Multicenter Prospective Observational Study Research Articles

Long-term outcomes of the first prospective study of active surveillance for prostate cancer in Japan.

Active surveillance for prostate cancer was initiated in the early 2000s. We assessed the long-term outcomes of active surveillance in Japan. This multicenter prospective observational cohort study enrolled men aged 50-80years with stage cT1cN0M0 prostate cancer in 2002 and 2003. The eligibility criteria included serum prostate-specific antigen level ≤ 20ng/mL, ≤ 2 positive cores per 6-12 biopsy samples, Gleason score ≤ 6, and cancer involvement < 50% in the positive core. Patients were encouraged to undergo active surveillance. Prostate-specific antigen levels were measured bimonthly for 6months and every 3months thereafter. Triggers for recommending treatment were prostate-specific antigen doubling time of < 2years and pathological progression on repeat biopsy. Among 134 patients, 118 underwent active surveillance. The median age, prostate-specific antigen level at diagnosis, and maximum cancer occupancy were 70years, 6.5ng/mL, and 11.2%, respectively. Ninety-one patients had only one positive cancer core. The median observation period was 10.7years. At 1year, 65.7% underwent a repeat biopsy, and 37% of patients experienced pathological progression. The active surveillance continuation rates at 5, 10, and 15years were 28%, 9%, and 4%, respectively. One prostate cancer-related death occurred in a patient who refused treatment despite pathological progression at the one-year repeat biopsy. Active surveillance according to this study protocol was associated with conversion to the next treatment without delay, when indicated, despite the selection criteria and follow-up protocols being less rigorous than those recommended in current international guidelines.

Incidence and Predictors of Cerebrovascular Accidents in Patients Undergoing Transcatheter Mitral Valve Repair with Mitraclip

Transcatheter mitral edge-to-edge repair (TEER) with transcatheter devices has become a mainstay in the minimally invasive treatment of patients with severe mitral regurgitation at increased surgical risk. Despite its apparently favorable risk profile, there is uncertainty on the risk and features of cerebrovascular accidents (CVA) early and long after TMVR. We aimed at appraising incidence and predictors of CVA in patients undergoing TEER. We explicitly queried the dataset of an ongoing multicenter prospective observational study dedicated to TEER with MitraClip (Abbott Vascular, Santa Clara, CA, USA). Incidence of CVA after TEER was formally appraised, and we explored also potential predictors of such event. Descriptive, bivariate and diagnostic accuracy analyses were performed. Out of 2238 patients undergoing TEER, CVA occurred in 33 (1.47% [95% confidence interval 1.02% to 2.06%]), including 6 (0.27% [0.10% to 0.58%]) inhospital strokes and 27 events after discharge (0.99% [0.66% to 1.44%]) over a median follow-up of of 14 months. Most CVA were major ischemic strokes, during the inhospital phase as well as subsequently. Overall, CVA were more common in patients with atrial fibrillation (p=0.018), renal dysfunction (p=0.032), higher EuroSCORE II (p=0.033), and, as expected, higher CHA2DS2-VASc score (p=0.033), despite the limited prognostic accuracy of such score. Notably, the occurrence of CVA did not confer a significantly increased risk of long-term death (p=0.136) or cardiac death (p=0.397). The incidence of CVA in patients undergoing TEER is low, with most events occurring after discharge, and being associated with pre-existing risk features. These findings, while reassuring on the safety of TEER, call for proactive antithrombotic therapy whenever CVA risk is increased before, as well as after such intervention.

A multicenter, prospective, non-interventional real-world study to assess the effectiveness of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal cancer.

Mecapegfilgrastim, a long-actinggranulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or thefluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

Impact of Serum Indoxyl Sulfate on One-Year Adverse Events in Chronic Kidney Disease Patients with Heart Failure

Background/Objectives: Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. Methods and Results: This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m2 or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, p = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Conclusions: Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events.

Characterization of omalizumab updosing patterns and predictive factors in chronic spontaneous urticaria: A prospective multicentric observational study.

Limited information is available on the use of omalizumab (OMA) updosing since its introduction as a second-line therapy in chronic spontaneous urticaria (CSU) in 2014. Practical guidelines from health authorities are lacking, and the specific characteristics of patients requiring higher doses remain unknown. Our objectives were to characterize the patterns of OMA updosing (defined as changes in dose and/or injection intervals), to identify the predictive factors associated with updosing, and to improve CSU management. We conducted a prospective, multicentric, real-life observational study, including patients diagnosed with CSU and starting OMA. The data were collected at 0, 3, 6, and 9 months. The primary endpoint was the frequency of OMA updosing at 3 months. The secondary endpoints included an analysis of updosed patients' profile, and an assessment of OMA efficacy and safety. We included 153 patients. Twenty percent of patients were updosed at 3 months, and 27% in total during the 9-month follow-up. Practitioners mainly chose to increase the frequency of injections (66%). At baseline, the updosed patients were more likely to have more severe CSU (UCT < 4, p < 0.030), a lower lymphocyte count (<2000/mm3, p = 0.037), and low IgE levels (<70 UI/mL, p = 0.024). The side effects of OMA were not more frequent after updosing. One in five patient underwent updosing within just 3 months. OMA updosing is frequent in particular in cases of severe disease and low IgE blood levels.

Frailty is associated with 30-day mortality: a multicentre study of Swedish emergency departments

BackgroundOlder patients living with frailty have an increased risk for adverse events. The Clinical Frailty Scale (CFS) is a 9-point frailty assessment instrument that has shown promise to identify frail...

Prospective multicenter study to identify optimal target population for motorized spiral enteroscopy

Motorized spiral enteroscopy (MSE) enhances small bowel exploration, but the optimal target population for this technique is unknown. We aimed to identify the target population for MSE by evaluating its efficacy and safety, as well as detecting predictors of efficacy. A prospective multicenter observational study was conducted at 9 tertiary hospitals in Spain, enrolling patients between June 2020–2022. Analyzed data included demographics, indications for the procedure, exploration time, depth of maximum insertion (DMI), technical success, diagnostic yield, interventional yield, and adverse events (AE) up to 14 days from enteroscopy. Patients with prior gastrointestinal surgery, unsuccessful balloon enteroscopy and small bowel strictures were analyzed. A total of 326 enteroscopies (66.6% oral route) were performed in 294 patients (55.1% males, 65 years ± 21). Prior abdominal surgery was present in 50% of procedures (13.5% gastrointestinal surgery). Lower DMI (162 vs 275 cm, p = 0.037) and diagnostic yield (47.7 vs 67.5%, p = 0.016) were observed in patients with prior gastrointestinal surgery. MSE showed 92.2% technical success and 56.9% diagnostic yield after unsuccessful balloon enteroscopy (n = 51). In suspected small bowel strictures (n = 49), the finding was confirmed in 23 procedures (46.9%). The total AE rate was 10.7% (1.8% classified as major events) with no differences related to prior gastrointestinal/abdominal surgery, unsuccessful enteroscopy, or suspected small bowel strictures. The study demonstrates that MSE has a lower diagnostic yield and DMI in patients with prior gastrointestinal surgery but is feasible after unsuccessful balloon-enteroscopy and in suspected small bowel strictures without safety concerns.

Clinical Utility of Plasma Microbial Cell-Free DNA Sequencing Among Immunocompromised Patients With Pneumonia.

Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying microbial DNA in plasma. However, data are needed to define the clinical scenarios where this tool offers the highest clinical benefit. We conducted a prospective multicenter observational study that evaluated the impact of plasma mcfDNA sequencing compared with usual care testing among adults with hematologic malignancies. This is a secondary analysis of an expanded cohort that evaluated the clinical utility of plasma mcfDNA sequencing across prespecified and adjudicated outcomes. We examined the percentage of participants for whom plasma mcfDNA sequencing identified a probable cause of pneumonia or clinically relevant nonpneumonia infection. We then assessed potential changes in antimicrobial therapy based on plasma mcfDNA sequencing results and the potential for early mcfDNA testing to avoid bronchoscopy and its associated adverse events. Of 223 participants, at least 1 microbial detection by plasma mcfDNA sequencing was adjudicated as a probable cause of pneumonia in 57 (25.6%) and a clinically relevant nonpneumonia infection in 88 (39.5%). A probable cause of pneumonia was exclusively identified by plasma mcfDNA sequencing in 23 (10.3%) participants. Antimicrobial therapy would have changed for 41 (18.4%) participants had plasma mcfDNA results been available in real time. Among the 57 participants with a probable cause of pneumonia identified by plasma mcfDNA sequencing, bronchoscopy identified no additional probable cause of pneumonia in 52 (91.2%). Plasma mcfDNA sequencing could improve management of both pneumonia and other concurrent infections in immunocompromised patients with suspected pneumonia.

Psychometric properties of patient-reported outcomes Common Terminology Criteria for adverse events (PRO-CTCAE®) in breast cancer patients: The prospective observational multicenter VIP study

Patients’ self-reporting is increasingly considered essential to measure quality-of-life and treatment-related side-effects. However, if multiple patient-reported instruments are used, redundancy may represent an overload for patients.Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) are a tool allowing direct patients’ reporting of side-effects.We tested psychometric properties of a selected list of PRO-CTCAE items, in a cohort of 303 breast cancer patients, using validated instruments for quality of life assessment as anchors.The analysis of convergent validity with HADS (Hospital Anxiety and Depression Scale) and EORTC BR-23 sub-scales, and the analysis of responsiveness with the PGIC (Patients Global Impression of Change) score supported that a selected list of PRO-CTCAE symptoms might represent a standardized, agile tool for both research and practice settings to reduce patient burden without missing relevant information on patient perceptions.Among patients using digital devices, those with a higher education levels required shorter time to fulfil questionnaires.In conclusion, a selected list of PRO-CTCAE items can be considered as a standardized, agile tool for capturing crucial domains of side-effects and quality of life in patients with breast cancer.The study is registered on clinicaltrials.gov (NCT04416672).

Survival impact of response within the first year in a multicenter prospective observational study of chronic GVHD in a Japanese cohort.

A prospective multicenter observational study of organ response was conducted in patients with chronic GVHD diagnosed by the NIH criteria. When response was assessed at 12months (12M) in 118 patients, 74.6% were classified as responders and 25.4% as non-responders. The skin and oral cavity were the most frequent organs used as the basis for determining overall response. The lungs, liver, and eyes were also used in 20% of patients. Non-response decisions at 12M were most frequent in the lungs. A significantly higher percentage of responders than non-responders completed systemic treatment (24.3% vs. 3.3%, P = 0.02). Global scoring showed significant changes, with improvement in responders and worsening in non-responders throughout the observation period. Two-year transplant-related mortality, using the 12M assessment as the landmark, was significantly worse in non-responders (28.5% vs. 2,7%, P = 0.0001), while the 2-year recurrence rate was equivalent (5.4% vs. 4.8%, P = 0.78). Consequently, the 2-year overall survival rate from the 12M assessment was significantly better in responders than non-responders (95% vs. 65.3%, P = 0.0001). Our data suggests that patients who do not achieve a response within the first year should be candidates for clinical studies on chronic GVHD.

Early resolution of bowel urgency by budesonide foam enema results in improved quality of life in patients with ulcerative colitis: a multicenter prospective observational study.

Bowel urgency is an important symptom for quality of life determination in patients with ulcerative colitis (UC). Few clinical studies have focused on bowel urgency as an efficacy endpoint. Budesonide foam enema has shown efficacy for clinical and endoscopic improvement in mild-to-moderate UC. We evaluated the improvement of clinical symptoms (bowel urgency), safety, and treatment impact of twice-daily budesonide foam enema on the quality of life in patients with UC. This open-label, multicenter, prospective observational study comprised a 4-week observation period assessing the effectiveness and safety of twice-daily budesonide foam enema. Mild-to-moderate UC patients who had bowel urgency were included. Patients collected data daily in an electronic patient-reported outcome system or logbooks. The primary endpoint was the rate of resolution of bowel urgency at the end of the 4-week observation period. The rate of bowel incontinence was also assessed. Sixty-one patients were enrolled. Of patients with a final evaluation, the rate of resolution of bowel urgency was 58.5% (31/53; 95% confidence interval, 44.1%-71.9%). Bowel urgency decreased over time, with a significant difference observed on day 7 versus day 0. Bowel incontinence showed a decreasing trend from day 5, with a significant difference confirmed on day 12 versus day 0. The clinical remission rate was 64.4% (38/59; 95% confidence interval, 50.9%-76.4%). One adverse event not related to budesonide rectal foam occurred. The findings suggest that bowel urgency can be improved early with twice-daily budesonide foam enema. No new safety signals were observed.

Root causes of first-case start time delays for elective surgical procedures: a prospective multicenter observational cohort study in Ethiopia

BackgroundDelays in surgery start times can lead to poor patient outcomes and considerable increases in healthcare expenditures. This is especially true in developing countries that often face systemic inefficiencies, such as a shortage of operating rooms and trained surgical personnel. With substantial effects on patient outcomes, healthcare efficiency, and resource allocation, identifying delays in first-case elective surgery is a crucial area of research.MethodsA multicenter observational study was conducted at three comprehensive and specialized hospitals in the Amhara region of Ethiopia from May 1 to October 30, 2023. The primary aim of the study was to determine the occurrence of late first-case start times, defined as a patient being in the operating room at or after the hospital’s incision time of 2:30 a.m. The secondary aim was to discover potential root causes of delayed first-case start times. All patients scheduled for elective surgery as the first case on the operating list throughout the study period were included in the study. Every emergency, day case, after-hours case, and canceled case was excluded.ResultsA total of 530 surgical patients were included during the study window from May 1 to October 1, 2023. Of these, 41.5% were general surgeries, 20.4% were gynecology and obstetrics surgeries, and 13.2% were orthopedic surgery procedures. Before the procedure started, nine (1.7%) of the participants had prolonged discussion with a member of the surgical team. Patients who arrived in the operating room waiting area at or after 2:30 a.m. were 2.5 times more likely to experience a first-case start time delay than those who arrived before or at 2:00 a.m. (AOR = 2.50; 95% CI: 1.13–5.14). Furthermore, participants with abnormal investigation results were 2.4 times more likely to have a late first-case start time (AOR = 2.41; 95% CI: 1.06, 5.50). Moreover, the odds of a late first-case start time were increased by 10.53 times with the surgeon being in the operating room at or after 2:30 a.m. (AOR = 10.53; 95% CI: 5.51, 20.11).ConclusionThe research highlights a significant occurrence of delayed start times for the first elective surgical procedures. Therefore, directing attention to aspects such as ensuring patients and surgical teams arrive promptly (by or before 2:00 a.m.) and timely evaluation and communication of investigative findings before the scheduled surgery day could facilitate efforts to maximize operating room efficiency and enhance patient health outcomes.

Females have lower salivary flow than males, before and after radiation therapy for head/neck cancer.

To compare salivary flow rates between females and males, before and after radiation therapy (RT) for head and neck cancer (HNC). Prospective observational multicenter cohort study (OraRad). Stimulated whole salivary flow was measured before RT and at 6 and 18 months after RT. Mean (95% confidence interval) salivary flow in g/min before RT was 0.81 (0.71, 0.90) in females (n = 107) and 1.20 (1.15, 1.25) in males (n = 391) (p < 0.001); at 6 months was 0.34 (0.24, 0.44) in females and 0.50 (0.44, 0.55) in males (p = 0.01); at 18 months was 0.49 (0.38, 0.59) in females and 0.70 (0.64, 0.75) in males (p < 0.001). Median nadir salivary flow after RT was 0.22 in females and 0.35 in males (p < 0.001). A lower nadir salivary flow in females, but not males, was associated with an increased risk for tooth failure (p = 0.02). Females with HNC have lower stimulated whole salivary flow than males, before and after RT. Low salivary flow after RT may be a risk factor for tooth failure among females. The lower pre-RT salivary flow rates in females, combined with prior literature in other populations, indicates that, in general, females have lower stimulated salivary flow than males.

Prognosis Following Sustained Virologic Response in Korean Chronic Hepatitis C Patients Treated with Sofosbuvir-Based Treatment: Data from a Multicenter Prospective Observational Study up to 7 Years.

Background and Objectives: Chronic hepatitis C (CHC) can be cured with direct-acting antiviral (DAA) therapy. In Korea, sofosbuvir (SOF) and ledipasvir (LDV)/SOF were launched in 2016. Patients who achieve a sustained virologic response (SVR) following DAA treatment are predicted to have a favorable prognosis. Nevertheless, little is known regarding the prognosis of Korean CHC patients who receive SOF-based treatment and achieve SVR. Therefore, the purpose of this study was to look into the long-term outcomes for these patients. Materials and Methods: This was a prospective, multicenter observational study. CHC patients were enrolled who, following SOF or LDV/SOF treatment, had achieved SVR. The last day for follow-up was December 2023. The primary endpoint was HCC occurrence, which was checked at least once per year. Results: A total of 516 patients were included in this analysis, with a median follow-up duration of 39.0 months. Among them, 231 were male patients (44.8%), with a median age of 62.0 years. Genotypes were 1 (90, 17.4%), 2 (423, 82.0%), and 3 (3, 0.6%). The combination of SOF plus ribavirin was the most common treatment (394, 76.4%). In total, 160 patients were cirrhotic (31.0%), and the mean Child-Pugh score was 5.1. Within a maximum of 7 years, 21 patients (4.1%) developed HCC. Patients with HCC were older (69 vs. 61 years, p = 0.013) and had a higher cirrhosis incidence (81.0 vs. 28.9%, p < 0.001), higher AFP (6.0 vs. 3.3, p = 0.003) and higher APRI (0.8 vs. 0.5, p = 0.005). Age over 65 (p = 0.016) and cirrhosis (p = 0.005) were found to be significant risk factors for HCC by Cox regression analysis. Conclusions: Patients who achieved SVR with SOF-based treatment had a relatively favorable prognosis. However, the risk of HCC was not eliminated, especially in older and cirrhotic patients. Therefore, routine follow-up, surveillance, and early treatment are required.

Cardiovascular and All-Cause Mortality Is Affected by Serum Magnesium and Diet Pattern in a Cohort of Dialysis Patients.

Background: Hypomagnesaemia is associated with an increased overall mortality in patients with chronic kidney disease on dialysis (CKD-5D). Mediterranean-style diet (MD), having a high magnesium content, can serve as a form of dietary magnesium supplementation. We examined whether there is a potential link between increased Mediterranean Diet score (MDS) and elevated serum magnesium (sMg) to assess its impact on reducing mortality risk in CKD-5D patients. Methods: In this multi-center prospective observational study, 117 CKD-5D patients (66 on hemodialysis and 51 on peritoneal dialysis) with a mean age of 62 ± 15 years were studied for a median follow-up period of 68 months. After baseline assessment, including measurement of sMg and MDS, all patients were followed up for cardiovascular (CV) and all-cause mortality. Results: Forty deaths occurred, 58% of which were cardiovascular. Patients who were above the median value of sMg (2.2 mg/dL) had a 66% reduction in CV (crude HR, 0.34; 95% CI, 0.11-0.70), and 49% reduction in all-cause (crude HR, 0.51; 95% CI, 0.27-0.96) mortality, even after adjustment for age, malnutrition inflammation score, left ventricular mass index, peripheral vascular disease and diabetes. Similar results were obtained when sMg was analyzed as a continuous variable. sMg was associated directly with MDS (r = 0.230; p = 0.012). Conclusions: Higher sMg levels are strongly and independently associated with reduced CV and all-cause mortality in CKD-5D patients. A strong correlation exists between MDS and sMg. Elevated sMg levels, achieved through MD adherence, can significantly reduce CV mortality, implicating MD as a mediator of the association between sMg and CV mortality.

The safety and effectiveness of naldemedine for opioid-induced constipation in patients with advanced cancer in real-world palliative care settings: a multicenter prospective observational study.

In this study, we aimed to evaluate the safety and effectiveness of naldemedine for treating opioid-induced constipation (OIC) in patients with advanced cancer, who are receiving palliative care, and particularly explored its early effects. Palliative care teams and inpatient palliative care units across 14 institutions in Japan were included in this multicenter, prospective, observational study. Patients who were newly prescribed a daily oral dose of 0.2mg naldemedine were enrolled. The spontaneous bowel movement (SBM) within 24h after the first dose of naldemedine was considered the primary outcome, whereas, the secondary outcomes included weekly changes in SBM frequency and adverse events. A total of 204 patients were enrolled and 184 completed the 7-day study. The average age of the participants (103 males, 101 females) was 63 ± 14years. The primary cancer was detected in the lungs (23.5%), gastrointestinal tract (13.7%), and urological organs (9.3%). A considerable proportion of patients (34.8%) had ECOG performance status of 3-4. Most patients were undergoing active cancer treatment, however, 40.7% of the patients were receiving the best supportive care. Within 24h of the first naldemedine dose, 146 patients (71.6%, 95% CI: 65.4-77.8%) experienced SBMs. The weekly SBM counts increased in 62.7% of the participants. The major adverse events included diarrhea and abdominal pain, detected in 17.6% and 5.4% of the patients, respectively. However, no serious adverse events were observed. Conclusively, naldemedine is effective and safe for OIC treatments in real-world palliative care settings. UMIN000031381, registered 20/02/2018.

Islet Isolation Outcomes in Patients Undergoing Total Pancreatectomy With Islet Autotransplantation in the POST Consortium.

In total pancreatectomy with islet autotransplantation (TPIAT), a greater number of islets transplanted produces more favorable outcomes. We aimed to determine predictors of islet isolation outcomes. We investigated factors associated with islet isolation outcomes expressed as islet number (IN), islet equivalents (IEQ; standardized to an islet with 150 μm diameter), IN/kg, or IEQ/kg using data from the multicenter Prospective Observational Study of TPIAT. Single-predictor linear regression was used to estimate the association of individual patient and disease characteristics with islet isolation outcomes, and augmented backward elimination was used to select variables to include in multivariable analyses. In multivariable analyses, only elevated hemoglobin A1c was associated with worse outcomes for all measures (P < 0.001 for all). Total IEQ obtained for transplant was higher for participants with Hispanic ethnicity (P = 0.002) or overweight status pre-TPIAT (P < 0.001) and lower with non-White race (P = 0.03), genetic pancreatitis (P = 0.02), history of lateral pancreaticojejunostomy (P = 0.03), and presence of atrophy (P = 0.006) or ductal changes (P = 0.014) on imaging. IEQ/kg was higher in females (P = 0.01) and Hispanic participants (P = 0.046) and generally lower with older age (nonlinear association, P < 0.001) and pancreatic atrophy (P < 0.001) on imaging. Total IN and IN/kg showed trends similar, but not identical, to IEQ and IEQ/kg, respectively. Patient demographics and certain pancreatic disease features were associated with outcomes from islet isolation. Hemoglobin A1c before TPIAT was the metabolic testing measure most strongly associated with islet isolation results.

Islet Isolation Outcomes in Patients Undergoing Total Pancreatectomy With Islet Autotransplantation in the POST Consortium.

In total pancreatectomy with islet autotransplantation (TPIAT), a greater number of islets transplanted produces more favorable outcomes. We aimed to determine predictors of islet isolation outcomes. We investigated factors associated with islet isolation outcomes expressed as islet number (IN), islet equivalents (IEQ; standardized to an islet with 150 μm diameter), IN/kg, or IEQ/kg using data from the multicenter Prospective Observational Study of TPIAT. Single-predictor linear regression was used to estimate the association of individual patient and disease characteristics with islet isolation outcomes, and augmented backward elimination was used to select variables to include in multivariable analyses. In multivariable analyses, only elevated hemoglobin A1c was associated with worse outcomes for all measures (P < 0.001 for all). Total IEQ obtained for transplant was higher for participants with Hispanic ethnicity (P = 0.002) or overweight status pre-TPIAT (P < 0.001) and lower with non-White race (P = 0.03), genetic pancreatitis (P = 0.02), history of lateral pancreaticojejunostomy (P = 0.03), and presence of atrophy (P = 0.006) or ductal changes (P = 0.014) on imaging. IEQ/kg was higher in females (P = 0.01) and Hispanic participants (P = 0.046) and generally lower with older age (nonlinear association, P < 0.001) and pancreatic atrophy (P < 0.001) on imaging. Total IN and IN/kg showed trends similar, but not identical, to IEQ and IEQ/kg, respectively. Patient demographics and certain pancreatic disease features were associated with outcomes from islet isolation. Hemoglobin A1c before TPIAT was the metabolic testing measure most strongly associated with islet isolation results.

Patent ductus arteriosus (also non-hemodynamically significant) correlates with poor outcomes in very low birth weight infants. A multicenter cohort study.

To standardize the diagnosis of patent ductus arteriosus (PDA) and report its association with adverse neonatal outcomes in very low birth weight infants (VLBW, birth weight < 1500 g). A multicenter prospective observational study was conducted in Emilia Romagna from March 2018 to October 2019. The association between ultrasound grading of PDA and adverse neonatal outcomes was evaluated after correction for gestational age. A diagnosis of hemodynamically significant PDA (hsPDA) was established when the PDA diameter was ≥ 1.6 mm at the pulmonary end with growing or pulsatile flow pattern, and at least 2 of 3 indexes of pulmonary overcirculation and/or systemic hypoperfusion were present. 218 VLBW infants were included. Among infants treated for PDA closure in the first postnatal week, up to 40% did not have hsPDA on ultrasound, but experienced clinical worsening. The risk of death was 15 times higher among neonates with non-hemodynamically significant PDA (non-hsPDA) compared to neonates with no PDA. In contrast, the risk of death was similar between neonates with hsPDA and neonates with no PDA. The occurrence of BPD was 6-fold higher among neonates with hsPDA, with no apparent beneficial role of early treatment for PDA closure. The risk of IVH (grade ≥ 3) and ROP (grade ≥ 3) increased by 8.7-fold and 18-fold, respectively, when both systemic hypoperfusion and pulmonary overcirculation were present in hsPDA. The increased risk of mortality in neonates with non-hsPDA underscores the potential inadequacy of criteria for defining hsPDA within the first 3 postnatal days (as they may be adversely affected by other clinically severe factors, i.e. persistent pulmonary hypertension and mechanical ventilation). Parameters such as length, diameter, and morphology may serve as more suitable ultrasound indicators during this period, to be combined with clinical data for individualized management. Additionally, BPD, IVH (grade ≥ 3) and ROP (grade ≥ 3) are associated with hsPDA. The existence of an optimal timeframe for closing PDA to minimize these adverse neonatal outcomes remains uncertain.

Usefulness of the one-step technique in functional end-to-end anastomosis for colonic surgery: results of a prospective multicentre cohort study from the Japanese KYCC group.

Although functional end-to-end anastomosis (FEEA) using a stapler in the colorectal field has been recognised worldwide, the technique varies by surgeon, and the safety of anastomosis using different techniques is unknown. This multicentre prospective observational cohort study was conducted by the KYCC Study Group in Yokohama, Japan, and included patients who underwent colonic resection at seven centres between April 2020 and March 2022. This study compared the incidence of surgery-related abdominal complications (SAC: anastomotic leakage [AL], anastomotic bleeding, intra-abdominal abscess, enteritis, ileus, surgical site infection, and other abdominal complications) between two different methods of FEEA (one-step [OS] method: simultaneous anastomosis and bowel resection; two-step [TS] method: anastomosis after bowel resection). Complications of Clavien-Dindo classification grade2 or higher were assessed. Among 293 eligible cases, the OS and TS methods were used in 194 (66.2%) and 99 (33.8%) patients, respectively. The baseline characteristics were similar between the groups. The OS method used fewer staplers (three vs. four staplers, p < 0.00001). There were no significant differences in SAC rate between the OS (19.1%) and the TS (16.2%) groups (p = 0.44). The OS group had four cases (2.1%) of AL (two patients; grade3, two patients; grade2) while the TS group had one case (1.0%) of grade2 AL (p = 0.67). Multivariate logistic regression analysis showed that male sex (odds ratio [OR] 3.95; p < 0.00001), an open surgical approach (OR 2.36; p = 0.03), and longer operative duration (OR,2.79; p = 0.002) were independent predictors of complications, whereas the OS method was not an independent predictor (OR 1.17; p = 0.66). The OS and the TS technique for stapled colonic anastomosis in a FEEA had a similar postoperative complication rate. UMIN000039902 (registration date 23 March 2020).