvage treatment (surgery, endoscopic treatment, transcatheter embolization, or re-irradiation) for bleeding gastric cancer. Re-bleeding was defined as the need for blood transfusion or salvage treatment. RESULTS: We enrolled 55 patients from 15 institutions. The ITT response rates were 47%, 53%, and 49% at 2, 4, and 8 weeks, respectively. The per-protocol response rates were 56%, 78%, and 90% at 2, 4, and 8 weeks, respectively. Neither response nor BED (α/ß = 10) predicted overall survival. Multivariable Fine-Gray model showed that BED was not a significant predictor of response. Univariable Cox model showed that BED was not significantly associated with re-bleeding. Grades 1, 2, 3, and, ≥ 4 radiation-related adverse events were reported in 11, 9, 1, and 0 patients, respectively. CONCLUSIONS: The per-protocol response rate increased to 90% during the 8-week follow-up. The frequent occurrence of death starting shortly after enrollment lowered the ITT response rate. BED was not associated with survival, bleeding response, or re-bleeding.

Systemic antifungal strategies in allogeneic hematopoietic stem cell recipients hospitalized in french hematology units: a post-hoc analysis of the cross-sectional observational AFHEM study.

BACKGROUND: Invasive fungal diseases (IFD) remain a major complication of allogeneic hematopoietic stem cell transplantation (alloHSCT) and are associated with high mortality rates in patients receiving alloHSCT. Antifungal prophylaxis is increasingly being used in the management of IFDs in patients receiving alloHSCT. METHODS: A post-hoc analysis of the cross-sectional observational AFHEM study was carried out to describe the use of antifungal drugs in real-life clinical practice in alloHSCT recipients hospitalized in French hematological units. RESULTS: A total of 147 alloHSCT recipients were enrolled; most were adults (n = 135; 92%) and had received alloHSCT < 6 months prior to enrollment (n = 123; 84%). Overall, 119 (81%) patients received a systemic antifungal therapy; of these, 95 (80%) patients received antifungal prophylaxis. Rates of patients receiving systemic antifungal treatment were similar irrespective of transplant time, neutropenic, and graft-versus-host disease status. Among patients on systemic antifungal treatment, 83 (70%) received an azole, 22 (18%) received an echinocandin, and 16 (13%) received a polyene. CONCLUSIONS: This work provides evidence of the antifungal strategies used in alloHSCT recipients hospitalized in French hematological units. Unlike earlier studies, the AFHEM study showed that prophylaxis appears to be the leading antifungal strategy used in alloHSCT recipients in France.

Initial screening by immunohistochemistry is effective in universal screening for Lynch syndrome in endometrial cancer patients: a prospective observational study.

BACKGROUND: Few prospective reports of universal screening for Lynch syndrome exist for patients with endometrial cancer. In this study, we performed immunohistochemical staining for DNA mismatch repair-related genes (MLH1, MSH2, MSH6 and PMS2), to determine the extent to which Lynch syndrome can be diagnosed in endometrial cancer patients through universal screening. METHODS: We recruited 116 consecutive patients assumed to have uterine corpus malignancy from October 2019 to February 2021 in a prospective observational study. We performed immunohistochemical for mismatch repair-related proteins on samples from 100 patients who had surgicopathologically confirmed diagnoses of endometrial cancer. Samples with missing immunohistochemical results for any of the proteins had subsequent universal screening tests for microsatellite instability, DNA methylation of the MLH1 promoter region and mismatch repair genetics. RESULTS: We identified 19 (19.0%) patients with lost results for any of the proteins. All 19 patient samples had subsequent screening tests. We identified the microsatellite instability-high phenotype in 84.2% (16/19) of these patients and MLH1 methylation in 57.9% (11/19). Mismatch repair genetic testing detected two pathological variants, in MSH2 and MSH6, which indicated that the prevalence of Lynch syndrome was 2.0% in our cohort. Two cases of unclassified variant (MSH6) and one case of benign variant (PMS2) were also detected. CONCLUSIONS: Initial screening by immunohistochemical is an effective method in universal screening for Lynch syndrome in endometrial cancer patients.

Percussion test: description and diagnostic accuracy of a new manual test for bone marrow edema of the knee.

BACKGROUND: Prompt diagnosis of bone marrow lesion (BML) is difficult but critical for correct treatment. Magnetic resonance imaging is the gold standard, although expensive and time consuming. Simple and reliable clinical test for BML detection is lacking. Aim of the study is to describe a new manual clinical test called Percussion Test (PT) and to statistically determine its diagnostic accuracy in BML, compared to MRI imaging. METHODS: After evaluation of the inclusion and exclusion criteria, 218 consecutive patients with unilateral knee pain and age comprised between 18 and 80 years old were enrolled in our observational prospective study. Informed consent was obtained for each patient. After medical history collection, PT was performed by a single operator as described. MRI was performed in the affected knee to detect the presence of BML. Coherence in PT and MRI assessment was evaluated in each quadrant of the knee via contingency tables, as sensitivity, specificity, NPV, PPV and diagnostic accuracy were calculated. RESULTS: No correlation with a positive PT was demonstrated for the covariables gender (p = 0.156), age (p = 0.272) and BMI (p = 0.639). PT showed a sensitivity ranging from 60.6 (40.6-80.6) to 79.5 (63.0-96.0) and a specificity ranging from 85.7 (80.0-91.5) to 96.0 (93.1-98.9) depending on knee quadrant. Diagnostic accuracy ranged from 81.6 (75.9-86.6) to 89.4 (84.6-93.2), and p-value was < 0.00001 in a chi-squared analysis for all quadrants. CONCLUSIONS: PT showed sensitivity and specificity values that are comparable with other clinical tests routinely adopted in clinical practice. In the absence of other reliable clinical test, PT has the potential to become a useful bedside tool in the diagnosis and management of BMLs.

Low-dose mepolizumab is effective as an add-on therapy for treating long-lasting peripheral neuropathy in patients with eosinophilic granulomatosis with polyangiitis.

OBJECTIVE: To assess the effectiveness of low-dose mepolizumab as an add-on therapy for treating peripheral neurological symptoms in eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: We prospectively studied 13 EGPA patients with conventional treatment-resistant peripheral neuropathy. Their symptoms (pain, numbness, and muscle weakness) were assessed on a visual analogue scale (VAS) before and after 12 months of mepolizumab therapy (100 mg every 4 weeks). Peripheral eosinophil levels and several biomarkers including urinary levels of eosinophil-derived neurotoxin (EDN) were measured before and after therapy. RESULTS: VAS scores for pain and numbness significantly improved after 12 months of mepolizumab therapy (from 67.0 to 48.0, P = 0.012, and from 67.0 to 51.0, P = 0.017, respectively). However, the VAS score for muscle weakness did not improve (P = 0.36). There were significant correlations between treatment-related changes in urinary EDN levels from baseline to 6 months later and percent changes in the VAS scores of pain and numbness (r = 0.75, P = 0.020; r = 0.88, P = 0.002). CONCLUSIONS: Treatment-resistant peripheral neuropathy in EGPA was significantly improved by low-dose mepolizumab, and effectiveness was correlated with decreased urinary EDN. Because the possibility of a placebo effect cannot be formally excluded, placebo-controlled studies will be required in the future.

Associations of Binge Drinking With the Risks of Ischemic Heart Disease and Stroke: A Study of Pooled Norwegian Health Surveys.

Norwegian health survey data (1987-2003) were analyzed to determine if binge drinking increases the risk of incident major events from ischemic heart disease (IHD) and stroke. Among current drinkers reporting average alcohol intakes of 2.00-59.99 g/day (n = 44,476), frequent binge drinking (≥5 units at least once per month) was not associated with a greater risk of IHD (adjusted hazard ratio (HR) = 0.91, 95% confidence interval (CI): 0.76, 1.09) or stroke (adjusted HR = 0.98, 95% CI: 0.81, 1.19), in comparison with participants who reported that they never or only infrequently (less than once per month) had episodes of binge drinking. Participants with an average alcohol intake of 2.00-59.99 g/day had a lower risk of IHD in comparison with participants with very low intakes (<2.00 g/day), both among frequent binge drinkers (adjusted HR = 0.67, 95% CI: 0.56, 0.80) and among never/infrequent binge drinkers (adjusted HR = 0.75, 95% CI: 0.67, 0.84). The findings suggest that frequent binge drinking, independent of average alcohol intake, does not increase the risk of incident IHD or stroke events. However, the findings should be interpreted in light of the limitations of the study design.

Influence of pain duration on pain outcomes following palliative radiotherapy for painful tumors: the sooner the irradiation, the better?

PURPOSE: The influence of pre-radiotherapy pain duration on post-treatment outcomes was assessed. METHODS: Patients that received palliative radiotherapy were analyzed in a prospective observational study investigating curative and palliative radiotherapy. Brief Pain Inventory data were acquired at baseline and 1, 2, and 3 months after commencing irradiation. The pain response in terms of the index pain (i.e., pain caused by the irradiated tumors) was assessed using the International Consensus Endpoint. Patients were diagnosed with predominance of other pain (POP) if non-index pain of malignant or unknown origin was present and showed a higher pain score than the index pain. Competing risk analyses were performed in which deaths without the pain endpoints were considered as competing events. RESULTS: Of 229 patients analyzed, 123 (54%) experienced a pain response and 43 (19%) experienced POP. Multivariable analyses using the Fine-Gray model revealed that patients with shorter pain duration (< 1 month) had higher cumulative incidence of pain response (subdistribution hazard ratio, 2.43; 95% confidence interval [CI], 1.35-4.38) and POP (subdistribution hazard ratio, 4.22; 95% CI, 1.30-13.70) compared with patients with longer pain duration (≥ 4 months). For patients with a pain duration of less than 1 month, cumulative incidence of pain response was estimated to be 69% (95% CI, 53-85%) and cumulative incidence of POP was estimated to be 15% (95% CI, 3-28%) at 1­month follow-up. CONCLUSION: Commencing palliative radiotherapy earlier may improve the probability of patients achieving a pain response, although POP may be more frequent.