Second-line treatment outcomes after first-line chemotherapy plus immunotherapy in Extensive-Stage small cell lung cancer (ES-SCLC) patients: A large French multicenter study.

INTRODUCTION: Chemotherapy combined with immunotherapy (CT-IO) is the standard treatment for patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC). This study evaluates the effectiveness of second-line (2L) following CT-IO. PATIENTS AND METHODS: All patients from 10 centers who received a 2L after a first-line CT-IO were included. They were divided into 3 groups: platinum-based, lurbinectedin or others (topotecan, CAV, taxanes). We assessed overall survival (OS) and 2L progression-free survival (2L-PFS) according to treatment and platinum free-interval (PFI) < or ≥ 90 days. RESULTS: Among 82 patients included, median age was 67.0 years, 29.3 % had a Performans Status ≥ 2, 36.6 % had brain progression, 69.5 % were considered "platine-sensitive" and 30.5 % "platine-resistant" (PFI ≥ or < 90 days, respectively). As 2L, 37/82 patients (45.1 %) received platinum-doublet, 21/82 (25.6 %) lurbinectedin and 24/82 (29.3 %) others. Patients with a PFI ≥ 90 days received mainly platinum-based rechallenge (34/57, 59.6 %). With a median follow-up of 18.5 months, the median OS was 5.0 months (95 %CI, 1.5-7.9) / 6.8 months (95 %CI, 5.5-8.7) for platinum-resistant / sensitive, respectively (log rank p = 0.017). The median 2L-PFS was 1.9 months (95 %CI, 1.2-4.7) / 3.9 months (95 %CI, 2.9-6.0) for platinum-resistant / sensitive, respectively. Median OS was 8.1 (95 %CI, 6.3-12.9) / 4.9 (95 %CI, 3.7-6.8) / 5.1 months (95 %CI, 2.5-7.8) with platinum rechallenge / lurbinectedin / others, respectively (p = 0.017). Median 2L-PFS was 4.6 (95 %CI, 3.9-7.2) / 2.7 (95 %CI, 1.6-3.9) / 2.2 months (95 %CI, 1.5-4.1) with platinum rechallenge / lurbinectedin / others, respectively (p = 0.025). DISCUSSION: Platinum-based rechallenge after a first-line CT-IO showed promising results despite particularly unfavorable characteristics within our real-word population. Lurbinectedin when used after IO demonstrated as low efficacy as other platinum-free regimens.

Chest tube placement incidence when using gelatin sponge torpedoes after pulmonary radiofrequency ablation.

Purpose: To assess the efficacy of the gelatin torpedoes embolization technique after lung neoplastic lesions percutaneous radiofrequency ablation (PRFA) to reduce chest tube placement rate and hospital length of stay, and the safety of this embolization technique. Materials and methods: A total of 114 PRFA of lung neoplastic lesions performed in two centers between January 2017 and December 2022 were retrospectively reviewed. Two groups were compared, with 42 PRFA with gelatin torpedoes embolization technique (gelatin group) and 72 procedures without (control group). Procedures were performed by one of seven interventional radiologists using LeVeen CoAccess™ probe. Multivariate analyses were performed to identify risk factors for chest tube placement and hospital length of stay. Results: There was a significantly lower chest tube placement rate in the gelatin group compared to the control group (3 [7.1 %] vs. 27 [37.5 %], p < 0,001). Multivariate analysis showed a significant association between chest tube placement and gelatin torpedoes embolization technique (OR: 0.09; 95 % CI: 0.02-0.32; p = 0.0006). No significant difference was found in hospital length of stay between the two groups. Multivariate analysis did not show a significant relationship between hospital length of stay and gelatin torpedoes embolization technique. No embolic complication occurred in the gelatin group. Conclusion: Gelatin torpedoes embolization technique after PRFA of lung neoplastic lesions resulted in significantly reduced chest tube placement rate in our patient population. No significant reduction in hospital length of stay was observed. No major complication occurred in the gelatin group.

Sepsis-trained macrophages promote antitumoral tissue-resident T cells.

Sepsis induces immune alterations, which last for months after the resolution of illness. The effect of this immunological reprogramming on the risk of developing cancer is unclear. Here we use a national claims database to show that sepsis survivors had a lower cumulative incidence of cancers than matched nonsevere infection survivors. We identify a chemokine network released from sepsis-trained resident macrophages that triggers tissue residency of T cells via CCR2 and CXCR6 stimulations as the immune mechanism responsible for this decreased risk of de novo tumor development after sepsis cure. While nonseptic inflammation does not provoke this network, laminarin injection could therapeutically reproduce the protective sepsis effect. This chemokine network and CXCR6 tissue-resident T cell accumulation were detected in humans with sepsis and were associated with prolonged survival in humans with cancer. These findings identify a therapeutically relevant antitumor consequence of sepsis-induced trained immunity.

Unplanned 30-day readmission rate after ophthalmological surgery as a quality-of-care indicator.

BACKGROUND: The 30-day readmission rate provides a standardised quantitative evaluation of some postoperative complications. It is widely used worldwide in many medical and surgical specialities, and the World Health Organization recommends its use for monitoring healthcare system performance. In ophthalmology, its measurement is biased by the frequent and close planned surgery on one eye and then the other, particularly in the case of cataract surgery. This study measures the 30-day unplanned readmission rate in ophthalmology, globally and by surgery subtype, and describes the causes of readmission. METHODS: All patients readmitted within 30 days of ophthalmic surgery at Nantes University Hospital between January 2017 and December 2020 were identified in the Medical Information System. An ophthalmologist examined each medical record and collected the following data: the reason for readmission, comorbidities, the pathology treated, surgery type, surgery duration, the surgeon's experience, anaesthesia type, severity and readmission morbidity. RESULTS: For the 8522 ophthalmic surgeries performed in the four-year study period, 282 30-day unplanned readmissions were identified. The overall 30-day unplanned readmission rate was 2.07% for elective surgery, with a high variability depending on the surgery type: 0.95% for phacoemulsification, 4.95% for vitreoretinal surgery (3.42% for non-elective vitreoretinal surgery, 5.44% for retinal detachment surgery), 5.66% for deep lamellar keratoplasty and 11.90% for trabeculectomy. The unplanned 30-day readmission rate for ocular trauma surgery (emergency care) was 11.0%. Seven percent of all unplanned 30-day readmissions were not associated with an ophthalmological problem. CONCLUSIONS: This study is the first to report 30-day unplanned readmission in ophthalmology, globally and by surgical subtype, for elective and urgent procedures. This indicator can be used longitudinally to detect an increase in risk or transversely to compare the quality of care between different public or private hospitals.

Primary hypocholesterolemia is associated with an increased risk of hepatic complications in the general population.

BACKGROUND & AIMS: Beyond cardiovascular disease protection, the health consequences of very low concentrations of low-density lipoprotein-cholesterol (LDL-C) remain a matter of debate. In primary hypobetalipoproteinemia (HBL), liver steatosis and cirrhosis have occasionally been reported. Here, we aimed to investigate the association between HBL and the risk of hepatic complications (cirrhosis complications and/or primary liver cancer) in the general population. METHODS: A cohort study was conducted in the French population-based cohort CONSTANCES. Participants with primary HBL (LDL-C <5th percentile for age and sex, [HBL]) were compared with those with normal LDL-C concentrations (40th-60th percentile, [Control]). Participants on lipid-lowering therapies were excluded. For hepatic complications, follow-up events were compared by calculating the incidence density ratio (IDR). The same analyses were replicated in the UK Biobank (UKBB) cohort. RESULTS: In the CONSTANCES and UKBB cohorts, 34,653 and 94,666 patients were analyzed, with median ages of 45 and 56 years, mean LDL-C concentrations (HBL vs. control) of 71 vs. 128 mg/dl and 86 vs. 142 mg/dl, and mean follow-up durations of 5.0 and 11.5 years, respectively. The HBL group presented a higher incidence of hepatic complications than the control group: 0.32/ vs. 0.07/1,000 person-years (IDR = 4.50, 95% CI 1.91-10.6) in CONSTANCES, and 0.69/ vs. 0.21/1,000 person-years (IDR = 3.27, 95% CI 2.63-4.06) in the UKBB. This risk proved to be independent of classic risk factors for liver disease (obesity, alcohol consumption, diabetes, viral hepatitis), including in a 5-year landmark analysis excluding early events. Sensitivity analyses based on apoliprotein-B levels (instead of LDL-C levels) or genetically defined HBL showed similar results. CONCLUSIONS: HBL is associated with a markedly increased risk of hepatic complications. HBL must be considered as a substantial independent risk factor for liver diseases which justifies specific prevention and screening. IMPACT AND IMPLICATIONS: Hypobetalipoproteinemia (HBL) is a lipid disorder characterized by permanent, inherited low levels (below the 5th percentile) of low-density lipoprotein-cholesterol. While HBL is associated with a lower risk of cardiovascular events, some studies suggest that it may be associated with a potential risk of hepatic steatosis and hepatic complications. Here, we studied the association between HBL and hepatic complications (defined as cirrhosis complications and/or primary liver cancer) in two populations of several hundred thousand people, both in France (CONSTANCES cohort) and the United Kingdom (UKBB). The results show that HBL is associated with a significant and independent excess risk of hepatic complications, including primary liver cancer. Thus, in people with HBL, the value of regular liver monitoring must be studied.

Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-small-cell Lung Cancer.

BACKGROUND: The prognostic impact of TP53 mutations in advanced or metastatic nonsquamous non-small-cell lung cancer (nsNSCLC) patients treated with chemotherapy and/or immune checkpoint inhibitors (ICI) remains unclear. MATERIALS AND METHODS: We retrospectively collected data from patients with nsNSCLC treated in the first line from January 2018 to May 2021. The patient was separated into 2 groups according to their TP53 mutation status (wt vs. mut). Survival was estimated through the Kaplan-Meier method and compared by log-rank test. RESULTS: Of 220 patients included, 126 were in the mutTP53 group, and 94 were in the wtTP53wt group. Median OS (mOS) was not significantly different between the mutTP53 and wtTP53 groups [17.5 months (95% confidence interval (CI), 11.3-21.5) vs. 9.5 months (95% CI, 7.4-14.2), (P = .051)]. In subgroup analyses, the mutTP53 group treated with ICI had a significantly improved mOS compared to the wtTP53 group [(24.7 months (95% CI, 20.8-not reach) vs. 12.0 months (95% CI, 4.7-not reach), (P = .017)] and mPFS [(9.6 months (95% CI, 5.8-not reach) vs. 3.2 months (95% CI, 1.3-13.8) (P = .048)]. There was no difference in terms of mOS and mPFS between the mutTP53 and the wtTP53 group treated by chemotherapy alone or combined with ICI. CONCLUSION: TP53 mutation had no survival impact in the overall population, but is associated with better outcomes with ICI alone. These results suggest that patients with TP53 mutations could be treated with ICI alone, and wild-type patients could benefit from the addition of chemotherapy.

A Multicenter Study Assessing the Real-World Use and Effectiveness of First-Line Chemotherapy Plus Immunotherapy in Advanced Small-Cell Lung Cancer (SCLC) Patients.

BACKGROUND: First-line chemotherapy plus immunotherapy (CT-IO) has recently demonstrated survival benefits over CT alone in extensive-stage small-cell lung cancer (ES-SCLC), based on randomized phase III studies. This retrospective multicenter study assessed the real-world use and effectiveness of CT-IO in ES-SCLC patients. PATIENTS AND METHODS: All newly diagnosed ES-SCLC patients from 4 French hospitals treated with CT alone or CT-IO between May 2020 and December 2021 were included. Overall survival (OS) and real-world progression-free survival (rwPFS) were estimated using the Kaplan-Meier method. Cox proportional hazard models were performed to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs) in univariate and multivariate models. The aim was not to compare efficacy between groups. RESULTS: Among 104 patients, 75 (72.1%) received CT-IO. Brain metastases were diagnosed in 28.3% of patients, and 29.8% were performance status (PS) ≥ 2. At a median follow-up of 16.8 months (95%CI, 14.9-23.4), the median OS was 11.4 months (95%CI, 7.7-14.7) in the CT-IO group, and the 12-month OS rate was 43.6% (95%CI, 33.3-57.2). In the CT group, the median OS was 7.8 months (95%CI, 5.4-11.8) and the 12-month OS rate was 15.3% (95%CI, 5.7-41.0). In multivariate analyses, baseline brain and liver metastases were associated with a shorter OS for patients treated in the CT-IO group (HR, 3.80 [95%CI, 1.90-7.60] and 3.12 [95%CI, 1.60-6.08] respectively; P < 0.001 for both). CONCLUSION: We showed that clinicians have chosen to use IO beyond the specific criteria defined in guidelines. Survival data appeared promising with a median OS comparable to the one previously demonstrated in clinical trials.

Impact of first-line immunotherapy on survival and intracranial outcomes in a cohort of non-small cell lung cancer patients with brain metastases at diagnosis.

BACKGROUND: Although brain metastases (BM) at diagnosis are common in non-squamous NSCLC patients (ns-NSCLC), they have been mostly excluded from randomized trials. The aim of this retrospective study was to evaluate real-word outcomes of frontline immune checkpoint inhibitor (ICI) in these patients. METHODS: Our study assess the intracranial and overall efficacy of first-line ICI-based therapy compared to chemotherapy (CT) in ns-NSCLC patients diagnosed with BM, showing no targetable alterations. Patients were divided according to systemic therapy: CT, ICI, or CT-ICI. Primary endpoint was overall survival (OS), compared using Kaplan-Meier and Cox methodology. Secondary endpoint was intracranial progression free survival (icPFS). RESULTS: Between 01 and 2018 and 05-2021, 118 patients were included (52 CT, 38 ICI and 28 CT-ICI). Median follow-up was 30.0 months. Intracranial radiotherapy was delivered for 75.0%, 68.4% and 67.9% of patients for CT, ICI and CT-ICI groups (p = 0.805). After adjustment, ICI and CT-ICI were associated with a better OS compared to CT (HR = 0.46, 95 %CI: 0.23-0.89, and HR = 0.52, 95 %CI: 0.27-1.01, respectively). ICI and CT-ICI were associated with a significant reduction in the risk of intracranial progression by 54% (HR = 0.46, 95 %CI: 0.25-0.84) and 59% (HR = 0.41, 95 %CI: 0.23-0.77) compared to CT. Stereotactic radiosurgery was associated with an increased icPFS compared to systemic therapy alone (HR = 0.51, 95% CI: 0.29 - 0.92), whereas whole-brain was not. CONCLUSIONS: Real-life ns-NSCLC patients with BM at diagnosis treated frontline with ICI presented OS and icPFS benefit compared to CT alone. A prospective assessment of the ideal type and sequence of systemic and local therapy should be conducted.

Panniculitis does not predict clinical response in patients with advanced melanoma under targeted therapy.

BACKGROUND: BRAF and MEK inhibitors have changed the landscape of treatment for advanced melanoma. Among their side effects, panniculitis has been hypothesized to be associated with better survival. OBJECTIVES: In this study, we aimed to explore the association between the occurrence of panniculitis during targeted therapy and outcome of metastatic melanoma. MATERIALS & METHODS: This was a retrospective single-centre comparative study from 2014 to 2019. An English literature review was also conducted to further our understanding of the mechanism(s) involved and identify characteristics of this association, in order to support better management. RESULTS: Ten patients who developed panniculitis during treatment were matched to 26 controls based on potential confounders at treatment introduction. The prevalence of panniculitis was 5.3%. Median progression-free survival (PFS) for all patients was 8.5 months (range: 3.0-94.0). The median PFS for the group with panniculitis was 10.5 months (7.0-undefined) and 7.0 months (6.0-32.0) for controls (p=0.39). According to the scientific literature, panniculitis occurring during targeted therapy affects mainly young people, predominantly women, with variable delay to onset (with half reported cases occurring in the first month). In addition, panniculitis usually only affects the lower limbs or is associated with other clinical signs (fever, arthralgia), without histological specificity. Discontinuation of targeted therapy is not required as spontaneous remission is usually experienced. Symptomatic treatment may be administered but systemic corticosteroids have not been proven to be effective. CONCLUSION: In contrast to the belief that there is a link between panniculitis and clinical response to targeted therapy according to the literature, our results show that there is no significant association between the two.

How to measure vessel caliber in microsurgery and super-microsurgery? Metrological study of three methods applicable in clinical practice.

INTRODUCTION: The microsurgical literature reports the vascular calibers of the vessels studied even though the method of measurement of these vessels is very rarely reported. MATERIAL AND METHOD: We performed a metrological study evaluating three methods to measure the external calibers of catheters corresponding to microsurgical and super-microsurgical vessels (1.2 mm, 0.8 mm, and 0.6 mm). Six evaluators measured 15 catheters of three different hidden diameters by each of the three methods applicable in clinical practice: standard graduated ruler, Shinwa® micrometric ruler, and ImageJ® software from a photograph. Accuracy and reliability of the measurements were assessed by studying the inter- and intra-rater and inter-method coefficients (variants of the intra-class coefficient (ICC)) and analysis of the IC95% of the ICCs. RESULTS: Intra class correlation ICC "intra-rater" coefficient finds for the standard rule 0.81 [0.65-0.93], Shinwa® rule 0.86 [0.67-0.96], and for the ImageJ® software 0.97 [0.94-0.99]. The "Inter-rater" ICC shows respectively the coefficient 0.51 [0.23 and max 0.93], 0.87 [0.75-0.95], and 0.95 [0.89-0.98]. It appears that the graduated decimeter is the least reliable method of measurement, the Shinwa® ruler presents acceptable reliability but requires the purchase of equipment. The reliability of ImageJ® software is the best and appears to be the most reliable method. CONCLUSION: Our original study, with no equivalent in the scientific literature, demonstrates objectively the great accuracy and reliability of a method of measurement of vascular calibers in micro and super microsurgery using intraoperative photography and the use of free computer software.

Patient-centric synthetic data generation, no reason to risk re-identification in biomedical data analysis.

While nearly all computational methods operate on pseudonymized personal data, re-identification remains a risk. With personal health data, this re-identification risk may be considered a double-crossing of patients' trust. Herein, we present a new method to generate synthetic data of individual granularity while holding on to patients' privacy. Developed for sensitive biomedical data, the method is patient-centric as it uses a local model to generate random new synthetic data, called an "avatar data", for each initial sensitive individual. This method, compared with 2 other synthetic data generation techniques (Synthpop, CT-GAN), is applied to real health data with a clinical trial and a cancer observational study to evaluate the protection it provides while retaining the original statistical information. Compared to Synthpop and CT-GAN, the Avatar method shows a similar level of signal maintenance while allowing to compute additional privacy metrics. In the light of distance-based privacy metrics, each individual produces an avatar simulation that is on average indistinguishable from 12 other generated avatar simulations for the clinical trial and 24 for the observational study. Data transformation using the Avatar method both preserves, the evaluation of the treatment's effectiveness with similar hazard ratios for the clinical trial (original HR = 0.49 [95% CI, 0.39-0.63] vs. avatar HR = 0.40 [95% CI, 0.31-0.52]) and the classification properties for the observational study (original AUC = 99.46 (s.e. 0.25) vs. avatar AUC = 99.84 (s.e. 0.12)). Once validated by privacy metrics, anonymous synthetic data enable the creation of value from sensitive pseudonymized data analyses by tackling the risk of a privacy breach.

Impact of the duration of oestradiol treatment on live birth rate in Hormonal Replacement Therapy cycle before frozen blastocyst transfer.

Although the duration of progesterone administration in Hormonal Replacement Therapy (HRT) cycles before frozen embryo transfer is standardized, the optimal duration of oestrogen treatment remains controversial. In this monocentric retrospective study conducted in all single frozen blastocyst transfer (FBT) performed with HRT between January 2016 and July 2019, we evaluated the association between the duration of oestradiol treatment before FBT and live birth rate (LBR) in HRT cycles. Cycles were gathered in 3 groups according to quartiles of duration of oestrogen treatment. LBR was compared across the 3 groups and multivariate analysis was performed. We included 2235 single FBT cycles; 507, 1257 and 471 with E2 treatment below 23 days, 23-30 days (reference) and more than 30 days respectively. After multivariate analysis and adjustment, no significant difference in LBR was found between below 23 or more than 30 days and reference groups (OR = 0.93 [0.68-1.27] and OR = 1.29 [0.88-1.89] respectively). Complementary sensitivity analysis led to a non-significant adjusted OR = 1.66 [IC 0.9-3.1]. In conclusion, our study showed that the duration of E2 treatment in HRT cycles before FBT is not associated with LBR.

Nutritional biomarkers and heart failure requiring hospitalization in patients with type 2 diabetes: the SURDIAGENE cohort.

BACKGROUND: Heart failure (HF) is a growing complication and one of the leading causes of mortality in people living with type 2 diabetes (T2D). Among the possible causes, the excess of red meat and the insufficiency of vegetables consumption are suspected. Such an alimentation is associated with nutritional biomarkers, including trimethylamine N-oxide (TMAO) and its precursors. Here, we aimed to study these biomarkers as potential prognostic factors for HF in patients with T2D. METHODS: We used the SURDIAGENE (SURvival DIAbetes and GENEtics) study, a large, prospective, monocentric cohort study including 1468 patients with T2D between 2001 and 2012. TMAO and its precursors (trimethylamine [TMA], betaine, choline, and carnitine) as well as thio-amino-acids (cysteine, homocysteine and methionine) were measured by liquid chromatography-tandem mass spectrometry. The main outcome was HF requiring Hospitalization (HFrH) defined as the first occurrence of acute HF leading to hospitalization and/or death, established by an adjudication committee, based on hospital records until 31st December 2015. The secondary outcomes were the composite event HFrH and/or cardiovascular death and all-cause death. The association between the biomarkers and the outcomes was studied using cause-specific hazard-models, adjusted for age, sex, history of coronary artery disease, NT-proBNP, CKD-EPI-derived eGFR and the urine albumin/creatinine ratio. Hazard-ratios (HR) are expressed for one standard deviation. RESULTS: The data of interest were available for 1349/1468 of SURDIAGENE participants (91.9%), including 569 (42.2%) women, with a mean age of 64.3 ± 10.7 years and a median follow-up of 7.3 years [25th-75th percentile, 4.7-10.8]. HFrH was reported in 209 patients (15.5%), HFrH and/or cardiovascular death in 341 (25.3%) and all-cause death in 447 (33.1%). In unadjusted hazard-models, carnitine (HR = 1.20, 95% CI [1.05; 1.37]), betaine (HR = 1.34, [1.20; 1.50]), choline (HR = 1.35, [1.20; 1.52]), TMAO (HR = 1.32, [1.16; 1.50]), cysteine (HR = 1.38, [1.21; 1.58]) and homocysteine (HR = 1.28, [1.17; 1.39]) were associated with HFrH, but not TMA and methionine. In the fully adjusted models, none of these associations was significant, neither for HFrH nor for HFrH and/or CV death, when homocysteine only was positively associated with all-cause death (HR = 1.16, [1.06; 1.27]). CONCLUSIONS: TMAO and its precursors do not appear to be substantial prognosis factors for HFrH, beyond usual cardiac- and kidney-related risk factors, whereas homocysteine is an independent risk factor for all-cause death in patients with T2D.

Impact of parathyroidectomy on kidney graft function in post-transplant tertiary hyperparathyroidism: a comparative study.

PURPOSE: Parathyroidectomy to treat tertiary hyperparathyroidism (THPT) is now on a par with calcimimetic treatment. The effects of cinacalcet and parathyroidectomy on kidney transplant function remain controversial. The aim of this study was to evaluate kidney transplant function in THPT patients treated either by parathyroidectomy, cinacalcet, or not treated. METHODS: Between 2009 and 2019, 231 patients with functional grafts presenting THPT, defined either by calcaemia superior to 2.5 mmol/L with elevated PTH level or hypercalcaemia with non-adapted PTH level 1 year after kidney transplantation, were included. Hyperparathyroid patients treated by cinacalcet and parathyroidectomy were matched for age, sex, graft rank, and baseline eGFR with cinacalcet-only and untreated patients. Conditional logistic regression models were used to compare eGFR variations 1 year after parathyroidectomy between operated patients and matched controls. Five-year survivals were compared with the Mantel-Cox test. RESULTS: Eleven patients treated with parathyroidectomy and cinacalcet were matched with 16 patients treated by cinacalcet-only and 29 untreated patients. Demographic characteristics were comparable between groups. Estimated odds ratios for eGFR evolution in operated patients compared with cinacalcet-only and untreated patients were 0.92 [95%CI 0.83-1.02] and 0.99 [0.89-1.10] respectively, indicating no significant impairment of eGFR 1 year after surgery. Five-year allograft survival was not significantly impaired in operated patients. CONCLUSIONS: Parathyroidectomy did not appear to substantially alter or improve graft function 1 year after surgery or 5-year allograft survival. It could be hypothesized that in addition to its known benefits, parathyroidectomy can be safely performed vis-à-vis graft function in tertiary hyperparathyroidism.

Baseline tumour size is an independent prognostic factor for overall survival in PD-L1 ≥ 50% non-small cell lung cancer patients treated with first-line pembrolizumab.

BACKGROUND: Advanced non-small cell lung cancer (NSCLC) with a PD-L1 tumour proportion score ≥ 50% can be treated with pembrolizumab alone. Our aim was to assess the impact of baseline tumour size (BTS) on overall survival (OS) in NSCLC patients treated with pembrolizumab versus chemotherapy. METHODS: This retrospective, multicentre study included all patients with untreated advanced NSCLC receiving either pembrolizumab (PD-L1 ≥ 50%) or platinum-based chemotherapy (any PD-L1). The primary endpoint was the impact of BTS (defined as the sum of the dimensions of baseline target lesions according to RECIST v1.1 criteria) on OS. RESULTS: Between 09-2016 and 06-2020, 188 patients were included, 96 in the pembrolizumab (P-group) and 92 in the chemotherapy group (CT-group). The median follow-up was 26.9 months (range 0.13-37.91) and 44.4 months (range 0.23-48.62), respectively, while the median BTS was similar, 85.5 mm (IQR 57.2-113.2) and 86.0 mm (IQR 53.0-108.5), respectively (p = 0.42). The median P-group OS was 18.2 months [95% CI 12.2-not reached (NR)] for BTS > 86 mm versus NR (95% CI 27.2-NR) for BTS ≤ 86 mm (p = 0.0026). A high BTS was associated with a shorter OS in univariate analyses (p = 0.009) as well as after adjustment on confounding factors (HR 2.16, [95% CI 1.01-4.65], p = 0.048). The CT-group OS was not statistically different between low and high BTS patients, in univariate and multivariate analyses (p = 0.411). CONCLUSIONS: After adjustment on major baseline clinical prognostic factors, BTS was an independent prognostic factor for OS in PD-L1 ≥ 50% advanced NSCLC patients treated first-line with pembrolizumab.

Parathyroidectomy or cinacalcet: Do we still not know the best option for graft function in kidney-transplanted patients? A meta-analysis.

BACKGROUND: Tertiary hyperparathyroidism occurs in 25% to 50% of kidney-transplanted patients. Indication of parathyroidectomy is now discussed, since the calcimimetic agent, cinacalcet, is an alternate option. The effects of either of these treatments on graft function remain controversial, studied only in small cohorts showing either decrease or absence of modification. We performed a meta-analysis to evaluate the evolution of graft function after surgical or medical treatment. METHODS: Studies assessing graft function in tertiary hyperparathyroidism after parathyroidectomy or cinacalcet introduction were enrolled into quantitative analysis using Pubmed, Embase, and Cochrane databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis reporting guidelines. Among 68 screened studies, 18 had no missing data and were included for statistical analyses. We performed random effect meta-analysis to determine changes in serum creatinine and estimated glomerular filtration rate. RESULTS: Seven studies assessing the evolution of graft function 6 and/or 12 months after parathyroidectomy and 13 after administration of cinacalcet were included. Meta-analysis found no significant variations after parathyroidectomy in serum creatinine (6 studies, 314 patients) and estimated glomerular filtration rate (2 studies, 105 patients). No significant variation was found after administration of cinacalcet in serum creatinine (10 studies, 404 patients) and estimated glomerular filtration rate (6 studies, 149 patients). A significant heterogeneity between the studies (P < .01, Cochran's Q) was found. CONCLUSION: Meta-analysis shows that parathyroidectomy and cinacalcet do not significantly impair graft function in patients with tertiary hyperparathyroidism. However, the significant heterogeneity between selected studies, partially explained by the lack of consensual definition of tertiary hyperparathyroidism, limits the conclusions of all previously published series.

Association between blastocyst morphology and maternal first trimester serum markers in ongoing pregnancies obtained after single fresh blastocyst transfer.

OBJECTIVE: Is there an association between blastocyst morphology and maternal first trimester serum markers in In Vitro Fertilization (IVF) pregnancies obtained after fresh single blastocyst transfer? STUDY DESIGN: This bi-centric retrospective study was conducted between January 2012 and August 2018. We included 122 women aged from 18 to 43 years-old, whose pregnancy progressed at least beyond 13 weeks after a single blastocyst transfer and who participated in the first trimester combined screening test. Day 5 and day 6 blastocysts were evaluated according to Gardner and Schoolcraft classification. Patients were classified into three groups according to blastocysts morphological quality: excellent (≥ 3AA), good (3-6AB, 3-6BA, B2), and medium to poor (3-6BB, 3-6AC, 3-6CA, B1, 3-6CB, 3-6BC). First trimester serum markers were measured in maternal blood between 9 and 11 + 6 gestational weeks. Univariate and multivariate analyses were performed. RESULTS: Female body mass index, smoking status, type of infertility, geographical origin, anti-mullerian hormone level, ovarian stimulation characteristics, pregnancy outcomes and obstetrical complications were comparable between the three groups. Patient's age was not distributed evenly across groups, with women in group "Medium to Poor" appearing to be slightly younger than in other groups. There were no significant differences in mean first trimester serum markers between the three groups (PAPP-A: excellent: 1.23 ± 0.59 MoM; good: 1.45 ± 0.71 MoM; medium to poor: 1.22 ± 0.52 MoM; p = 0,20; free beta-HCG: excellent: 1.66 ± 1.38 MoM; good: 1.19 ± 0.76 MoM; medium to poor: 1.81 ± 1.34 MoM; p = 0,12). No significant difference was found either between mean first trimester serum markers and inner cell mass morphology (PAPP-A: grade A: 1.23 ± 0.58 MoM; grade B: 1.26 ± 0.60 MoM; medium to poor: 1.64 ± 0.87 MoM; p = 0,67 ; free beta-HCG: grade A: 1.66 ± 1.36 MoM; grade B: 1.52 ± 1.10 MoM; medium to poor: 1.57 ± 0.39 MoM p = 0,60), trophectoderm cells morphology (PAPP-A: grade A: 1.25 ± 0.63 MoM; grade B: 1.26 ± 0.51 MoM; medium to poor: not comparable; p = 0,66; free beta-HCG: grade A: 1.60 ± 1.34 MoM; grade B: 1.69 ± 1.14 MoM; medium to poor: not comparable; p = 0,25), or blastocoel expansion (PAPP-A: B1: 1.08 ± 0.51MoM; B2: 1.57 ± 0.70 MoM; B3: 1.26 ± 0.61 MoM; B4: 1.28 ± 0.62 MoM; B5: 1.04 ± 0.38 MoM; p = 0,22; free beta-HCG: B1: 2.01 ± 1.88 MoM; B2: 1.07 ± 0.49 MoM; B3: 1.43 ± 0.87 MoM; B4: 1.68 ± 1.28 MoM ; B5: 1.82 ± 2.03 MoM; p = 0,48). After adjustment on potential confounding factors (female age, type of gonadotropin, parity, number of oocytes retrieved and occurrence of ovarian hyperstimulation syndrome), we did not observe any association between PAPP-A or free beta-HCG levels and blastocyst morphology. CONCLUSION: Our study concluded that first trimester serum markers were not associated with blastocyst morphological characteristics. Although this needs further confirmation, this suggests that blastocyst morphology would not have an impact on placentation. Therefore, these findings are reassuring for couples undergoing IVF and blastocyst transfer.

VALIDation of the IBD-Disk Instrument for Assessing Disability in Inflammatory Bowel Diseases in a French Cohort: The VALIDate Study.

BACKGROUND AND AIMS: Inflammatory bowel diseases [IBD] are disabling disorders. The IBD-Disability Index [IBD-DI] was developed for quantifying disability in IBD patients but is difficult to use. The IBD-Disk is a visual adaptation of the IBD-DI. It has not been validated yet. The main objectives were to validate the IBD-Disk and to assess the clinical factors associated with a change in the score and its variability over time. METHODS: From May 2018 to July 2019, IBD patients from three university-affiliated hospitals responded twice to both IBD-Disk and IBD-DI at 3-12 month intervals. Validation included concurrent validity, reproducibility, and internal consistency. Mean IBD-Disk scores were compared according to clinical factors. Variability was assessed by comparing scores between baseline and follow-up visits. RESULTS: A total of 447 patients [71% Crohn's disease, 28% ulcerative colitis] were included in the analysis at baseline and 265 at follow-up. There was a good correlation between IBD-Disk and IBD-DI [r = 0.75, p <0.001]. Reproducibility was excellent [intra-class correlation coefficient = 0.90], as well as internal consistency [Cronbach's α = 0.89]. The IBD-Disk was not influenced by IBD type but was associated with female gender and physician global assessment. Extra-intestinal manifestations, history of resection, elevated C-reactive protein and faecal calprotectin also tended to be associated with higher disability. The IBD-Disk score decreased in patients becoming inactive over time. CONCLUSIONS: This study validated the IBD-Disk in a large cohort of IBD patients, demonstrating that it is a valid and reliable tool for quantifying disability for both CD and UC.