Multicenter Retrospective Study Research Articles

Outcome study of the Pipeline Vantage Embolization Device (second version) in unruptured (and ruptured) aneurysms (PEDVU(R) study)

BackgroundThe Pipeline Vantage Embolization Device (PEDV) is the fourth-generation pipeline flow diverter for intracranial aneurysm treatment. There are no outcome studies for the second PEDV version. We aimed to evaluate...

Safety of the use of dinoprostone gel and vaginal insert for induction of labor: A multicenter retrospective cohort study.

To assess adverse obstetric and neonatal outcomes associated with the use of dinoprostone for induction of labor, with particular attention on categories for which caution is recommended by the Italian Medicines Agency and the European Medicine Agency. A retrospective multicenter observational study was conducted on a population of 1687 patients undergoing induction of labor with vaginal dinoprostone (gel or insert) between August 2019 and June 2022. Patients were subdivided based on maternal age, gestational age, and obstetric disorders. Data regarding the mode of delivery, the incidence of tachysystole, and the obstetric and perinatal outcomes were collected. The main adverse event associated with the use of dinoprostone was tachysystole. However, tachysystole was not associated with an increased risk of cesarean section (CS), neonatal intensive care (NICU) admission, low 1-min Apgar, or umbilical cord acidosis. Maternal age greater than 35 years, gestational age greater than 40 weeks, and obstetric disorders were not associated with an increased rate of tachysystole, NICU admission, low 1- and 5-min Apgar scores, and cord acidosis. The only associated adverse outcomes in those categories were postpartum hemorrhage with age greater than 35 years and tachysystole with gestational diabetes mellitus and hypertensive disorders. Not a single case of severe outcome (disseminated intravascular coagulation, uterine rupture, maternal and fetal death) was reported in the cohort. Providing there is adequate maternal and fetal surveillance, in an inpatient setting, dinoprostone could be safely administered for the induction of labor and considered appropriate in high-risk pregnancies. Tachysystole can be self-identified by the patient and effectively managed.

Vitrectomy in Small idiopathic MAcuLar hoLe (SMALL) study: Internal limiting membrane peeling versus no peeling.

To compare vitrectomy with and without internal limiting membrane (ILM) peeling in small idiopathic macular holes. Retrospective multicentre study including consecutive eyes with ≤250 μm idiopathic macular hole treated with vitrectomy. The primary outcome was hole closure rate. Best-corrected visual acuity (BCVA) change, closure patterns on optical coherence tomography, rates of external limiting membrane (ELM) and ellipsoid zone (EZ) recovery, and rate of complications were also investigated. In total, 693 eyes were included. Hole closure rate was 98% in the peeling and 85% in the no-peeling group (p < 0.001). At 12 months, mean BCVA change was 0.38 ± 0.22 logMAR in the peeling and 0.45 ± 0.21 logMAR in the no-peeling group (p = 0.02); 66% versus 80% of eyes had a U-shaped morphology, respectively; EZ recovery rate was 75% and 93%, respectively (p = 0.02). In the no-peeling group, eyes with a vitreomacular traction (VMT) showed a 96% closure rate, comparable to the peeling group (p = 0.40). The incidence of adverse events was similar except for dissociated optic nerve fibre layer (55% in the peeling vs. 9% in the no-peeling group, p < 0.001). In small idiopathic macular holes, ILM peeling provides a higher closure rate compared to no-peeling; however, if a VMT is present closure rates are comparable. In closed macular holes, the no-peeling technique provides advantages in terms of visual outcome and anatomical recovery.

A 3-Year Multicentric Study on Switching from Ustekinumab to Guselkumab in Partial Responders with Psoriasis-IL PSO (Italian Landscape Psoriasis).

Guselkumab, a human monoclonal antibody targeting the p19 subunit of interleukin-23 (IL-23), has shown efficacy in psoriasis and psoriatic arthritis. However, long-term real-world data on its effectiveness in patients with inadequate response to ustekinumab are limited. This study investigates guselkumab's long-term effectiveness and safety in patients with psoriasis with partial response to ustekinumab. We performed a retrospective multicentric study analyzing data of patients with psoriasis from seven Italian hospitals between January 2021 and May 2024. The study included 169 patients who switched from ustekinumab to guselkumab. Primary endpoints were Psoriasis Area and Severity Index (PASI) 75, PASI 90, PASI 100, and absolute PASI ≤ 2. Site-specific Physician Global Assessment (PGA) scores were also collected for difficult-to-treat areas. The study included 169 patients. After 3years of treatment, PASI 75, PASI 90 and PASI 100 were achieved by 88.4%, 55.8%, and 32.6% of patients, respectively. Site-specific PGA showed significant improvements, especially in the scalp and genital areas. After 3years of treatment, no significant impact of higher body mass index (BMI) or cardiometabolic comorbidities on guselkumab effectiveness was detected. No severe adverse events were reported during the study period. In our study, guselkumab provided significant long-term effectiveness and safety in patients partially responsive to ustekinumab, improving both PASI score and site-specific PGA and confirming its potential use for patients with psoriasis switching from ustekinumab.

Propensity score matching analysis of early vs. delayed surgery for intertrochanteric fracture in older patients: a retrospective multicenter cohort study of 7414 patients with a mean 4-year follow up

BackgroundThe widespread acceptance of early surgery as a treatment for acute intertrochanteric fracture (ITF) has been accompanied by ongoing controversy due to conflicting conclusions presented in previous studies. This study aims to compare the occurrence of perioperative complications and mortality, as well as functional outcomes in older patients with ITF who underwent either early or delayed surgery.MethodsA retrospective multicenter cohort study involving 7414 patients with ITF between Jan. 2017 and Dec. 2021 was conducted. After predefined participants selection inclusion and exclusion criteria, 2323 surgically treated ITF patients were included and analyzed utilizing propensity score matching (PSM) method. Their demographics, injury-related data, surgery-related data, and perioperative adverse outcomes during hospitalization were collected and compared between the early or delayed surgery groups by PSM with a 1:4 ratio. All participants received a minimum of two-year follow-up and perioperative outcomes, functional outcomes, and survival analyses were conducted and compared.ResultsAfter adjustment for potential confounders, there were no significant difference in surgery duration, intraoperative blood loss, transfusion rate, mortality rates, functional outcomes, and perioperative complications rates including severe complications, cardiac complications, pulmonary complications, and neurological complications regardless of whether the patient was treated with early or delayed surgery (all P > 0.05). Although length of hospital stay (mean, 11.5 versus 14.4 days, P < 0.001), total hospital costs (mean, 39305 versus 42048 yuan, P < 0.001), and minor complications rates including hematological complications (31.7% versus 41.2%, P = 0.007) and nutritional/metabolic complications (59.3% versus 66.4%, P = 0.039) were lower in the early surgery group, our result indicated patients with early surgery were more inclined to receive more blood transfusion (mean, 2.8 versus 2.2 units, P = 0.004).ConclusionsOur findings suggest that a 48-hour delay in surgical intervention for older patients with an ITF does not result in a higher mortality rate, worse functional outcomes, and increased incidence of major perioperative complications when compared to early surgery. While expedited surgery is undoubtedly necessary for suitable patients, a reasonable preoperative delay of 48 h may be justified and safe for those with severe conditions, rather than strictly adhering to the current guidelines.

Deep Fungal Infections of Skin and Role of Histopathology in Diagnosis

Abstract Introduction: Deep mycoses acquired by penetrating trauma to the skin can have varied and sometimes atypical morphological presentations resulting in diagnostic dilemmas and delay in treatment onset. Histopathology can be a useful tool in not only diagnosing but also differentiating various deep mycoses. Aims and Objectives: To observe various morphological presentations and histopathological features of deep fungal infections. Materials and Methods: A retrospective multi-centric study was conducted from 2010 to 2020 at 16 centres. The cases with diagnoses of various deep mycoses were included in the study. The patients presenting with cutaneous manifestations were included in the study. Their demographic details, history, presenting signs and symptoms, morphological presentations, histopathological features and treatment details were collected from the case sheets. Results: A total of 124 cases were found from the case records. The most common type was chromoblastomycosis (42) followed by mycetoma (28) and rhinosporidiosis (17). The mean age was 43.76 ± 5.44 years. The average duration of symptoms before presentation was between 2 months to 10 years (average 2.5 ± 1.33 years). Male to female ratio was 1:0.7. Prior history of trauma was recorded in 36% of cases. Chromoblastomycosis cases presented with verrucous to atrophic plaques with black dots on the surface and histopathology findings included pesudoepitheliomatous hyperplasia, epithelioid cell granulomas, copper penny bodies within granulomas and abscesses. Rhinosporidiosis cases had polypoid grape-like lesions in the nose and eyes most commonly with histopathology findings of abundant thick-walled sporangia in dermis packed with thousands of spores. Eumycetoma patients had pigmented, indurated swelling with multiple sinuses discharging black granules and histopathology showed dermal abscesses and foreign body granulomatous reaction with PAS-positive hyphae. Histoplasmosis patients presented with few to multiple nodulo-pustular lesions on skin and palatal ulcers while small basophilic bodies packed in the cytoplasm of histiocytes were noted in histopathology. Phaeohyphomycosis cases presented as deep-seated cystic lesions and biopsy revealed deepithelialized cysts in the dermis or hypodermis with lumen showing necro inflammatory debris and fungal hyphae. Sporotrichosis cases had erythematous, tender nodules and papules either as single lesions or as multiple lesions arranged in a linear fashion and histopathology showed pseudoepitheliomatous hyperplasia of epidermis, loose to well-defined epithelioid cell granulomas and microabscesses. Spores were found in two cases. Cryptococcosis patient had multiple umbilicated lesions resembling giant molluscum contagiosum loose epithelioid cell granulomas and medium-sized spores lying in both intra and extracellularly on histopathology. Penicilliosis patients had nodulo-pustular lesions and histopathology showed an admixture of histiocytes, epithelioid cells, plasma cells, lymphocytes and polymorphs in the dermis with the presence of yeast-like spores in the cytoplasm of histiocytes and epithelioid cells. Entomophthoromycosis cases presented with asymptomatic subcutaneous firm swelling with loss of skin pinchability. Conclusion: Though clinical findings of deep fungal infections are characteristic similar morphology and atypical presentations can be sometimes confusing. Histopathology is useful for confirming the diagnosis.

Optimal timeframe for achieving biochemical remission in Crohn's disease patients treated with first-line biologics: A retrospective multicenter study.

Predicting treatment response in Crohn's disease (CD) patients initiating biological therapy is crucial. The first step involves considering symptom control and normalization of C-reactive protein (CRP). However, data on the actual rates of achieving CRP normalization and the appropriate timeframe are lacking. Therefore, we aim to investigate the rate of attaining CRP normalization and identify its optimal timeframe in CD patients initiating biological therapy. In this retrospective multi-center study, we analyzed moderate to severe CD patients initiating biological therapy from January 2012 to July 2023. The primary outcome was the rate and timeframe for achieving CRP normalization. Secondary outcomes included clinical outcomes in patients who achieved CRP normalization and factors associated with early CRP normalization. Of 183 patients, 123 (67.2%) achieved CRP normalization, with a median duration of 3.8 months (interquartile range 1.4 to 7.4 months). The duration and value difference for CRP normalization between anti-tumor necrosis factor agents, ustekinumab, and vedolizumab were statistically insignificant. Cumulative rates of CD-related hospitalization, intestinal resection, and drug discontinuation over 8 years were 11.4%, 2.4%, and 12.2%, respectively. The duration of CRP normalization correlates with drug discontinuation (area under the curve: 0.64). Treatment with 5-aminosalicylic acid (HR 2.77; 95% confidence interval [CI] 1.26-6.11) and high albumin level (HR 1.64, 95% CI 1.04-2.61) favored early CRP normalization, whereas structuring behavior less likely than inflammatory behavior (HR 0.43, 95% CI 0.19-0.96). We have provided the actual rate of achieving CRP normalization and its appropriate timeframe as an initial target in CD treatment.

Incidence and Outcomes of Pregnant Trauma Patients With Positive Urine Toxicology: A Southern California Multicenter Study.

Background: The use of illicit substances during pregnancy has increased 4-fold in the past two decades, negatively impacting both mother and fetus. The rate and clinical outcomes of substance use in pregnant trauma patients (PTPs) are not well studied. We sought to evaluate clinical outcomes of PTPs with positive urine toxicology, hypothesizing a higher rate of in-hospital maternal complications for PTPs with a positive urine toxicology ((+)Utox) compared to those testing negative ((-)Utox). Methods: PTPs (≥18years old) were included in this multicenter retrospective study between 2016 and 2021. We included patients with known urine toxicology results and compared (+)Utox vs (-)Utox PTPs. Results: From 852 PTPs, 84 (9.8%) had a (+)Utox with the most common illicit substance being THC (57%) followed by methamphetamine (44%). (+)Utox PTPs had higher rates of blunt head injury (9.5% vs 4.2%, P = .028), extremity injury (14.3% vs 6.5%, P = .009), domestic violence (21.4% vs 5.9%, P < .001), suicide attempt (3.6% vs 0.3%, P < .001), and uterine contractions (46% vs 23.5%, P < .001). Abnormal fetal heart tracing, premature rupture of membranes and placental injury were similar between groups (all P > .05). The rate of maternal complications was similar in both groups (all P > .05). Conclusion: In this study, the rate of (+)Utox in PTPs was 9.8%. The (+)Utox group had similar rates of maternal complications but more commonly experienced uterine contractions which may be related to the physiology of drugs such as methamphetamines. PTPs with (+)Utox also more commonly were victims of domestic violence and suicide attempt, which merits further prevention research efforts.

Clinical and Histopathological Features of Thyroid Cancer with TERT Promoter Molecular Alterations in Isolation Versus with Concurrent Molecular Alterations: A Multicenter Retrospective Study

Background/Objectives: Molecular testing of thyroid nodules enables the detection of genetic alterations, which can help assess the risk of malignancy and tumor behavior. While telomerase reverse transcriptase (TERTp) mutations are known to be associated with aggressive disease, their exact prognostic significance when occurring alone or with other molecular alterations remains underreported. Methods: This study examined patients with thyroid cancer treated at two tertiary care hospitals from 2017 to 2024. We compared tumor behavior in patients with TERTp molecular alterations occurring alone and with concurrent molecular alterations. Aggressive histologic subtypes were defined as tall-cell, hobnail, and columnar variants of papillary carcinoma, as well as poorly differentiated and anaplastic carcinoma. High-risk disease was defined according to the 2015 ATA guidelines as gross extrathyroidal extension, lymph node metastasis &gt;3 cm, postoperative elevated serum thyroglobulin, distant metastases, and/or positive resection margins. Statistical analysis was performed to assess differences between groups. Results: 30 patients with TERTp-positive thyroid malignancies were included. TERTp/BRAF V600E was the most prevalent mutation combination (n = 13, 43.3%), followed by TERTp alone (n = 8, 26.7%) and TERTp/RAS (n = 7, 23.4%). TERTp/EIF1AX/GNAS and TERTp/EIF1AX/PIK3CA were the least common combinations (n = 1, 3.3% each). Nodules with TERTp and concurrent mutations were significantly more likely to be classified as high-risk (p = 0.006) and were more frequently associated with aggressive histologic subtypes (p = 0.003) compared to those with TERTp mutations alone, which tended to exhibit more benign behavior. Conclusions: Thyroid carcinomas harboring both TERTp and concurrent molecular alterations are associated with more aggressive features and a higher likelihood of being classified as high-risk. In contrast, TERTp mutations occurring alone do not confer an elevated risk.

Comparison of clinical, laboratory and radiological characteristics between COVID-19 and Chlamydia psittaci pneumonia: a multicenter retrospective study

Chlamydia psittaci pneumonia (CPP) exhibits similar characteristics as of COVID-19 with respect to clustering outbreaks and onset symptoms. This study is aimed at exploring the different clinical manifestations of both pneumonias to establish a simple nomogram to distinguish them. This multicenter, retrospective, case–control study compared two independent cohorts of patients with CPP or COVID-19. The risk factors of CPP were analyzed using multivariate logistic regression, which was used to establish the nomogram. Both patients with CPP and COVID-19 exhibited similar clinical symptoms. As compared to patients with COVID-19, a higher proportion of patients with CPP had nervous system symptoms. Patients with CPP had higher inflammatory indicators, creatine kinase, and lower lymphocyte and albumin. They also had lower proportions of ground-glass opacity and bilateral lung involvement than COVID-19 patients. Furthermore, patients with CPP had higher 30 day mortality as well as higher rates of severe pneumonia, septic shock, and ICU admission. Multivariate logistic regression showed that nervous system symptoms, lymphocytes, creatine kinase, bilateral lung lesions, and ground-glass opacity were risk factors for CPP. Incorporating these five factors, the nomogram achieved good concordance index of 0.989 in differentiating CPP from COVID-19, and had well-fitted calibration curves. Despite similar clinical characteristics, nervous system symptoms, lymphocyte, creatine kinase, lesions in bilateral lungs, and ground-glass opacity may help in differentiating the pneumonias. These were combined into a clinically useful nomogram for rapid and early identification of CPP to avoid misdiagnosis and help in the decision-making process.

The efficacy and safety of a novel PD-1/CTLA-4 bispecific antibody cadonilimab (AK104) in advanced non-smallcell lung cancer: A multicenter retrospective observational study.

For patients with advanced non-small cell lung cancer (NSCLC) who have received frontline immunochemotherapy, subsequent treatment options are limited. As the first dual programmed cell death-1 (PD-1)/cytotoxic T lymphocyte-associated antigen-4 bispecific antibody approved globally, cadonilimab demonstrated potential antitumor activity in advanced NSCLC patients resistant to anti-PD-1/PD-L1 antibodies. We retrospectively collected efficacy and safety data from advanced NSCLC patients treated with cadonilimab-based regimens in later therapy lines. A total of 41 advanced NSCLC patients refractory to anti-PD-1/PD-L1 therapy were enrolled. More than half of the patients received cadonilimab-based regimen as a fourth or later line of treatment. At the data cutoff date, treatment efficacy could be evaluated in 23 patients. One patient (4.3%) achieved partial response, eight patients (34.8%) experienced stable disease, and 14 patients (60.9%) progressed. The objective response rate and disease control rate were 4.3% and 39.1%, respectively. The median progression-free survival for all evaluated patients was 108.0 days. Due to the short follow-up period, the median overall survival has not yet been reached. Treatment-related adverse events (TRAEs) and immune-related AEs occurred in 63.4% and 22% patients, respectively. The most common TRAEs included gamma-glutamyl transferase elevation (17.1%), coughing (14.6%), and fatigue (12.2%). Five patients (12.2%) experienced grade ≥3 TRAEs. In this heavily pretreated cohort of advanced NSCLC patients, cadonilimab-based regimens showed moderate antitumor efficacy with a generally tolerable and manageable safety profile. However, more evidence is needed to support the administration of cadonilimab in NSCLC patients refractory to previous anti-PD-1/PD-L1 therapy.

Incidence and predictors of opportunistic infections among HIV-infected children on antiretroviral therapy at public health facilities of Southwest Ethiopia People Regional State, 2023: a multicenter retrospective follow-up study

BackgroundOpportunistic infections (OIs) pose a significant threat to children infected with HIV. Despite advancements in antiretroviral therapy (ART), these infections continue to be a public health concern. However, there is limited evidence regarding the incidence and predictors of OIs among HIV-infected children in Ethiopia, particularly in the study area. Therefore, the objective of this study was to assess the incidence and predictors of OIs among HIV-infected children on ART at public health facilities of Southwest Ethiopia People Regional State.MethodsThe study employed an institution-based retrospective cohort design, conducted from July 1, 2018 to July 31, 2023, among HIV-infected children aged less than 15 years. Data were extracted using the national ART intake and follow-up forms. KoboCollect version 2023.2.4 and STATA version 14.0 were used for data collection and analysis, respectively. The Kaplan-Meier survival curve was used to estimate the probability of OI-free survival time. Variables with P-value < 0.25 in the bivariable Cox proportional hazard model were selected as candidates. In multivariable analysis, P-value < 0.05 and adjusted hazard ratio (AHR) with 95% confidence interval (CI) were used to declare statistically significant predictors.ResultsOf the total 409 HIV infected children, 122(29.8%) developed at least one OI, contributing to 954.95 person-years of risk. The overall incidence rate was 12.8 (95% CI: 10.7, 15.2) per 100 person-years. The OI-free survival probability at the end of the follow-up period was 0.277(95% CI: 0.139, 0.434). The commonest OI was pulmonary tuberculosis, 30.33% (95% CI: 22.7, 39.2). Non-disclosing HIV status (AHR: 2.56, 95% CI: 1.42, 4.63), children aged 10–14 years (AHR: 2.34, 95% CI: 1.10, 4.95), no history of prevention of mother-to-child transmission of HIV (AHR: 2.33, 95% CI: 1.48, 3.66), hemoglobin level < 10 mg/dL (AHR: 2.26, 95% CI: 1.37, 3.75), fair or poor adherence to ART (AHR: 1.74, 95% CI: 1.09, 2.79), and having past history of OIs (AHR: 1.61, 95% CI: 1.03, 2.55) were statistically significant predictors of OIs.Conclusion and recommendationsThe incidence of OIs was high in the study area. Hence, health facilities need to regularly monitor hemoglobin, enhance ART adherence, provide OI prophylaxis for at-risk children, reinforce PMTCT programs for early OI detection and management, and encourage timely and age-appropriate HIV status disclosure. Caregivers of HIV-infected children are also required to oversee and assist their children in adhering to the ART.

Multicenter Analysis of Valganciclovir Prophylaxis in Pediatric Solid Organ Transplant Recipients

Abstract Background Valganciclovir (VGCV) prophylaxis against cytomegalovirus (CMV) infection and disease has provided an important advance in the management of pediatric solid organ transplantation (SOT) recipients over the past two decades. However, there remain significant questions regarding its relative safety and efficacy, optimal dosing strategies, and toxicities including neutropenia and lymphopenia. We performed a multi-center retrospective study of children post SOT who were to receive at least 3 months of valganciclovir. The primary outcomes were CMV DNAemia while receiving prophylaxis (breakthrough) and post-prophylaxis CMV DNAemia within the first year. Methods The study population included patients ≤ 20 years of age at the time of their first transplant between January 2016 and December 2019 from 8 US centers in PIDTRAN Network. Data for each patient was extracted from the electronic medical record and entered into a REDcap database hosted by St. Jude Children’s Research Hospital. Variables analyzed included demographics, donor/recipient CMV serostatus, immunosuppression, trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis use, rejection, other viral or bacterial infections and one-year survival. Statistics were performed using STATA software for univariate and multivariate models; p-value&amp;lt; 0.05 was considered statistically significant. Results 749 pediatric SOT patients were enrolled over the 3-year study period. Breakthrough DNAemia occurred in 85 (11.4%) patients and post-prophylaxis CMV DNAemia was documented in an additional 46 (6.9%) patients. CMV disease occurred in only 30 patients (4%). In univariate analysis, there were no differences in age, sex, race/ethnicity, or immunosuppression comparing those who experienced breakthrough or post-prophylaxis CMV DNAemia compared to those without CMV DNAemia, but there were differences based on transplanted organ (p&amp;lt; 0.001, liver and lung &amp;gt; heart &amp;gt; kidney) and CMV risk status (high and intermediate) (p&amp;lt;0.001). Neutropenia (p&amp;lt;0.001) and lymphopenia (p=0.003) as well as VGCV discontinuation or dose reduction for perceived toxicity (p&amp;lt;0.001) were associated with breakthrough CMV infection. Bacteremia (p=0.001), EBV viremia (p=0.02), and adenovirus viremia (p=0.002) were also documented more in those with breakthrough compared to those who never had CMV DNAemia. In an adjusted Cox regression hazard model using all significant univariate variables, transplanted organ, CMV risk status, toxicity related VGCV modification (p=0.005), and bacteremia (p=0.01) were independently associated with breakthrough CMV infection. Breakthrough CMV was also associated with rejection (p=0.01) in a separate logistic multivariable model. Both liver (p&amp;lt;0.001) and heart transplant (p&amp;lt;0.001) patients had a greater risk of rejection over the first year of transplantation, but only liver transplant patients had a greater risk of rejection with breakthrough CMV infection (p=0.004). Post prophylaxis CMV DNAemia was associated with mortality at 1 year in the univariate analysis in the full cohort (p=0.001). Conclusion Rates of CMV disease when using valganciclovir prophylaxis were low in this large, multicenter cohort of pediatric SOT recipients. However, breakthrough CMV infection continues to be a problem in intermediate- and high-risk CMV patients and is associated with significant morbidity and rejection, particularly in the liver transplant population. Alternative approaches to prevent breakthrough and post-prophylaxis CMV and with a better safety profile should be studied in pediatric SOT patients.

Real-World Evidence on Prognostic Value of MRD in Multiple Myeloma Using Flow Cytometry.

Minimal residual disease (MRD) is one of the most important prognostic factors in multiple myeloma (MM) and a valid surrogate for progression-free survival (PFS) and overall survival (OS). Recently, MRD negativity was approved as an early clinical endpoint for accelerated drug approval in MM. Nevertheless, there is limited evidence of MRD utility in real-world setting. In this retrospective multicenter study, we report outcomes of 331 newly diagnosed MM patients with MRD evaluation at Day+100 after autologous stem cell transplantation using flow cytometry with a median limit of detection of 0.001%. MRD negativity was reached in 47% of patients and was associated with significantly prolonged median PFS (49.2 months vs. 18.4 months; hazard ratios (HR) = 0.37; p < 0.001) and OS (not reached vs. 74.9 months; HR = 0.50; p = 0.007). Achieving MRD negativity was associated with PFS improvements regardless of age, International Staging System (ISS) stage, lactate dedydrogenase (LDH) level, or cytogenetic risk. Importantly, MRD positive patients benefited from lenalidomide maintenance versus no maintenance (18-months PFS: 81% vs. 46%; HR = 0.24; p = 0.002) while in MRD negative patients such benefit was not observed (p = 0.747). The outcomes of our real-world study recapitulate results from clinical trials including meta-analyses and support the idea that MRD positive patients profit more from lenalidomide maintenance than MRD negative ones.

Prevalence and outcomes of germline pathogenic variants of homologous recombination repair genes in ovarian cancer.

Germline pathogenic variants (PVs) are pivotal in gynecological oncology. We focused on the prevalence, clinicopathological features, and survival impact of homologous recombination repair (HRR) PVs in patients with epithelial ovarian cancer (EOC). This was a multicenter retrospective cohort study, and 1248 patients with EOC were registered. Eligible patients (n = 1112) underwent germline DNA analysis for 26 cancer predisposition genes, including nine HRR-related genes, such as BRCA1/2, BRIP1, PALB2, RAD51C/D, and ATM. The associations between clinicopathological factors and HRR-related PVs were examined. Kaplan-Meier and Cox regression analyses were conducted. Among 1091 analyzed patients, 153 (14.0%) carried PVs and 140 (12.8%) were HRR-related. HRR-PV-positive status significantly correlated with serous carcinoma (22.9% vs. 4.8%, P < 0.0001) and advanced disease (18.5% vs. 5.9%, P < 0.0001). The HRR-PV-positive group exhibited higher prevalence of personal breast (12.9%) and familial breast/ovarian (29.2%) cancer history. HRR status independently improved overall survival in stage III/IV disease (P = 0.04) but not progression-free survival. HRR-related germline PVs exhibit distinct clinicopathological features with survival implications. Variants were significantly associated with serous carcinoma and advanced disease, underscoring the importance of genetic testing to develop individualized EOC treatment strategies. Considering the study period (2000-2019), the limited use of bevacizumab and poly (ADP-ribose) polymerase inhibitors as maintenance therapy should be recognized.

Unlocking the Potential of Computed Tomography-Guided Tracers in Pinpointing Lung Lesions during Surgery: A Collaborative Multi-Institutional Journey.

Background: Multiple techniques exist for the preoperative localization of small, deeply located solid or subsolid pulmonary nodules to guide limited thoracoscopic resection. This study aims to conduct a multi-institutional comparison of three different tomography-guided tracers' methods. Methods: A retrospective multicenter cross-sectional study was conducted. All patients suitable for CT-guided tracers with microcoil (GROUP1, n = 58), hook wire (GROUP2, n = 86), or bioabsorbable hydrogel plug (GROUP3, n = 33) were scheduled for video-assisted thoracoscopic wedge resection. Outcome variables: successful nodule localization, safety, and the feasibility of the tracers' placement. A χ2 test or Fisher's test for expected numbers less than five and a Kruskal-Wallis test were used to analyze the categorical and continuous variables, respectively. For the power calculations, we used G*Power version 3.1.9.6. Results: One hundred seventy-seven patients underwent the localization and resection of 177 nodules detected with three different CT-guided tracers. A significant difference was recorded for cancer history (p = 0.030), respiratory function, Charlson comorbidity index (p = 0.018), lesion type (p < 0.0001), distance from pleura surface (p < 0.0001), and time between preoperative CT-guided tracers and surgical procedures (p < 0.0001). Four post-procedural complications were recorded and in GROUP2, four cases of tracer dislocations occurred. Finally, hook wire group was associated with the shortest surgical time (93 min, p = 0.001). Conclusions: All methods were feasible and efficient, resulting in a 100% success rate for the microcoils and the bioabsorbable hydrogel plugs and a 94.2% success rate for the hook wires. Our results highlight the need to choose a technique that is less stressful for the patient and helps the surgeon by extending the approach to deep nodules and resecting over the course of several days from deployment.

Congenital Diaphragmatic Eventration: Should we Maintain Surgical Treatment? A Retrospective Multicentric Cohort Study

BackgroundThe aims of this study were to describe the characteristics of children with congenital diaphragmatic eventration (CDE) and compare the outcomes of surgical and conservative treatment of pediatric CDE in France. MethodsRetrospective study on cohort data conducted in 22 paediatric surgery departments, including patients less than 16 years of age diagnosed with CDE between 2010 and 2021. Patients with surgical or conservative treatment were compared. Results139 patients were included, with a median age of 8 [1–16] months. CDE occurred in boys in 68.3% and was right-sided in 66.7% of the cases. Indication for treatment depended essentially on respiratory symptoms and level of the diaphragmatic dome. The initial treatment was a surgical, with a diaphragmatic plication, in 87 cases (62%) and conservative, consisting of clinical follow-up in 52 children (38%). Of the latter, 25 children underwent surgery secondarily. Intra- and early post-operative complications occurred in 32 children (29%) and eventration recurrence in 8 children (7%). With a median follow-up of 28 months, the median level of diaphragmatic dome improved from the 6th to the 9th back rib, and the rate of respiratory symptoms decreased from 64% to 14% in the overall cohort of patients. ConclusionsDiaphragmatic plication is effective in symptomatic patients with a dome level above the 6th posterior rib, but is associated with a 29% complication rate and 7% of recurrence. ClinicalTrialsNCT04862494, April 28, 2021. Level of evidencelevel III treatment study.

Impact of Clinical and Pharmacological Parameters on Faecal Microbiota Transplantation Outcome in Clostridioides difficile Infections: Results of a 5-Year French National Survey.

Detailed comparative assessment of procedure-related factors associated with faecal microbiota transplantation (FMT) efficacy in Clostridioides difficile infection (CDI) is limited. We took advantage of the differences in procedures at the various French FMT centres to determine clinical and procedure-related factors associated with FMT success in CDI. We performed a nationwide retrospective multicentre cohort study. All FMTs performed within The French Faecal Transplant Group for CDI from 2018 to 2022 were included. Clinical data were collected retrospectively from recipient medical files, characteristics of stool transplant preparations were prospectively collected by each Pharmacy involved. Univariate and multivariate analyses were performed using Fisher's test and multiple logistic regression. Six hundred fifty-eight FMTs were performed for 617 patients in 17 centres. The overall efficacy of FMT was 84.3% (520/617), with 0.5% of severe adverse events possibly related to FMT (3/658). Forty-seven patients were treated at the first recurrence of CDI with a similar success rate (85.1%). Severe chronic kidney disease (CKD; OR: 2.18, 95%CI [1.20-3.88]), non-severe refractory CDI (OR: 15.35, [1.94-318.2]), the use of ≥ 80% glycerol (OR: 2.52, [1.11-5.67]), insufficient bowel cleansing (OR: 5.47, [1.57-20.03]) and partial FMT retention (OR: 9.97, [2.62-48.49]) were associated with CDI recurrence within 8 weeks. Conditions of transplant manufacturing, bowel cleansing, and a route of delivery tailored to the patient's characteristics are key factors in optimising FMT efficacy. FMT at first recurrence showed high success in real-life practice, whereas it had lower efficacy in severe CDI and non-severe refractory CDI.

Comparative efficacy of intrathecal morphine and adductor canal block in the knee arthroplasty population: a retrospective multi-centre cohort study

BackgroundFinding the balance of good postoperative analgesia while facilitiating mobility is important for a safe and satisfactory patient experience during Total Knee Arthroplasty (TKA). This study aimed to compare the efficacy of intrathecal morphine, adductor canal block, and their combination in optimizing pain management and postoperative recovery in TKA patients. This retrospective analysis of prospectively collected data evaluated postoperative pain scores, time to mobilisation, and length of hospital stay.Methods1006 consecutive patients undergoing elective TKA across two large tertiary centres were included over six years. They were divided into one of four groups according to the type of analgesia received: Group N patients received no neuraxial morphine or regional block. Group B patients received adductor canal block (ACB) only. Group M patients received intrathecal morphine (ITM) but no regional block. Group BM patients received both ACB and ITM.ResultsPatients who received an ACB had faster postoperative mobilization compared to those without (p < 0.001). Patients in Group BM had the lowest pain scores at rest (Visual Analogue Scale (VAS) 2.9) and with movement (VAS 5.3), while Group B patients experienced the highest pain scores at rest (VAS 3.7) and on movement (VAS 6.5) (p = 0.005). Patients who received ITM had the lowest opioid requirements (p < 0.001). There was no significant differences between groups in requirement for rescue pain management strategies (p = 0.06).ConclusionsThe combination of ITM and ACB in patients undergoing TKA provides improved postoperative analgesia with lower postoperative opioid requirement and earlier mobilization compared with ACB or ITM alone.

Non-pharmaceutical infection prevention measures in nosocomial SARS-CoV-2 outbreaks: a retrospective multicentre cohort study

Hospital severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks are relevant for patients and healthcare systems within and beyond the pandemic. We aimed to explore the characteristics of SARS-CoV-2 outbreaks and their infection prevention and control (IPC) measures during the different pandemic waves. A comprehensive structured template for SARS-CoV-2 outbreaks was developed and filled out by six university hospitals. The main outcome variable was outbreak size (OS). A total of 80 outbreaks and 734 infection cases were enrolled between 03/2020-02/2023. In the majority of outbreaks (85%) a contact tracing (CT) team was in place. In 13 (16%) outbreaks the CT team was exclusively responsible for CT, which was negatively linked to OS when adjusting for SARS-CoV-2 waves (Estimate (β)=-1.350; Standard Error (SE) =.274; p<0 .0001). Patients as index had a greater association with OS than healthcare workers (HCWs) (β=-0.29; SE=0.098; p=0.003). Additionally, the mandatory use of facemasks by patients in the presence of HCWs was negatively linked to OS (β=-0.237; SE=0.08; p=0.003). The frequency of patient screening during outbreaks varied considerably, whereby higher frequency screenings for SARS-CoV-2 were negatively associated with OS (β=-0.358; SE=0.109; p=0.001). Our data provides insights in non-pharmaceutical outbreak prevention and management revealing that the mandatory use of facemasks by patients in the presence of HCWs and a high patient screening frequency in ongoing outbreaks were significantly associated with smaller outbreaks. Further studies are required to allow for generalizability.