Multicenter Retrospective Cohort Study Research Articles

Mediation Analysis of Acute Carotid Stenting in Tandem Lesions: Effect on Functional Outcome in a Multicenter Registry.

Current evidence suggests that acute carotid artery stenting (CAS) for cervical lesions is associated with better functional outcomes in patients with acute stroke with tandem lesions (TLs) treated with endovascular therapy (EVT). However, the underlying causal pathophysiologic mechanism of this relationship compared with a non-CAS strategy remains unclear. We aimed to determine whether, and to what degree, reperfusion mediates the relationship between acute CAS and functional outcome in patients with TLs. This subanalysis stems from a multicenter retrospective cohort study across 16 stroke centers from January 2015 to December 2020. Patients with anterior circulation TLs who underwent EVT were included. Successful reperfusion was defined as a modified Thrombolysis in Cerebral Infarction scale ≥2B by the local team at each participating center. Mediation analysis was conducted to examine the potential causal pathway in which the relationship between acute CAS and functional outcome (90-day modified Rankin Scale) is mediated by successful reperfusion. A total of 570 patients were included, with a median age (interquartile range) of 68 (59-76), among whom 180 (31.6%) were female. Among these patients, 354 (62.1%) underwent acute CAS and 244 (47.4%) had a favorable functional outcome. The remaining 216 (37.9%) patients were in the non-CAS group. The CAS group had significantly higher rates of successful reperfusion (91.2% vs 85.1%; p = 0.025) and favorable functional outcomes (52% vs 29%; p = 0.003) compared with the non-CAS group. Successful reperfusion was a strong predictor of functional outcome (adjusted common odds ratio [acOR] 4.88; 95% CI 2.91-8.17; p < 0.001). Successful reperfusion partially mediated the relationship between acute CAS and functional outcome, as acute CAS remained significantly associated with functional outcome after adjustment for successful reperfusion (acOR 1.89; 95% CI 1.27-2.83; p = 0.002). Successful reperfusion explained 25% (95% CI 3%-67%) of the relationship between acute CAS and functional outcome. In patients with TL undergoing EVT, successful reperfusion predicted favorable functional outcomes when CAS was performed compared with non-CAS. A considerable proportion (25%) of the treatment effect of acute CAS on functional outcome was found to be mediated by improvement of successful reperfusion rates.

Long-term survival comparison of patients admitted to the intensive care unit following in-hospital cardiac arrest in perioperative and ward settings. A multicentre retrospective cohort study.

Perioperative in-hospital cardiac arrests (Perioperative IHCAs) may have better outcomes than IHCAs in the ward (Ward IHCAs), due to enhanced monitoring and faster response. However, quantitative comparisons of their long-term outcomes are lacking, posing challenges for prognostication. This retrospective multicentre study included adult intensive care unit (ICU) admissions from theatre/recovery or wards with a diagnosis of cardiac arrest between January 2018 and March 2022. We used data from 175 ICUs in the ANZICS adult patient database. The primary outcome was a survival time of up to 4 years. We used the Cox proportional hazards model adjusted for Sequential Organ Failure Assessment (SOFA) score, age, sex, comorbidities, hospital type, treatment limitation on admission to the ICU, and ICU treatments. Subgroup analyses examined age (≥ 65years), intubation within the first 24h, elective vs. emergency admission, and survival on discharge. Of 702,675 ICU admissions, 5,659 IHCAs were included (Perioperative IHCA 38%; Ward IHCA 62%). Perioperative IHCA group were younger, less frail, and less comorbid. Perioperative IHCA were most frequent in patients admitted to ICU after cardiovascular, gastrointestinal, or trauma surgeries. Perioperative IHCA group had longer 4-year survival (59.9% vs. 33.0%, p < 0.001) than the Ward IHCA group, even after adjustments (adjusted hazard ratio [HR]: 0.63, 95% confidence interval [CI] 0.57-0.69). This was concordant across all subgroups. Of note, older patients with Perioperative IHCA survived longer than both younger and older patients with Ward IHCA. Patients admitted to the ICU following Perioperative IHCA had longer survival than Ward IHCA. Future studies on IHCA should distinguish these patients.

Neighborhood-level deprivation and survival in lung cancer

BackgroundDespite recent advances in lung cancer therapeutics and improving overall survival, disparities persist among socially disadvantaged populations. This study aims to determine the effects of neighborhood deprivation indices (NDI) on lung cancer mortality. This is a multicenter retrospective cohort study assessing the relationship between NDI and overall survival adjusted for age, disease stage, and DNA methylation among biopsy-proven lung cancer patients. State-specific NDI for each year of sample collection were computed at the U.S. census tract level and dichotomized into low- and high-deprivation.ResultsA total of 173 non small lung cancer patients were included, with n = 85 (49%) and n = 88 (51%) in the low and high-deprivation groups, respectively. NDI was significantly higher among Black patients when compared with White patients (p = 0.003). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZFP42, HOXA9, CDO1 and TAC1. Only HOXA7 DNA methylation was positively correlated with NDI. The high-deprivation group had a statistically significant shorter survival than the low-deprivation group (p = 0.02). After adjusting for age, race, stage, and DNA methylation status, belonging to the high-deprivation group was associated with higher mortality with a hazard ratio of 1.81 (95%CI: 1.03–3.19).ConclusionsIncreased neighborhood-level deprivation may be associated with liquid biopsy DNA methylation, shorter survival, and increased mortality. Changes in health care policies that consider neighborhood-level indices of socioeconomic deprivation may enable a more equitable increase in lung cancer survival.

Clinical outcomes and short-term survival of neoadjuvant immunochemotherapy for resectable esophageal cancer: a multi-center retrospective cohort study

Objective: The present retrospective cohort study aims to evaluate the efficacy and safety of neoadjuvant immunochemotherapy for resectable esophageal cancer and report the preliminary short-term survival. Methods: A multi-center, retrospective study was conducted concerning patients who received neoadjuvant PD-1 agents plus platinum-based chemotherapy between January, 2019 to January, 2022. The primary endpoint was the tumor pathologic complete response (pCR) rate. Results: Two hundred and thirteen patients with initial stage cI-IVA esophageal cancer who received neoadjuvant immunochemotherapy were identified. Complete tumor resection(R0) rate was 99.1%. The pCR rate was 31.9%, and the overall major pathological response rate was 49.8%. The 2-year DFS rate was 78.9% (95%CI: 72.9%-85.4%) and 2-years OS rate was 80.9% (95%CI: 75.3%-86.9%). The incidence of TRAEs and surgical complications rate were 68.5% and 35.2%, respectively. Conclusion: The PD-1 agents combined with chemotherapy in the neoadjuvant treatment for resectable stage I–IVA esophageal cancer had a high pCR rate as well as good short-term survival benefit and tolerable toxicity.

Negative Association of GNRI with All-Cause Mortality in Chinese Atrial Fibrillation Patients: A Multicenter Retrospective Cohort Study.

Malnutrition is common in older atrial fibrillation (AF) patients and results in poor clinical outcomes. The Geriatric Nutritional Risk Index (GNRI) is a straightforward method for evaluating nutritional health. However, its prognostic value in AF patients is unclear. This research focused on examining the correlation between GNRI and overall mortality in Chinese individuals with AF. We performed a multicenter retrospective study at four Chinese hospitals involving patients diagnosed with AF between January 2019 and August 2023. Using GNRI, nutritional status was evaluated, classifying patients into three categories. Multivariable logistic regression and restricted cubic spline analysis assess the relationship between GNRI and mortality, with exploratory subgroup analyses investigating potential effect modifiers. The study included 4,878 AF patients with a median follow-up of 19 months. The mean age was 71 (63-78), and the mean GNRI was 102 (95-108). Malnutrition was identified in 1,776 patients (36.41%). During the study, 419 (8.59%) deaths occurred. After controlling for confounders, moderate to severe malnutrition was linked to an increased risk of all-cause mortality compared to no malnutrition (OR 1.50, 95% CI, 1.17-1.94). The relationship between GNRI and mortality risk was approximately linear, with consistent associations across subgroups. Malnutrition, as assessed by GNRI, is prevalent among Chinese AF patients and is independently linked to higher all-cause mortality risk.

Association between EMS response times, low socioeconomic status, and poorer outcomes in out-of-hospital cardiac arrest: the MEDIC multicenter retrospective cohort study for disparities in access to prehospital critical care in the Paris metropolitan area

Background and importance Prolonged emergency medical services’ response times (EMS-RT) are associated with poorer outcomes in out-of-hospital cardiac arrest (OHCA). The patient access time interval (PATI), from vehicle stop until contact with patient, may be increased in areas with low socioeconomic status (SES). Objectives The objective of this study is to identify predictors of prolonged EMS-RT intervals, and to evaluate associations with clinical outcomes in OHCAs occurring in the largest metropolitan area in France. Design Using the Utstein-style, prospectively implemented, population-based SDEC registry for OHCAs, we conducted a multicenter, region-wide, retrospective cohort study of EMS dispatches for OHCA cases occurring in the 152 cities of the Greater Paris area, France, between January 1, 2017 and December 31, 2018. Settings and participants Adult, nontraumatic, EMS-assessed, non-EMS witnessed OHCAs. Exposure Geographic location and scene-level SES. Outcome measures and analysis The primary outcome was the EMS-RT interval, from activation until arrival at patient’s side. As secondary outcomes, we evaluated patient access outcomes of: (1) dispatch-to-patient contact interval (‘EMS-RT’); and (2) vehicle scene arrival-to-patient contact interval (PATI); and patient clinical outcomes of: (1) death; and (2) unfavorable neurological status, both at 30 days. Area-level SES was assessed at census tract level using the European Deprivation Index (EDI; continuous, and divided into quintiles, Q5 = most deprived). We fitted multilevel mixed-effects regression models to identify predictors of patient access outcomes, and their association with clinical outcomes. Main results We included 4082 cases; the median EMS-RT was 10.85 min (interquartile range [8.87–13.15]), and 138 (3.4%) survived to hospital discharge. Independent predictors of increased EMS-RT and PATI were age &gt;65, female sex, residential location, occurrence at elevated floors, arrest unwitnessed by a bystander, and low EDI (all P &lt; 0.018). After multivariable analysis, an overall EMS-RT interval &gt;8 min was associated with higher mortality and poorer neurological status at hospital discharge (both P &lt; 0.001). Conclusion In OHCA cases occurring in the Greater Paris metropolitan area, after adjustment for scene characteristics, EMS delays until patient contact were longer in neighborhoods of low SES, and were associated with poorer clinical outcomes.

Laparoscopic vs. open surgery for rectal cancer in patients with obesity: short-term outcomes and relapse-free survival across age groups.

To investigate the efficacy of laparoscopic surgery for rectal cancer in obese and older patients, who are often characterized by a higher prevalence of comorbidities and physical decline. This large-scale multicenter retrospective cohort study included 524 patients with a body mass index of 25 or higher who underwent either open or laparoscopic surgery for stage II or III rectal cancer between 2009 and 2013. We assessed the short-term outcomes and relapse-free survival by comparing these surgical modalities. The patients were stratified into 404 non-elderly (< 70years) and 120 elderly (≥ 70 years) patients. In both patient groups, laparoscopic surgery was associated with a significantly reduced blood loss (non-elderly: 41 vs. 545ml; elderly: 50 vs. 445ml) and shorter hospital stays (non-elderly: 10 vs. 19days; elderly: 15 vs. 20days) than open surgery. The overall complications and relapse-free survival showed no significant differences between the two surgical techniques in either age group. Additionally, the impact of the laparoscopic procedure on the relapse-free survival remained consistent between the age groups. Laparoscopic surgery offers short-term benefits for patients with obesity and rectal cancer compared to open surgery, regardless of age, without influencing the long-term prognosis.

Long-Term Outcomes of Living Donor Liver Transplantation for Methylmalonic Acidemia.

Despite early diagnosis and medical interventions, patients with methylmalonic acidemia (MMA) suffer from multi-organ damage and recurrent metabolic decompensations. We conducted the largest retrospective multi-center cohort study so far, involving five transplant centers (NCCHD, KUH, KUHP, ATAK, and EMC), and identified all MMA patients (n = 38) undergoing LDLT in the past two decades. Our primary outcome was patient survival, and secondary outcomes included death-censored graft survival and posttransplant complications. The overall 10-year patient survival and death-censored graft survival rates were 92% and 97%, respectively. Patients who underwent LDLT within 2 years of MMA onset showed significantly higher 10-year patient survival compared to those with an interval more than 2 years (100% vs. 81%, p = 0.038), although the death-censored graft survival were not statistically different (100% vs. 93%, p = 0.22). Over the long-term follow-up, 14 patients (37%) experienced intellectual disability, while two patients developed neurological complications, three patients experienced renal dysfunction, and one patient had biliary anastomotic stricture. The MMA level significantly decreased from 2218.5 mmol/L preoperative to 307.5 mmol/L postoperative (p = 0.038). LDLT achieves favorable long-term patient and graft survival outcomes for MMA patients. While not resulting in complete cure, our findings support the consideration of early LDLT within 2 years of disease onset. This approach holds the potential to mitigate recurrent metabolic decompensations, and preserve the long-term renal function.

Treatment outcomes and prognostic factors in nonmetastatic metaplastic breast cancer patients: a multicenter retrospective cohort study.

Metaplastic breast carcinoma (BC-Mp) is an uncommon subtype that poses unique challenges. The limited information on patient prognosis and therapeutic strategies motivated our research initiative. We aimed to assess disease-free survival (DFS), overall survival (OS), and influential factors in patients with nonmetastatic BC-Mp. In this multicenter retrospective cohort study, clinicopathological data for nonmetastatic BC-Mp patients treated at four oncology units in Poland (2012-2022) were gathered. Among 115 women (median age 61, range: 28-91), the median tumor size was 40 mm (range 20-130); 30% of patients exhibited positive local lymph nodes. The majority of patients presented with stage II (46%) and triple-negative breast cancer (TNBC) (84%). Radiotherapy was administered to 61% of patients. Surgical procedures included breast-conserving surgery in 31% of patients and mastectomy in 68%. Eighty-three per cent of patients received chemotherapy. The median estimated DFS and OS were 59 and 68 months, respectively. Multivariable analysis revealed that tumor size influenced DFS and OS (Hazard ratios [HR] = 1.02, 95%CI 0.01-0.03 for both endpoints) and taxanes application improved DFS (HR = 0.47, 95%CI 0.24-0.93), but other factors did not. For patients receiving neoadjuvant systemic therapy (N = 51), taxanes improved DFS and OS according to univariable analysis. Our findings highlight poor DFS and OS regardless of receiving optimal treatment, emphasizing the need for tailored therapeutic strategies for BC-Mp patients. Taxanes appear promising in a neoadjuvant setting, particularly within the current standard of care for the TNBC subtype.

Prognostic impact of aberrant right hepatic artery involvement in patients with pancreatic cancer: A multicenter retrospective cohort study.

This study aimed to evaluate the prognostic value of aberrant right hepatic artery (A-RHA) involvement in patients with pancreatic cancer (PC). This study enrolled 474 patients who underwent upfront pancreatectomy or neoadjuvant treatment for resectable (R) or borderline resectable (BR) PC from four institutions. The patients were divided into three groups: A-RHA involvement group (n = 12), patients who had sole A-RHA involvement without major arterial involvement; BR-A group (n = 104), patients who had major arterial involvement; R/BR-PV group (n = 358), others. All patients in the A-RHA involvement group underwent margin-negative resection. The median overall survival of the entire cohort in the A-RHA involvement, R/BR-PV, and BR-A groups was 41.2, 33.5, and 25.2 months, respectively. Although survival in the R/BR-PV group was significantly more favorable than that in the BR-A group (p = 0.0003), no significant difference was observed between the A-RHA involvement group and the R/BR-PV (p = 0.7332) and BR-A (p = 0.1485) groups. The prognosis of patients with PC and sole A-RHA involvement was comparable to that of patients with R/BR-PV.

A window of opportunity for ICU end-of-life care-A retrospective multicenter cohort study.

The "window of opportunity" for intensive care staff to deliver end-of-life (EOL) care lies in the timeframe from "documenting the diagnosis of dying" to death. Diagnosing the dying can be a challenging task in the ICU. We aimed to describe the trajectories for dying patients in Danish intensive care units (ICUs) and to examine whether physicians document that patients are dying in time to perform EOL care and, if so, when a window of opportunity for EOL care exists. From the Danish Intensive Care Database, we identified patients ≥18 years old admitted to Danish ICUs between January and December 2020 with an ICU stay of >96 h (four days) and who died during the ICU stay or within 7 days after ICU discharge. A chart review was performed on 250 consecutive patients admitted from January 1, 2020, to ICUs in the Central Denmark Region. In most charts (223 [89%]), it was documented that the patient was dying. Of those patients who received mechanical ventilation, 171 (68%) died after abrupt discontinuation of mechanical ventilation, and 63 (25%) died after gradual withdrawal. Patients whose mechanical ventilation was discontinued abruptly died after a median of 1 h (interquartile range [IQR]: 0-15) and 5 h (IQR: 2-15) after a diagnosis of dying was recorded. In contrast, patients with a gradual withdrawal died after a median of 108 h (IQR: 71-189) and 22 h (IQR: 5-67) after a diagnosis of dying was recorded. EOL care hinges on the ability to diagnose the dying. This study shows that there is a window of opportunity for EOL care, particularly for patients who are weaned from mechanical ventilation. This highlights the importance of intensifying efforts to address EOL care requirements for ICU patients and those discharged from ICUs who are not eligible for readmission.

Influence of Hospital Transfer Status on Surgical Outcomes for Traumatic Thoracolumbar Spine Fractures: Insights from a Multicenter Investigation

Surgical intervention for unstable thoracolumbar spine fractures is common, but delayed management and complications can impact outcomes. This study compares perioperative outcomes between patients directly admitted and those transferred from another facility for thoracolumbar spine surgery, aiming to identify predictors of complications and mortality. A multicenter retrospective cohort study used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database from 2011 to 2021 identified 61,626 patients undergoing fusion surgeries for thoracolumbar spine fractures, excluding spinal cord injury or pathological fractures. Patients were categorized as Direct (admitted from the emergency department) and Transfer (transferred from another facility). Perioperative outcomes, including operative time, length of stay (LOS), 30-day mortality, and complications were compared. Our patient population (54.3% female, mean age 62.4 ± 12.9 years) comprised 12.2% Transfer and 87.8% Direct patients. Following propensity score matching, Transfer patients had a longer hospital LOS (5.1±5.7 days vs 4.5±4.6 days, p<0.001). Transfer exhibited higher rates of superficial incisional surgical site infection (1.7% vs 1.1%, p=0.003), sepsis (1.7% vs 1.3%, p=0.038), pneumonia (1.7% vs 1.2%, p=0.019), postoperative reintubation (0.9% vs 0.6%, p=0.036), and failure to wean off ventilator >48 hours post-surgery (0.7% vs 0.3%, p=0.005) compared to Direct admissions. Direct group had higher rate of perioperative transfusion (16.5% vs 13.4%, p<0.001). Transfer patients also had higher 30-day mortality rate compared to Direct admissions (1.1% vs 0.6%, p=0.002). Interhospital transfers significantly affect hospital LOS, postoperative morbidity, and mortality in thoracolumbar spine surgery. Enhancing postoperative monitoring for transfer patients is crucial.

Identifying risk factors for anal cancer in people with HIV in Spain: a multicentre retrospective cohort study nested in the PISCIS cohort

People with HIV have a substantially higher risk of anal cancer than the general population. We aimed to identify risk factors associated with the development of anal cancer among people with HIV to implement more effective and targeted screening strategies. We conducted a multicentre retrospective cohort study in 16 hospitals across Catalonia and the Balearic Islands, Spain, between Jan 1, 1998, and Dec 31, 2022. Treatment-naive people with HIV nested in the PISCIS cohort aged 16 years and older with biopsy-proven squamous cell carcinoma of the anus or anal canal were eligible for inclusion. Data were retrieved from every hospital registry and were centrally validated in the PISCIS cohort and the Public Data Analysis for Health Research and Innovation Program. The primary outcome was the incidence rate (IR) of histologically confirmed anal cancer. We used Poisson regression to examine the association between the following risk factors and incidence of anal cancer: age, mode of HIV transmission, nadir CD4 cell count, and time period of HIV diagnosis. Among 14 238 people with HIV, 107 (0·8%) developed anal cancer, with an overall IR of 72·5 cases per 100 000 person-years (95% CI 59·4-87·6) and median follow-up of 9·5 years (IQR 4·4-15·7). Of these patients with anal cancer, 37 (34·6%) died, of which 24 (64·9%) deaths were related to anal cancer. Incidence was highest among people with HIV with historical nadir CD4 counts of less than 200 cells per μL (IR 105·0 person-years, 95% CI 82·0-132·5) and lowest among those with counts of more than 350 cells per μL (2·9 person-years, 0·1-16·0). Among men who have sex with men (MSM), the IR was 211·5 person-years (95% CI 151·1-211·7) among those with a CD4 count of less than 200 cells per μL, 37·6 person-years (16·2-74·1) among those with a count of 200-350 cells per μL, and 4·8 person-years (0·1-26·9) among those with a count of more than 350 cells per μL. Among people with HIV younger than 30 years, there were no cases of anal cancer among women or men who do not have sex with men, and one case among MSM with a nadir CD4 count of more than 350 cells per μL (IR 4·8 person-years, 95% CI 0·1-26·9). In the multivariable analysis, people with HIV with nadir CD4 counts of more than 350 cells per μL had the lowest risk of developing anal cancer, compared with people with HIV with counts of less than 200 cells per μL (adjusted IR ratio 0·03, 95% CI 0·00-0·25; p=0·0010) or 200-350 cells per μL (0·30, 0·17-0·55; p<0·0001). Compared with people with HIV younger than 30 years, people with HIV aged 60 years and older had an adjusted IR ratio of 27·6 (3·7-206·9; p=0·0010) and people with HIV aged 45-59 years of 21·6 (3·0-156·4; p=0·0020). Compared with individuals diagnosed after 2015, a diagnosis of HIV before 1998 had an adjusted IR ratio of 33·0 (7·9-137·5; p<0·0001). A nadir CD4 count threshold below 350 cells per μL, particularly less than 200 cells per μL, has the potential to identify people with HIV at heightened risk of developing anal cancer. Customised screening strategies that prioritise screening for individuals at high risk with this surrogate marker could maximise available resources. External validation of these data with other cohorts is required before screening recommendations can be updated. Catalan Health Department, Generalitat de Catalunya.

Comparison of resection, ablation and stereotactic body radiation therapy in treating solitary hepatocellular carcinoma ≤ 5 cm: a retrospective, multicenter, cohort study.

Few studies have focused on the efficacy of stereotactic body radiation therapy (SBRT) in treating early hepatocellular carcinoma (HCC) for curative intention. This study aims to determine the best option among resection, ablation and SBRT in dealing with single HCC no more than 5cm. This multicenter retrospective cohort study included 985 patients from 3 hospitals: 495, 335 and 155 in the resection, ablation and SBRT groups, respectively between January 2014 and December 2021. Subgroup analysis and propensity score matching (PSM) were performed. The SBRT group had unfavorable clinical features including larger tumor size, poorer liver function and more relapsed tumors. The 1-, 3-, and 5-year recurrence free survival (RFS) rates were 84.3%, 66.8% and 56.2% with resection, 73.3%, 49.8% and 37.2% with ablation and 73.2%, 56.4% and 53.6% with SBRT, respectively (P<0.001). The 3-year overall survival (OS) rates were 89.0%, 89.2% and 88.8% in the resection, ablation and SBRT group, respectively (P=0.590). The three modalities resulted in similar RFS and OS after adjusting for clinical factors. Resection provided ideal local tumor control, successively followed by SBRT and ablation. SBRT led to comparable RFS time compared to resection for tumors < 3cm (HR=0.75, P=0.205), relapsed tumors (HR=0.83, P=0.420) and patients with poor liver function (HR=0.70, P=0.330). In addition, SBRT was superior to ablation regarding RFS when tumors were adjacent to intra-hepatic vessels (HR=0.64, P=0.031). SBRT were more minimally invasive, however, gastrointestinal disorders, hepatic inflammation and myelosuppression occurred more frequently. All three approaches could be applied as curative options. Resection remains the best choice for preventing tumor recurrence, and SBRT showed advantages in treating small, recurrent and vascular-type lesions as well as patients with relatively poor liver function.

Six-minute walk test as outcome measure of fatigability in adults with spinal muscular atrophy treated with nusinersen.

Fatigue (subjective perception) and fatigability (objective motor performance worsening) are relevant aspects of disability in individuals with spinal muscular atrophy (SMA). The effect of nusinersen on fatigability in SMA patients has been investigated with conflicting results. We aimed to evaluate this in adult with SMA3. We conducted a multicenter retrospective cohort study, including adult ambulant patients with SMA3, data available on 6-minute walk test (6MWT) and Hammersmith Functional Motor Scale-Expanded (HFMSE) at baseline and at least at 6 months of treatment with nusinersen. We investigated fatigability, estimated as 10% or higher decrease in walked distance between the first and sixth minute of the 6MWT, at baseline and over the 14-month follow-up. Forty-eight patients (56% females) were included. The 6MWT improved after 6, 10, and 14 months of treatment (p < 0.05). Of the 27 patients who completed the entire follow-up, 37% improved (6MWT distance increase ≥30 m), 48.2% remained stable, and 14.8% worsened (6MWT distance decline ≥30 m). Fatigability was found at baseline in 26/38 (68%) patients and confirmed at subsequent time points (p < 0.05) without any significant change over the treatment period. There was no correlation between fatigability and SMN2 copy number, sex, age at disease onset, age at baseline, nor with 6MWT total distance and baseline HFMSE score. Fatigability was detected at baseline in approximately 2/3 of SMA3 walker patients, without any correlation with clinical features, included motor performance. No effect on fatigability was observed during the 14-month treatment period with nusinersen.

Effectiveness and feasibility of nerve real-time monitoring and intermittent monitoring in endoscopic thyroidectomy: A multicenter retrospective cohort study of 1621 patients.

Protecting recurrent laryngeal nerve (RLN) and external branch of the superior laryngeal nerve (EBSLN), a crucial indicator for assessing the quality of thyroid surgery, poses a challenge in endoscopic thyroidectomy. The aim of this study was to investigate the effectiveness and feasibility of nerve real-time monitoring and intermittent monitoring in endoscopic thyroidectomy. In this retrospective cohort study, patients underwent endoscopic thyroidectomy were included, and the characteristics and outcomes of real-time monitoring and intermittent monitoring groups were compared. Thereafter, the outcomes of four surgical types (unilateral lobectomy, total thyroidectomy, unilateral lobectomy + lymph node dissection (LND), and total thyroidectomy + LND) were compared in both groups. A total of 1621 patients were enrolled. Compared to intermittent monitoring group, real-time monitoring group significantly shortened operation durations in the four surgical types (30.8 ± 6.1 min vs. 35.7 ± 5.7 min, 54.7 ± 4.4 min vs. 59.1 ± 5.2 min, 39.3 ± 4.6 min vs. 42.0 ± 4.7 min, 59.1 ± 4.9 min vs. 66.0 ± 5.8 min, respectively). As for surgical complications, compared to intermittent monitoring group, real-time monitoring group had lower rates of transient vocal cord paralysis among the four surgical types (0.0% vs. 3.3%, 0.0% vs. 4.0%, 0.8% vs. 3.2%, 2.8% vs. 6.7%, respectively), and lower rates of EBSLN injury (1.1% vs. 4.4%, 0.0% vs. 12.0%, 0.8% vs. 3.8%, 0.9% vs. 4.8%, respectively). Clinicopathologic characteristics and postoperative inflammatory reactions were similarly paralleled in both groups. Implementation of real-time monitoring in endoscopic thyroidectomy effectively protects the RLN and EBSLN while shortening operation duration, demonstrating its feasibility and efficacy in enhancing nerve protection and surgical efficiency.

Evolving trends in the management of pelvic inflammatory disease (PID) during SARS-CoV-2 pandemic: A multicenter retrospective cohort study.

Pelvic inflammatory disease (PID) is usually managed by conservative treatment, but in selected cases, especially in the presence of a tubo-ovarian abscess (TOA), surgical management is a recognized treatment option. We compared the trends in managing PID and short-term outcomes before and during the SARS-CoV-2 pandemic. This is a retrospective study performed in three Italian gynecological centers. We included patients admitted to hospital with a diagnosis of PID. Demographic characteristics, management, time to diagnosis, and time to treatment were compared before versus during the SARS-CoV-2 pandemic. One hundred nineteen PID patients were screened, eighty-one before the SARS-CoV-2 pandemic, and thirty-eight after the onset. At admission, leukocytosis (median 19.73 vs. 13.99 WBC/mm3, p-value = 0.02) was significantly higher in patients who underwent surgery after the onset of the pandemic. TOA incidence was higher in patients who underwent surgery during the SARS-CoV-2 pandemic, but the difference did not reach statistically significance (p = 0.06). The proportion of patients treated with surgery dropped to 26.3% after the onset from 46% of patients before the onset of pandemic (p = 0.03). Furthermore, a higher percentage of emergency surgical procedures on day 0 of hospital admission were performed after the onset of the pandemic (50% vs. 13.1%, p = 0.01). In this retrospective cohort study, we found that the SARS-CoV-2 pandemic influenced the clinical presentation and management of PID in favor of conservative treatment. Patients who underwent surgery during the SARS-CoV-2 pandemic had higher inflammatory markers.

Safety and Effectiveness of Selexipag in Pediatric Pulmonary Hypertension: A Retrospective Multi-Center Cohort Study

ObjectiveTo describe the safety and effectiveness of treating pediatric patients who have pulmonary arterial hypertension (PAH) with selexipag in a real-world, multi-center cohort, given that data supporting its use in pediatric PAH are sparse. Study designWe report a multi-center, retrospective, cohort study of children with PAH treated with selexipag. Demographic and clinical variables were extracted from the medical records. Clinical parameters were analyzed at 3 timepoints: pre-selexipag, 3-12 months post-selexipag, and >12 months follow-up. ResultsEighty-seven patients were included, 32 received selexipag as add-on to background therapy, and 55 transitioned from another prostanoid. Median starting and final doses were 4.7 and 28.5 μg/kg/dose BID, respectively. Add-on patients demonstrated improved indexed pulmonary to systemic vascular resistance ratio after selexipag initiation (PVRi/SVRi, 0.62v0.53, p=0.034) with a lower average mean pulmonary artery pressure (MPAP, 46v39 mmHg, p=NS), and oxygen consumption (VO2 max 27.8v30.9 mL/kg/min, p=NS). Transition patients demonstrated stable MPAP (47v45 mmHg, p=NS) and a lower mean PVRi (10.9v8.2 Wood units*m2, p=NS) but late functional worsening in some with VO2 max decreased at follow-up (26.0v19.5 ml/kg/min). Side effects were noted in 40% of the cohort but prompted discontinuation in only 2%. ConclusionsIn a large, multi-center cohort, the oral prostacyclin agonist selexipag demonstrates favorable tolerability and effectiveness. Add-on patients demonstrated early hemodynamic improvement. Transition patients demonstrated early stability with risk of late functional worsening, highlighting the importance of ongoing monitoring.

Recurrence in Eyelid Sebaceous Carcinoma: A Multicentric Study of 418 Patients.

Local recurrence predicts dismal prognosis in eyelid sebaceous carcinoma (SC). Recurrence predictors vary across studies. Accurate recurrence estimation is essential for individualized therapy in eyelid SC. This study aims to identify recurrence predictors and develop a nomogram for personalized prediction in eyelid SC. We conducted a multicenter retrospective cohort study. Chart reviews were performed in 418 consecutive patients with eyelid SC. All patients were followed up after their initial surgery. Multivariate Cox regression was used to explore the independent predictors of recurrence. A nomogram for recurrence prediction was developed and validated with bootstrap resampling. The predictive accuracy and discriminative ability were compared with the Tumor, Node, Metastasis (TNM) staging system. Over a median of 60-month follow-up, 167 patients (40%) had local recurrence. The median time from diagnosis to recurrence was 14months. The 1-year cumulative recurrence rate was 18%. Diagnostic delay (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00-1.01, P = 0.001), orbital involvement (HR = 4.47, 95% CI = 3.04-6.58, P < 0.001), Ki67 (HR = 1.01, 95% CI = 1.00-1.02, P = 0.008) and initial surgery of Mohs micrographic surgery with intraoperative frozen section control (HR = 0.53, 95% CI = 0.35-0.80, P = 0.003) were independent influencing factors of recurrence. A nomogram integrating these four factors combined with pagetoid spread displayed satisfactory discriminative ability (C-index = 0.80-0.83; area under the curve [AUC] = 0.82-0.84), which compared favorably than TNM staging (all P < 0.05). The recurrence rate is high in eyelid SC. Early detection and primary resection with Mohs micrographic surgery are recommended in controlling recurrence. Patients with orbital involvement, high Ki67 expression, and pagetoid spread may require adjuvant measures. This nomogram offers more accurate recurrence estimates, aiding in therapeutic decision making.

Norovirus Management and Outcomes in a Multicenter Pediatric Kidney Transplant Population.

Norovirus is the most common cause of viral gastroenteritis. Studies in adult kidney recipients have documented significant morbidity associated with norovirus infection, but there are few studies in pediatric recipients. Multicenter retrospective cohort study of pediatric kidney transplant recipients with norovirus, confirmed by stool PCR, between January 1, 2008, and December 31, 2018. Outcomes of interest included duration of diarrhea, incidence of chronic diarrhea, management strategies, and graft function. Forty pediatric kidney transplant recipients from four centers were identified for inclusion. Median age at transplant was 5.4 years (IQR 2.2-11.2 years), and median time post-transplant was 1.9 years (IQR 0.8-3.8 years). Median diarrheal duration was 16 days (IQR 6.0-41.5 days); 15 patients (43%) had acute diarrhea, 8 (23%) had persistent, and 12 (30%) had chronic diarrhea. Twenty-one (53%) patients developed acute kidney injury. Thirty-five (88%) patients required supplemental fluids, 8 (20%) patients underwent immunosuppression reduction for a median of 22 days, 5 (13%) were treated with nitazoxanide, and 5 (13%) received oral immunoglobulin. Acute rejection was diagnosed in 3 (8%) patients within 6 months of norovirus diagnosis. We observed no sustained decline in eGFR at 12 months after diarrhea resolution (median eGFR difference: 2.8 mL/min/1.73 m2 [IQR: -17.1, 7.4]). Of the patients in the cohort, two lost their graft at 6.8 and 30.0 months after the onset of diarrhea. Norovirus is associated with significant morbidity in pediatric kidney transplant recipients. Various treatment interventions are being employed for norovirus infection. Larger studies, both observational and interventional, are needed to determine the optimal treatment.