Multicenter Retrospective Observational Study Research Articles

Perception of endoscopic endonasal surgery training by French otolaryngology residents: A STROBE analysis of expectations

ObjectivesTo analyze the perception of endoscopic endonasal surgery training by French otolaryngology residents. Material and methodsA multicenter retrospective observational study was conducted from March to April 2023. Otolaryngology residents from 7 French regions filled out a 27-item questionnaire on their training in endoscopic endonasal surgery. ResultsOut of 283 residents contacted, 126 (45%) filled out the questionnaire. Seventy-four (59%) had already partially or completely performed the surgeries specified in their diploma course. The level of mastery of the main steps of endonasal surgery and the level of autonomy were higher in the consolidation stage group than in the basic and advanced stages. Seventy residents (56%) felt they had gaps in their level of training. To improve training, 94 (75%) wished for more dissection sessions, surgical skills assessments each semester and simulation sessions. Eighty-nine (71%) felt they needed to find their own teaching aids and other methods to complete their training. One hundred and thirteen (90%) felt that the lack of funding available for congresses and training courses was detrimental. ConclusionThis study highlighted the overall satisfaction of residents with their training in endoscopic endonasal surgery. They expressed a desire for more dissection, simulation and evaluation.

2021 European Resuscitation Council/European Society of Intensive Care Medicine Algorithm for Prognostication of Poor Neurological Outcome After Cardiac Arrest-Can Entry Criteria Be Broadened?

To explore broadened entry criteria of the 2021 European Resuscitation Council/European Society of Intensive Care Medicine (ERC/ESICM) algorithm for neuroprognostication including patients with ongoing sedation and Glasgow Coma Scale-Motor score (GCS-M) scores 4-5. Retrospective multicenter observational study. Four ICUs, Skane, Sweden. Postcardiac arrest patients managed at targeted temperature 36°C, 2014-2018. Neurologic outcome was assessed after 2-6 months according to the Cerebral Performance Category scale. None. In 794 included patients, median age was 69.5 years (interquartile range, 60.6-77.0 yr), 241 (30.4%) were female, 550 (69.3%) had an out-of-hospital cardiac arrest, and 314 (41.3%) had a shockable rhythm. Four hundred ninety-five patients were dead at follow-up, 330 of 495 died after a decision on withdrawal of life-sustaining therapies. At 72 hours after cardiac arrest 218 patients remained unconscious. The entry criteria of the original algorithm (GCS-M 1-3) was fulfilled by 163 patients and 115 patients with poor outcome were identified, with false positive rate (FPR) of 0% (95% CI, 0-79.4%) and sensitivity of 71.0% (95% CI, 63.6-77.4%). Inclusion of patients with ongoing sedation identified another 13 patients with poor outcome, generating FPR of 0% (95% CI, 0-65.8%) and sensitivity of 69.6% (95% CI, 62.6-75.8%). Inclusion of all unconscious patients (GCS-M 1-5), regardless of sedation, identified one additional patient, generating FPR of 0% (95% CI, 0-22.8) and sensitivity of 62.9% (95% CI, 56.1-69.2). The few patients with true negative prediction (patients with good outcome not fulfilling guideline criteria of a poor outcome) generated wide 95% CI for FPR. The 2021 ERC/ESICM algorithm for neuroprognostication predicted poor neurologic outcome with a FPR of 0%. Broadening inclusion criteria to include all unconscious patients regardless of ongoing sedation identified an additional small number of patients with poor outcome but did not affect the FPR. Results are limited by high rate of withdrawal of life-sustaining therapies and few patients with true negative prediction.

Accredited cardiac arrest centers facilitate eCPR and improve neurological outcome

BackgroundOut-of-hospital cardiac arrest (OHCA) remains a frequent medical emergency with low survival rates even after a return of spontaneous circulation (ROSC). Growing evidence supports formation of dedicated teams in scenarios like cardiogenic shock to improve prognosis. Thus, the European Resuscitation Council (ERC) recommended introduction of Cardiac Arrest Centers (CAC) in their 2015 guidelines. Here, we aimed to elucidate the effects of newly introduced CACs in Germany regarding survival rate and neurological outcome. MethodsA multicenter retrospective observational cohort study was performed at three university hospitals and outcomes after OHCA were compared before and after CAC accreditation. Primary outcomes were survival until discharge and favorable neurological status (CPC 1 or 2) at discharge. ResultsIn total 784 patients (368 before and 416 after CAC accreditation) were analyzed. Rates of immediate percutaneous coronary intervention (40 vs. 52%, p = 0.01) and implementation of extracorporeal CPR (8 vs. 13%, p < 0.05) increased after CAC accreditation. Likelihood of favorable neurological status at discharge was higher after CAC accreditation (71 vs. 87%, p < 0.01), whereas overall survival remained similar (35 vs. 35%, p > 0.99). ConclusionCAC accreditation is linked to higher rates of favorable neurological outcome and unchanged overall survival.

Correlation of cervical cancers with long-term use of hormonal oral contraceptive pills - A retrospective observational multicentric study in suburban-based medical colleges in West Bengal

Background: Hormonal oral contraceptive pills (OCP) may increase the risk of carcinoma cervix by changing the susceptibility of cervical cells to persistent infection with high-risk human papilloma virus. There is a causal and promoting association with long-term use of these pills for more than 5 years of use, and the association is diminished 10 years after last use. Aims and Objectives: In this study, retrospective data were collected to analyze the risk of association of carcinoma cervix with hormonal contraceptive pill use. Materials and Methods: Interview-based retrospective observational study to enquire about the history of hormonal OCP use and duration of intake in all diagnosed cases of cervical carcinoma attending gynecology and oncology outpatient departments over the period of 2 years in two medical colleges in suburban West Bengal. Results: Of the total 401 subjects, 119 have a history of intake of hormonal OCPs, and 198 have a history of other methods of contraception. Among the subjects, 67.58% had squamous cell carcinoma (SCC), 31.67% had adenocarcinoma of the cervix, and 0.75% had other varieties. There is no correlation between the duration of hormonal OCP use and SCC cervix (P=0.269), whereas there is a significant correlation between adenocarcinoma of the cervix and duration of intake of hormonal OCP (P=0.002). Conclusion: Studies have shown that women who have used OCPs for 5 or more years have a higher risk of cervical cancer than women who have never used oral contraceptives. This study reported a statistically significant increase in the relative risk of adenoca of the cervix but not of the SCC of the cervix, even after long-term use of hormonal OCPs.

Associations of frailty with RA-ILD and poor control of disease activity in patients with rheumatoid arthritis: a multi-center retrospective observational study

BackgroundThis study aimed to investigate factors associated with frailty in rheumatoid arthritis (RA) patients. MethodsA total of 656 RA patients were evaluated using data from an observational study in 2022. Among these patients, 152 with frailty were assigned to the frailty group, and 504 without frailty were assigned to the non-frailty group. Patient characteristics were compared between the two groups by univariate analysis, and factors associated with frailty were assessed by logistic regression analysis. Patient characteristics were also compared between patients with RA-associated interstitial lung disease (RA-ILD) (n=102) and those without RA-ILD (n =554). ResultsThe frailty group was older (mean: 73.6 vs. 66.8 years) and had a higher DAS28-ESR (3.67 vs. 2.66), a higher HAQ-DI (1.13 vs. 0.32), and a higher rate of RA-ILD (25.0 vs. 12.7%) than the non-frailty group. Age (OR: 1.03, 95% CI: 1.01-1.05), HAQ-DI (3.22, 2.28-4.56), DAS28-ESR (1.44, 1.19-1.75), and RA-ILD (2.21, 1.24-3.94) were associated with frailty. RA patients with RA-ILD were older (73.3 vs. 67.5 years) and had a higher DAS28-ESR (3.30 vs. 2.80), a higher HAQ-DI (1.19 vs. 0.32), a higher proportion of frail patients (37.3 vs. 20.6%), lower MTX use (26.5 vs. 62.9%), and higher steroid use (44.1 vs. 26.8%) than those without RA-ILD. ConclusionsMaintaining reasonable control of disease activity is necessary for RA patients, including those with RA-ILD, to recover from frailty.

PARAKID: Navigating the relation between paraproteins and kidney lesions: A multi-center retrospective observational study.

Monoclonal gammopathy is a heterogeneous group of disorders due to the clonal proliferation of immunoglobulin-producing plasma cells or B lymphocytes. Patients develop kidney disease not only due to malignant transformation but also due to the idiosyncratic properties of the M protein and the host factors. We aim to study the spectrum of kidney diseases in patients with paraproteinemia. A retrospective observational study was performed at three tertiary care centers in Southern India. Kidney biopsies conducted in these three centers were reviewed from June 1, 2020 to November 30, 2022. All biopsies suggestive of monotypic immunoglobulin or light chain restriction were included in the study. A total of 122 patients were included in the study with an incidence of 2.4%. The mean age was 52.27 ± 13.27 years, and majority (63.1%) were males. AL amyloidosis was most common in the monoclonal gammopathy of renal significance (MGRS) group, and cast nephropathy was most common in the multiple myeloma (MM) group. On histopathology, 83.6% had a single lesion, followed by 14.8% with double lesion, and 1.6% with triple lesion. Paraproteinemia is associated with a myriad of kidney lesions. MGRS and MM are usually present in the 6th decade of life and beyond, while proliferative glomerulonephritis with monoclonal immunoglobulin deposits is more common in the younger age group. Older age group, high creatinine, hyperuricemia, hyperphosphatemia, presence of more than one lesion on kidney biopsy, and presence of cast nephropathy was significantly associated with the requirement of kidney replacement therapy.

Characteristics of Nonunion After Arthroscopic Ankle Arthrodesis: A Multicenter Retrospective Cohort Study

Nonunion is a major complication of arthroscopic ankle arthrodesis. However, the characteristics and risk factors of nonunion are not well understood. This retrospective multicenter observational study aimed to clarify the characteristics of nonunion after arthroscopic ankle arthrodesis. We included 154 patients who underwent arthroscopic ankle arthrodesis at any 1 of 5 institutions. Patients were divided into 2 groups: union and nonunion, and the groups were compared. Age, sex, body mass index, diabetes, smoking, corticosteroid use, diagnosis, treatment information, treatment protocol, radiographic evaluation, and patient-reported outcomes were recorded and analyzed. On radiographs, bony union was observed in 142 ankles (91.0%) but not in 12 ankles (9.0%). Postoperative radiographic tibial bony gap (mm) was significantly larger in the nonunion group (medial = 1.98, center = 1.65, anterior = 2.21, middle = 1.72, posterior = 3.01) than in the union group (medial = 1.35, center = 1.13, anterior = 1.28, middle = 1.03, posterior = 2.03). Furthermore, the visual analog score (VAS) of pain and pain-related self-administered foot evaluation questionnaire (SAFE-Q) subscale score significantly worsened in the nonunion group (VAS = 3.83, SAFE-Q subscale score = 69.8) compared to that in the union group (VAS = 1.35, SAFE-Q subscale score = 76.6). A larger radiographic tibiotalar bony gap was observed in the nonunion group. Other measurement outcomes were not associated with nonunion. Additionally, patient-reported outcomes markedly worsened in the nonunion group.

Impact of Mogamulizumab-Containing Chemotherapy on HBV Reactivation in Patients with T-Cell Lymphoma: A Multicenter Retrospective Observational Study (PROACTIVE-MOGA)

INTRODUCTION Reactivation of hepatitis B virus (HBV) infection is a potentially lethal complication, but may be preventable in patients with chronic HBV infection or resolved HBV infection who receive systemic chemotherapy.The risk of HBV reactivation (HBVR) depends on not only HBV infectious status but also type of systemic chemotherapy. An anti-CCR4 antibody, mogamulizumab (Moga), has been developed for the treatment of peripheral T-cell lymphomas. Moga is known to suppress CCR4-positive regulatory T cells and helper T cells, which can lead to immunological dysfunction. However, there is little evidence regarding the risk of HBVR in patients with chronic HBV infection or resolved HBV infection who receive Moga-containing systemic chemotherapy. We conducted a retrospective observational study to evaluate the risk of HBVR and clinical outcome in those patients. METHODS &amp; MATERIALS: Patients treated with Moga-containing chemotherapy for T-cell lymphoma between May 2012 and March 2021, who were chronic HBV infection (defined as seropositive for HBsAg) or resolved HBV infection (defined as seronegative for HBsAg, but seropositive for anti-HBc or anti-HBs), were included. The primary endpoint was the rate of HBVR; HBVR in HBsAg-positive patients was defined as any of the following three criteria: 1) 2 log or more increase in HBV DNA from baseline, 2) 3.0 Log IU/ml or more of HBV DNA in patients with undetectable HBV DNA at baseline, 3) 4.0 Log IU/ml or more of HBV DNA in patients not available for HBV DNA at baseline. HBVR in HBsAg-negative patients was defined as any of following three criteria: 1) detectable for HBV DNA in patients with undetectable HBV DNA at baseline, 2) 1.3 Log IU/mL or more of HBV DNA in patients not available for HBV DNA at baseline, 3) seroconversion of HBsAg. RESULTS: A total of 23 HBsAg-positive patients and 246 resolved HBV-infected patients were retrospectively reviewed. Among the 23 HBsAg-positive patients, the median age was 65 years (interquartile range [IQR], 63-73) and 19 patients (82%) had adult T-cell leukemia-lymphoma (ATL). Baseline HBV DNA was undetectable level, detectable not quantifiable, and detectable in 9 (39%), 2 (9%), and 12 (52%) patients, respectively. All 23 HBsAg-positive patients received anti-HBV prophylaxis prior to Moga treatment. One of 23 (4.3%) patients experienced HBVR who led to HBV-related hepatitis. Among the 241 patients with resolved HBV infection, the median age was 65 years (IQR, 63-73) and 223 patients (91%) had ATL. Baseline serostatus of anti-HBc and anti-HBs were as follows: anti-HBc positive and anti-HBs positive in 177 patients (72%), anti-HBc-positive but anti-HBs negative in 50 (20%), the remaining 9 were anti-HBc negative but anti-HBs positive. Baseline HBV DNA was undetectable in 233 (95%), detectable not quantifiable in 5 (2%), and the remaining 3 were detectable for HBV DNA. Only 3 patients received anti-HBV prophylaxis. HBVR occurred in 11 patients, and the 2-year cumulative HBVR rate was 3.5% (95% CI, 1.6-16.5). Among the 11 patients with HBVR, the median peak HBV DNA level was 2.1 Log IU/mL (IQR, 1.7-5.0), the median time from first dose of Moga to HBVR was 140 days (IQR, 82-765) and 2 had HBV-related hepatitis. CONCLUSION: Our current study showed that the risk of HBVR was 4.3% (1 of 23) among HBsAg-positive patients with antiviral prophylaxis and 4.6% (11 of 238) among resolved HBV-infected patients without antiviral prophylaxis following Moga-containing chemotherapy. Anti-HBV prophylaxis and HBV DNA monitoring guided preemptive anti-HBV therapy are recommended to prevent HBV-related hepatitis for HBsAg-positive and resolve HBV-infected patients, respectively.

Outcomes of Chronic Myeloid Leukemia Patients after Therapeutic Failure to Asciminib, a Multicenter Observational Study

Introduction: Asciminib has recently entered the market as a promising option for patients with chronic myeloid leukemia (CML) and therapeutic failure to ³ 2 tyrosine kinase inhibitors (TKIs). It presents a relevant rate of therapeutic success thanks to its different mechanism of action, being the first in its class to produce an allosteric inhibition on the myristoylated pocket of ABL. However, a percentage of patients fail this drug due to intolerance or resistance. This group constitutes a highly polytreated population with few therapeutic options. The aim of this analysis is to determine the most frequent treatment strategies in this setting, as well as to ascertain the prognosis in this difficult to treat group. Material and methods: a retrospective descriptive multicenter observational study was carried out. Eligible patients were those with a diagnosis of CML, &amp;gt;18 years and who had presented a therapeutic failure to asciminib, due to resistance or intolerance. Patients were selected from a cohort of 85 CML patients who received asciminib through a managed-access program. Results: A total of 19 patients were recruited from 17 centers in Spain. Median age at the time of therapeutic failure to asciminib was 61.7 years. Median time from diagnosis to asciminib failure was 7.9 years (range 1.7-25.5), median number of previous lines was 5. 47% of patients had previously received ponatinib and 15.8% (3/19) had received an allogeneic hematopoietic stem cell transplantation (allo-HSCT) prior to asciminib. Median time on asciminib was 5.6 months (range 0.7- 40.9). 42% of patients (8/19) failed treatment due to intolerance and 58% (11/19) due to resistance. Four of them had progression to accelerated/blastic phase at the time of withdrawal. Of the intolerant patients, the most frequent reason for discontinuation was pancreatitis (50%, 4/8). The remaining causes were renal failure (1), pleural effusion (1), fatigue (1), and neurological symptoms (1). Regarding the intolerant group, 2 patients did not require restart of treatment due to a sustained deep molecular response (MR). The rest (6/8) required treatment, which in all cases involved restarting a classic TKI that they had already received (2 imatinib, 2 dasatinib, 2 nilotinib). In 50% (3/6) dose reductions were used to control adverse events (AEs), which in 2/3 patients compromised efficacy. In another case, low-dose corticosteroid therapy was used for the management of pleural effusion, maintaining standard dose. Only 1/8 intolerant patients required an additional change of treatment, and all of them are still alive and without progression to advanced stages at the last follow-up. Regarding the patients that required treatment change due to progression to advanced phases, one patient underwent allo-HSCT. The rest were not candidates due to age or clinical impairment (1 received dasatinib, 1 hydroxyurea (HU), 1 without treatment). Only the patient who underwent HSCT is alive more than one year after the procedure with a grade 5 MR. In the rest the median overall survival (OS) was less than 1 month. Of the remaining resistant patients, 4/7 (57%) received ponatinib (1 of 4 had received it previously), 1 imatinib, 1 allo-HSCT and the other patient received cytarabine + interferon + HU. Three of 7 patients required additional lines including change of TKI (asciminib, nilotinib, dasatinib) and other strategies (HU, busulfan, interferon, cytarabine). In terms of response, only the patient undergoing HSCT maintained a mayor MR (1/7). One patient maintained a complete cytogenetic response and the other 2 patients were unable to improve response despite treatment (maintaining worse response than CHR at the end of follow-up). Two patients died (1 acute myocardial infarction, 1 digestive neoplasia). With a median follow-up of 11.2 months, OS of the global cohort is 73%; 100% for intolerant patients, 71% for resistant patients and 25% for those in accelerated/blastic phase. Conclusions: Patients who fail asciminib are a particularly difficult to manage group. In intolerant patients, dose reductions and symptomatic management of AEs may be an appropriate strategy. Resistant patients currently represent an unmet therapeutic need, with low cytogenetic and molecular response rates and poor survival with current strategies. Patients with progression to advanced phases have a dismal prognosis, HSCT may be the only option that provides long-term survival in this group.

Fecal Calprotectin at Postinduction Is Capable of Predicting Persistent Remission and Endoscopic Healing after 1 Year of Treatment with Infliximab in Pediatric Patients with Crohn's Disease.

: The recent update on Selecting Therapeutic Targets in Inflammatory Bowel Disease initiative has added a decrease in fecal calprotectin (FC) to an acceptable range as an intermediate target for Crohn's disease (CD). We aimed to investigate whether postinduction FC could predict future persistent remission (PR) and endoscopic healing (EH) after 1 year of treatment with infliximab (IFX) in pediatric patients with CD. : This multicenter retrospective observational study included pediatric patients with CD who were followed up for at least 1 year after starting IFX. The association of postinduction FC with PR and EH was investigated. : A total of 132 patients were included in this study. PR and EH were observed in 71.2% (94/132) and 73.9% (82/111) of the patients, respectively. In multivariate logistic regression analysis, only the postinduction FC level was associated with PR (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.08 to 0.66; p=0.009). The FC levels at initiation of IFX and postinduction were significantly associated with EH (OR, 0.73; 95% CI, 0.53 to 0.99; p=0.044 and OR, 0.20; 95% CI, 0.06 to 0.49; p=0.002, respectively). According to the receiver operating characteristic curve analysis, the optimal cutoff level for postinduction FC associated with PR was 122 mg/kg, and that associated with EH was 377 mg/kg. : Postinduction FC was associated with PR and EH after 1 year of treatment with IFX in pediatric patients with CD. Our findings emphasize the importance of FC as an intermediate target in the treat-to-target era.

Validez predictiva del Clinical Risk Groups en pacientes crónicos en el ambito de la atencion primaria

ObjectiveTo analyse a prediction model for admissions and hospital emergencies based on Clinical Risk Groups, in a population of complex chronic patients demanding primary care. DesignA multicentric retrospective observational study, of a cohort of chronic patients with comorbidity, from January until December 2013. PlaceThe study population was assigned to the Santa Pola and Raval health centres from the Health Department of Elche. ParticipantsCohort of chronic patients with comorbidity, from January to December 2013. InterventionsData about the number of admissions, reasons and complexity level associated with the admission were collected by the review of medical records. Main measuresTo determine the level of complexity, the classification included in the chronicity strategy of the Valencian Community based on Clinical Risk Groups was used. ResultsFive hundred and four patients were recruited with a high complexity degree (N3) and 272 with moderate/low complexity (N1–N2). A higher comorbidity was observed in N3 patients with high complexity [Charlson 2.9 (DE 1.8) vs. 1.9 (DE 1.3); P<.001], and higher dependence degree for basic diary activities [Barthel 16.1 (n=81) vs. 7.3 (n=20); P<.001].Association between the number of admissions [0.4 (DE 0.8) vs. 0.1 (DE 0.5); P<.001] and emergency visits [0.8 (DE 1.5) vs. 0.3 (DE 0.8), P<.001] was significatively higher in patients from N3 group than N1-N2 groups. ConclusionsThe predictive capacity of CRG grouper showed high sensibility for the patient classification with a high degree of complexity. Its specificity and positive predictive value were lower for the association of the N3 complexity stratum.

Pet-2 Positive during Frontline Therapy: An Early Unfavorable Predictor for Subsequent Salvage High-Dose Chemotherapy (HD-CT) and Autologous Stem Cell Transplant in Relapsed or Refractory Classical Hodgkin Lymphoma

Background: Interim PET (PET-2), performed after two cycles of chemotherapy (CT), is widely adopted to select patients (pt) with classical Hodgkin lymphoma (cHL), who might benefit from omitting radiotherapy (RT) or reducing the number of CT cycles in early stages, as well as intensifying or de-escalating first-line therapy in advanced stages. Furthermore, PET-2 has prognostic value in the front-line and in the salvage treatment. In a retrospective multicenter Italian study on patients experiencing failure of first-line treatment, we recently observed that PET-2 seems to be an early unfavorable predictor for subsequent salvage high-dose (HD) CT and autologous stem cell transplant (ASCT). Aims of Study and Methods: To evaluate the impact of the prognostic factor PET-2, we performed a retrospective observational multicenter study on individual data of 184 pt with relapsed or refractory (R/R) cHL after first-line CT given according to a PET-adapted strategy. R/R pt were treated at 11 Italian centers with one or more lines of salvage CT followed by HD-CT and ASCT from 2009 to 2021. We compared characteristics and outcomes of 125 PET-2 negative with those of 59 PET-2 positive (PET-2+) R/R pt. Study endpoints included Progression-free survival (PFS) (defined as the time from the date of ASCT to progression or death after ASCT, whichever occurred first), Overall Survival (OS) (defined as the time from the date of ASCT to death from any cause or the last date for which information was available), and factors associated with ASCT outcome evaluated by univariate and multivariate analysis. Results Main pt characteristics at relapse or progression among 125 PET-2 negative and 59 PET-2+ pt were as follows: median age 34 vs 32 years, M/F 64/61 vs 28/31, refractory disease 38% vs 76%, early relapse (within 12 months from end of first-line CT) 27% vs 19%, late relapse 35% vs 5%, stage III or IV 43% vs 44%, B symptoms 24% vs 27%, extranodal involvement 26% vs 24% bulky disease 12% each, anemia 9% vs 22%, ECOG PS &amp;gt;1 11% vs 8%. First salvage treatment regimen was BeGEV in 34% vs 14%, IGEV in 34% each, Brentuximab Vedotin +/- Bendamustine in 6% vs 24%, DHAP or DHAOX in 17% vs 24% and other regimens in 10% vs 5% of pt, respectively. Before ASCT, 95 (76%) in the PET-2 negative and 32 (54%) in the PET-2+ group achieved a complete metabolic remission (mCR). After a median follow-up of 36 months, the 3-year PFS and OS were 73.8% (95% CI: 66.2-80.0%) and 89.3% (95% CI: 83.0-93.3%), respectively. Figure 1 shows PFS by PET-2 status. A total of 99 patients underwent ASCT after one line of salvage therapy. At 3 years PFS and OS in patients who underwent ASCT after one line of salvage therapy were 80.6% (95% CI: 68.9-88.3) and 92.2% (95% CI: 82.2-96.7) in the PET-2 negative group, and 56.2% (95% CI: 33.6-73.7) and 90.9% (95% CI: 68.1-97.6) in the PET-2+ group. Thirty-six patients required two and 14 more than two lines of salvage therapy in the PET-2 negative group; the same figures in the PET-2+ group were 21 and 14. There was no significant difference in PFS or OS by type of salvage therapy received in the two groups. In univariate analysis PET-2+ during frontline treatment (HR 2.68, P=0.001), anemia (HR 2.18, P=0.038), &amp;gt;2 lines of salvage therapy to enter a response (HR 3.68, P&amp;lt;0.001), achieving less than mCR prior to ASCT (HR 3.19, P&amp;lt;0.001) and RT performed before ASCT (HR 3.11, P=0.017) were associated with inferior PFS. Achieving less than mCR prior to ASCT (HR 2.86, P= 0.026), &amp;gt;2 lines of salvage therapy needed to enter a response prior to ASCT (HR 4.93, P=0.002), anemia (HR 2.96, P=0.040) and checkpoint inhibitors before ASCT (HR=5.10, P=0.032) were adverse prognostic factors for OS, whereas transplant performed after 2012 was associated with improved OS (HR 0.20, P&amp;lt;0.001). Cox regression multivariable analysis led to the identification of more than two lines of salvage therapy needed before ASCT (HR 3.14, P=0.008) as an independent adverse prognostic factor for PFS. PET-2+ at front-line treatment (HR 1.94, P=0.052), anemia at relapse or progression (HR 2.07, P=0.080) and RT before ASCT (HR=2.52, P=0.086) were associated with increased risk of failing ASCT, although they did not reach statistical significance Conclusions: PET-2+ during frontline CT may represent an early marker of chemo-refractoriness. Nevertheless, PET-2+ patients experiencing failure of a PET-guided treatment intensification can benefit from a prolonged OS after HDCT and ASCT.

Real-world treatment outcome of direct-acting antivirals and patient survival rates in chronic hepatitis C virus infection in Eritrea

Reliable real-world data on direct acting anti-retroviral (DAA) uptake and treatment outcomes are lacking for patients with hepatitis C virus (HCV) in sub-Saharan Africa. This study provides data on HCV DAA-based treatment outcomes, mortality, loss-to-follow up, and associated factors among patients in Eritrea. A multicenter retrospective observational cohort study was conducted in two tertiary hospitals in Asmara, Eritrea. A structured checklist was used to collect data from patient’s cards. Descriptive and inferential statistics used included means (± Standard deviation (SD), medians (Interquartile range (IQR), chi-squire (χ2), Kaplan–Meier estimates, and multivariate Cox proportional hazard models. A total of 238 patients with median age of 59 years (IQR 50–69 years) were enrolled in the study. Out of the 227 patients initiated on treatment, 125 patients had viral load measurements at 12 weeks after end of treatment (EOT) whereas 102 patients had no viral load measurements at 12 weeks EOT. Among the patients with HCV RNA data post-EOT 12, 116 (92.8%) had sustained viral response (SVR). The prevalence of death and loss-to-follow up (LTFU) were (7.5%, 95% CI 1.7–4.1) and 67 (28.1%, 95% CI 22.3–33.9) translating into an incidence of 1.1 (95% CI 0.8–1.5) per 10,000 person days. Independent predictors of LTFU included the enrollment year (2020: aHR = 2.2, 95% CI 1–4.7; p value = 0.04); Hospital (Hospital B: aHR = 2.2, 95% CI 1–4.7; p value = 0.03) and the FIB-4 score (FIB-Score < 1.45: aHR = 3.7, 95% CI 1.2–11.5; p value = 0.02). The SVR rates achieved in this cohort were high. However, high LTFU and high mortality driven largely by late presentation and suboptimal population screening/case finding, were uncovered. These challenges can be addressed by test-and-treat programs that simultaneously prioritize programmatic screening, decentralization of care, and better patient tracking in the HCV care cascade.

Clinical presentation, course, and prognosis of patients with mixed connective tissue disease: A multicenter retrospective cohort.

The objective of this study is to better characterize the features and outcomes of a large population of patients with mixed connective tissue disease (MCTD). We performed an observational retrospective multicenter cohort study in France. Patients who fulfilled at least one diagnostic criterion set for MCTD and none of the criteria for other differentiated CTD (dCTD) were included. Three hundred and thirty patients (88% females, median [interquartile range] age of 35 years [26-45]) were included. The diagnostic criteria of Sharp or Kasukawa were met by 97.3% and 93.3% of patients, respectively. None met other classification criteria without fulfilling Sharp or Kasukawa criteria. After a median follow-up of 8 (3-14) years, 149 (45.2%) patients achieved remission, 92 (27.9%) had interstitial lung disease, 25 (7.6%) had pulmonary hypertension, and 18 (5.6%) died. Eighty-five (25.8%) patients progressed to a dCTD, mainly systemic sclerosis (15.8%) or systemic lupus erythematosus (10.6%). Median duration between diagnosis and progression to a dCTD was 5 (2-11) years. The presence at MCTD diagnosis of an abnormal pattern on nailfold capillaroscopy (odds ratio [OR]=2.44, 95% confidence interval [95%CI] [1.11-5.58]) and parotid swelling (OR=3.86, 95%CI [1.31-11.4]) were statistically associated with progression to a dCTD. Patients who did not progress to a dCTD were more likely to achieve remission at the last follow-up (51.8% vs. 25.9%). This study shows that MCTD is a distinct entity that can be classified using either Kasukawa or Sharp criteria, and that only 25.8% of patients progress to a dCTD during follow-up.

2753. Real-World Use of Cefiderocol Treating Non-COVID Patients with Confirmed Gram-Negative Infections in US Hospitals During January 2020-June 2022

Abstract Background Cefiderocol (CFDC) has broad activity against Gram-negative (GN) pathogens. This study describes the CFDC usage in treating non-COVID patients with microbiology data in US hospitals from Jan 2020-Jun 2022. Methods This retrospective multicenter observational study included adult non-COVID hospitalized patients treated with CFDC consecutively for ≥3 days after laboratory confirmed GN infections between Jan 2020 to Jun 2022, as captured by Premier Healthcare data. This study describes the patient characteristics, microbiological profile, and overall, as well as 14-day and 28-days, in-hospital all-cause mortality (IHACM). Index culture was defined as the first clinical culture with GN pathogens. Index pathogens were all pathogens identified from the index culture. Results Patient characteristics of 275 hospitalized patients who received ≥3 days CFDC after the microbiological results are shown in Table 1. For index culture, 61.1% were taken ≤3 days of admission, 53.1% were taken during ICU stay, 45.8% involved respiratory culture, followed by urinary (19.6%), wound (18.2%) and blood (16.4%). Also 65.8% of patients had one index pathogen and 34.2% had ≥2 index pathogens. The most common index pathogens were Pseudomonas aeruginosa (48.7%), Acinetobacter baumannii (23.6%), Klebsiella pneumoniae (14.2%), and Stenotrophomonas maltophilia (13.1%). On the index culture day, 62.2% of patients had one pathogen from a single site and 37.8% had either one pathogen identified in multiple culture sites or multiple pathogens from ≥1 culture site. CFDC was used as monotherapy in 92 (33%) patients, though 253 (92%) had used other GN antibiotics before starting CFDC. A total of 135 (49.1%) patients started CFDC ≤ 5 days of index culture, 108 (39.3%) patients between 6-20 days, and 32 (11.6%) patients &amp;gt; 20 days. Crude overall IHACM was 16.4% (95%CI:12.0%-20.7%): 10.4% for those who started CFDC ≤ 5 days of index culture, 19.4% for 6-20 days, and 31.3% for &amp;gt; 20 days. Crude 14-day and 28-day IHACM from index culture or starting CFDC had the same trend and were lower than overall IHACM (see Table 2). Conclusion The study demonstrated that CFDC is effective in treating patients with GN infections. Patients receiving CFDC earlier had lower IHACM than those receiving CFDC later but need further investigation. Disclosures Bin Cai, MD, PhD, Shionogi Inc.: Shionogi employee Christine M. Slover, PharmD, Shionogi,INC: Employee Jennifer D. copeland, MS, Shionogi, Inc.: Employee (Medical/Micro) Sean T. Nguyen, PharmD, Shionogi: Employee|Shionogi, Inc: Employee

202. Association of Neutrophil - Lymphocyte Ratio with Bacteremia and In-Hospital Mortality in Sepsis Patients: A Retrospective Multicenter Study

Abstract Background Early diagnosis, prognostication, and treatment initiation are the cornerstones of sepsis management. There remains an immense interest in exploring the diagnostic and prognostic roles of neutrophil-lymphocyte ratio (NLR) in the sepsis population. Methods We performed a retrospective multi-center observational study including patients admitted to different Mayo Clinic sites with a diagnosis of sepsis between October 2018 and August 2022. Patients were excluded if they were aged &amp;lt; 18 years, lacked research authorization, or had missing Neutrophil or Lymphocyte count at admission. Data were collected from an existing sepsis database and Mayo Data Explorer (MDE). Categorical variables were summarized as percentages and continuous variables were summarized as medians. Chi-square test for significance, independent sample t-test, and multivariate Cox Proportional Hazard models were performed on IBM SPSS Statistics v28.0. Results Our study cohort consisted of 13968 patients, of which the majority were males (55.9%), Caucasian (91.6%), and non-Hispanic or Latino (94.3%). The median age of the cohort was 71 (60, 80) years, and the median BMI was 27.7 (23.4, 33.3) kg/m2. Among all sepsis patients, 6.0% had a positive blood culture and the most common organisms were E. coli (26.5%), Klebsiella sp. (15.6%), Streptococcus sp. (12.8%) and Staphylococcus aureus (9.9%). 13131 patients (94.1%) survived the hospital stay and 837 (5.9%) did not. There was no difference in mortality based on blood culture positivity status (6.0% vs 6.6%, p=0.41). However, the median NLR was higher among patients with a positive blood culture (16.4 vs. 12.1, p&amp;lt; 0.001) and among non-survivors (14.3 vs 12.2, p&amp;lt; 0.001). NLR did not significantly vary based on the type of organism growing in the blood culture. A multivariate model revealed NLR as an independent predictor of mortality (HR 1.003, 95% CI: 1.000-1.006, p=0.029) after adjusting for comorbidities, baseline clinical and laboratory variables. (Tables 1 &amp; 2) Conclusion Our retrospective multicentric study showed that the Neutrophil-Lymphocyte ratio at admission was higher among bacteremic sepsis patients and non-survivors. Further prospective studies are needed to explore its diagnostic and prognostic utility. Disclosures All Authors: No reported disclosures

ADA_ETA_BIO2021: real-world evaluation of adherence, persistence, and cost-effectiveness of originator and biosimilar biologic drugs in the treatment of rheumatoid arthritis: a multicenter study in Italy

Objectives The objective was to assess the adherence, persistence, and costs of bDMARDs through a multicentre study of nine Italian hospital pharmacies. Methods The drugs analysed were Abatacept, Adalimumab, Certolizumab, Etanercept, Golimumab and Tocilizumab. Adult subjects with Rheumatoid Arthritis were considered in the analysis. In this study, we calculated the following metrics: Adherence to treatment was evaluated as dose-intensity, which is the ratio between the amount of medication received and probably taken by the patient at home (Received Daily Dose, RDD) and the amount prescribed by the clinician (Prescribed Daily Dose, PDD). Persistence was calculated as the number of days between the first and last dispensing of the same drug. Lastly, costs were assessed based on persistence to treatment and normalized for adherence. Results Adherence to treatment was found to be above 0.8 for all drugs studied. The median persistence for a 5-year treatment period was 1.4 years for Abatacept, 1.7 years for Adalimumab, 1.8 years for Certolizumab, 1.4 years for Etanercept, 1.3 years for Golimumab, and 1.6 years for Tocilizumab. Conclusions This multicentre retrospective observational study of bDMARDs used in the treatment of RA showed that, for all the drugs studied, there was no problem with adherence to treatment but rather a difficulty in maintaining treatment with the same drug over time.

Clinical and Radiographic Outcomes of a Monoblock Fluted Titanium Tapered Stem Following Complex and Revision Total Hip Arthroplasty

AbstractAchieving femoral stem stability in complex primary and revision total hip arthroplasty (rTHA) cases is a challenging goal that monoblock fluted titanium tapered stems (FTTS) were designed to address. However, as more modern FTTS are developed, there are still questions regarding outcomes for these stems. The purpose of this study is to determine the radiographic and clinical outcomes of a modern monoblock FTTS. A multicenter retrospective observational study examined the hip databases of three institutions to obtain all monoblock FTTS with up to 5 years of radiographic follow-up. Stem subsidence and osteointegration were assessed on the most recent radiograph. All-cause re-revisions and survival of the stem at latest follow-up were recorded. Descriptive statistics were calculated for demographics and outcomes. Ninety-six monoblock FTTS were examined. Median clinical follow-up was 28.5 months (range: 18.0–57.8 months). Median subsidence was 1.4 mm (range: 0–15.0 mm). Sixteen (16.7%) and 3 (3.1%) stems had subsidence greater than 5 and 10 mm, respectively. Overall, thirteen hips (13.5%) required reoperations, of which 5 stems were revised (5.2%). Four stems were revised for periprosthetic joint infection (PJI), and one stem was explanted for exposure during acetabular revision. Kaplan–Meier analysis yielded an all-cause stem survivorship of 95.8% at 2 years and 88.5% at 4 years. Stem survivorship excluding septic causes for revision was 99.0% at both 2 and 4 years. Monoblock FTTS in complex primary and rTHA demonstrate encouraging clinical and radiographic results at up to 5 years of follow-up.

Can the Modified Frailty Index (mFI) Predict Intraoperative and Postoperative Complications in Older Women with Endometrial Cancer Undergoing Laparoscopic or Robotic Surgery? A Multicenter Observational Study

Background: This study aims to evaluate the strength of the association between frailty and intraoperative/postoperative complications in patients undergoing minimally invasive surgery (MIS) for endometrial cancer. Methods: In this retrospective observational multicenter cohort study, frailty was defined beforehand by a modified frailty index (mFI) score of ≥3. Multiple logistic regressions were performed to investigate possible preoperative predictors—including frailty, age, and body mass index—of intraoperative and early (within 30 days from surgery) or delayed (beyond 30 days from surgery) postoperative complications. Results: The study involved 577 women, of whom 6.9% (n = 40) were frail with an mFI ≥ 3, while 93.1% (n = 537) were non-frail with an mFI of 0–2. Frail women had a significantly higher rate of intraoperative complications (7.5% vs. 1.7%, p = 0.01), with odds 4.54 times greater (95% CI: 1.18–17.60, p = 0.028). There were no differences in the rate of early postoperative complications (15% vs. 6.9%, p = 0.06) and delayed postoperative complications (2.5% vs. 3.9%, p = 0.65) for frail versus non-frail patients. The odds of early postoperative complications increased by 0.7% (95% CI: 1.00–1.15) for every one-unit increase in age (p = 0.032). Conclusions: Frailty was associated with a significantly higher risk of intraoperative complications in older women undergoing MIS for endometrial cancer. Likewise, increasing age was an independent predictor of early postoperative complications. Our findings support the practice of assessing frailty before surgery to optimize perioperative management in this patient population.

The relationship between observation interval and prognosis in pancreatic cancer concomitant with intraductal papillary mucinous neoplasia

BackgroundIntraductal papillary mucinous neoplasia (IPMN) is a risk factor for pancreatic cancer (PC). PC concomitant with IPMN shows rapid progression similar to de novo PC, therefore, the appropriate observation interval (OI) is not yet clear. Patients and methodThis was a multicenter retrospective observational study, and patients with PC concomitant with IPMN were analyzed. OI was defined as the interval between the date of imaging at PC diagnosis and just before the diagnosis. Clinical factors of PC and prognosis were assessed according to OI. ResultsFrom January 2010 to December 2018, 73 patients from 11 institutions were enrolled. The images performed just before PC diagnosis were contrast-enhanced CT/magnetic resonance imaging/endoscopic ultrasonography in 44/27/2 patients, respectively. The median cyst size was 14.0 mm, and the median main pancreatic duct diameter was 3.0 mm. The median OI was 6.8 months. In OI 6 months or less (OI ≤ 6 M)/OI more than 6 months (OI > 6 M), the mean tumor size, the frequencies of metastatic PC, resectable PC and early-stage PC were 20.1/21.5 mm (P = 0.91), 12.1 %/32.5 % (P = 0.05), 72.7 %/52.5 % (P = 0.09) and 27.3 %/25.0 % (P = 1.00), respectively. The median overall survival was 35.5 months in OI ≤ 6 M and 16.2 months in OI > 6 M (P = 0.05). ConclusionIn OI 6 months or less, the rate of resectable PC was high, however, the rate of early PC was almost the same as that of OI more than 6 months. Approximately 10 % of cases found in the advanced stage with metastasis even if OI 6 months or less.