Global prevalence of anxiety and depression among medical students during the COVID-19 pandemic: a systematic review and meta-analysis.

PURPOSE: As future physicians, medical students have experienced tremendous pressure during the ongoing COVID-19 pandemic, which is associated with a high risk of depression and anxiety. We aimed to investigate an overview of the prevalence of anxiety and depression among medical students in various countries during the global COVID-19 pandemic, and discuss associated stressors. METHODS: We systematically searched CINAHL, EMBASE, MEDLINE, PubMed, and Web of Science for relevant articles from December 1, 2019 to March 15, 2023. We performed meta-analysis using a random-effects model with REML method to calculate the pooled prevalence of anxiety and depression. Begg's and Egger's tests were used to identify the potential risk of publication bias. Meta-regression was used to explore potential sources of heterogeneity. RESULTS: We identified 130 studies reporting anxiety and depression among 132,068 medical students during the COVID-19 pandemic. Eight screening tools were identified for anxiety and six for depression. The pooled prevalence of mental health outcomes for anxiety and depression was 45% (95% confidence interval [CI], 40%-49%) and 48% (95% CI, 43%-52%), respectively. The pooled prevalence of mental health outcomes for moderate and severe anxiety and moderate and severe depression was 28% (95% CI, 24%-32%) and 30% (95% CI, 26%-35%), respectively. There was high heterogeneity between studies, with I2 ranging from 99.58%-99.66%. Continent and survey date were included in the meta-regression model. The results of meta-regression revealed that medical students in Asia had a lower prevalence of anxiety, and depression than those in other regions. The survey date (from February to June, 2020) showed a significantly positive correlation with the prevalence of anxiety and depression. CONCLUSIONS: We demonstrated the global prevalence of anxiety and depression among medical students during the COVID-19 pandemic. The data highlight that medical students worldwide are at high risk of experiencing anxiety and depression. The reported stressors can be categorized into personal, academic, environmental and cultural, and pandemic factors. Schools and institutions should ensure optimal alternative learning environments for uninterrupted provision of medical education. The appropriate authorities should prioritize the provision of adequate protection for medical students and establish policies to promote new methods of training and education during a disaster, such as via distance learning.

Efficacy of transarterial chemoembolization with drug-eluting beads combined with systemic chemotherapy and targeted therapy in colorectal cancer liver metastasis.

BACKGROUND: Systemic therapy is the standard treatment for unresectable colorectal cancer with liver metastasis (CRCLM). Transarterial chemoembolization with drug-eluting beads (DEB-TACE) is considered an effective treatment option for CRCLM. Few studies have investigated the combination of DEB-TACE, chemotherapy, and targeted therapy for CRCLM. In the present study, we evaluated the disease control rate (DCR), adverse events, and survival among patients with CRCLM who underwent the combination of DEB-TACE and chemotherapy/targeted therapy. MATERIALS: We retrospectively reviewed 35 patients with CRCLM who were treated between January 2015 and January 2021. Standard systemic chemotherapy, targeted therapy, and 66 DEB-TACE procedures were administered. Data were collected on each DEB-TACE procedure, including chemotherapy agents, tumor burden of liver metastasis, number of DEB-TACE courses, and adverse events. Patients who received DEB-TACE after failure of first-line systemic therapy were categorized into the first-line failure group. Patients who received DEB-TACE after the failure of second-line, third-line, or fourth-line therapy were categorized into the other group. Subgroup analysis was performed to compare overall survival (OS) and progression-free survival (PFS) between the two groups. RESULTS: In total, 35 patients with CRCLM (34 patients with adenocarcinoma and 1 patient with neuroendocrine carcinoma) were enrolled. In total, 13 patients (37.1%) had extrahepatic metastases at initial diagnosis. In this study, 66 DEB-TACE procedures were performed. The DCR was 54.3%. The median OS period was 47.4 months, and the estimated 3-year OS rate was 59.5%. The median PFS period was 6.3 months, and the estimated 1-year PFS rate was 20.6%. The PFS period was longer in the first-line failure group than in the other group (7.2 vs. 6.3 months). No significant difference was observed in OS between the two groups. Four episodes (6.1%) of grade 3 intra-abdominal infection were observed. CONCLUSION: The combination of chemotherapy, targeted therapy, and DEB-TACE can lead to a favorable DCR and survival outcomes in patients with CRCLM. Early intervention with DEB-TACE (i.e., after the failure of first-line therapy) has the potential to extend the PFS period in patients with CRCLM. Severe adverse events were rare and manageable. Further prospective, randomized controlled studies are warranted to obtain more conclusive findings.

Clinical and cost-effectiveness analysis of mFOLOFX6 with or without a targeted drug among patients with metastatic colorectal cancer: inverse probability of treatment weighting.

This study investigated the cost-effectiveness and quality of life (QoL) within 1 year of receiving mFOLOFX6 with or without a targeted drug (bevacizumab or ramucirumab) as second-line treatment among patients with metastatic colorectal cancer (mCRC) following the failure of FOLFIRI + bevacizumab as first-line treatment. This prospective cohort study included patients who received a diagnosis of mCRC between March 2015 and May 2020. QoL was evaluated before treatment and at 6 months and 1 year posttreatment. All related variables were controlled using the inverse probability of treatment weighting method. Generalized estimating equations with the difference-in-difference method was used to explore changes in QoL. The incremental cost-utility ratio (ICUR) of the two groups was simulated using the annual-cycle Markov decision tree model. Finally, 39 and 76 patients were included in the targeted and nontargeted agent groups, respectively. At 6 months after treatment, QoL of the two groups improved significantly, but the targeted agent group had significantly better QoL than did the nontargeted agent group at 1 year posttreatment (P < 0.05). When the time frame was set to 20 years, the ICUR of the targeted agent group compared with the nontargeted agent group was US$32,052 per quality-adjusted life years. Addition of a targeted drug to the second-line mFOLOFX6 regimen not only improved the patients' QoL but was also more cost effective when the willingness-to-pay threshold was set at US$33,004 (the per capita gross domestic product of Taiwan). These patients should be reimbursed for these targeted agents by the National Health Insurance scheme in Taiwan.

The Auxiliary Effects of Low-Molecular-Weight Fucoidan in Locally Advanced Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy Before Surgery: A Double-Blind, Randomized, Placebo-Controlled Study.

Patients with cancer use low-molecular-weight fucoidan (LMF) as a supplement to therapy. However, most studies of LMF are in vitro or conducted using animals. Concurrent chemoradiotherapy (CCRT) is the gold standard for locally advanced rectal cancer (LARC). This study investigated the quality of life (QoL) and clinical outcomes of patients with LARC taking LMF as a supplement to neoadjuvant CCRT. This was a double-blind, randomized, placebo-controlled study. The sample comprised 87 patients, of whom 44 were included in a fucoidan group and 43 were included in a placebo group. We compared their QoL scores and clinical outcomes before treatment, and at 1 month, 2 months, and 3 months posttreatment. Pretreatment and posttreatment gut microbiota differences were also compared. Although enhanced physical well-being (PWB) at 2 months and 3 months posttreatment in the fucoidan group were observed (both P < .0125), the improvements of the Functional Assessment of Cancer Therapy for Patients with Colorectal Cancer (FACT-C) were nonsignificant (all P > .0125). Skin rash and itching and fatigue were less common in the fucoidan group (both P < .05). Posttreatment, the genus Parabacteroides was significantly more common in the gut microbiota of the fucoidan group. LMF administration improved the QoL, skin rash and itching, fatigue, and gut microbiota composition of the patients with LARC receiving CCRT.Clinical Trial Registration: NCT04342949.

Heterotopic intestine and abdominal wall transplantation in a miniature swine: A model for graft immunology.

In order to accurately monitor graft immunology, we have developed a method for performing intestine and abdominal wall transplantation heterotopically in miniature swine. The procedure consisted of simultaneous segmental terminal ileum and full-thickness abdominal wall transplantation in Lanyu miniature swine, with the intestinal and the abdominal wall grafts being placed on the recipient's bilateral rear flank. Five transplantations were technically successful. One animal died on the first post-transplant day due to anesthesia-related issues, three abdominal wall and four intestinal grafts survived, while one abdominal wall graft failed due to vascular thrombosis. Acute cellular rejection (ACR) of the intestinal graft could occur preceding, simultaneously with or following ACR of the abdominal wall graft. Our experimental model demonstrates the technical feasibility of heterotopic intestine and abdominal wall transplantation in miniature swine without grafting in gastrointestinal continuity. This model could be suitable for further studies of graft immunology.

Efficacy of concurrent radiotherapy in patients with locally advanced rectal cancer and synchronous metastasis receiving systemic therapy.

Background: Neoadjuvant chemoradiotherapy followed by total mesorectal excision is the standard treatment for patients with nonmetastatic locally advanced rectal cancer (LARC). However, for patients with LARC and synchronous metastasis, the optimal treatment strategy and sequence remain inconclusive. In the present study, we evaluated the efficacy and safety of concurrent radiotherapy in patients with de novo metastatic rectal cancer who received chemotherapy and targeted therapy. Methods: We retrospectively reviewed the data of 63 patients with LARC and synchronous metastasis who received intensive therapy at the study hospital between April 2015 and November 2018. The included patients were divided into two groups: RT-CT, those who received systemic chemotherapy with targeted therapy and concurrent radiotherapy (for primary rectal cancer), and CT, those who received only systemic chemotherapy with targeted therapy. Results: Treatment response was better in the RT-CT group than in the CT group. The rate of primary tumor resection (PTR) was higher in the RT-CT group than in the CT group (71.4% and 42.9%, respectively; P = .0286). The RT-CT group exhibited considerably longer local recurrence-free survival (P = .0453) and progression-free survival (PFS; from 13.3 to 22.5 months) than did the CT group (P = .0091); however, the groups did not differ in terms of overall survival (OS; P = .49). Adverse events were almost similar between the groups, except frequent diarrhea, the prevalence of which was higher in the RT-CT group than in the CT group (59.5% and 23.8%, respectively; P = .0075). Conclusions: In the era of biologics, radiotherapy may increase the resectability of primary rectal tumors, reducing the risk of locoregional failure and prolonging PFS. Concurrent pelvic radiotherapy may not substantially improve OS, which is indicated by metastasis. Hence, the resection of the distant metastases may be essential for improving long-term OS. To further determine the efficacy of concurrent radiotherapy, additional prospective, randomized studies must combine preoperative pelvic radiotherapy with PTR and metastectomy to treat patients with stage IV LARC.

Unknown­primary neuroendocrine neoplasms diagnosed by short­acting somatostatin test: Case series in one institution.

Neuroendocrine neoplasms (NENs) are a rare heterogeneous group of neoplasms that arise from neuroendocrine cells. Unknown-primary NENs (UP-NENs) are particularly challenging to diagnose and treat. Techniques such as immunohistochemical stains, functional imaging studies, and molecular cancer classifier assays may help clinicians identify the origin of a tumor. However, numerous medical facilities lack the necessary medical equipment, such as functional imaging scanning, to provide patients with a complete primary tumor survey. Even these tests are not enough to determine the original tumor in some cases. The present case series described the diagnosis and treatment outcomes of patients with UP-NEN in a single institution. The medical records of four patients treated between November 2012 and January 2022 were retrospectively reviewed and clinical symptoms, diagnostic methods, image findings and treatment modalities were considered. All patients were diagnosed having functional UP-NENs by using a short-acting somatostatin test. These patients were treated with long-acting release somatostatin analogs along with a positive result. Short-acting somatostatin is an alternatively simple method to determine if a patient has UP-NENs that are functional or expresses somatostatin receptors in the absence of imaging scanning.

MicroRNAs as Predictive Biomarkers in Patients with Colorectal Cancer Receiving Chemotherapy or Chemoradiotherapy: A Narrative Literature Review.

Colorectal cancer (CRC) is one of the most common malignancies and is associated with high mortality rates worldwide. The underlying mechanism of tumorigenesis in CRC is complex, involving genetic, lifestyle-related, and environmental factors. Although radical resection with adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy and neoadjuvant chemoradiotherapy have remained mainstays of treatment for patients with stage III CRC and locally advanced rectal cancer, respectively, the oncological outcomes of these treatments are often unsatisfactory. To improve patients' chances of survival, researchers are actively searching for new biomarkers to facilitate the development of more effective treatment strategies for CRC and metastatic CRC (mCRC). MicroRNAs (miRs), small, single-stranded, noncoding RNAs, can post-transcriptionally regulate mRNA translation and trigger mRNA degradation. Recent studies have documented aberrant miR levels in patients with CRC or mCRC, and some miRs are reportedly associated with chemoresistance or radioresistance in CRC. Herein, we present a narrative review of the literature on the roles of oncogenic miRs (oncomiRs) and tumor suppressor miRs (anti-oncomiRs), some of which can be used to predict the responses of patients with CRC to chemotherapy or chemoradiotherapy. Moreover, miRs may serve as potential therapeutic targets because their functions can be manipulated using synthetic antagonists and miR mimics.

Identifying and clinically validating biomarkers for immunotherapy in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is a leading cause of death. For three decades, chemotherapy with or without targeted therapy (provided before or after tumor resection surgery) has been the standard treatment for patients with CRC. Biomarkers are key tools for performing early detection, prognostication, and survival and treatment response predictions. Notably, immune checkpoint inhibitors (ICIs) have transformed prognoses for solid tumors (including CRC). AREA COVERED: Although immunotherapy has developed considerably, it is only effective for a small number of microsatellite instability-high (MSIH) cancer cases; such cases represent only 5% of metastatic CRC (mCRC) cases, which are characterized by an immune-inflamed microenvironment that can be rewired against cancer cells through ICI administration. Immunotherapy research is gradually uncovering the mechanism underlying immune resistance in patients with CRC and discovering new biomarkers. For example, studies have clinically validated the associations of deficient mismatch repair system/microsatellite instability, tumor mutation burden, programmed death ligand 1 expression, and polymerase epsilon with CRC in patients undergoing immunotherapy. EXPERT OPINIONS: Clinical trials documenting the effect of immune checkpoints were performed to produce long-lasting effects for patients with mCRC. Consequently, therapeutic decision-making models are further refined by the inclusion of powerful molecular biomarkers in patients with CRC.

Clinicopathological Features and Oncological Outcomes of Early and Late Recurrence in Stage III Colorectal Cancer Patients after Adjuvant Oxaliplatin-Based Therapy.

Aims: An adjuvant oxaliplatin-based regimen is the standard of care for patients with stage III colorectal cancer (CRC). Few reports have compared the clinicopathological features and oncological outcomes of such treatment between patients with early (≤1 year) and late recurrence (>1 year). Methods: Between January 2012 and December 2019, CRC recurred in 128 (24.1%) of 531 patients with consecutive stage III CRC after they received curative resection and an adjuvant oxaliplatin-based regimen. The clinicopathological features and oncological outcomes of the 128 patients were analyzed retrospectively. Results: The median follow-up period after the first chemotherapy cycle was 35.0 months (range, 7-100.9), and the median recurrence time was 16.1 months. Forty-seven patients (36.7%) had an early recurrence and eighty-one patients (63.3%) had a late recurrence. Compared with patients with late recurrence, those with early recurrence were mostly younger (median: 58 vs. 64 years, p=0.009), had less oxaliplatin-based therapy cycles (median: 8 vs. 12 cycles, p < 0.001), and had a shorter overall survival time (median: 23.3 vs. 39.7 months, p < 0.001). The area under the curve of patient age and chemotherapy cycles for predicting early recurrence was 0.629 and 0.705 (p=0.015 and p < 0.001), respectively. The receiver operating characteristic curve analysis demonstrated that the cutoff level for patient age was 57 years and the number of chemotherapy cycles was 8. A multivariate analysis revealed that patient age ≤57 years and oxaliplatin-based therapy ≤8 cycles were independent risk factors for early recurrence (odds ratio (OR) = 3.049, p=0.022; OR = 4.995, p=0.002). These factors were associated with an approximately 77.8% risk of recurrence within 1 year, compared with the 21.5% risk associated with patient age >57 years and oxaliplatin-based therapy >8 cycles (p = 0.003). Conclusion: Patients with early recurrence had poorer survival than those with late recurrence. If >8 cycles of oxaliplatin-based therapy can be administered without disease progression, then patients with stage III CRC would have a lower risk of early recurrence.

Comprehensive Review of Biomarkers for the Treatment of Locally Advanced Colon Cancer.

Despite the implementation of global screening programs, colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide. More than 10% of patients with colon cancer are diagnosed as having locally advanced disease with a relatively poor five-year survival rate. Locally advanced colon cancer (LACC) presents surgical challenges to R0 resection. The advantages and disadvantages of preoperative radiotherapy for LACC remain undetermined. Although several reliable novel biomarkers have been proposed for the prediction and prognosis of CRC, few studies have focused solely on the treatment of LACC. This comprehensive review highlights the role of predictive biomarkers for treatment and postoperative oncological outcomes for patients with LACC. Moreover, this review discusses emerging needs and approaches for the discovery of biomarkers that can facilitate the development of new therapeutic targets and surveillance of patients with LACC.

Parental Educational Intervention to Facilitate Informed Consent for Pediatric Procedural Sedation in the Emergency Department: A Parallel-Group Randomized Controlled Trial.

Obtaining valid parental informed consent for pediatric procedures in the emergency department (ED) is challenging. We compared a video-assisted informed consent intervention with conventional discussion to inform parents about pediatric procedural sedation in the ED. We conducted a prospective randomized controlled trial using a convenience sample including the parents of children in the ED in whom procedural sedation for facial laceration was recommended. The video group watched an informational video. Conventional group participants received information from physicians during conventional discussion. The primary outcome was knowledge improvement of the video intervention compared with conventional discussion. The secondary outcome was parental satisfaction. Video and conventional groups comprised 32 and 30 participants, respectively. Mean knowledge scores of parents after intervention [±standard deviation] were higher in the video group (91.67 ± 12.70) than in the conventional group (73.33 ± 19.86). Knowledge score differences were significantly bigger in the video group (coefficient: 18.931, 95% confidence interval: 11.146-26.716). Video group participants reported greater satisfaction than conventional group participants. Parents' comprehension of and satisfaction with the informed consent process for pediatric procedural sedation may be improved with the use of an educational video. Standardized approaches should be developed by healthcare institutions to better educate parents, facilitate treatment decisions, and boost satisfaction in the ED.

Joint Effect of Heavy Vehicles and Diminished Light Conditions on Paediatric Pedestrian Injuries in Backover Crashes: A UK Population-Based Study.

Backover crashes cause considerable injuries especially among young children. Prior research on backover crashes has not assessed the joint effect of heavy vehicles and diminished light conditions on injuries. By analysing the United Kingdom STATS19 crash dataset from 1991 to 2020, this study focused on backover crashes involving paediatric cyclists or pedestrians aged ≤17 years and other motorised vehicles. By estimating the adjusted odds ratio (AOR) of multiple logistic regression models, pedestrians appeared to have 82.3% (95% CI: 1.78-1.85) higher risks of sustaining killed or serious injuries (KSIs) than cyclists. In addition, casualties involved in backover crashes with heavy vehicles were 39.3% (95% CI: 1.35-1.42) more likely to sustain KSIs than those involved in crashes with personal cars. The joint effect of heavy vehicles and diminished light conditions was associated with a 71% increased probability of sustaining KSIs (AOR = 1.71; 95% CI: 1.60-1.83). Other significant joint effects included young children (aged 0 to 5 years) as pedestrian (AOR = 1.92; 95% CI: 1.87-1.97), in diminished light conditions (AOR = 1.23; 95% CI: 1.15-1.31), and with heavy vehicle (AOR = 1.37; 95% CI: 1.28-1.47).

Role of non-coding RNAs in radiosensitivity of colorectal cancer: A narrative review.

Colorectal cancer (CRC) is a global public health concern because of its high prevalence and mortality. Although radiotherapy is a key method for treating CRC, radioresistance is an obstacle to radiotherapy use. The molecular mechanisms underlying the radioresistance of CRC remain unclear. Increasing evidence has revealed the multiple regulatory functions of non-coding RNAs (ncRNAs) in numerous malignancies, including CRC. Several ncRNAs have been reported to be involved in the determination of radiosensitivity of CRC cells, and some have excellent potential to be prognostic biomarkers or therapeutic targets in CRC treatment. The present review discusses the biological functions and underlying mechanisms of ncRNAs (primarily lncRNA, miRNA, and circRNA) in the regulation of the radiosensitivity of CRC. We also evaluate studies that examined ncRNAs as biomarkers of response to radiation and as therapeutic targets for enhancing radiosensitivity.

MicroRNA-148a induces apoptosis and prevents angiogenesis with bevacizumab in colon cancer through direct inhibition of ROCK1/c-Met via HIF-1α under hypoxia.

Angiogenesis and antiapoptosis effects are the major factors influencing malignancy progression. Hypoxia induces multiple mechanisms involving microRNA (miRNA) activity. Vascular endothelial growth factor (VEGF) is correlated with angiogenesis. An antiapoptotic factor, myeloid leukemia 1 (Mcl-1) is the main regulator of cell death. This study examined the role of miR-148a in inhibiting VEGF and Mcl-1 secretion by directly targeting ROCK1/c-Met by downregulating HIF-1α under hypoxia. The protein expression of ROCK1 or Met/HIF-1α/Mcl-1 in HCT116 and HT29 cells (all P < 0.05) was significantly reduced by miR-148a. The tube-formation assay revealed that miR-148a significantly suppressed angiogenesis and synergistically enhanced the effects of bevacizumab (both P < 0.05). The MTT assay revealed the inhibitory ability of miR-148a in HCT116 and HT29 cells (both P < 0.05). miR-148a and bevacizumab exerted synergistic antitumorigenic effects (P < 0.05) in an animal model. Serum miR-148a expression of metastatic colorectal cancer (mCRC) patients with a partial response was higher than that of mCRC patients with disease progression (P = 0.026). This result revealed that miR-148a downregulated HIF-1α/VEGF and Mcl-1 by directly targeting ROCK1/c-Met to decrease angiogenesis and increase the apoptosis of colon cancer cells. Furthermore, serum miR-148a levels have prognostic/predictive value in patients with mCRC receiving bevacizumab.

Neoadjuvant Chemoradiotherapy for Locally Advanced Gastric Cancer: Where Are We at?

Locally advanced gastric cancer (LAGC) has a poor prognosis with surgical resection alone, and neoadjuvant treatment has been recommended to improve surgical and oncological outcomes. Although neoadjuvant chemotherapy has been established to be effective for LAGC, the role of neoadjuvant chemoradiotherapy (NCRT) remains under investigation. Clinical experience and research evidence on esophagogastric junction adenocarcinoma (e.g., cardia gastric cancers) indicate that the likelihood of achieving sustainable local control is higher through NCRT than through resection alone. Furthermore, NCRT also has an acceptable treatment-related toxicity and adverse event profile. In particular, it increases the likelihood of achieving an R0 resection and a pathological complete response (pCR). Moreover, NCRT results in higher overall and recurrence-free survival rates than surgery alone; however, evidence on the survival benefits of NCRT versus neoadjuvant chemotherapy (NCT) remains conflicting. For noncardia gastric cancer, the efficacy of NCRT has mostly been reported in retrospective studies, and several large clinical trials are ongoing. Consequently, NCRT might play a more essential role in unresectable LAGC, for which NCT alone may not be adequate to attain disease control. The continual improvements in systemic treatments, radiotherapy techniques, and emerging biomarkers can also lead to improved personalized therapy for NCRT. To elucidate the contributions of NCRT to gastric cancer treatment in the future, the efficacy, potential toxicity, predictive biomarkers, and clinical considerations for implementing NCRT in different types of LAGC were reviewed.

Metformin Enhancement of Therapeutic Effects of 5-Fluorouracil and Oxaliplatin in Colon Cancer Cells and Nude Mice.

Studies have demonstrated that metformin has antitumor effects in addition to therapeutic effects on hyperglycemia; however, few studies have explored the effects of metformin in chemotherapy. Therefore, we hypothesized that the administration of metformin would enhance the therapeutic effects of 5-fluorouracil and oxaliplatin (FuOx) to inhibit the growth of colorectal cancer (CRC) cells in vitro and in vivo. The results of our in vitro experiments demonstrated that metformin significantly increased the effects of FuOx with respect to cell proliferation (p < 0.05), colony formation (p < 0.05), and migration (p < 0.01) and induced cell cycle arrest in the G0/G1 phase in HT29 cells and the S phase in SW480 and SW620 cells (p < 0.05). Flow cytometry analysis revealed that metformin combined with FuOx induced late apoptosis (p < 0.05) by mediating mitochondria-related Mcl-1 and Bim protein expression. Furthermore, in vivo, metformin combined with FuOx more notably reduced tumor volume than FuOx or metformin alone did in BALB/c mice (p < 0.05). These findings demonstrate that metformin may act as an adjunctive agent to enhance the chemosensitivity of CRC cells to FuOx. However, further clinical trials are warranted to validate the clinical implications of the findings.

Surgical Efficacy and Safety of Patients with Locally Advanced Gastric Cancer following Neoadjuvant Concurrent Chemoradiotherapy and Chemotherapy.

Background: The safety and efficacy of gastrectomy for locally advanced gastric cancer (LAGC) following neoadjuvant therapy have gained increasing attention. In this article, we present our preliminary treatment results and compare the surgical safety and outcomes of neoadjuvant concurrent chemoradiotherapy (CCRT) with those of chemotherapy in patients with LAGC. Patients and Methods. Sixty-three patients with a diagnosis of LAGC (clinical staging cT3N2+, cT4aN+, or cT4b) who had received neoadjuvant therapy at any period from January 2014 to December 2020 were enrolled. Among 63 patients who received neoadjuvant therapy, 38 were treated with CCRT and 25 were treated with chemotherapy. They regularly received follow-up until July 2021. The patients' characteristics, including their clinical data, perioperative results, and pathologic outcomes, were analyzed. Results: The CCRT and chemotherapy groups did not significantly differ with respect to age, sex, or clinical stage (all p > 0.05). Finally, radical gastrectomy was performed in 15 (39.5%) patients with neoadjuvant CCRT and 10 (40.0%) patients with neoadjuvant chemotherapy. Both groups did not significantly differ with respect to operation time, blood loss, operative morbidities, or postoperative length of stay (both p > 0.05). The patients in the CCRT group exhibited favorable pathologic responses after treatment: three patients exhibited a pathologic complete response (pCR) and four, seven, and one patients exhibited a response at pathologic stages I, II, and III, respectively. By contrast, among the patients in the chemotherapy group after treatment, one patient exhibited a pCR and one, four, and four patients exhibited a response at pathologic stages I, II, and III, respectively. Conclusions: Radical resection in patients with LAGC is challenging. This study reports that neoadjuvant CCRT is associated with better pathologic response with no increase in serious postoperative complications. However, further prospective randomized trials involving patients with LAGC receiving neoadjuvant CCRT should be conducted to verify the findings of this retrospective study.

Effects of the number of neoadjuvant therapy cycles on clinical outcomes, safety, and survival in patients with metastatic colorectal cancer undergoing metastasectomy.

The controversial outcomes in patients with metastatic colorectal cancer (mCRC) highlight the need for developing effective systemic neoadjuvant treatment strategies to improve clinical results. The optimal treatment cycles in patients with mCRC for metastasectomy remain undefined. This retrospective study compared the efficacy, safety, and survival of cycles of neoadjuvant chemotherapy/targeted therapy for such patients. Sixty-four patients with mCRC who received neoadjuvant chemotherapy/targeted therapy following metastasectomy were enrolled between January 2018 and April 2022. Twenty-eight patients received 6 cycles of chemotherapy/targeted therapy, whereas 36 patients received ≥7 cycles (median, 13; range, 7-20). Clinical outcomes, including response, progression-free survival (PFS), overall survival (OS), and adverse events, were compared between these two groups. Of the 64 patients, 47 (73.4%) were included in the response group, and 17 (26.6%) were included in the nonresponse group. The analysis revealed chemotherapy/targeted therapy cycle and pretreatment serum carcinoembryonic antigen (CEA) level as independent predictors of the response as well as overall survival and chemotherapy/targeted therapy cycle as an independent predictor of progression (all p < 0.05). Furthermore, our results revealed shorter operation time, lower estimated operative blood loss, higher response rate, lower progression rate, and higher survival rate in ≥7 cycles of chemotherapy/targeted therapy group (all p < 0.05), but no statistical differences in adverse events were observed between the two groups (all p > 0.05). The median OS and PFS were 48 months (95% CI, 40.855-55.145) and 28 months (95% CI, 18.952-37.48) in the ≥7-cycle group and 24 months (95% CI, 22.038-25.962) and 13 months (95% CI, 11.674-14.326) in the 6-cycle group, respectively (both p < 0.001). The oncological outcomes in the ≥7-cycle group were significantly better than those in the 6-cycle group, without significant increases in adverse events. However, prospective randomized trials are mandatory to confirm the potential advantages of cycle numbers of neoadjuvant chemotherapy/targeted therapy.

K-Rod: An Innovative Method of Personalized Rib Splinting for Expeditious Management of Flail Chest in Acute Care Settings.

Flail chest is a severe type of multiple rib fracture that can cause ventilation problems and respiratory complications. Historically, flail chest has been mainly managed through pain control and ventilatory support as needed. Operative fixation has recently become popular for the condition, and some studies have revealed its potentially positive effects on the outcomes of patients with flail chest. However, for those for whom surgery is unsuitable, few treatment options, other than simply providing analgesia, are available. Herein, we introduce our innovative method of applying personalized rib splinting for quick management of flail chest, which is easy, tailor-made, and has significant effects on pain reduction.