Post-Kidney Transplant Cancer: A Real-World Retrospective Analysis From a Single Italian Center.

We describe the epidemiology of cancer after kidney transplantation (KTx), investigating its risk factors and impact on therapeutic management and survival in KTx recipients (KTRs). The association between modification of immunosuppressive (IS) therapy after cancer and survival outcomes was analyzed. We collected data from 930 KTRs followed for 7 [1-19] years. The majority of KTRs received KTx from a deceased donor (84%). In total, 74% of patients received induction therapy with basiliximab and 26% with ATG. Maintenance therapy included steroids, calcineurin inhibitors, and mycophenolate. Patients with at least one cancer (CA+) amounted to 19%. NMSC was the most common tumor (55%). CA+ were older and had a higher BMI. Vasculitis and ADPKD were more prevalent in CA+. ATG was independently associated with CA+ and was related to earlier cancer development in survival and competing risk analyses (p = 0.01 and <0.0001; basiliximab 89 ± 4 vs. ATG 40 ± 4 months). After cancer diagnosis, a significant prognostic impact was derived from the shift to mTOR inhibitors compared to a definitive IS drug suspension (p = 0.004). Our data confirm the relevance of cancer as a complication in KTRs with ATG as an independent risk factor. An individualized choice of IS to be proposed at the time of KTx is crucial in the prevention of neoplastic risk. Finally, switching to mTORi could represent an important strategy to improve patient survival.

Locally Advanced Pancreas Cancer, Is There a Role for Surgery?

Locally advanced pancreatic cancer (LAPC) represents a unique clinical scenario in which the tumor is considered localized but unresectable due to anatomic factors. Despite a consensus against upfront surgery, no standard approach to induction therapy exists for patients with LAPC. Extended systemic therapy has shown promise in establishing tumor response and remains the standard of care. While associated with improved local control, the timing and role of radiation therapy remain in question. Following adequate response to induction chemotherapy, a safe attempt at margin-negative resection can be considered. Special attention should be given to required vascular skeletonization and/or resection with reconstruction.

Emergency medicine updates: Endotracheal intubation.

INTRODUCTION: Airway management including endotracheal intubation (ETI) is a key skill for emergency clinicians. Therefore, it is important for emergency clinicians to be aware of the current evidence regarding the identification and management of patients requiring ETI. OBJECTIVE: This paper evaluates key evidence-based updates concerning ETI for the emergency clinician. DISCUSSION: ETI is commonly performed in the emergency department (ED) setting but has many nuanced components. There are several tools that have been used to predict a difficult airway which incorporate anatomic and physiologic features. While helpful, these tools should not be used in isolation. Preoxygenation and apneic oxygenation are recommended to reduce the risk of desaturation and patient decompensation, particularly with noninvasive ventilation in critically ill patients. Induction and neuromuscular blocking medications should be tailored to the clinical scenario. Video laryngoscopy is superior to direct laryngoscopy among novice users, while both techniques are reasonable among more experienced clinicians. Recent literature suggests using a bougie during the first attempt. Point-of-care ultrasound is helpful for confirming correct placement and depth of the endotracheal tube. CONCLUSIONS: An understanding of literature updates can improve the ED care of patients requiring emergent intubation.

Dose-dependent responses to canonical Wnt transcriptional complexes in the regulation of mammalian nephron progenitors.

In vivo and in vitro studies argue that concentration dependent Wnt signaling regulates mammalian nephron progenitor cell (NPC) programs. Canonical Wnt signaling is regulated through the stabilization of ß-catenin, a transcriptional co-activator when complexed with Lef/Tcf DNA binding partners. Utilizing the GSK3ß inhibitor CHIR99021 (CHIR), to block GSK3ß-dependent destruction of ß-catenin, we examined dose-dependent responses to ß-catenin in NPCs, using mRNA transduction to modify gene expression. Low CHIR-dependent proliferation of NPCs was blocked on ß-catenin removal with evidence of NPCs arresting at the G2-M transition. While NPC identity was maintained following ß-catenin removal, mRNA-seq identified low CHIR and ß-catenin dependent genes. High CHIR activated nephrogenesis. Nephrogenic programming was dependent on Lef/Tcf factors and ß-catenin transcriptional activity. Molecular and cellular features of early nephrogenesis were driven in the absence of CHIR by a mutated, stabilized form of ß-catenin. Chromatin association studies indicate low and high CHIR response genes are likely direct targets of canonical Wnt transcriptional complexes. Together these studies provide evidence for concentration dependent Wnt-signaling in the regulation of NPCs and provide new insight into Wnt targets initiating mammalian nephrogenesis.

New induction chemotherapy using intra-arterial infusion for tongue squamous cell carcinoma to avoid reconstructive surgery: A 6 case reports.

Most tongue squamous cell carcinoma (TSCC) classified as T3 require reconstructive surgery, which inevitably causes problems with oral functions. We propose new induction chemotherapy using intra-arterial infusion for TSCC classified as T3 to avoid reconstructive surgery. This chemotherapy regimen consists of intra-arterial infusion of docetaxel and cisplatin and systemic administration of 5-fluorouracil. As a result of this treatment, the therapeutic effect was a complete response in five patients and a partial response in one patient, and the overall response rate was 100%. All six patients underwent partial resection because their tumors shrank with this induction chemotherapy. In addition, adverse events of grade 3 or more did not occur in all six patients. The median follow-up duration for all patients was 34 months, and they are alive. This intra-arterial chemotherapy regimen was shown to be highly efficacious and safe.

Aromatic components and endophytic fungi during the formation of agarwood in Aquilaria sinensis were induced by exogenous substances.

The process of formation of aromatic components for agarwood in Aquilaria sinensis is closely related to endophytic fungi and the result of complex multiple long-term joint interactions with them. However, the interactions between the aromatic components and endophytic fungi remain unclear during the formation of agarwood. In this study, precise mixed solution of hormones, inorganic salts, and fungi was used to induce its formation in A. sinensis, and sample blocks of wood were collected at different times after inoculation. This study showed that the aromatic compounds found in the three treatments of A. sinensis were primarily chromones (31.70-33.65%), terpenes (16.68-27.10%), alkanes (15.99-23.83%), and aromatics (3.13-5.07%). Chromones and terpenes were the primary components that characterized the aroma. The different sampling times had a more pronounced impact on the richness and diversity of endophytic fungal communities in the A. sinensis xylem than the induction treatments. The species annotation of the operational taxonomic units (OTUs) demonstrated that the endophytic fungi were primarily composed of 18 dominant families and 20 dominant genera. A linear regression analysis of the network topology properties with induction time showed that the interactions among the fungal species continued to strengthen, and the network structure tended to become more complex. The terpenes significantly negatively correlated with the Pielou evenness index (p < 0.05), while the chromones significantly positively correlated with the OTUs and Shannon indices.

Induction chemotherapy with cemiplimab in a patient with coexistent vulvar cancer and autoimmune disease: A case report.

There is limited data regarding the use of immunotherapy for patients with vulvar squamous cell carcinoma and coexisting autoimmune disease. Cemiplimab is a PD-1 inhibitor approved for use in patients with locally advanced and metastatic cutaneous squamous cell carcinoma. However, little is known about its efficacy in the setting of vulvar cancer. We present a case of advanced vulvar squamous cell carcinoma treated with induction chemotherapy and immunotherapy with cemiplimab followed by definitive chemoradiation in the setting of multiple autoimmune diseases. She achieved a complete clinical response and experienced no worsening of her autoimmune conditions despite cessation of her immunosuppressants and initiating an immune checkpoint inhibitor. We review existing data on neoadjuvant treatment of vulvar cancer and the use of cemiplimab in genital and inguinal squamous cell carcinomas. Ongoing exploration of cemiplimab's efficacy in vulvar cancer and safety in immunosuppressed patients is critical.

Risk Factor for Rash in Patients Receiving Cytarabine and Idarubicin Induction Therapy for Acute Myeloid Leukemia.

Background/Aim: Rash is a common adverse event (AE) observed during cytarabine and idarubicin induction therapy in patients with acute myeloid leukemia (AML). Previous studies have highlighted the challenge in predicting the onset and duration of rash. This study aimed to determine the factors that affect the onset of rash in patients receiving induction therapy for AML. Patients and Methods: This retrospective study involved 97 patients with AML who received induction chemotherapy with cytarabine and idarubicin at the Department of Hematology, Kyushu University Hospital between January 2008 and June 2022. The factors associated with rash were identified through a multivariate stepwise logistic regression analysis. Subsequently, the patient's characteristics were compared between those with risk factors and those without risk factors using a matched pair analysis. Results: Pre-existing leukopenia [odds ratio (OR)=3.294; 95% confidence interval (CI)=1.272-8.531] and good performance status (PS=0) (OR=2.717; 95%CI=1.087-6.792) were significant risk factors for rash development. Conversely, the matched pair analysis indicated that patients with pre-existing leukopenia, excluding those with a PS score of 0, exhibited a significantly (p=0.015) higher incidence of rash than those without it. Conclusion: Both multivariate logistic regression analysis and matched pair analysis identified pre-existing leukopenia as a primary risk factor for rash development associated with cytarabine and idarubicin chemotherapy.

Introducing an Emergency Department Electronic Handbook to Junior Doctors New to Emergency Medicine.

Background The transition of junior doctors into working in the emergency department (ED) in the United Kingdom often poses challenges in adapting to new hospital systems and protocols. To address this issue at Queen Elizabeth Hospital, King's Lynn (QEHKL), a quality improvement project (QIP) was undertaken to develop an electronic ED handbook with the primary aim of enhancing the confidence and knowledge of newly appointed doctors during their ED rotation. This electronic handbook serves as a comprehensive repository for vital medical protocols, guidelines, and trust referral pathways, offering an easily accessible resource for junior doctors. Objectives The primary objective of this study was to determine whether there was an improvement in the confidence and knowledge of ED junior doctors following the introduction of the Electronic ED Handbook. The secondary objectives were to determine whether introducing the ED Handbook increased the overall satisfaction rating of the content of the ED Junior Doctor Induction program and assess the level of recommendation for the ED Handbook among the doctors for inclusion in future ED inductions. Method The QIP was designed using the Model for Improvement framework, Plan, Do, Study, Act (PSDA). The aims were designed to be Specific, Measurable, Achievable, Relevant, and Time-bound (SMART). Pre- and post-intervention surveys were conducted for comparison before and after the ED Handbook was introduced. Results Regarding the confidence of junior doctors to proceed into their new roles, the responses of "quite confident" or "very confident" increased from 77.8% (before) to 100% (after the ED Handbook introduction). One hundred percent of the responders found the ED Handbook to be either "very useful" or "extremely useful" in increasing their confidence and knowledge in the first month of their ED rotation. The satisfaction rating of "excellent" for the content of the ED Junior Doctor Induction program increased from 55.5% to 66.7%. One hundred percent of the responders recommended the inclusion of the ED Handbook for future inductions. Conclusion and recommendations Comparing the results from the pre- and post-intervention surveys shows a significant improvement in the confidence and knowledge of ED junior doctors following the introduction of the Electronic ED Handbook. The handbook was formally endorsed by the ED clinical governance team as an integral component of the ED induction process, aiding junior doctors in making a seamless transition into their new roles in emergency medicine. This study emphasizes the importance of utilizing digital resources to improve the confidence and knowledge of junior doctors and recommends the continued use of the handbook in future induction programs.

Balancing Maternal Melanoma and Vaginal Birth After Cesarean (VBAC) Delivery: A Case Report Highlighting Shared Decision-Making.

Melanoma is increasingly common among reproductive-age women and is one of the most common cancers diagnosed during pregnancy. The literature for melanoma in pregnancy, especially among those with prior uterine scars, is limited. We present an interesting case of a 22-year-old woman who went to her dermatologist for a suspicious lesion on her thigh. The lesion was excised, and histopathology confirmed that it was a melanoma. The dermatologist recommended immediate delivery. The patient then urged her obstetrician to undergo the risks of an induction of labor (IOL) for a trial of labor after cesarean (TOLAC) because she desired a large family, and a second cesarean would make this more difficult to happen. She ultimately had a successful vaginal birth after cesarean (VBAC) and subsequent excision of the melanoma with surgical oncology in the immediate postpartum period. Therefore, the decision for IOL for TOLAC in this case was based on the patient's fears regarding melanoma disease progression in her 39th week. Given the short time course between delivery and excision of her melanoma, it is possible that she may have been able to wait for spontaneous labor, which would have avoided the risks associated with IOL for TOLAC. The optimal timing of surgical intervention for melanoma in pregnant patients who desire TOLAC is unknown. In pregnancies that are approaching their due date, waiting for spontaneous labor may be a reasonable approach to avoid the risks of labor induction, especially in women with prior cesarean delivery. A multidisciplinary approach involving dermatology, surgical oncology, and the obstetric team is warranted to optimize both dermatologic and obstetric outcomes.

Outcome after ablation of atypical atrial flutter: Is induction a feasible approach?

Background: Atypical atrial flutter (AAF) is an increasingly relevant clinical problem. Despite advancements in mapping and ablation techniques, the general management of these patients remain challenging especially when mapping cannot be performed during ongoing arrhythmia. There are no data whether induction of AAF is a feasible approach in these cases. Methods: We retrospectively analyzed patients who underwent catheter ablation of AAF and compared procedural results between patients with ongoing tachycardia when starting the procedure and patients with induced AAF. Results: We analyzed 97 ablation procedures performed in 76 patients with a mean follow-up of 13.2 ± 12.2 months. In 68 procedures (70.1 %) AAF was ongoing at the beginning of the procedure and in 29 cases (29.9 %) AAF had to be induced.There was no statistically significant difference regarding acute procedural success. The recurrence rate of any arrhythmia during follow-up was significantly higher after ablation of ongoing AAF compared to induced AAF (63.2 % vs. 42.9 %; p = 0.047) driven by a significant higher rate of AAF-recurrence (57.4 % vs. 34.5 %; p = 0.039). The number of ablated tachycardias per patient as well as the number of de-novo tachycardias found during re-ablation showed no significant difference between both groups. Conclusion: Starting a procedure with ongoing arrhythmia did not result in better short- or mid-term outcome in patients undergoing AAF ablation. Furthermore, based on our results inducing AAF seems a legitimate approach for AAF ablation in patients presenting in sinus rhythm.

Evaluating the Efficacy of Different Treatment Intensities in Nasopharyngeal Carcinoma Patients: A Nationwide Cancer Registry-Based Study.

OBJECTIVE: The aim of this study was to evaluate the efficacy of different treatment intensities (TIs) in patients with nasopharyngeal carcinoma (NPC). METHODS: The study assessed newly diagnosed, non-metastatic NPC patients from the Taiwan Cancer Registry between 2010 and 2017. TIs were divided into four groups: TI1 [radiotherapy (RT) alone or induction chemotherapy (IC) followed by RT); TI2 (concurrent chemoradiotherapy (CRT) alone); TI3 (IC followed by CRT or CRT followed by adjuvant chemotherapy (AC)]; and TI4 (IC followed by CRT followed by AC). The primary outcome was cancer-specific survival (CSS). RESULTS: The study included 9863 patients. For stage I-II NPC patients, there was no significant difference in CSS among the different TI groups. For stage III patients, those receiving TI3 had better CSS (hazard ratio [HR] 0.69) compared with those receiving TI1. No significant differences in CSS were noted among those receiving TI2, TI3, and TI4. For stage IVA-B patients, those receiving TI2 (HR 0.70), TI3 (HR 0.49), and TI4 (HR 0.43) had better CSS compared with those receiving TI1. Compared with stage IVA-B patients receiving TI2, those receiving TI3 (HR 0.70) and TI4 (HR 0.61) had significantly better CSS. No differences in CSS were noted between those receiving TI3 and TI4. CONCLUSIONS: For stage I-II NPC patients, RT alone is appropriate. For stage III and IVA-B patients, IC + CRT or CRT + AC may be needed to achieve optimal outcomes. No advantage of IC + CRT + AC over IC + CRT or CRT + AC was observed.

Induced ruminative and mindful self-focus in daily life across the menstrual cycle in women with and without premenstrual dysphoric disorder.

Rumination and mindfulness are transdiagnostic risk and protective factors while their role in Premenstrual Dysphoric Disorder (PMDD) is unclear. Thus, we aimed to investigate the cycle-phase-specific effects of rumination and mindful self-focus on momentary mood and cognitions in women with and without PMDD. This study involved brief ambulatory inductions of ruminative and mindful self-focus along with ambulatory assessments of negative (NA) and positive affect (PA), and rumination, present-moment-awareness (PMA) and self-acceptance on two days during both the follicular and late luteal phase in women with and without PMDD (n = 60 each). Compared to healthy controls, women with PMDD showed stronger increases in PA in response to mindful self-focus inductions during the late luteal phase, whereas no such group differences were identified during the follicular phase. Independent of clinical status and cycle phase, induced ruminative self-focus immediately increased momentary NA and rumination and decreased PMA, whereas induced mindful self-focus inductions increased momentary self-acceptance. Overall, higher PA-reactivity toward mindful self-focusing during late luteal phase in women with PMDD points to the potential of cycle-phase-specific mindfulness interventions for PMDD. Irrespective of cycle phase, rumination and mindfulness appear to represent targets for brief prevention and intervention measures for both non-clinical and clinical groups.

Transperineal sonographic assessment of the angle of progression before the onset of labour: how well does it predict the mode of delivery in late-term pregnancy.

OBJECTIVES: Predicting the success of vaginal delivery is an important issue in preventing adverse maternal and neonatal outcomes. This study sought to examine whether measurement of the angle of progression (AoP) can predict a successful vaginal delivery following induction of labour (IoL) among late term nulliparous women with a low (4>) Bishop score. METHODS: This prospective study included consecutive nulliparous pregnant women whose gestational age was 41 weeks and 1-6 days (late-term). The AoP was measured at least three times and their means were calculated. RESULTS: During the study period, data of 150 women were included in the final analysis. Thirty-eight women underwent CS due to failure to progress (n=30) or NRGHR (n=8), while the remaining 112 women underwent NVD, with four women requiring vacuum extraction. The two groups were similar with respect to age, gestational age, BMI, estimated foetal weight, and birth weight. Women undergoing NVD differed significantly from those undergoing CS with respect to a greater ultrasonographic AoP (113.8±11.9° vs. 98.1±10.9°, p=0.0001), a shorter duration of dinoprostone use, shorter time to labour contraction, and a shorter duration of labour. In ROC analysis, the cut-off value for AoP was 100° for the prediction of successful IoL for NVD, with a sensitivity of 96 % and a specificity of 63 %. CONCLUSIONS: AoP may be a useful sonographic parameter for predicting successful vaginal delivery among nulliparous women at late term undergoing IoL; an AOP wider than 100° is associated with a high rate of vaginal delivery.

Evaluation of pembrolizumab plus cisplatin and fluorouracil in radical treatment for patients with T4b esophageal squamous cell carcinoma.

BACKGROUND: Pembrolizumab plus cisplatin and 5-fluorouracil administered as first-line therapy for advanced esophageal cancer patients has shown a better objective response and survival than conventional chemotherapy with less severe hematological adverse events. The safety and efficacy of this regimen were evaluated in patients with T4b esophageal squamous cell carcinoma (ESCC). METHODS: Eight consecutive patients with T4b ESCC received this regimen according to KEYNOTE-590 as induction, and they were evaluated after 1-3 courses. The programmed death-ligand 1 (PD-L1) combined positive score (CPS) was also evaluated before chemotherapy. Efficacy for the primary lesion was evaluated by our original formula for the tumor reduction rate. RESULTS: The numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients had relief from T4b. Two patients underwent conversion surgery with R0 resection. PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients. PD-L1 CPS was under 10 in PD patients. One patient had hyperprogression, resulting in an esophago-pulmonary fistula. Greater than grade 3 adverse events were bleeding gastric ulcer in one patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient had febrile neutropenia. CONCLUSIONS: Marked tumor reduction was confirmed in 62.5% of patients with pembrolizumab plus cisplatin and 5-fluorouracil with less adverse events. This regimen could be administered as induction chemotherapy for patients with T4b ESCC.

Physical radiation induced the yield of triterpenoids in hypha of Inonotus obliquus to increase.

HSD-IO01, a new pure strain of I. obliquus, was isolated and purified from the sclerotium of I. obliquus of Daxing'an Mountains. Physical radiation-assisted liquid fermentation technology was explored to increase the triterpenoids yield of HSD-IO01. In the 100 mL optimized liquid fermentation system, the hypha dry weight of HSD-IO01 was 1.7734 g, and the triterpenoids yield was 43.43 mg. Yields of triterpenoids increased after induction with ultrasound, microwave, or UV light, respectively. Among them, ultrasonic treatment had the most remarkable induction effect. The yield of triterpenoids would be increased to 68.35 mg (57.38 %) when the HSD-IO01 was treated by 100 W ultrasonic for 45 min. Establishing ultrasonic-assisted liquid fermentation technology could further promote the detailed development and comprehensive utilization of I. obliquus resources.

Reduced-dose chemotherapy and blinatumomab as induction treatment for newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia: a phase 2 trial.

Blinatumomab has emerged as a promising component of first-line therapy for acute B-cell precursor lymphoblastic leukemia (BCP-ALL), bolstering treatment efficacy. To mitigate CD19 selection pressure and reduce the incidence of blinatumomab-associated toxicities, pre-treatment chemotherapy is recommended before administering blinatumomab. From September 2022 to December 2023, we conducted a single-arm, multicenter, phase 2 trial (NCT05557110) in newly diagnosed Philadelphia chromosome-negative BCP-ALL (Ph-negative BCP-ALL) patients. Participants received induction treatment with reduced-dose chemotherapy (RDC), comprising idarubicin, vindesine, and dexamethasone over 7 days, followed by 2 weeks of blinatumomab. Those failing to achieve composite complete remission (CRc) received an additional 2 weeks of blinatumomab. The primary endpoint was the CRc rate post initial induction treatment. Of the 35 enrolled patients, 33 (94%) achieved CRc after 2 weeks of blinatumomab, with 30 (86%) achieving measurable residual disease (MRD) negativity. Two patients extended blinatumomab to 4 weeks. With either 2 or 4 weeks of blinatumomab treatment, all patients achieved CR (35/35) and 89% (31/35) were MRD negativity. The median time to CR was 22 days. Immune effector cell-associated neurotoxicity syndrome was limited (14%, all grade 1). Non-hematological adverse events of grade 3 or higher included pneumonia (17%), sepsis (6%), and cytokine release syndrome (9%). With a median follow-up of 11.5 months, estimated 1-year overall survival and 1-year progression-free survival rates were 97.1% and 82.2%, respectively. These findings affirm that RDC followed by blinatumomab is an effective and well-tolerated induction regimen for newly diagnosed Ph-negative BCP-ALL, supporting a shift towards less intensive and more targeted therapeutic approaches. Trial registration: https://www.clinicaltrials.Gov . Identifier NCT05557110.

Development of an AI-based support system for controlled ovarian stimulation.

Purpose: Controlled ovarian stimulation (COS) is vital for IVF. We have developed an AI system to support the implementation of COS protocols in our clinical group. Methods: We developed two models as AI algorithms of the AI system. One was the oocyte retrieval decision model, to determine the timing of oocyte retrieval, and the other was the prescription inference model, to provide a prescription similar to that of an expert physician. Data was obtained from IVF treatment records from the In Vitro Fertilization (IVF) management system at the Asada Ladies Clinic, and these models were trained with this data. Results: The oocyte retrieval decision model achieved superior sensitivity and specificity with 0.964 area under the curve (AUC). The prescription inference model achieved an AUC value of 0.948. Four models, namely the hCG prediction model, the hMG prediction model, the Cetrorelix prediction model, and the Estradiol prediction model included in the prescription inference model, achieved AUC values of 0.914, 0.937, 0.966, and 0.976, respectively. Conclusion: The AI algorithm achieved high accuracy and was confirmed to be useful. The AI system has now been implemented as a COS tool in our clinical group for self-funded treatments.

Pathologic response evaluation of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy: a clinical trial.

Objective: Esophageal cancer is a therapeutic challenge in most healthcare systems. Most patients present with locally advanced disease at diagnosis. Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced esophageal carcinoma. Since achieving a complete pathological response in postoperative specimens following neoadjuvant therapy is associated with improved patient survival, this study was designed to evaluate the pathologic response of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy (HFR). Methods: This single-arm clinical trial (IRCT20210623051676N1) evaluated patients with squamous cell carcinoma or adenocarcinoma of the esophagus, stage cT2-T4a N0 M0 or cT1-T4a N+ M0. Patients received 3-5 cycles of weekly induction chemotherapy with the paclitaxel (50 mg/m2) and carboplatin (AUC=2) regimen, followed by weekly concurrent CRT with the same chemotherapy regimen. The radiation dose was 40 Gy, delivered over 16 fractions, 5 days per week (2.5 Gray/fraction). Patients underwent surgery 4-6 weeks after completion of CRT. The surgical specimens were evaluated for pathological response. A p-value of < 0.05 was considered significant in all analyses. Results: Out of 54 patients enrolled in this study, 45 completed the neoadjuvant protocol. Of these 45 patients, 32 underwent surgery and were finally analyzed. The mean age of the patients was 59.9 ± 8.6 years (range, 37-75 years). The location of the tumor was in the mid-thoracic esophagus in most patients (21, 65.6%) and the most common histological type was SCC (29, 90.6%). The median number of induction and concurrent chemotherapy cycles was 5 (4.8 ± 1.3 course, range, 1-10) and 3 (2.6 ± 0.8 course, range, 0-4), respectively. Among 45 patients who completed the neoadjuvant protocol, the most common toxicities were grade 3 neutropenia (15.6%), acute renal failure (4.4%), and odynophagia (37.8%). Nearly two-thirds of the patients experienced complete or near-complete responses (71.9%, 23 patients). Partial response was reported in 6 patients (18.8%) and poor response in 3 patients (9.4%). Conclusion: Preoperative induction chemotherapy followed by HFR with concurrent chemotherapy has low toxicity and side effects, good tolerance, and significant efficacy in the treatment of patients with esophageal cancer. Clinical trial registration: https://irct.behdasht.gov.ir/trial/59930, identifier NCT05745545.

Magnetic-Nanorod-Mediated Nanowarming with Uniform and Rate-Regulated Heating.

Rewarming cryopreserved samples requires fast heating to avoid devitrification, a challenge previously attempted by magnetic nanoparticle-mediated hyperthermia. Here, we introduce Fe3O4@SiO2 nanorods as the heating elements to manipulate the heating profile to ensure safe rewarming and address the issue of uneven heating due to inhomogeneous particle distribution. The magnetic anisotropy of the nanorods allows their prealignment in the cryoprotective agent (CPA) during cooling and promotes subsequent rapid rewarming in an alternating magnetic field with the same orientation to prevent devitrification. More importantly, applying an orthogonal static magnetic field at a later stage could decelerate heating, effectively mitigating local overheating and reducing CPA toxicity. Furthermore, this orientational configuration offers more substantial heating deceleration in areas of initially higher heating rates, therefore reducing temperature variations across the sample. The efficacy of this method in regulating heating rate and improving rewarming uniformity has been validated using both gel and porcine artery models.