Coincidence of antibodies against Hwp1 and ASCA, two distinct molecular targets of Candida albicans, reinforces the link between this fungal species and coeliac disease.

Candida albicans is an immunogen for anti-Saccharomyces cerevisiae antibodies (ASCA), a serological marker of Crohn's disease. ASCA has also been reported in other autoimmune diseases, including coeliac disease (CeD). A strong antibody response against Hwp1, a protein associated with invasive hyphal form of C. albicans which presents peptide sequence homologies with gliadin, has also been described in CeD. This observation supports the hypothesis that C. albicans hyphal transition in C. albicans may trigger CeD onset through a mechanism of molecular/antigenic mimicry. In this study, we assessed whether the anti-C. albicans oligomannose and anti-Hwp1 protein responses may be linked despite their different pathophysiological significance. The measurement of ASCA levels in a cohort of patients involved in our previous Hwp1 study showed a significant correlation between the two biomarkers. This new observation further reinforces the link between C. albicans and CeD.

Robotic Anatomical Pulmonary Resections: An Australian Experience.

BACKGROUND: Robotic thoracic surgery is a minimally invasive technique that allows the surgeon to perform delicate, accurate surgical manoeuvres within the chest cavity without rib spreading. Previous studies have suggested potential benefits of the robotic platform in nodal upstaging due to its versatility, seven degrees of freedom of movement, and superior vision. However, there is currently a paucity of robust clinical data from Australia. AIMS: This study aimed to assess the perioperative safety and oncological efficacy of anatomical pulmonary resections performed using the robotic platform. Endpoints included mortality and major morbidity outcomes according to Clavien-Dindo classification and rate of pathological nodal upstaging compared with preoperative imaging using positron emission tomography. METHODS: A single-surgeon retrospective analysis was performed using data collected from two institutions from July 2021 to May 2022, after ethics committee approval. Consecutive patients who underwent anatomical robotic resections were included in the study, with subsequent analysis of patients who had confirmed primary lung cancer. RESULTS: A total of 52 patients underwent robotic anatomical pulmonary resection during the study period. Safety was demonstrated by 0% mortality and a 9.6% major complication rate, which was related to chest tube insertion for prolonged air leak or intensive care unit monitoring during treatment of atrial arrhythmia. After excluding patients who did not have primary lung cancer, 48 patients remained for further analysis; pathological nodal upstaging was observed in nine (18.8%) of these patients. On multivariate analysis, the total number of lymph nodes harvested was found to be a statistically significant predictor of nodal upstaging. Complete microscopic resection (R0) was achieved in 100% of patients. CONCLUSIONS: This study represents the most extensive documentation of robotic thoracic procedures in Australia in the existing literature. It demonstrated a satisfactory safety profile with a relatively high rate of nodal upstaging, possibly reflecting the ability of the robotic instruments to perform comprehensive and complete nodal resection at the time of anatomical pulmonary resection.

Segmentectomy versus lobectomy in the United States: Outcomes after resection for first primary lung cancer and treatment patterns for second primary lung cancers.

OBJECTIVE: The study objective was to identify whether the results of JCOG0802 could be generalized to US clinical settings. METHODS: Patients diagnosed with clinical stage IA (≤2 cm) non-small cell lung cancer who underwent segmentectomy versus lobectomy (2004-2017) in the National Cancer Database were identified. Overall survival of patients in the National Cancer Database was assessed using propensity score-matched analysis. A separate analysis of the Surveillance Epidemiology End Results database was conducted to evaluate treatment patterns of second primary lung cancers among patients who underwent segmentectomy versus lobectomy for a first primary lung cancer. RESULTS: Of the 23,286 patients in the National Cancer Database meeting inclusion criteria, 1397 (6.0%) underwent segmentectomy and 21,889 (94.0%) underwent lobectomy. In a propensity score-matched analysis of all patients in the study cohort, there were no significant differences in overall survival between patients undergoing segmentectomy versus lobectomy (5-year overall survival: 79.9% [95% CI, 76.7%-82.0%] vs 81.8% [95% CI, 78.7%-84.4%], log-rank: P = .72). In subgroup analyses by tumor grade and histologic subtype, segmentectomy was associated with similar overall survival compared with lobectomy in all subgroups evaluated. In a propensity score-matched analysis of patients in the Surveillance Epidemiology End Results database, there were no significant differences in treatment patterns of second primary lung cancers between patients who underwent segmentectomy and patients who underwent lobectomy for their first primary lung cancer. CONCLUSIONS: In this national analysis of US patients diagnosed with stage IA (≤2 cm) non-small cell lung cancer, there were no significant differences in overall survival between segmentectomy and lobectomy in the overall cohort or in subgroup analyses by tumor grade or histologic subtype.

PREBIOTIC: a study protocol of a randomised controlled trial to assess prebiotic supplementation in kidney transplant recipients for preventing infections and gastrointestinal upset - a feasibility study.

BACKGROUND: Modulating the microbiota in the large intestine of kidney transplant recipients through prebiotic supplementation may prevent infectious complications from occurring. To date, there have been no interventional trials which have investigated this novel treatment in kidney transplantation. The aim of PREBIOTIC is to assess the feasibility of performing a randomised controlled trial of prebiotics in reducing infections and gastrointestinal symptoms in kidney transplant recipients. METHODS: Sixty kidney transplant patients will be recruited to a double-blind, placebo-controlled, randomised feasibility trial. Patients will be provided with prebiotic therapy or placebo for 4 to 6 weeks. Outcomes will include recruitment, adherence, tolerance, retention, laboratory parameters (including serum indoxyl sulphate, ρ-cresyl sulphate and stool collection), patients' self-assessed quality of life, gastrointestinal symptoms and clinical outcomes. DISCUSSION: This trial will assess the feasibility of prebiotic supplementation in kidney transplant recipients. Prebiotics not only may alter the gut microbiota and their inherent metabolism and production of uraemic toxins but also may prevent infections from occurring in kidney transplant recipients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry number ACTRN12618001057279p. The date of registration was 25th June 2018, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375370&isReview=true .

Treatment of Severe Swallowing Dysfunction in Systemic Sclerosis with IVIG: Role of Antimuscarinic Antibodies.

Oropharyngeal and esophageal dysmotility can cause serious clinical complications such as aspiration pneumonia, cachexia, and sarcopenia, with a resulting increase in mortality and disability. The current standard of care for the treatment of SSc-associated swallowing dysfunction is mainly supportive, although severe cases are usually refractory to conventional management. Recent studies have shown that the abnormal production of functional autoantibodies such as anti-cholinergic muscarinic receptor III antibodies may participate in the pathogenesis of SSc-associated gastrointestinal dysmotility and may provide a novel target for therapeutic intervention. We describe two patients with severe and rapid onset of SSc-associated severe swallowing dysfunction and esophageal dysmotility who had failed standard of care therapy, requiring complete enteral and parenteral nutrition. Both patients were positive for the presence of circulating antimuscarinic III receptor antibodies. They were treated with IVIG at a dose of 2 g/Kg/month divided in two consecutive days, for six months. Following IVIG therapy, both patients markedly improved their symptoms as shown by a reduction in their UCLA2.0 score, and achieved an improvement of esophageal motility documented radiologically. Both patients resumed oral feeding and had their feeding tubes removed within the treatment period. None of the patients developed severe adverse events attributable to IVIG, except for low-grade fever during IVIG infusion in one of the cases. These results provide support for the role of functional autoantibodies in the development of SSc-associated gastrointestinal dysfunction.

Complications of Robotic Video-Assisted Thoracoscopic Surgery Compared to Open Thoracotomy for Resectable Non-Small Cell Lung Cancer.

(1) Background: Conventional open thoracotomy has been the accepted surgical treatment for resectable non-small cell lung cancer. However, newer, minimally invasive approaches, such as robotic surgery, have demonstrated similar safety and efficacy with potentially superior peri-operative outcomes. The present study aimed to quantitatively assess these outcomes through a meta-analysis. (2) Methods: A systematic review was performed using electronic databases to identify all of the relevant studies that compared robotic surgery with open thoracotomy for non-small cell lung cancer. Pooled data on the peri-operative outcomes were then meta-analyzed. (3) Results: Twenty-two studies involving 12,061 patients who underwent robotic lung resection and 92,411 patients who underwent open thoracotomy were included for analysis. Mortality rates and length of hospital stay were significantly lower in patients who underwent robotic resection. Compared to open thoracotomy, robotic surgery was also associated with significantly lower rates of overall complications, including atrial arrhythmia, post-operative blood transfusions, pneumonia and atelectasis. However, the operative times were significantly longer with robotic lung resection. (4) Conclusions: The present meta-analysis demonstrated superior post-operative morbidity and mortality outcomes with robotic lung resection compared to open thoracotomy for non-small cell lung cancer.

Critically important outcomes for infection in trials in kidney transplantation: An international survey of patients, caregivers, and health professionals.

BACKGROUND: Infections are a common complication following kidney transplantation, but are reported inconsistently in clinical trials. This study aimed to identify the infection outcomes of highest priority for patients/caregivers and health professionals to inform a core outcome set to be reported in all kidney transplant clinical trials. METHODS: In an international online survey, participants rated the absolute importance of 16 infections and eight severity dimensions on 9-point Likert Scales, with 7-9 being critically important. Relative importance was determined using a best-worst scale. Means and proportions of the Likert-scale ratings and best-worst preference scores were calculated. RESULTS: 353 healthcare professionals (19 who identified as both patients/caregiver and healthcare professionals) and 220 patients/caregivers (190 patients, 22 caregivers, eight who identified as both) from 55 countries completed the survey. Both healthcare professionals and patients/caregivers rated bloodstream (mean 8.4 and 8.5, respectively; aggregate 8.5), kidney/bladder (mean 7.9 and 8.4; aggregate 8.1), and BK virus (mean 8.1 and 8.6; aggregate 8.3) as the top three most critically important infection outcomes, whilst infectious death (mean 8.8 and 8.6; aggregate 8.7), impaired graft function (mean 8.4 and 8.7; aggregate 8.5) and admission to the intensive care unit (mean 8.2 and 8.3; aggregate 8.2) were the top three severity dimensions. Relative importance (best-worst) scores were consistent. CONCLUSIONS: Healthcare professionals and patients/caregivers consistently identified bloodstream infection, kidney/bladder infections, and BK virus as the three most important infection outcomes, and infectious death, admission to intensive care unit and infection impairing graft function as the three most important infection severity outcomes.

Prebiotic Supplementation in Kidney Transplant Recipients for Preventing Infections and Gastrointestinal Upset: A Randomized Controlled Feasibility Study.

OBJECTIVES: Modulating the large intestinal microbiome of kidney transplant recipients (KTRs) may reduce infectious complications. The aim of this study is to assess the feasibility of a randomized controlled trial of prebiotics in reducing infections and gastrointestinal symptoms in KTRs. (DESIGN) AND METHODS: Acute KTRs were recruited to a double-blind, placebo-controlled, randomized trial at a single kidney transplant center. Patients were provided with prebiotics or placebo for 7 weeks. The primary outcome was feasibility, defined as recruitment of ≥80% of eligible people within 6 months. Secondary outcomes included adherence and tolerability, participant retention in trial, proportions of participants providing serum and stool specimens, self-reported quality of life, gastrointestinal symptoms, and infection events. RESULTS: During the 7-week period, 72 patients met eligibility criteria, of whom 60 (83%) consented to participate (mean ± standard deviation age 53 ± 12 years; 62% males). Fifty-six (78%) participants were randomized (27 interventions and 29 controls). Although participants receiving intervention experienced reduced gastrointestinal symptoms (-0.28 [interquartile range, IQR -0.67 to 0.08] vs. -0.07 [IQR -0.27 to 0], P = .03), both control and intervention groups were similar in adherence (67% vs. 72%, P = .36), tolerability (56% vs. 62%, P = .64), quality of life (-0.2 [IQR -0.6 to 0] vs. -0.2 [IQR -0.8 to 0], P = .82), and infection events (33% vs. 34%, P = .83). Blood and stool samples were collected from ≥90% of participants in both groups. CONCLUSIONS: It is feasible to recruit and retain acute KTRs in a randomized, placebo-controlled trial examining the effect of prebiotics on infections and gastrointestinal symptoms. This study also showed that prebiotics significantly reduced gastrointestinal symptoms.

Perioperative Outcomes and Survival After Preoperative Immunotherapy for Non-Small Cell Lung Cancer.

BACKGROUND: Although preoperative immunotherapy is increasingly utilized for non-small cell lung cancer, there remains a paucity of robust clinical data on its safety and long-term survival. Our objective was to evaluate the perioperative outcomes and survival associated with immunotherapy followed by surgery for patients with non-small cell lung cancer. METHODS: Outcomes of patients with non-small cell lung cancer who underwent lung resection after preoperative chemotherapy with or without radiation or immunotherapy (with or without chemotherapy or chemoradiation) in the National Cancer Database (2010 to 2017) were evaluated using Kaplan-Meier analysis, multivariable logistic regression, multivariable Cox proportional hazards analysis, and propensity score-matched analysis. RESULTS: From 2010 to 2017, 236 patients (2.2%) received immunotherapy and 10 715 patients received preoperative chemotherapy followed by surgery. There were no significant differences between the immunotherapy and preoperative chemotherapy groups with regard to margin positivity (8.5% [n = 20] vs 7.5% [n = 715], P = .98), 30-day readmission (4.2% [n = 10] vs 4.1% [n = 440], P = .87), and 30-day mortality (0.4% [n = 1] vs 2.4% [n = 253], P = .25). The immunotherapy and preoperative chemotherapy groups had similar overall survival (5-year survival 63% [95% confidence interval, 50% to 74%] vs 51% [95% confidence interval, 50% to 52%], log rank P = .06; multivariable adjusted hazard ratio 0.98; 95% confidence interval, 0.67 to 1.41; P = .90). A propensity score matched analysis of 344 patients, well matched by preoperative characteristics, showed no significant differences in short-term outcomes and overall survival (log rank P = 1.00) between the two groups. CONCLUSIONS: In this national analysis, preoperative immunotherapy followed by surgery for non-small cell lung cancer was found to be safe and feasible with similar short-term outcomes and overall survival when compared with preoperative chemotherapy followed by surgery.

Meta-Analysis of Neoadjuvant Immunotherapy for Patients with Resectable Non-Small Cell Lung Cancer.

PURPOSE: Immunotherapy has created a paradigm shift in the treatment of metastatic non-small cell lung cancer (NSCLC), overcoming the therapeutic plateau previously achieved by systemic chemotherapy. There is growing interest in the utility of immunotherapy for patients with resectable NSCLC in the neoadjuvant setting. The present systematic review and meta-analysis aim to provide an overview of the existing evidence, with a focus on pathological and radiological response, perioperative clinical outcomes, and long-term survival. METHODS: A systematic review was conducted using electronic databases from their dates of inception to August 2021. Pooled data on pathological response, radiological response, and perioperative outcomes were meta-analyzed where possible. RESULTS: Eighteen publications from sixteen studies were identified, involving 548 enrolled patients who underwent neoadjuvant immunotherapy, of whom 507 underwent surgery. Pathologically, 52% achieved a major pathological response, 24% a complete pathological response, and 20% reported a complete pathological response of both the primary lesion as well as the sampled lymph nodes. Radiologically, 84% of patients had stable disease or partial response. Mortality within 30 days was 0.6%, and morbidities were reported according to grade and frequency. CONCLUSION: The present meta-analysis demonstrated that neoadjuvant immunotherapy was feasible and safe based on perioperative clinical data and completion rates of surgery within their intended timeframe. The pathological response after neoadjuvant immunotherapy was superior to historical data for patients who were treated with neoadjuvant chemotherapy alone, whilst surgical and treatment-related adverse events were comparable. The limitations of the study included the heterogenous treatment regimens, lack of long-term follow-up, variations in the reporting of potential prognostic factors, and potential publication bias.

Range and Consistency of Infection Outcomes Reported in Trials Conducted in Kidney Transplant Recipients: A Systematic Review.

BACKGROUND: Infection remains a leading cause of death in kidney transplant recipients. This study aimed to assess the scope and consistency of infection outcomes reported in contemporary trials conducted in kidney transplant recipients. METHODS: A literature review of all randomized trials and trial protocols reporting infection outcomes in adult kidney transplant recipients was identified in the Cochrane Kidney and Transplant Specialized Register from January 2014 to July 2019. Characteristics and infection outcomes from the trials were analyzed. RESULTS: From 102 included trials, 772 outcome measures were extracted and categorized into 216 unique measures with a median of 3.2 outcome measures per trial (range: 1-9). Measures were further grouped into 32 outcomes based on site of infection (14 outcomes) and organism (18 outcomes). The most commonly reported site-specific outcome and organism-specific outcome were systemic infection (71% trials) and cytomegalovirus infection (62% trials), respectively. Outcome metric and methods of aggregation included mean, median, proportion, proportional change, and number of patients with at least 1 episode. Across all trials, measures were assessed at 55 different time points with a range of 1-11 time points per trial. CONCLUSIONS: Infection outcomes in kidney transplant recipients were frequently reported by site and organism but varied widely in terms of outcome, metrics, method of aggregation, and time point of measurement. Establishment of core outcomes for infection based on the shared priorities of patients/caregivers and health professionals may improve the consistency, comparability, and usefulness of trial evidence.

Patient-Reported Gastrointestinal Symptoms and the Association With Quality of Life Following Kidney Transplantation.

BACKGROUND: There has been limited study of the prevalence of gastrointestinal symptoms and their impact on the quality of life (QOL) in kidney transplant recipients. The aim of this study was to examine the prevalence and predictors of gastrointestinal symptoms and the association with QOL in kidney transplant recipients. METHODS: All chronic kidney transplant recipients at the Princess Alexandra Hospital were provided with 3 questionnaires, the Gastrointestinal Quality of Life Index (GIQLI), the Gastrointestinal Symptoms Rating Scale (GSRS), and Structured Assessment of Gastrointestinal Symptoms (SAGIS) scale, to ascertain QOL impairment and to screen gastrointestinal symptom severity. Linear regression was used to determine the predictors of gastrointestinal QOL and gastrointestinal symptom severity. RESULTS: Of the 343 participants, the median age was 47 (interquartile range [IQR] 36-55) years, 58% were men, 79% were white, 39% had chronic glomerulonephritis, 83% had received their first graft, and median time since transplant was 6.3 (IQR 1.8-13.1) years. Using GSRS, 88% of participants reported at least 1 gastrointestinal symptom, most commonly indigestion (57%) and diarrhea (54%). Using GIQLI, 42% and 38% of participants reported mild and moderate QOL impairment, respectively. Gastrointestinal symptoms were predicted by female sex (coefficient -0.11, 95% CI -0.21 to -0.02) and mycophenolate (coefficient 0.0001, 95% CI 0.0001 to 0.0002), and were associated with poorer QOL (coefficient -0.38, 95% CI -0.45 to -0.30). Similar findings were observed using SAGIS for gastrointestinal symptoms. CONCLUSIONS: Gastrointestinal symptoms are frequent in kidney transplant recipients, particularly in women and those receiving mycophenolate, and are strongly associated with poorer QOL.