bluuebunny/crossref_metadata_2025 huggingface dataset:
EX103: A newly designed CD20×CD3 molecule in heavily pre-treated patients with B-cell non-Hodgkin lymphoma from a phase I/II trial.
Authors: Sun Mingyuan , Qi Junyuan , Zhou Keshu , Liu Xingchen , Hu Kai , Chang Chunkang , Wu Dong , Li Zhenling , Gong Ming , ZHANG WENJUN , Yang Daniel Chunxu , LU JIALI
Published: July 2024

7022

Background: T-cell-engaging bispecific antibody (TCB) had emerged as a promising therapy for blood malignancies, including relapsed/refractory (R/R) B-NHL. However, severe cytokine release syndrome (CRS) remains to be a significant challenge in TCB treatment. To overcome this setback, we re-designed a new CD20xCD3 bispecific antibody (EX103) with a lower affinity to CD3. Clinical data from an ongoing first-in-human phase I/II study demonstrates that EX103 has an encouraging safety and promising single-agent antitumor activity in heavily pretreated R/R B-NHL patients. We present updated safety and efficacy data from the ongoing trial (CTR20212096). Methods: Eligible patients received EX103 with 3 step-up doses followed by target doses in 28-day cycles (iv, QW: cycle 1-2; Q2W thereafter) until disease progression or unacceptable toxicity. At data cut off (Dec 24, 2023), a total of 23 patients were evaluated, including 18 patients in dose-escalation part and 5 patients in dose-expansion part. Results: Among 23 evaluable patients (median age: 51 years [range 42-70]; median prior lines of treatment: 4 [range 2-10]), 13 patients had diffuse large B-cell lymphoma (DLBCL), 4 had FL 1-3a, 2 had FL grade 3B, 1 had marginal zone lymphoma, 1 had mantle cell lymphoma, and 2 had chronic lymphocytic leukemia. Median time since last therapy was 2.5 (range 0.3-39.2) months. No DLT and treatment-related death were observed. CRS was the most common treatment related adverse event. All CRS events were grade (Gr) 1-2 (Gr 1: 78.3%, Gr 2: 13.0%), no Gr 3 or higher events. Most CRS events occurred in the first or second treatment cycle, and all CRS-related clinical symptoms were resolved within 48 hours. No cases of immune effector cell-associated neurotoxicity syndrome or other clinically significant neurologic AEs were observed. For dose ≥ 6 mg cohorts, the overall response rate (ORR) for aggressive B-NHL is 78.6% and the complete response (CR) rate is 50.0% (14 patients). Meanwhile, the ORR for indolent B-NHL is 100%, and CR rate is 25.0% (4 patients). The overall DCR is 89.5%. Currently, treatment is ongoing for 18 patients. The longest duration of response is 14 months. Patients who were refractory to previous therapies achieved impressive responses to EX103 treatment. 3 patients who failed CAR-T therapy achieved either CR or partial response (PR) (2 CR and 1 PR), 2 patients who failed CD19×CD3 bispecific antibody treatment both achieved PR, and 4 patients who failed ASCT achieved either CR or PR (2 CR and 2 PR). Conclusions: EX103 can induce deep and durable responses in heavily pretreated patients with R/R B-NHL, such as those patients who failed CAR-T treatment (3 cases), CD19xCD3 bispecific antibody treatment (2 cases) and ASCT (4 cases). Clinical trial information: CTR20212096.
Neoadjuvant hypofractionated radiotherapy combined with pembrolizumab plus chemotherapy for potentially resectable non-small cell lung cancer: A phase Ib study.
Authors: Ding Naixin , Zhao Lijun , Zhang Shuai , Qiu Ninglei , Song Xue , Kong Cheng , Jiang Ning , Zhao Yang , Huang Jianfeng , Jiang Feng , Jiang Ming , Zhu Zihao , Yin Rong , Ren Binhui , Zhu Xiangzhi , Li Ming
Published: July 2024

8054

Background: Neoadjuvant PD-1 inhibitor plus chemotherapy in resectable non-small cell lung cancer (NSCLC) has become a standard of care. hypofractioned radiotherapy (HFRT) served as an immunomodulator and enhanced the effect of preoperative immunotherapy. In this phase Ib study, we evaluated the safety and feasibility of neoadjuvant HFRT with pembrolizumab plus chemotherapy in patients with potentially resectable stage III NSCLC. Methods: Patients with potentially resectable stage III NSCLC with EGFR/ALK wild-type were recruited to receive HFRT to the primary tumor followed by two cycles of pembrolizumab (100 mg/body) plus platinum-based doublet chemotherapy (Q3W). HFRT was delivered using 3 daily fractions, with a dose of 24 Gy for peripheral lesions and 12 Gy for central lesions. Central lesion is defined as a 2 cm area around the pulmonary artery and main bronchus. The decision for surgery was made through multidisciplinary team (MDT) discussion within a 4–6-week period after the completion of neoadjuvant treatment. Patients underwent surgery followed by adjuvant pembrolizumab for 2 years. Primary endpoint was safety. Secondary endpoints were efficacy, such as pathological complete response (pCR), progression-free survival (PFS), and overall survival (OS). Results: Between April 2021 and November 2023, 17 patients were enrolled with a median age of 66 years (range 54-74) and 15 (88.2%) having squamous cell lung cancer. 12 (70.6%) patients had stage IIIB disease, and 10 (58.8%) had central primary lesion. PD-L1 was ≥1% in 9 patients (52.9%). All patients received HFRT and at least one cycle of immunochemotherapy. No grade 3 or high adverse events were observed during neoadjuvant therapy. Only one patient had grade 1 nephrotoxicity, and another patient had grade 2 pneumonitis. A partial response was achieved in 16 out of 17 patients (94.1%), while one patient had stable disease after neoadjuvant therapy. Following MDT discussion, 11 patients (64.7%) met the surgical standards, while the remaining 6 patients were transitioned to definitive chemoradiotherapy. Among the 11 patients who underwent surgery, 8 (72.7%) achieved R0 resection, and 6 patients (54.5%) attained pCR. Only one patient died from intraoperative bleeding, and the remaining patients were followed up. The median PFS was 21.7 months, median OS were not reached, and the 2-year OS rate was 85.6%. The study was terminated early due to slow recruitment. Conclusions: Neoadjuvant HFRT with immunotherapy for potentially resectable stage III NSCLC is a tolerable treatment with an improved surgical conversion rate and pCR rate. Clinical trial information: ChiCTR2100045361.
The safety and efficacy of induction chemoimmunotherapy in initially unresectable stage III non-small cell lung cancer.
Authors: Tang Min , Zhao Zhe , Zhang Ping , Nie Xin , Wu Xiaonan , Yuan Yue , Liu Lian , Liu Lipin , Jiao Peng , Li Lin
Published: July 2024

8058

Background: Definitive concurrent chemoradiation followed by consolidation immunotherapy is the standard of care for unresectable stage III non-small cell lung cancer. Several studies demonstrated addition of induction immunotherapy may further improve outcome, and it is necessary to assess the response-adapted strategy based on early tumor retraction to induction therapy. This study evaluated safety and treatment outcomes of induction chemoimmunotherapy followed by surgery or RT in unresectable stage III NSCLC. Methods: Patients with previously untreated, unresectable, pathologically and radiologically confirmed stage III NSCLC, EGFR/ALK-wild-type, with measurable disease were included. Patients received 3 to 4 cycles (Q3W) of chemoimmunotherapy including carboplatin (area under the curve [AUC] 5mg/mL/min), nab-paclitaxel (squamous NSCLC, 260mg/m2) or pemetrexed (non-squamous NSCLC, 500mg/m2), and tislelizumab(200mg). After Multi-Disciplinary Treatment, those operable patients after induction chemoimmunotherapy received radical minimally invasive surgery followed by 14 cycles of tislelizumab. The still unresectable patients received standard thoracic radiotherapy followed by 14 cycles of tislelizumab. Coprimary end points include 24-month progression-free survival (PFS) rate and incidence of grade 3 to 5 pneumonitis. Results: Between May 2020 and November 2023, a total of 59 patients received treatment (54 men [91.5%]; median [range] age, 65 [46-82] years; 34 patients [57.7%] with programmed cell death ligand 1 [PD-L1] tumor proportion score ≥ 1%); 40 patients [67.8%] were squamous cell NSCLC; 33.9%, 45.8%, and 20.3% patients were stage IIIA, IIIB and IIIC. Sixteen patients received radical minimally invasive surgery (9 pCR), 42 patients received thoracic radiotherapy, and 1 patient had brain metastasis after 2 cycles of induction therapy. The median follow-up period was 20.1 (1.9-44.1) months, and median PFS was not reached, the 24-months PFS rate was 77.6% (95%CI, 59.9%-88.2%). The objective response rate was 93.2% (95%CI, 83.5%-98.1%), and DCR was 98.3% (95%CI, 90.9%-100.0%). Grade 3 pneumonitis occurred in 2 of 59 patients (3.4%). Conclusions: The findings of this study indicate encouraging antitumor activity and manageable safety of induction chemoimmunotherapy, and the response-adapted strategy requires further exploration in locally advanced unresctable non-small cell lung cancer. Clinical trial information: ChiCTR2200064104. [Table: see text]
Comparison of ICI plus chemotherapy or ipilimumab plus nivolumab based therapy for patients with NSCLC with TPS (1-49%): TOPGAN2023-01.
Authors: Tozuka Takehiro , Tanaka Hisashi , Makiguchi Tomonori , Kawashima Yosuke , Oba Tomohiro , Tsugitomi Ryosuke , Koyama Junji , Tambo Yuichi , Ogusu Shinsuke , Saiki Masafumi , Gyotoku Hiroshi , Hasegawa Tsukasa , Miyauchi Eisaku , Sonoda Tomoaki , Saito Ryota , Nakatomi Katsumi , Sakatani Toshio , Kudo Keita , Tsuchiya-Kawano Yuko , Nishio Makoto
Published: July 2024

8550

Background: Nowadays,immune checkpoint inhibitor (ICI) plus chemotherapy is a standard treatment for non-small cell lung cancer (NSCLC) without targetable oncogene alternations. Recently, ipilimumab plus nivolumab-based therapies (CM227 or CM9LA) are also used as standard treatments for NSCLC. Whether ICI plus chemotherapy (ICI-chemo) or ipilimumab plus nivolumab-based therapy (I-N) is better for patients with NSCLC with PD-L1 tumor proportion score (TPS) 1-49% has not been investigated. Here, we report the results of real-world data in NSCLC patients with PD-L1 TPS 1-49%. Methods: We conducted a multicenter (19 centers in Japan) retrospective cohort study. NSCLC patients with PD-L1 TPS 1-49% who received ICI-chemo or I-N as first-line systemic therapy between January 2018 and March 2022 were eligible. Patients with major epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements were excluded. Results: A total of 401 patients were enrolled: median (range) age 69 (35-90) years; 322 (80.3%) male; ECOG PS 0-1, 372 (92.7%); PS ≥2, 29 (7.3%); 233 (58.1%) adenocarcinoma; PD-L1 TPS 1-24%, 312 (77.8%); 25-49%, 82 (20.4%); 1-49% (details are unknown), 7 (1.8%); ICI-chemo 308 (76.8%); I-N, 93 (23.2%). The median overall survival (OS) was 21.0 months (95%CI, 16.7–27.5) in the ICI-chemo group and 20.0 months (95%CI, 15.1–not reached) in the I-N therapy group, respectively. After propensity score matching, there were no differences in OS and progression-free survival (PFS) between ICI-chemo group (n=92) and I-N group (n=92) (OS: HR, 0.83; 95% CI, 0.54-1.26; p=0.38, PFS: HR, 0.72; 95% CI, 0.52-1.00; p=0.05). Among patients with PD-L1 TPS 25-49%, there was a tendency for better OS in the ICI-chemo group (OS: HR, 0.30; 95% CI, 0.09–0.85, p=0.02). In contrast, among PD-L1 TPS 1-24%, significant difference in OS was not observed. Regarding safety, treatment discontinuation due to adverse events was observed 26.2% in the ICI-chemo group and 41.9% in the I-N group. Treatment related death was seen in 4.5% of the ICI-chemo group and in 3.2% of the I-N group. Pneumonitis was seen in 13.9% of the ICI-chemo group and in 17.6% of the N-I group. Conclusions: In real-world data for NSCLC with PD-L1 TPS 1-49%, there were no significant differences in both OS and PFS between ICI-chemo group and I-N group. Toxicity discontinuation rate was higher in I-N group. Based on the subgroup-analysis results, ICI-chemo might be better for NSCLC with PD-L1 TPS 25-49%. Clinical trial information: UMIN000016441.
Long-term efficacy and safety of larotrectinib in patients with TRK fusion lung cancer.
Authors: Drilon Alexander E. , Kummar Shivaani , Lin Jessica Jiyeong , Tan Daniel Shao-Weng , Moreno Victor , Leyvraz Serge , Dubashi Biswajit , KP Haresh , Burcoveanu Domnita-Ileana , Neu Natascha , Mussi Chiara E. , Shen Lin
Published: July 2024

8570

Background: NTRK gene fusions are oncogenic drivers in lung cancer and other cancers. Larotrectinib is the highly selective and central nervous system (CNS)-active TRK inhibitor approved for use in patients with TRK fusion cancer based on a robust and durable overall response rate (ORR) in patients with various tumor types. Here, we report long-term efficacy and safety in a cohort of patients with TRK fusion lung cancer treated with larotrectinib. Methods: Patients with TRK fusion lung cancer treated with larotrectinib in two clinical trials (NCT02122913, NCT02576431) were included. Larotrectinib was administered at 100 mg twice daily. Response was assessed by an independent review committee (IRC) per RECIST v1.1. Results: As of July 20, 2023, 32 patients with a median age of 55.5 years (range 25-81) with TRK fusion lung cancer were enrolled, including 12 patients with CNS metastases at baseline. NTRK gene fusions were identified by next-generation sequencing in all 32 patients. The gene fusions involved NTRK1 (n=24; 75%) and NTRK3 (n=8; 25%). Patients had received a median of two prior lines of systemic therapies; one patient was treatment-naïve. The ORR per IRC was 66% (95% confidence interval [CI] 47-81): four complete responses, 17 partial responses, seven stable disease, two progressive disease, and two not evaluable. Median time to first response was 1.8 months (range 1.5-7.3). Median duration of response (DoR) was 33.9 months (95% CI 9.5-not estimable [NE]); median follow-up was 25.8 months. Median progression-free survival (PFS) was 22.0 months (95% CI 9.9-NE); median follow-up was 27.7 months. Median overall survival (OS) was 39.3 months (95% CI 17.2-NE); median follow-up was 32.9 months. The 48-month rates for DoR, PFS, and OS were 47% (95% CI 19-76), 34% (95% CI 11-56), and 38% (95% CI 13-64), respectively. Duration of treatment ranged from 2 to 75+ months. At the data cutoff, 11 patients had progressed; six patients continued treatment post-progression for ≥4 weeks due to continued clinical benefit. Treatment-related adverse events (TRAEs) were predominantly Grade 1/2. Grade 3/4 TRAEs were reported in nine patients. One patient discontinued treatment due to TRAEs (increased alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase). Conclusions: Larotrectinib continued to demonstrate rapid and durable responses, extended survival benefit, and a favorable safety profile in patients with advanced TRK fusion lung cancer. These results support the wider adoption of next-generation sequencing panels that include NTRK gene fusions in patients with lung cancer to identify those who may benefit from targeted treatment. Clinical trial information: NCT02122913 , NCT02576431 .
An open-label, multicenter phase 1 study to characterize safety, tolerability, preliminary antitumor activity, and pharmacokinetics of VIP236 monotherapy in patients with advanced cancer.
Authors: Vandross Andrae L. , Stein Brian N. , Coward Jermaine , Sharma Sunil , Johnson Amy J. , Birkett Joseph , Huang Xin , Frigault Melanie M. , Lerchen Hans-georg , Stelte-Ludwig Beatrix , Navarro Tasheda , Peck Jim , Gross Wyatt , Izumi Raquel , Hamdy Ahmed M. , Rodriguez Rivera Ildefonso
Published: July 2024

TPS3168

Background: VIP236, a first-in-class SMDC, consists of an αvβ3 integrin small molecule binder, a peptide linker cleaved by neutrophil elastase (NE) in the tumor microenvironment (TME), and a camptothecin (CPT) payload VIP126 which was optimized for high permeability and low efflux. The overall drug design strategy for VIP236 is targeted delivery to the TME and tumors expressing αVβ3 integrin on their cell surface with release of the optimized CPT derivative by NE also present in the TME. VIP126, when delivered as a component of VIP236, is anticipated to kill tumor cells while reducing effects to normal tissue. VIP236 exhibits convincing single agent in vivo antitumor efficacy and acceptable tolerability in multiple human tumor cell line- and patient- derived xenograft models in mice, including breast, colorectal, small cell lung, gastric, metastatic breast and metastatic colon cancer. In three gastric cancer xenograft models, VIP236 caused statistically significant tumor growth inhibition across the models independent of HER2 status. VIP236 outperformed an anti-HER2 ADC, trastuzumab deruxtecan, in all three models. Methods: This trial in progress is an open-label, global, multicenter Phase 1 study to characterize safety, tolerability, preliminary antitumor activity and pharmacokinetics of VIP236 monotherapy in subjects with advanced cancer. Enrollment includes all comer patients with histologically confirmed advanced or metastatic solid tumors that are relapsed or refractory to standard of care. Subjects must have exhausted all available standard therapies or be deemed ineligible for potential available therapies. Frequency, severity, and relationship to study drug of any treatment-emergent adverse events or abnormalities of laboratory tests will be studied. Tumor response will be assessed using RECIST 1.1 criteria. The following dose schedules are being evaluated: 1) Cohorts 1, 2a, and 3a: A cycle is 21 days 1-hour intravenous (IV) infusions on a 2 days on/5 days off schedule with no pause between cycles. 2) Cohorts 2b, 3b, 4b, 5b, 6b, 7b, and 8b: A cycle is 21 days of VIP236 given as a 1-hour IV infusion once every three weeks (Q3W) with no pause between cycles. 3) Cohorts 1, 2a, 3a, 2b, 3b and 4b have been completed. Enrollment continues in the Q3W cohorts. Clinical trial information: NTC05371054.
A Comprehensive Training Model for Simulation of Intracranial Aneurysm Surgery Using a Human Placenta and a Cadaveric Head
Authors: De Schlichting Emmanuel , Zaldivar-Jolissaint Julien Francisco , Molter Nicolas , Chenevas-Paule Marion , Hamadmad Ayah , Giroux Luc , Lazard Arnaud , Riethmuller Didier , Chaffanjon Philippe , Coll Guillaume , Lechanoine François
Published: July 2024

BACKGROUND AND OBJECTIVES:

Aneurysmal surgery is technically complex, and surgeon experience is an important factor in therapeutic success, but training young vascular neurosurgeons has become a complex paradigm. Despite new technologies and simulation models, cadaveric studies still offer an incomparable training tool with perfect anatomic accuracy, especially in neurosurgery. The use of human placenta for learning and improving microsurgical skills has been previously described. In this article, we present a comprehensive simulation model with both realistic craniotomy exposure and vascular handling consisting of a previously prepared and perfused human placenta encased in a human cadaveric specimen.

METHODS:

Humans' placentas from the maternity and cadaveric heads from the body donation program of the anatomy laboratory were used. Placentas were prepared according to the established protocol, and aneurysms were created by catheterization of a placental artery. Ten participants, including senior residents or young attendees, completed an evaluation questionnaire after completing the simulation of conventional unruptured middle artery aneurysm clipping surgery from opening to closure.

RESULTS:

The skin incision, muscle dissection, and craniotomy were assessed as very similar to reality. Brain tissue emulation and dissection of the lateral fissure were judged to be less realistic. Vascular management was evaluated as similar to reality as closure. Participants uniformly agreed that this method could be implemented as a standard part of their training.

CONCLUSION:

This model could provide a good model for unruptured aneurysm clipping training.
3-Dimensional Printed Model of the Temporal Bone for Neurosurgical Training
Authors: Piazza Amedeo , Corvino Sergio , Colosso Giulio Quarta , Campeggi Alice , Agosti Edoardo , Serioli Simona , Frati Alessandro , Santoro Antonio
Published: July 2024

BACKGROUND AND OBJECTIVES:

The development of neurosurgical skills stands out as a paramount objective for neurosurgery residents during their formative years. Mastery of intricate and complex procedures is a time-intensive process marked by a gradually ascending learning curve. Consequently, the study and simulation on surgical models assume significant importance. One of the most intricate neuroanatomical regions includes the petrous and mastoid portions of the temporal bone. These regions host critical, highly functional, and vital neurovascular structures, including the facial nerve, cochlea, semicircular canals, internal carotid artery, and middle ear. This fully open-source 3-dimensional (3D) model of the temporal bone, created for educational purposes, should be easily and economically reproducible using a 3D printer, offering all residents the opportunity to understand the spatial location, three-dimensional anatomical structures, and fundamental intricacies of mastoidectomy.

METHODS:

A 3D model of the temporal bone was fabricated using a computed tomography (CT) scan derived from an actual human body. The CT scan of the model was meticulously juxtaposed with the reference sample CT scan. Neurosurgical residents were recruited as participants for this study. Each participant was tasked with executing a mastoidectomy on 2 separate occasions, with a 2-week interval between attempts. Throughout these sessions, various parameters, including the time taken for task completion, the volume of bone removal, and any potential complications, were systematically registered.

RESULTS:

The mean volume of bone removed increased by 34.5%, and the mean task time and the mean number of complications decreased by 10.3% and 25%, respectively, during the training.

CONCLUSION:

Engaging in training with cost-effective anatomical models constitutes a valuable tool for refining technical skills during residency. We posit that this type of model training should be incorporated as part of the trainee's curriculum during the residency program because of the myriad advantages evidenced by the findings of this study.
Omentomyelopexy for the Treatment of a Persistent Lumbar Pseudomeningocele: A Case Report With Technical Note
Authors: Stanković Svetozar , Minić Ljubodrag , Stanković Jadranka , Djurdjević Alekandar , Lepić Milan , Pavlićević Goran
Published: July 2024

BACKGROUND AND IMPORTANCE:

Pseudomeningoceles are extradural accumulations of cerebrospinal fluid. In most cases, they appear as a complication of spinal operations. Omentomyelopexy is a surgery in which an autologous omentum flap is implanted over the dural opening. We describe a case of persistent pseudomeningocele treated with omentomyelopexy.

CLINICAL PRESENTATION:

A 37-year-old man sustained a T12-L1 AO B3 fracture during a motorcycle accident. He underwent posterolateral fusion and then neurological rehabilitation. Two years later, however, his condition worsened, and he experienced progressive weakness—he was diagnosed with an intramedullary cyst, which was treated with laminectomy, arachnolysis and cystotomy. A pseudomeningocele developed afterward, and the patient underwent multiple reoperations in the following years, none of which were effective. Omentomyelopexy, a complex procedure aimed to facilitate cerebrospinal fluid absorption and subsequent formation of a permanent membrane, was offered to the patient as a “last resort.” After undergoing omentomyelopexy, his pseudomeningocele resolved.

CONCLUSION:

Although it should be reserved for exceptionally pertinent cases, omentomyelopexy is a viable option for managing persistent pseudomeningocele. However, further research is needed to better understand the effects and benefits of omentomyelopexy in this context.
Prognostic Relevance of the Proximal Resection Margin Distance in Distal Gastrectomy for Gastric Adenocarcinoma
Authors: Rompen Ingmar F. , Schütte Isabel , Crnovrsanin Nerma , Schiefer Sabine , Billeter Adrian T. , Haag Georg Martin , Longerich Thomas , Czigany Zoltan , Schmidt Thomas , Billmann Franck , Sisic Leila , Nienhüser Henrik
Published: July 2024

Background

The risk for recurrence in patients with distal gastric cancer can be reduced by surgical radicality. However, dispute exists about the value of the proposed minimum proximal margin distance (PMD). Here, we assess the prognostic value of the safety distance between the proximal resection margin and the tumor.

Patients and Methods

This is a single-center cohort study of patients undergoing distal gastrectomy for gastric adenocarcinoma (2001–2021). Cohorts were defined by adequacy of the PMD according to the European Society for Medical Oncology (ESMO) guidelines (≥ 5 cm for intestinal and ≥ 8 cm for diffuse Laurén’s subtypes). Overall survival (OS) and time to progression (TTP) were assessed by log-rank and multivariable Cox-regression analyses.

Results

Of 176 patients, 70 (39.8%) had a sufficient PMD. An adequate PMD was associated with cancer of the intestinal subtype (67% vs. 45%, p = 0.010). Estimated 5-year survival was 63% [95% confidence interval (CI) 51–78] and 62% (95% CI 53–73) for adequate and inadequate PMD, respectively. Overall, an adequate PMD was not prognostic for OS (HR 0.81, 95% CI 0.48–1.38) in the multivariable analysis. However, in patients with diffuse subtype, an adequate PMD was associated with improved oncological outcomes (median OS not reached versus 131 months, p = 0.038, median TTP not reached versus 88.0 months, p = 0.003).

Conclusion

Patients with diffuse gastric cancer are at greater risk to undergo resection with an inadequate PMD, which in those patients is associated with worse oncological outcomes. For the intestinal subtype, there was no prognostic association with PMD, indicating that a distal gastrectomy with partial preservation of the gastric function may also be feasible in the setting where an extensive PMD is not achievable.
School responses to the COVID-19 pandemic: An analysis of the state education system of Minas Gerais, Brazil
Authors: Queiroz Melissa Dias , Costa Bruno Lazzarotti Diniz
Published: July 2024

In addition to the health and economic effects, the COVID- 19 pandemic shocked educational systems with school closures. The Brazilian state of Minas Gerais adopted the Regime Especial de Atividades Não Presenciais (Reanp), followed by heterogeneous strategies and results in each school. This article seeks to understand and analyze how public schools in Minas Gerais responded to the pandemic in 2020 and 2021 regarding the main strategies imposed for the continuity of activities and their possible effects. This descriptive research with a qualitative nature is based on documentary research and semistructured interviews. The results demonstrate the validity of the official strategies but also highlight their limitations and criticisms regarding their content and applicability. Learning losses and impacts related to health, socialization, and engagement in studies were observed, influenced by the socioeconomic contexts of school communities.
Περιβάλλον υποστήριξης για την αποκατάσταση ηλεκτρικού συστήματος μετά από διακοπή ισχύος
Authors: Φούντας Νικόλαος
Published: July 2024

Στα πλαίσια της παρούσας Διατριβής εξετάζεται το θέμα της επαναφοράς ενός συστήματος ισχύος στην ομαλή λειτουργία μετά από μερικοί ή ολική απώλεια ισχύος. Αναπτύσσεται ένα γραφικό αλληλεπιδραστικό περιβάλλον υποστήριξης των χειριστών και μηχανικών για τον προγραμματισμό ενεργειών αποκατάστασης του συστήματος, με βάση αναλυτικά εργαλεία μελέτης του ηλεκτρικού συστήματος σε μεγάλες χρονικές κλίμακες και εξελιγμένες τεχνικές τεχνητής νοημοσύνης. Στην περιοχή της μελέτης των δυναμικών φαινομένων σε διάφορες χρονικές κλίμακες της αποκατάστασης συστήματος μετά από διακοπή ισχύος, προτείνεται μια αποτελεσματική η υλοποίηση του αλγορίθμου ημι-μόνιμης (δυναμικής) ροής φορτίου για την προσομοίωση των μεταβατικών φαινομένων. Αναπτύσσεται ένα ενιαίο αλληλοδραστικό υπολογιστικό περιβάλλον εργασίας με επέκταση των δυνατοτήτων του για τη μελέτη μεγάλου φάσματος δυναμικών φαινομένων χαρακτηριστικών του προβλήματος της αποκατάστασης. Στα πλαίσια της Διατριβής επίσης, αναπτύσσεται η πρωτότυπη εφαρμογή των Δικτύων Petri, ενός αποδοτικού γραφικού και μαθηματικού εργαλείου τεχνητής νοημοσύνης δεύτερης γενιάς (deep reasoning system) στο πρόβλημα της αποκατάστασης. Μέσα από τη μελέτη των βασικών ιδιοτήτων συμπεριφοράς και την κατασκευή των γράφων προσπελασιμότητας των Ιεραρχικά Χρονικά Εκτεταμένων Δικτύων Petri, διερευνάται η δυναμική συμπεριφορά του συστήματος ισχύος σε διάφορες φάσεις της αποκατάστασης και εξάγονται χρήσιμα συμπεράσματα.
Ετυμολογικές σημειώσεις του Κυπριακού ιδιώματος: Μνήμη Κυριάκου Χατζηιωάννου
Authors: Κονομής Νικόλαος
Published: July 2024

This paper constitutes the second part of a previous study (Konomis 1998). It offers new etymologies for a several words of the Cypriot dialect, which should be taken into consideration in modern dialectal and standard lexicography.
Τhe loss of the partitive genitive in Greek
Authors: Μερτύρης Διονύσιος
Published: July 2024

Η γενική στην Αρχαία Ελληνική διέθετε τρεις σημασίες, καθώς εκτός από τις κτητικές και μεριστικές (διαιρετικές) λειτουργίες που κληρονόμησε από την Πρωτο-Ινδο-Ευρωπαϊκή γενική, μπορούσε να έχει και αφαιρετική σημασία, την οποία απέκτησε λόγω της απώλειας της αφαιρετικής πτώσης πριν από τον 8ο αι. π.Χ. Ωστόσο, η γενική της Νέας Ελληνικής έχει χάσει τόσο τη μεριστική όσο και την αφαιρετική χρήση της, με την κτήση να είναι η μόνη αρχαία σημασία που έχει διατηρηθεί. Αυτές οι αλλαγές εντάσσονται στην ευρύτερη αναδόμηση του αρχαίου πτωτικού συστήματος στο πλαίσιο της σταδιακής υποχώρησης των σημασιολογικών χρήσεων των πλάγιων πτώσεων εξαιτίας της εκτεταμένης χρήσης των προθετικών φράσεων και άλλων αναλυτικών δομών. Έτσι, το παρόν άρθρο επιχειρεί να ανιχνεύσει την πορεία της απώλειας των μεριστικών λειτουργιών της γενικής στην Ελληνική και να εντοπίσει τους παράγοντες που οδήγησαν σε αυτήν.
Η φωνητική απόδοση των νεοελληνικών διαλέκτων και ιδιωμάτων
Authors: Μανωλέσσου Ιώ , Μπέης Σταμάτης , Μπασέα-Μπεζαντάκου Χριστίνα
Published: July 2024

The present paper discusses the phonetic transcription methods applied in the Historical Dictionary of Modern Greek and in Modern Greek dialectology in general. It provides a categorisation of the available transcriptions systems, an overview of transcription practice for each MG dialect, and a discussion of the main transcription problems in oral and written dialectological sources. It presents and justifies the principles and solutions adopted by the Historical Dictionary for the transcription of dialect material, and also offers correspondence tables for the phonetic symbols adopted in the major dialectological studies for each dialect as compared to the symbols of the Historical Dictionary and of the IPA.
Acne during Covid-19-The effect of pandemic and quarantine on skin care of patients with acne
Authors: Niewinna Patrycja , Kołodziej Klaudia , Żuchowski Michał , Mańdziuk Dominika , Zaroda Przemysław , Dąda Paweł , Pawlik Paweł , Kołodziej Wojciech , Wawrzkowicz Jakub , Korga Monika
Published: July 2024

Introduction:Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from androgen-induced increased sebum production, altered keratinisation, inflammation, on the face, neck, chest and back.[1] During the COVID-19 pandemic, many patients with acne complained of worsening symptoms. This investigation was designed to survey the impact of COVID-19 regulations on acne and guide patients with acne on symptom management during the pandemic.[2]
Aim of the study:The study aimed to investigate whether the problem of acne increased during the pandemic.Has the pandemic affected the level of people's awareness of acne and skin care?Did wearing masks affect the condition of the skin? 
Methods and Materials:Research was conducted on a group of 484 people (female – 97%, male – 3%).The study group included patients who suffered from acne before the pandemic and patients who developed it during the pandemic (from March 2020). 
Results:The conducted research confirms that the restrictions introduced during the COVID-19 pandemic (face masks) had a significant impact on the skin condition of patients with acne and their care habits. Patients' interest in the subject of acne and involvement in the treatment has increased significantly - that is a positive trend.
Conclusion:
The COVID-19 pandemic has given rise to the need to use personal protective equipment such as masks.[4]The use of face masks is associated with high rates of acne eruption.[5]Patients with acne vulgaris continue to present increasingly in dermatology outpatient clinics and seek treatment during the COVID-19 pandemic.[6] Patients during COVID-19 intensify their dermatology treatment.
Identity, Diversity, and Team Performance: Evidence from U.S. Mutual Funds
Authors: Evans Richard B. , Prado Melissa Porras , Rizzo A. Emanuele , Zambrana Rafael
Published: July 2024

We examine team diversity and performance in the asset management industry through the lens of identity. Focusing on political ideology as the relevant dimension of identity, we find that diverse teams outperform homogeneous teams. The mechanism involves both improved decision making due to more diverse perspectives and increased monitoring by heterogeneous team members. The benefits of ideological diversity are undone when political polarization is higher, consistent with increased intrateam conflict. In examining why less diverse teams are prevalent in asset management, we find entrenched managers prefer homogeneous teams, and the local labor market supply of ideologically diverse managers is constrained.

This paper was accepted by Victoria Ivashina, finance.

Funding: This work was funded by the Fundação para a Ciência e a Tecnologia [UID/ECO/00124/2013 and Social Sciences DataLab, Project 22209], POR Lisboa [LISBOA-01-0145-FEDER-007722 and Social Sciences DataLab, Project 22209], and POR Norte [Social Sciences DataLab, Project 22209].

Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.00544 .
Correlation of ankle–wrist pressure index with ankle–brachial pressure index to assess lower limb perfusion in diabetic foot ulcer: a pilot study
Authors: Roshan Ravi , Chaudhary Natasha , Chouhan Udit , Huda Farhanul , Basu Somprakas
Published: July 2024

Objective:

The presence of peripheral artery disease (PAD) in patients with diabetic foot ulcers (DFUs) is a significant risk factor for chronicity and amputation. Ankle–brachial pressure index (ABPI) is a screening tool for PAD. Brachial systolic pressure measurement, used as a denominator in the calculation of ABPI, produces inaccurate results in patients with obesity and the presence of heavy clothing. The wrist, however, is easily accessible, and the ankle–wrist pressure index (AWPI), if comparable with ABPI, may be useful in screening selected patients. This study aimed to assess the efficacy of AWPI in diagnosing perfusion in DFUs and compare it to ABPI in patients with DFUs.

Method:

ABPI and AWPI were calculated by measuring systolic blood pressure in the arteries of the ankle, arm and wrist with a handheld Doppler. Actual perfusion was determined by the presence or absence of PAD by duplex ultrasound.

Results:

A total of 46 lower extremities in 41 patients were studied. The prevalence of PAD was 61%. Duplex ultrasound confirmed that the sensitivity of ABPI and AWPI in detecting PAD in patients with DFUs was 67.9% and 71.4% respectively, whereas the specificity of ABPI and AWPI was 94.4% and 88.9% respectively. On receiver operating characteristic analysis, the area under the curve of ABPI and AWPI was 0.804 and 0.795, respectively. A statistically significant positive correlation between ABPI and AWPI was found (r=0.986; p<0.001).

Conclusion:

There was a good correlation between ABPI and AWPI over a wide range of values. ABPI and AWPI may have a similar role in predicting perfusion in patients with DFUs. AWPI could be used in place of ABPI in selected patients in whom measuring ABPI may be difficult.

Declaration of interest:

The authors have no conflicts of interest to declare.
Effectiveness and safety of an innovative silicone extender in suture reinforcement or dermatotraction: a retrospective study
Authors: Yailian Anne-Laure , Careé Emmanuelle , Rioufol Catherine , Thomas Luc , Beatrix Olivier
Published: July 2024

Objective:

Multiple techniques are available for closing skin defects, such as skin grafts, flaps and tissue expansion. The tissue extender MID SEW (MID, France) was developed to achieve dermatotraction or suture reinforcement. The aim of this study was to evaluate the effectiveness and safety of this innovative silicone extender for large surgical wounds.

Method:

A single-centre retrospective and observational study on an unselected consecutive cohort of patients treated with a tissue extender was conducted. Indications, initial and final wound surfaces, and adverse events (AEs) were retrieved from electronic medical records. The main outcome measure was the time to complete wound closure.

Results:

We identified 50 patients from July 2017 to December 2018. Patients underwent cutaneous tumour-wide excision (n=44), or pilonidal disease surgical treatment (n=6). The average initial wound area was 53.3±42.4cm 2 . Healing was complete, without secondary dehiscence, within the first seven days after device withdrawal for 41 patients (82%). At least one AE was experienced by eight patients (16%) during the study period: five inflammation; five wound dehiscence; two skin necrosis; and one pain.

Conclusion:

This case series suggests that the tissue extender may be effective and safe in its dermatotraction and suture reinforcement indications in the treatment of large wounds after wide excision of skin cancer or treatment of pilonidal disease.

Declaration of interest:

This work was supported in part by the Hospices Civils de Lyon, France and in part by the University Claude Bernard Lyon 1, France. OB co-owns the patent on the MID SEW system. The authors have no other conflicts of interest to declare.
Maggot therapy for resistant infections: the disconnect between scientific evidence, clinical acceptance and practice
Authors: Coombes Joseph , Gammon John , Nigam Yamni
Published: July 2024

Objective:

Practitioners and scientists are re-examining marginalised wound care therapies to find strategies that combat the growing problem of antimicrobial resistance (AMR) without compromising patient outcomes. Maggot therapy (MT) makes up just an estimated 0.02% of UK's National Health Service spending on wound care. This study aims to uncover why MT is not used more often, despite its affordability and high level of efficacy for both debridement and disinfection, particularly in the context of AMR infections, and to determine what can be done to ensure MT is more effectively used in the future to improve patient outcomes and manage the growing problem of AMR.

Method:

For this investigation, a qualitative review of case studies using MT against AMR infections and a quantitative analysis of randomised control trials (RCTs) were performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework.

Results:

Analysis showed that MT is highly effective against a range of infections and wound types, and compares well against conventional therapies. The low use of MT may be due in part to the documented ‘yuck factor’, often associated with maggots as well as misconceptions around the cost, efficacy and accessibility of MT. To overcome these factors, more RCTs on the spectrum and efficacy of MT across various clinical manifestations are needed, as well as professional and public engagement campaigns.

Conclusion:

MT is an underused therapy, particularly regarding AMR infections, and expanding its use in these circumstances appears warranted. MT could play a vital role in conserving the efficacy of the existing pool of antimicrobials available and should be considered in the development of antimicrobial stewardship programmes.

Declaration of interest:

This work was supported by the Swansea Employability Academy, Swansea University (internal funding). The authors have no conflicts of interest to declare.
Management of a complicated colonexposed sacrococcygeal wound after pelvic exenteration: a case report
Authors: Geng Yingnan , Ding Neng , Zou Jiefeng , Zhou Haiyang , Zhu Lie
Published: July 2024

Sacrococcygeal wound management can be challenging, especially when complicated by chronic infection, radiation and exposure of the underlying structures. Vascularised soft-tissue reconstruction is the only option when conservative wound care fails. Previous reports have mainly focused on the treatment of pressure ulcers. This report describes the case of a 54-year-old female patient with a colon-exposed, large sacrococcygeal wound after pelvic exenteration for recurrent rectal cancer. The wound was closed without dead space using two approaches: innovative vacuum sealing drainage (VSD); and gluteus maximus myocutaneous flap repair. Timely debridement, accurate assessment of intervention, appropriate design of composite tissue flap, and conscientious wound care contributed to complete wound healing within two months.

Declaration of interest:

This work was supported by the Naval Medical University and the University of Shanghai for Science and Technology Joint Projects (2020-RZ04), the Innovative Clinical Research Program of Shanghai Changzheng Hospital (2020YLCYJ-Y16), and the academic project of Naval Medical University (2022QN073). The authors have no conflicts of interest to declare.
Performance of a gelling fibre dressing in management of wounds in a community setting: a sub-analysis of the VIPES study
Authors: Klein Arthur , Ayoub Nayla , Juhel Christine , Schueller Romain , Armstrong Florence , Pegalajar-Jurado Adoración
Published: July 2024

Objective:

To evaluate the use and performance of a gelling fibre dressing (Biatain Fiber; Coloplast A/S, Denmark) in the management of wounds in community nursing practice.

Method:

A sub-analysis of the prospective, observational, real-world VIPES (Observatoire en Ville des Plaies ExSudatives) study was conducted. Patients with exuding wounds, for which nurses chose to apply the gelling fibre as a primary dressing, were included. Outcomes included assessments of wound condition and patient/nurse opinion.

Results:

Overall, 149 patients with acute (n=52; 34.9%) or hard-to-heal (chronic) (n=97; 65.1%) wounds were included. At baseline, mean±standard deviation wound age was 351.5±998.2 days, 108 (72.5%) wounds were moderately-to-highly exuding, and 126 (84.6%) showed exudate pooling in the wound bed. At the last follow-up visit, 29 (19.5%) wounds had healed, within a median of 36 days, and 64 (43.0%) were progressing towards healing. From baseline to the last follow-up visit, significant reductions in wound surface area (p<0.05), depth (p<0.01), exudate level (p<0.0001), and in the proportion of wounds with sloughy tissue (p<0.0001) were observed. Most wounds had no (n=86; 58.5% (two missing values)) or low exudate pooling (n=45; 30.6% (two missing values)) at the last visit and proportions of patients with healthy wound edges/periwound skin increased from baseline. At the last visit, wounds were considered improved by nurses in 71.4% (n=105) of cases, and by patients in 66.7% (n=98) of cases (two patients missing).

Conclusion:

Patients who received treatment with the gelling fibre experienced improvements in the condition of a range of complex wounds. This analysis highlights the importance of adequate exudate management, and indicates how the selection of an appropriate wound dressing can encourage healing progression.

Declaration of interest:

This study was financially supported by Laboratoires Coloplast SAS, Paris, France. Coloplast A/S funded the writing and editing of the article and contributed to its content. Coloplast A/S and Laboratoires Coloplast SAS reviewed the article for scientific accuracy. Nurses received financial compensation for their participation in the study. NA is a full-time employee of Coloplast A/S. APJ was an employee of Coloplast A/S when this article was written. FA was a full-time employee of Laboratoires Coloplast SAS at the time of publication development. RS and CJ are full-time employees of CEN Biotech. AK received an educational grant from Coloplast A/S to provide scientific input to the publication. The authors have no other conflicts of interest to declare.
Pay attention to the application of indocyanine green fluorescence imaging technology in laparoscopic liver cancer resection
Authors: Kang Li-Min , Zhang Fu-Wei , Yu Fa-Kun , Xu Lei
Published: July 2024

Traditional laparoscopic liver cancer resection faces challenges, such as difficulties in tumor localization and accurate marking of liver segments, as well as the inability to provide real-time intraoperative navigation. This approach falls short of meeting the demands for precise and anatomical liver resection. The introduction of fluorescence imaging technology, particularly indocyanine green, has demonstrated significant advantages in visualizing bile ducts, tumor localization, segment staining, microscopic lesion display, margin examination, and lymph node visualization. This technology addresses the inherent limitations of traditional laparoscopy, which lacks direct tactile feedback, and is increasingly becoming the standard in laparoscopic procedures. Guided by fluorescence imaging technology, laparoscopic liver cancer resection is poised to become the predominant technique for liver tumor removal, enhancing the accuracy, safety and efficiency of the procedure.
Evaluating the role of interleukin-2 and interleukin-12 in pediatric patients with concurrent Mycoplasma pneumoniae and Epstein-Barr virus infections
Authors: Hao Yan-Ping
Published: July 2024

BACKGROUND

Mycoplasma pneumoniae (MP) frequently causes respiratory infections in children, whereas Epstein-Barr virus (EBV) typically presents subclinical manifestations in immunocompetent pediatric populations. The incidence of MP and EBV co-infections is often overlooked clinically, with the contributory role of EBV in pulmonary infections alongside MP remaining unclear.

AIM

To evaluate the serum concentrations of interleukin-2 (IL-2) and interleukin-12 (IL-12) in pediatric patients with MP pneumonia co-infected with EBV and assess their prognostic implications.

METHODS

We retrospectively analyzed clinical data from patients diagnosed with MP and EBV co-infection, isolated MP infection, and a control group of healthy children, spanning from January 1, 2018 to December 31, 2021. Serum IL-2 and IL-12 levels were quantified using enzyme-linked immunosorbent assay. Logistic regression was employed to identify factors influencing poor prognosis, while receiver operating characteristic (ROC) curves evaluated the prognostic utility of serum IL-2 and IL-12 levels in co-infected patients.

RESULTS

The co-infection group exhibited elevated serum IL-2 and C-reactive protein (CRP) levels compared to both the MP-only and control groups, with a reverse trend observed for IL-12 (P < 0.05). In the poor prognosis cohort, elevated CRP and IL-2 levels, alongside prolonged fever duration, contrasted with reduced IL-12 levels (P < 0.05). Logistic regression identified elevated IL-2 as an independent risk factor and high IL-12 as a protective factor for adverse outcomes (P < 0.05). ROC analysis indicated that the area under the curves for IL-2, IL-12, and their combination in predicting poor prognosis were 0.815, 0.895, and 0.915, respectively.

CONCLUSION

Elevated serum IL-2 and diminished IL-12 levels in pediatric patients with MP and EBV co-infection correlate with poorer prognosis, with combined IL-2 and IL-12 levels offering enhanced predictive accuracy.