Higher Proportion Of Patients Research Articles

Abstract 117: The Impact Of De-escalating Antihypertensive Drugs: A Secondary Analysis Of The Systolic Blood Pressure Intervention Trial (sprint)

Introduction: As a chronic disease, patients with hypertension typically receive more antihypertensive drugs. Though this rarely happens, patients may receive fewer antihypertensive drugs (de-escalation) when the SBP is well controlled. SPRINT is a uniquely designed trial to study this impact. In the trial, patients were randomly assigned to two groups where systolic blood pressure (SBP) targets: 1) <120 mmHg (intensive treatment group (IG)); 2) <140 mmHg (standard treatment group (SG)). In both groups, their antihypertensive drugs were continuously adjusted to achieve the SBP targets. Before randomization, physicians may adopt more intensive SBP targets than the above two given patients’ disease severity, and personal preference. This study aims to investigate the impact of de-escalation on cardiovascular outcomes, adverse events, and antihypertensive treatment patterns among hypertensive patients. Methods: By comparing the number of antihypertensives a patient received at the screening visit, and at randomization, we categorized patients into de-escalation (less medications) and normal groups. The primary outcome was a composite of myocardial infarction, acute coronary, heart failure, and cardiovascular death. Secondary outcomes included individual components of the primary outcome and all-cause mortality. Adverse events include hypotension, syncope, and acute kidney injury. Cox proportional-hazards regressions were applied. Results: In the IG, there were 427 and 4,007 patients in the de-escalation and normal groups, respectively. There were 794 and 3,733 patients in these two groups in the SG. The median follow-up time was 3.26 years. In both IG and SG, higher proportions of patients in the de-escalation used thiazide diuretics, ARA, or k-sparing diuretics. In the IG, patients in the de-escalation group were associated with a higher risk of heart failure (HR: 2.66, 95% CI: 1.39-5.09) than the normal group. A similar trend was identified in the de-escalation group for the primary outcome (HR: 1.34, 95% CI: 1.04-1.74). Conclusion: De-escalation is associated with an increased risk of cardiovascular events. It reassures the importance of intensive SBP on patients at high CVD risk and indicates a more intensive SBP target may be needed.

GBP5 Expression Predicted Prognosis of Immune Checkpoint Inhibitors in Small Cell Lung Cancer and Correlated with Tumor Immune Microenvironment.

The discovery and development of immune checkpoint inhibitors (ICIs) has significantly enhanced the arsenal of immunotherapy treatments available for cancer patients. The identification of biomarkers that are indicative of an individual's sensitivity to treatment with ICIs is useful for screening SCLC patients prior to commencement of any ICIs based immunotherapy. However, the relationship between GBP5 and the prognosis of SCLC immunotherapy is still unclear and requires further study. We downloaded two SCLC datasets, namely the George-SCLC and Jiang-SCLC cohorts. We used the TIDE algorithm to predict the efficacy of immunotherapy for SCLC patients. The QuanTIseq, MCPcounter, and EPIC algorithms are used to calculate the proportions of immune cells in SCLC patients. Additionally, we retrospectively collected 35 SCLC samples from the first affiliated hospital of the Hengyang Medical school. Patients in each cohort were devided into two groups with high (GBP5-High) and low (GBP5-Low) expression of GBP5. In both cohorts, the GBP5-High population had a higher proportion of patients that responded well to immunotherapy (responders) (p < 0.05). In addition, both GBP5-High subgroups had significantly increased cytotoxicity, chemokines, antigen presenting, and TNF family related genes. We also determined that GBP5 was related to high-level infiltration of B cells, CD4+T cells, CD8+T cells and NK cells. In this study, we found that GBP5 has the potential to be used as a biomarker of ICIs efficacy for SCLC patients. GBP5 is related to the quantity of inflammatory molecules, a high level of immune infiltration, and a highly activated immune response pathway.

Extreme Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA): a discrete group of patients

ObjectivePeriodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children; by definition, episodes occur every 2 to 8 weeks. However, in a subset of our patients, we noticed a higher frequency of attacks, of less than 2 weeks, which we refer to as extreme PFAPA (ePFAPA). This group consisted of patients who were extreme upon presentation of PFAPA, and those who became extreme after initiation of abortive corticosteroid treatment. We aimed to characterize demographic and clinical features of ePFAPA, including the two groups, and to compare them to patients with non-extreme PFAPA (nPFAPA).Study design: The medical records of 365 patients with PFAPA who attended Schneider Children’s Medical Center of Israel from March 2014 to April 2021 were reviewed. Patients with concomitant familial Mediterranean fever were excluded. Characteristics of the ePFAPA (including subgroups) and nPFAPA groups were compared using Wilcoxon rank sum, Pearson’s chi-squared, and Fisher’s exact tests.ResultsForty-seven patients (12.9%) were identified as having ePFAPA. Among patients with ePFAPA, compared to patients with nPFAPA, the median (interquartile range) age at disease onset was earlier: 1.5 years (0.7–2.5) vs. 2.5 years (1.5-4.0), P < 0.001; and diagnosis was younger: 2.6 years (2.0-3.6) vs. 4.5 years (3.0-6.2), P < 0.001. A higher proportion of patients with ePFAPA than nPFAPA were treated with colchicine prophylaxis (53% vs. 19%, P < 0.001), but symptoms and signs during flares did not differ significantly between these groups. Demographic and clinical characteristics were similar between patients with ePFAPA from presentation of PFAPA (22, 47% of those with ePFAPA) and ePFAPA from after corticosteroid treatment.ConclusionAbout half the patients categorized with ePFAPA syndrome already had extreme features upon presentation. Patients with ePFAPA compared to nPFAPA presented and were diagnosed at an earlier age.

Contemporary outcomes of patients undergoing robotic-assisted radical cystectomy: A comparative analysis between intracorporeal ileal conduit and neobladder urinary diversions

ObjectiveWe aimed to compare perioperative and oncologic outcomes for patients undergoing robotic-assisted radical cystectomy (RARC) with intracorporeal ileal conduit (IC) and neobladder (NB) urinary diversion. MethodsPatients undergoing RARC with intracorporeal urinary diversion between January 2017 and January 2022 at the Icahn School of Medicine at Mount Sinai, New York, NY, USA were indexed. Baseline demographics, clinical characteristics, perioperative, and oncologic outcomes were analyzed. Survival was estimated with Kaplan-Meier plots. ResultsOf 261 patients (206 [78.9%] male), 190 (72.8%) received IC while 71 (27.2%) received NB diversion. Median age was greater in the IC group (71 [interquartile range, IQR 65–78] years vs. 64 [IQR 59–67] years, p<0.001) and BMI was 26.6 (IQR 23.2–30.4) kg/m2. IC group was more likely to have prior abdominal or pelvic radiation (15.8% vs. 2.8%, p=0.014). American Association of Anesthesiologists scores were comparable between groups. The IC group had a higher proportion of patients with pathological tumor stage 2 (pT2) tumors (34 [17.9%] vs. 10 [14.1%], p=0.008) and pathological node stages pN2–N3 (28 [14.7%] vs. 3 [4.2%], p<0.001). The IC group had less median operative time (272 [IQR 246–306] min vs. 341 [IQR 303–378] min, p<0.001) and estimated blood loss (250 [150–500] mL vs. 325 [200–575] mL, p=0.002). Thirty- and 90-day complication rates were 44.4% and 50.2%, respectively, and comparable between groups. Clavien-Dindo grades 3–5 complications occurred in 27 (10.3%) and 34 (13.0%) patients within 30 and 90 days, respectively, with comparable rates between groups. Median follow-up was 324 (IQR 167–552) days, and comparable between groups. Kaplan-Meier estimate for overall survival at 24 months was 89% for the IC cohort and 93% for the NB cohort (hazard ratio 1.23, 95% confidence interval 1.05–2.42, p=0.02). Kaplan-Meier estimate for recurrence-free survival at 24 months was 74% for IC and 87% for NB (hazard ratio 1.81, 95% confidence interval 0.82–4.04, p=0.10). ConclusionPatients undergoing intracorporeal IC urinary diversion had higher postoperative cancer stage, increased nodal involvement, similar complications outcomes, decreased overall survival, and similar recurrence-free survival compared to patients undergoing RARC with intracorporeal NB urinary diversion.

Real-world study on microsatellite instability and mismatch repair deficiency testing patterns among patients with metastatic colorectal cancer in Spain

PurposeClinical practice guidelines recommend that all patients with metastatic colorectal cancer (mCRC) should be tested for mismatch repair deficiency (dMMR) or microsatellite instability-high (MSI-H). We aimed to describe the dMMR/MSI-H testing practice in patients with mCRC in Spanish centers.MethodsMulticenter, observational retrospective study that included patients newly diagnosed with mCRC or who progressed to a metastatic stage from early/localized stages.ResultsThree hundred patients were included in the study from May 2020 through May 2021, with a median age of 68 years, and two hundred twenty-five (75%) had stage IV disease at initial diagnosis; two hundred eighty-four patients received first-line treatment, and dMMR/MSI-H testing was performed in two hundred fifty-one (84%) patients. The results of the dMMR/MSI-H tests were available in 61 (24%) of 251 patients before the diagnosis of metastatic disease and in 191 (81%) of 236 evaluable patients for this outcome before the initiation of first-line treatment. Among the 244 patients who were tested for dMMR/MSI-H with IHC or PCR, 14 (6%) were MMR deficient. The most frequent type of first-line treatment was the combination of chemotherapy and biological agent, that was received by 71% and 50% of patients with MMR proficient and deficient tumors, respectively, followed by chemotherapy alone, received in over 20% of patients in each subgroup. Only 29% of dMMR/MSI-H tumors received first-line immunotherapy.ConclusionOur study suggests that a high proportion of patients with mCRC are currently tested for dMMR/MSI-H in tertiary hospitals across Spain. However, there is still room for improvement until universal testing is achieved.Trial registration: Not applicable.

312. H ANASTOMOSIS IN MECKOWN ESOPHAGECTOMY FOR THE REDUCED ANASTOMOTIC LEAKAGE, OBSTRUCTION, AND GASTROESOPHAGEAL REFLUX

Abstract Background Anastomotic Leakage, obstruction, and gastroesophageal reflux are the major conditions to be taken into account during restoration of alimentary transit in Meckown esophagectomy. There are numerous types of anastomosis techniques to achieve different emphases while the optimal one has not been established. The outcomes of the novel H anastomosis and the conventional end to end layered anastomosis were explored in a prospective cohort study. Methods Patients with resectable esophageal cancer underwent Meckown esophagectomy applying end to end layered anastomosis (Conventional group) or H anastomosis (H group) were included. Besides demographic information, the incidence of anastomotic leakage and other major complications were also recorded. The incidence and severity of postoperative digestive symptoms were assessed by a standard questionnaire including Mellow-Pinkas score for dysphagia and reflux frequency at 6 months after surgery. 24 h-PH and impedance surveillance was also performed on patients receiving H anastomosis. Results Of the 122 eligible patients, 88 received end to end layered anastomosis and 34 underwent H anastomosis respectively. 3(3.4%) patients underwent anastomotic leakage in Conventional group and 1(2.9%) in H group (P = 0.897) The incidences of other perioperative complications were comparable between two groups. The H anastomosis was associated with lower incidence of gastroesophageal reflux (17.2% vs 35.8%, P = 0.117) and higher proportion of patients without food solidity limitation (Mellow-Pinkas score = 0) (79.4% versus 69.1% P = 0.305). The DeMeester score extracted from 24 h-PH and impedance surveillance showed the H anastomosis achieved 70% objective reflux free rate. Conclusion H anastomosis is a refinement of intussusception anastomosis and layered anastomosis to preserve the anti-reflux function of one-direction valve formed by intussuscepted tissues, leakage free from the different locations of layers of anastomosis and obstruction prevention from the removal of intussuscepted muscular layer of esophagus and seromuscular layer of stomach. A multicenter randomized trial comparing the outcomes of the H anastomosis and end to end anastomosis is in process to validate these conclusions.

Clinical, economic, and humanistic impact of a multidisciplinary medication review with follow-up for anticoagulated patients treated with vitamin K antagonists in primary care: A cluster randomised controlled trial

BackgroundInterdisciplinary collaboration between general practitioner, nurses and pharmacists can favour the control of patients treated with vitamin K antagonists (VKA), increasing their safety and effectiveness. The aim of the study was to evaluate the impact of pharmaceutical interventions on patients treated with VKA within the framework of a Pharmacotherapeutic Follow-up service on clinical, economic and humanistic outcomes. MethodsControlled and randomized study in patients from two health areas of Zaragoza in treatment with VKA with Time in Therapeutic Range (TTR) according to the Rosendaal method less than 70% in the last 6 months. Patients were recruited at the pharmacy and assigned to two groups: control and intervention. A Pharmacotherapeutic Follow-up Program was established for the intervention group for 6 months. The outcome variables were INR stability, pharmacological adherence, vitamin K intake, knowledge about the use of acenocoumarol, quality of life, satisfaction with treatment, associated costs and avoided costs. A descriptive analysis was performed, and the Students' T test or Mann-Whitney U test was used for the association between quantitative variables and Chi-square or Fisher's test for qualitative variables. ResultsA total of 123 patients were included, 65 in the intervention group (IG) and 58 in the control group (CG). A total of 108 interventions were conducted (1.7 interventions/patient) and the most common were those related to the proper taking of medications (41.0%). In IG, TTR (p = 0.019), adherence to treatment (p = 0.038) and knowledge about acenocoumarol (p = 0.031) improved, compared to CG. A higher proportion of patients in IG achieved a TTR>65% (p = 0.024). In addition, patients whose interventions were accepted by the physician (p = 0.027) and those who received vitamin K optimization interventions (p = 0.003) achieved TTR>65% in greater proportion. ConclusionsCommunity pharmacist medication review, in collaboration with general practitioners improve knowledge and adherence of patients treated with oral anti-vitamin K agents and enhances the achievement of their therapeutic INR ranges. Investment needed to achieve this clinical impact is low and patient satisfaction is high. Trial registrationThis study has been registered with Clinical Trials.gov dated 25/05/2017: NCT03154489.

Delaying Cardiac Catheterization in Favor of Endoscopy in Non-ST Elevation Myocardial Infarction Patients Is Associated with Worse Outcomes: A Nationwide Analysis.

Non-variceal upper gastrointestinal bleeding (NVUGIB) in non-ST-elevation myocardial infarction (NSTEMI) is associated with substantial morbidity and mortality. We evaluated inpatient outcomes of esophagogastroduodenoscopy (EGD) before cardiac catheterization in patients with NSTEMI and NVUGIB. We utilized the National Readmission Database (2016-2019) to identify all index hospitalizations with a primary diagnosis of NSTEMI and a secondary diagnosis of NVUGIB that underwent EGD before cardiac catheterization (cases). A matched comparison cohort of similar hospitalizations that undergo EGD after cardiac catheterization were identified (controls) after 1:1 propensity score matching for age, gender, cardiac comorbidities, causes, and severity of bleeding. A total of 796 cases were matched with 796 controls. There was a higher median length of hospital stay (8 vs. 5days, P = 0.01) and median hospital charges ($111,218 vs. $99,115, P = 0.002) for cases compared to controls. There was a higher all-cause inpatient mortality in cases compared to controls (5.5% vs. 3.9%, P = 0.26). Furthermore, there was a higher proportion of patients with ICU admission (7% vs. 3%, P < 0.001), septic shock (7.1% vs. 5.8%, P = 0.41), atrial fibrillation (27.1% vs. 19.8%, P < 0.001) and acute kidney injury (42.8% vs. 29.1%, P < 0.001) for cases compared to controls. Delaying cardiac catheterization in favor of EGD is associated with increased hospital stay, costs, and cardiac complications. Further studies are warranted to establish our findings.

Correlation Between Abdominal Wall Stimulation and Spinal Cord Stimulator Tip Location: A Nonrandomized Clinical Trial

ObjectivesThis study aimed to investigate the correlation between the vertebral level of paddle placement and abdominal wall stimulation (AWS) after differential target multiplexed spinal cord stimulation (SCS) to improve the safety and effectiveness of SCS for patients with chronic pain, particularly those with low back pain (LBP). Materials and MethodsThe Correlation Between Abdominal Wall Stimulation and Spinal Cord Stimulator Tip Location study was a nonrandomized clinical trial that included 24 patients with SCS for persistent spinal pain syndrome (PSPS) type 2 (trial ID: NCT05565469). The intervention involved increasing stimulation amplitude to a maximum tolerable value and obtaining numerical rating scores for AWS. The primary outcome measure was the association between AWS, the neurostimulator tip, and conus medullaris location, whereas the secondary outcome was the pre-postinterventional difference in proportion of patients experiencing AWS. Patient demographics and postoperative imaging were assessed. Statistical analyses involved descriptive statistics, a descriptive logistic regression, and a McNemar test. ResultsThe results of the study showed that seven (29%) of the 24 patients experienced AWS either previously or during interventional stimulation. However, there was no significant correlation found between AWS and the location of the neurostimulator tip or conus medullaris, and there was no difference in the pre-postinterventional proportion of patients experiencing AWS. ConclusionsThe study concludes that a relatively high proportion of patients who received SCS for PSPS type 2 experienced or previously experienced AWS. There was no significant correlation found between the location of the neurostimulator tip and the occurrence of AWS. This suggests that AWS may not be solely dependent on the stimulation itself and emphasizes the need to consider other factors. Nonetheless, this study provides important insights into the occurrence of AWS in patients receiving SCS for PSPS type 2 and highlights the need for further research in this area. Clinical Trial RegistrationThe Clinicaltrials.gov registration number for the study is NCT05565469.

Impact of Time to Metastasis (Synchronous vs. Metachronous) on Outcomes in Metastatic Renal Cell Carcinoma Patients Treated with First Line Immune-Checkpoint Inhibitors (ICI)-based Combinations

Abstract Background Metastatic renal cell carcinoma (RCC) can present as synchronous metastatic disease, where primary metastases are detected at the time of diagnosis, or metachronous disease, where metastases appear during follow-up after initial RCC diagnosis. The effect of time to metastasis on patient outcomes is not well characterized in the era of immune checkpoint inhibitor (ICI)-based combinations. Herein, we assess the differences in clinical outcomes between patients with synchronous and metachronous mRCC. Methods Data for mRCC patients treated with first line ICI-based combination therapies between 2014 and 2023 were retrospectively collected from two NCI-designated comprehensive cancer centers. Patients were categorized as having synchronous or metachronous disease based on the time of presentation of metastases. Synchronous disease was defined as the presence of metastases at the time of RCC diagnosis or within 3 months thereafter. The study endpoints were time to treatment failure (TTF), overall survival (OS), and disease control rate (DCR). TTF and OS were estimated by Kaplan-Meier method and compared based on the time of presentation of metastases using log-rank tests. Univariable and multivariable Cox proportional hazard models and logistic regression models were used to examine the impact of sex, IMDC risk score, histology, and age at treatment start on TTF, OS and DCR. Results A total of 223 patients (126 synchronous and 97 metachronous) diagnosed with mRCC were included in the analysis. No significant difference was seen in gender distribution or age at first line treatment between these two groups. Although not statistically significant, the synchronous group had a higher proportion of patients with non-clear cell histology compared to those with metachronous disease (21% vs. 11%, P = 0.057). The median TTF was shorter in patients with synchronous disease but did not reach statistical significance (9 vs. 19.8 months for synchronous and metachronous, respectively, HR 1.37, 95% CI [0.98, 1.92], P = 0.064). Median OS was significantly shorter in patients with synchronous disease (28.0 vs. 50.9 months, adjusted HR 2.23, 95% CI [1.36, 3.65], P = 0.001). Similarly, patients with synchronous mRCC had a lower DCR than patients with metachronous (58.7% vs 78.4%, adjusted odds ratio (OR) 0.29, 95% CI [0.13, 0.64], P = 0.002). In the multivariable analysis, synchronous disease remained an independent factor associated with worse OS and DCR. Conclusions Patients with metastatic disease at the time of RCC diagnosis who were treated with first line ICI-based combinations have a poorer OS, and worse DCR than those who develop metastatic disease during follow-up. Although further validation is needed, these findings could be valuable in designing clinical trials and selecting patients for treatment escalation and closer clinical follow-up. CDMRP DOD Funding: no

Demographic and clinical characteristics of acute myeloid leukaemia diagnosed and treated at the tertiary level in Afghanistan.

A retrospective case series design was conducted to elucidate the demographic features of acute myeloid leukaemia in Afghanistan. This study was conducted at Jamhuriat Hospital and French Medical Institute for Mothers and Children, Kabul, Afghanistan. A total of 203 patients with AML diagnosed and managed at Jamhuriat Hospital from 1 March 2018 to 31 March 2020, were included in the current study. The median age at diagnosis was 27 years. Housewives represented the largest subset of patients from an occupational point of view constituting 37.44% of the total sample population and 81.72% of the female population, followed by 20.69% patients who were students of which 14.77% were male and 5.91% were female, and 17.24% were farmers, which constituted 31.81% of the male population. Similarly, 69.95% of individuals presented with infection, 57.14% presented with bone tenderness, 46.3% presented with bleeding tendencies, 55.66% had hepatomegaly and/or splenomegaly, and 27.58% of patients had lymphadenopathy. Considering the chemotherapeutic regime,64.53% of the individuals received standard 7 + 3 (cytarabine + daunorubicin) induction regimen, 10.68% of those received 5 + 2 re-induction chemotherapy (cytarabine + daunorubicin). 10.84% who were diagnosed with acute promyelocytic leukaemia received all-trans-retinoic acid + arsenic trioxide, while 5.42% of patients defaulted chemotherapy. High prevalence was noted in young individuals. Similarly, a high proportion of patients were constituted by housewives.

Complications in simultaneous bilateral total knee arthroplasty, is it a safe procedure?

BackgroundThere is controversy regarding various aspects of simultaneous bilateral total knee replacement (SBTKR). We found disparity in the postoperative outcomes and complications associated with the procedure in the literature linked with the topic. ObjectiveTo retrospectively analyze the need for blood transfusion after surgery and complications associated with total knee replacement according to the type of procedure (SBTKR or unilateral). MethodsRetrospective cohort analytical study. We included 251 patients with severe knee osteoarthritis that were divided into two groups. 124 (49%) who underwent SBTKR and 127 upon whom unilateral total knee replacement (UTKR) was performed. Demographic data, days of hospitalization, complications within the first 90 days after surgery (thromboembolic events, superficial and deep infection, stiffness, death); and percentages of patients transfused with blood products during hospitalization were evaluated. ResultsThere were no statistical differences in the analysis of postoperative complications in the first 90 days after surgery. In the SBTKR group, 8 patients (6.5%) presented some thromboembolic complication during the postoperative period, while this event was observed in only 2 patients (1.5%) from the other group. The analysis showed a statistically significant drop in postoperative hemoglobin, on average that of 0.8 ​g/dl, in the SBTKR patient group compared to the UTKR group (95% CI 0.44–1.13; p ​< ​0.001). A higher proportion of patients who required transfusion were observed in the SBTKR group (40%) (OR ​= ​7.12; 95% CI 3.3–16; p ​< ​0.001).We analyzed the cause of postoperative transfusion in the patients who required transfusion taking into account two parameters: hemoglobin less than 8 ​g/dl and the clinical needs of the patients (symptoms of hypotension, decay, difficulty to rehabilitate without pain, dyspnea). 59 patients received transfusion (50 in the SBTKR group and 9 in the other group). Of these, 19 patients (32.2%) did not meet any transfusion criteria. ConclusionWe consider SBTKR a safe procedure, which does not increase postoperative complications compared to UTKR. Although there is an increase in blood loss in SBTKR, it does not generate clinical symptoms of relevance. Level of evidenceLevel III.

Patient-reported experiences and satisfaction with head and neck surgery outreach clinics in regional New South Wales, Australia: A cross-sectional survey.

Head and neck surgery services are increasingly being centralised in Australia. Outreach models can overcome burdens of travel that patients in regional and rural areas experience when attending routine appointments, by providing services closer to home. To explore patient-reported experiences and satisfaction with regional outreach services for head and neck surgery in Australia. Patients who attended two regional outreach clinics in New South Wales (NSW), Australia, were surveyed over a 6-month period. Patients completed the Outpatient Cancer Clinics Survey (2020 version) that explored perceptions and experiences of the clinic. Patients with cancer were asked to complete the Edmonton Symptom Assessment System and the Communication and Attitudinal Self-Efficacy scale. Descriptive statistics and analysis of data was performed, and results were compared to the NSW statewide Outpatient Cancer Clinics Survey (2020). Content analysis of free text responses was performed. Some 128 patients responded (56% response rate; mean age 67.2 years, 46.1% female). Compared to the 2020 NSW survey, a higher proportion of patients in our cohort responded positively to 14 of the 26 questions, with the greatest differences observed for questions regarding waiting area comfort (+12.1%, p = 0.008), being informed about different treatment options (+9.5%, p = 0.04), and issues relating to parking (+9.5%, p = 0.03). A lower proportion of our sample responded positively to the question about whether health professionals knew enough about their medical history (-19.3%, p < 0.001). Respondents appreciated having a local clinic that helped them avoid travel to major cities and associated expenses and highlighted benefits of expert consultation and timeliness of investigations. However, cost of appointments and level of reimbursements remain barriers for some patients. Patients had a high level of satisfaction with regional outreach clinics for head and neck surgery across most domains, indicating patients highly value this service.

Clinical characteristics and prognostic outcomes for adenocarcinoma of esophagogastric junction in early-onset patients: a population-based appraisal.

Malignancies of the upper gastrointestinal tract are rare in early-onset patients outside the hereditary genetic disorders. There are few reports describing adenocarcinoma of the esophagogastric junction (AEG) in extremely early-onset patients aged under 50years old. The aim of this study was to describe the clinicopathological features and prognosis of adenocarcinoma of esophagogastric junction (AEG) in early-onset patients among three successive periods: 1975-1989 (period 1), 1990-2004 (period 2), and 2005-2017 (period 3). Between 1975 and 2017, data were extracted from the Surveillance, Epidemiology, and End Results database, and 18,278 patients with AEG were enrolled. Three age groups of patients were identified: < 50, 50-69, and ≥ 70years of age. Clinicopathological characteristics and prognostic outcomes were reviewed and compared among three groups over three periods (1975-89, 1990-04, and 2005-2017). Multivariate Cox regression analysis was performed to adjust for covariate effects related to both overall survival (OS) and cancer-specific survival (CSS). Among three age groups, early-onset patients were more likely to present with higher tumor grade, advanced nodal, and distant metastatic disease at diagnosis than other groups (p < 0.01 for both). In comparison to the older group, a higher proportion of patients in the early-onset group received chemotherapy and radiation treatment. After adjusting for covariates, early-onset patients had a better CSS and OS than elderly patients. Early-onset AEG patients were more likely than other age groups to present with advanced disease upon diagnosis. However, the prognosis of early-onset patients was better than their older counterparts after adjustment for covariates. The dissimilarities in tolerance to treatment among early-onset, middle-aged, and elderly patients could be the reason for this difference.

Disease Activity Patterns of Paediatric Inflammatory Bowel Disease - A Danish Nationwide Cohort Study (1996-2018).

Inflammatory bowel diseases (IBD) are heterogeneous in the frequency and severity of their flare-ups. We aimed to describe disease activity patterns in a Danish nationwide paediatric IBD cohort. Paediatric patients (<18 years at diagnosis) with Crohn's disease (pCD) or ulcerative colitis (pUC) in the study period from 1996 to 2018 were identified in national registers. Disease activity (severe, moderate-to-mild, remission) was assessed at diagnosis according to medications prescribed, hospitalisations and surgeries. 1,965 pCD and 1,838 pUC incident patients were included in the cohort. At diagnosis, severe disease activity was found in 87%/80% of pCD/pUC in addition to 6.1% of pUC patients had undergone a colectomy during the first year after diagnosis. Five years after diagnosis, the annual proportions of pCD/pUC with no disease activity were 70%/72%, and 10 years after diagnosis the proportions were 61%/64%. Colectomy was required in 6.1%, 12% and 16% of pUC patients after 1, 5 and 10 years.No improvement of disease activity was seen in the proportion of prevalent pCD (N=2,515) and pUC (N=2,428) in the study period 2000-2018 concomitant with the introduction of biological treatment. Albeit decreasing disease activity was the most common pattern in both pCD and pUC (43% and 47%), respectively. pIBD was characterised by a high proportion of patients with severe activity at diagnosis, followed by an improvement after five and ten years of follow-up. Notably, the proportion of patients with no disease activity was unchanged when biological treatment was introduced and the number of colectomies in pUC remained high.

Contraceptive preferences and adoption following female genital fistula surgery in Uganda: a mixed-methods study

BackgroundFemale genital fistula, largely caused by prolonged obstructed labour, is treated by surgical repair. Preventing pregnancy for a minimum period post-repair is recommended to ensure adequate healing and optimize post-repair outcomes.MethodsWe examined contraceptive preferences and use among Ugandan fistula patients (n = 60) in the year following genital fistula surgery using mixed-methods. Sexual activity, contraceptive use and pregnancy status were recorded quarterly for 12 months after surgery. In-depth interviews among purposively selected participants (n = 30) explored intimate relationships, sexual experiences, reproductive intentions, and contraceptive use.ResultsMedian participant age was 28 years and almost half (48%) were married or living with partners. Counselling was provided to 97% of participants on delaying sexual intercourse, but only 59% received counselling on contraception. Sexual activity was reported by 32% after 6 months and 50% after 12 months. Eighty-three percent reported not trying for pregnancy. Among sexually active participants, contraceptive use was low at baseline (36%) but increased to 73% at 12 months. Six (10%) women became pregnant including two within 3 months post-repair. Interview participants who desired children immediately were young, had fewer children, experienced stillbirth at fistula development, and felt pressure from partners. Women adopted contraception to fully recover from fistula surgery and avoid adverse outcomes. Others simply preferred to delay childbearing. Reasons cited for not adopting contraception included misconceptions related to their fertility and to contraceptive methods and insufficient or unclear healthcare provider advice on their preferred methods.ConclusionsA high proportion of patients were not counselled by healthcare providers on contraception. Provision of comprehensive patient-centred contraceptive counselling at the time of fistula surgery and beyond is important for patients to optimize healing from fistula and minimize recurrence, as well as to meet their own reproductive preferences.

Using immunogenic cell death to improve anticancer efficacy of immune checkpoint inhibitors: From basic science to clinical application.

Even though the discovery of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, a high proportion of patients do not respond. Moreover, some types of cancers are refractory to these treatments. Thus, the need to find predictive biomarkers of efficacy and to evaluate the association with other treatments, such as chemotherapy or radiotherapy, appears to be essential. Because ICIs reactivate or maintain an active status of T cells, one possibility is to combine these treatments with therapies that engage an immune response against tumor cells. Thus, by inducing immunogenic cell death (ICD) of cancer cells, some conventional anticancer treatments induce such immune response and may have an interest to be combined with ICIs. In this review, we explore preclinical studies and clinical trials that evaluate the combination of ICIs with ICD inducers. More than inducing ICD, some of these treatments appear to modulate the tumor microenvironment and more particularly to inhibit immunosuppression, thus improving treatment efficacy.

Meta-regression to explain the placebo effects in clinical trials of anti-CGRP monoclonal antibodies for migraine prevention

Background: Commonly used methods of comparison (e.g. network meta-analyses) require common comparator(s) across trials, such as placebo in placebo-controlled trials. Recent literature indicates that route of administration differences across placebo arms of clinical trials in pain disorders may contribute to differences in placebo effect.Methods: We conducted a meta-regression on placebo data from pivotal clinical trials of anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies for migraine prevention to quantify the impact of route of administration, migraine type (episodic/chronic), and number of prior treatment failures on placebo reduction in monthly migraine days (MMDs) across weeks 1–12 of treatment. A systematic literature review of Embase, MEDLINE, the Cochrane Library, and grey literature conducted in June 2021 identified 14 relevant, randomized placebo-controlled trials for analysis.Results: After testing models with different covariates, a meta-regression was fitted to the extracted placebo data with the covariates of route of administration, migraine type, and proportion of patients with ≥2 prior preventive treatment failures. An intravenous route of administration for the placebo arm was a predictor for higher MMD reduction. Predictors of lower MMD reduction were migraine type (episodic migraine) and a higher proportion of patients having ≥2 failed preventive treatments.Conclusions: The efficacy of intravenous anti-CGRP monoclonal antibodies are likely underestimated, and differences in the route of administration of placebo may necessitate use of alternative methods that do not assume the presence of a common comparator when comparing anti-CGRP monoclonal antibodies in migraine prevention. Further research into the contextual effects of the placebo effect is warranted.

A gene signature of cancer-associated fibroblasts predicts prognosis and treatment response in bladder cancer.

Due to the pivotal role cancer-associated fibroblasts (CAFs) play in tumor progression, our study aimed to develop a signature of CAFs-related gene (CRG) to predict the survival outcomes and treatment response of bladder cancer (BLCA). The transcriptome data and relevant clinical information about BLCA were collected from publicly available databases, including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. Weighted gene co-expression network analysis was utilized to uncover CAFs-associated hub genes, and subsequently, a risk model for survival prognosis was constructed using LASSO-Cox regression. The immune microenvironment, immune infiltration, immunotherapy response, and drug sensitivity were explored using ESTIMATE, CIBERSORT, TIDE, and oncoPredict algorithms. To verify the expression of the CRGs, additional analyses were performed using online databases (HPA, CCLE, TIMER, cBioPortal, and TISCH). Our study developed a CRG signature and constructed a prognostic model. Significant differences in overall survival were observed between the two risk stratifications. The risk score increased with the infiltration of CAFs and tumor staging progression, while closely correlating with immune checkpoint expression and infiltration of CD8 T cells, follicular helper T cells, regulatory T cells, activated dendritic cells, M0 macrophages, M2 macrophages, and resting mast cells. Furthermore, a higher proportion of patients in the low-risk stratification exhibited responsiveness to immunotherapy, and significant variances in sensitivity to multiple chemotherapy medications were observed between the two risk stratifications. The construction of the risk model based on the CRG signature offers new avenues for the prognosis evaluation and development of personalized treatment strategies for BLCA.

Open IPOMs for medium/large incisional ventral hernia repairs in the French Hernia Registry: factors associated with their use and mesh-related outcomes.

The use of open intra-peritoneal onlay mesh repairs (O-IPOMs) for treating medium/large incisional ventral hernias has come into question due to the development of minimally invasive and sublay procedures. This study aimed to identify factors that are associated with the use of O-IPOMs in France. We analysed prospectively collected data from the French Hernia Registry on incisional ventral hernia repairs (IVHR) for hernias ≥ 4cm in width. We obtained data for 2261 IVHR (from 11/09/2011 to 30/03/2020): 733 O-IPOMs and 1,528 other techniques. We found that the O-IPOMs were performed on patients with more patient-related risk factors compared with the other techniques. Specifically, there was a higher proportion of patients with ASA III/IV (40.47% vs. 28.02%; p < 0.00001) and at least one patient-related risk factor (66.17% vs. 58.51%; p = 0.0005). Of the 733 O-IPOMs, 195 used Ventrio ST™ (VST), the most commonly used mesh for such IPOMs in our database; the other 538 O-IPOMs used other meshes (OM). The VST subgroup had a higher proportion of patients with ASA III/IV (52.58% vs. 36.07%; p < 0.0001) and on anticoagulants (26.04% vs. 18.41%; p = 0.0229) compared with the OM subgroup; they also had a lower recurrence rate after 2years (5.83% vs. 15.41%; p = 0.008). However, large (≥ 10cm) or lateral defects were more common in the OM subgroup, and their mesh/defect area ratio was lower. O-IPOMs were performed on patients with more comorbidities and/or complex incisional hernias compared with other techniques.