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Background . The outbreak of COVID-19 has attracted the attention of the whole world. Our study aimed to describe illness progression and risk profiles for mortality in non-survivors.Methods . We retrospectively analyzed 155 patients with COVID-19 in Wuhan and focused on 18 non-survivors among them. Briefly, we compared the dynamic profile of biochemical and immune parameters and drew an epidemiological and clinical picture of disease progression from disease onset to death in non-survivors. The survival status of the cohort was indicated by a Kaplan–Meier curve.Results . Of the non-survivors, the median age was 73.5 years, and the proportion of males was 72.2%. Five and 13 patients were hospital-acquired and community-acquired infection of SARS-CoV-2, respectively. The interval between disease onset and diagnosis was 8.5 days (IQR, [4–11]). With the deterioration of disease, most patients experienced consecutive changes in biochemical parameters, including lymphopenia, leukocytosis, thrombocytopenia, hypoproteinemia, as well as elevated D-dimer and procalcitonin. Regarding the immune dysregulation, patients exhibited significantly decreased T lymphocytes in the peripheral blood, including CD3+T, CD3+CD4+Th, and CD3+CD8+Tc cells. By the end of the disease, most patients suffered from severe complications, including ARDS (17/18; 94.4%), acute cardiac injury (10/18; 55.6%), acute kidney injury (7/18; 38.9%), shock (6/18; 33.3%), gastrointestinal bleeding (1/18; 5.6%), as well as perforation of intestine (1/18; 5.6%). All patients died within 45 days after the initial hospital admission with a median survivor time of 13.5 days (IQR, 8–17).Conclusions . Our data show that patients experienced consecutive changes in biochemical and immune parameters with the deterioration of the disease, indicating the necessity of early intervention.

Background Locally advanced rectal cancer (LARC) represents a pivotal stage of rectal cancer where it is possible to completely cure the cancer before its systemic spread, thus often requiring an aggressive multimodal therapy. Recent trials suggest that programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors combined with neoadjuvant chemoradiotherapy (CRT) may improve treatment outcomes. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of PD-1/PD-L1 inhibitors when integrated into neoadjuvant CRT regimens for LARC patients. Methods A systematic search of PubMed, Embase, ClinicalTrials.gov, and Cochrane Central Library was conducted up to October 11, 2024. Randomized controlled trials (RCTs) comparing neoadjuvant CRT with or without PD-1/PD-L1 inhibitors were included. The primary outcomes assessed were pathological complete response (pCR), clinical complete response (cCR), and serious adverse events (SAEs). Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup analyses were performed to explore variations in radiotherapy strategies, types of PD-1/PD-L1 inhibitors used, and mismatch repair (MMR) status. Results Six RCTs (861 patients) met the inclusion criteria. PD-1 inhibitors significantly improved pCR rates (OR = 2.10, 95% CI: 1.32–3.32, p  = 0.001), particularly with short-course radiotherapy (SCRT) and agents like Camrelizumab and Tislelizumab. However, PD-1 inhibitors did not significantly enhance cCR (OR = 1.54, 95% CI: 0.51–4.63, p  = 0.44) or increase SAEs (OR = 1.08, 95% CI: 0.73–1.60). Subgroup analysis based on MMR status revealed a significantly higher pCR rate in the proficient MMR (pMMR) subgroup compared to the deficient MMR (dMMR) subgroup, although the result for dMMR was non-significant due to limited sample size and the absence of reported events. Conclusions The addition of PD-1 inhibitors to neoadjuvant CRT significantly improves pCR rates in LARC without increasing toxicity. These findings support their potential role in standard treatment protocols, warranting further phase III trials. Registration number CRD42024619949.

Background: Total neoadjuvant therapy is becoming a preferred option for locally advanced rectal cancer, particularly in patients with high-risk baseline features. However, real-world evidence comparing tumor response, MRI-defined high-risk feature clearance, surgical outcomes, and survival after total neoadjuvant therapy versus conventional long-course chemoradiotherapy remains limited. This study aimed to compare outcomes between total neoadjuvant therapy and long-course chemoradiotherapy in patients with locally advanced rectal cancer treated in routine clinical practice. Methods: This is a retrospective, single-centre cohort study focused on patients with stage II–III locally advanced rectal adenocarcinoma treated with curative-intent neoadjuvant therapy using either total neoadjuvant therapy or long-course chemoradiotherapy. Tumor response was assessed using restaging MRI, clinical complete response, and pathological complete response. Surgical outcomes and overall survival were evaluated. Results: A total of 110 patients were included. Patients treated with total neoadjuvant therapy had a higher baseline disease burden reflected by a greater proportion of cT4 tumors (40.6% vs. 19.2%; p = 0.014). Radiologic tumor-length response and clearance of MRI-defined high-risk features were comparable between treatment strategies. Clinical and pathological complete response rates were numerically higher in the total neoadjuvant therapy group, but the differences were not significant (cCR: 15.6% vs. 6.4%, p = 0.151; pCR: 18.5% vs. 9.7%, p = 0.301). Conclusions: In this real-world cohort, TNT was preferentially used in patients with more advanced baseline disease and showed numerically higher complete response rates, although differences were not statistically significant. Radiologic response, surgical outcomes, and short-term survival were comparable between treatment strategies. These findings support the feasibility of TNT in routine clinical practice but should be interpreted as exploratory and hypothesis-generating rather than evidence of treatment superiority.

Background Neoadjuvant chemoradiotherapy followed by total mesorectal excision is a standard treatment for locally advanced rectal cancer. Mismatch repair-deficient locally advanced rectal cancer (LARC) was highly sensitive to PD-1 blockade. However, most rectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes for which PD-1 blockade is ineffective. Radiation can trigger the activation of CD8 + T cells, further enhancing the responses of MSS/pMMR rectal cancer to PD-1 blockade. Radioimmunotherapy offers a promising therapeutic modality for rectal cancer. Progenitor T exhausted cells are abundant in tumour-draining lymph nodes and play an important role in immunotherapy. Conventional irradiation fields include the mesorectum and regional lymph nodes, which might cause considerable damage to T lymphocytes and radiation-induced fibrosis, ultimately leading to a poor response to immunotherapy and rectal fibrosis. This study investigated whether node-sparing modified short-course irradiation combined with chemotherapy and PD-1 blockade could be effective in patients with MSS/ pMMR LARC. Methods This was a open-label, single-arm, multicentre, prospective phase II trial. 32 LARC patients with MSS/pMMR will receive node-sparing modified short-course radiotherapy (the irradiated planned target volume only included the primary tumour bed but not the tumour-draining lymph nodes, 25 Gy/5f, 5 Gy/f) followed by CAPOX and tislelizumab. CAPOX and tislelizumab will be started two days after the completion of radiotherapy: oxaliplatin 130 mg/m 2 intravenous infusion, day 1; capecitabine 1000 mg/m 2 oral administration, days 1–14; and tislelizumab 200 mg, intravenous infusion, day 1. There will be four 21-day cycles. TME will be performed at weeks 14–15. We will collect blood, tumour, and lymphoid specimens; perform flow cytometry and in situ multiplexed immunofluorescence detection; and analyse the changes in various lymphocyte subsets. The primary endpoint is the rate of pathological complete response. The organ preservation rate, tumour regression grade, local recurrence rate, disease-free survival, overall survival, adverse effects, and quality of life will also be analysed. Discussion In our research, node-sparing modified radiotherapy combined with immunotherapy probably increased the responsiveness of immunotherapy for MSS/pMMR rectal cancer patients, reduced the occurrence of postoperative rectal fibrosis, and improved survival and quality of life. This is the first clinical trial to utilize a node-sparing radiation strategy combined with chemotherapy and PD-1 blockade in the neoadjuvant treatment of rectal cancer, which may result in a breakthrough in the treatment of MSS/pMMR rectal cancer. Trial registration This study was registered at www.clinicaltrials.gov . Trial registration number: NCT05972655. Date of registration: 31 July 2023.

Background For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. Methods This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local–regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. Discussion This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. Trial registration This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

Background The integration of immunotherapy with neoadjuvant therapy for proficient mismatch repair (pMMR) locally advanced rectal cancer (LARC) is a promising strategy. However, the optimal treatment platform, a short-course radiotherapy (SCRT)-based regimen or a long-course chemoradiotherapy (LCRT)-based regimen, remains uncertain due to the absence of direct comparative trials. This network meta-analysis (NMA) aimed to compare the efficacy and safety of these two platforms, each with or without immune checkpoint inhibitors (ICIs). Methods We systematically searched PubMed/MEDLINE, Embase, and Cochrane Library from inception to September 20, 2025, for randomized controlled trials (RCTs) comparing neoadjuvant SCRT-based or LCRT-based regimens combined with ICIs versus the corresponding regimens without ICIs in LARC. A frequentist NMA was performed using random-effects models. The co-primary outcomes were the curative-intent response rate [a composite of pathological complete response (pCR) or clinical complete response followed by a Watch-and-Wait strategy (WW)] and the incidence of grade ≥ 3 treatment-related adverse events (TRAEs). The pCR rate was a key secondary endpoint. Treatments were ranked using surface under the cumulative ranking curve (SUCRA) probabilities. Results Seven RCTs (1132 patients) evaluating four strategies (SCRT-based regimen alone, SCRT-based regimen with ICIs, LCRT-based regimen alone, and LCRT-based regimen with ICIs) were included. For the primary endpoint of curative-intent response, SCRT + ICIs had the highest probability of being the most effective treatment (SUCRA, 98.5%). SCRT + ICIs significantly outperformed SCRT alone (RR, 1.82; 95% CI, 1.27–2.60) and LCRT alone (RR, 2.23; 95% CI, 1.33–3.76). It also showed a numerical, but non-significant, advantage over LCRT + ICIs (RR, 1.63; 95% CI, 0.88–3.02). The addition of ICIs to LCRT resulted in a numerical increase in response (RR, 1.37; 95% CI, 0.98–1.90) compared to LCRT alone. Results for the pCR rate were consistent in treatment ranking. Regarding safety, the addition of ICIs to either platform was not associated with a significant increase in grade ≥ 3 TRAEs, and no significant difference was observed between the two combination strategies (SCRT + ICIs vs. LCRT + ICIs: RR, 0.87; 95% CI, 0.38–2.04). Conclusions This NMA suggests that the SCRT-based platform may be the preferred option to combine with immunotherapy in pMMR LARC. The results support direct comparison of these platforms in future phase III trials focused on long-term survival and organ preservation.

Abstract Objective To evaluate the clinical efficacy and safety of ultra-short-course chemotherapy (<4 months) in treating spinal tuberculosis following complete debridement. Methods Clinical data of patients diagnosed with spinal tuberculosis, who underwent surgery with postoperative chemotherapy for < 4 months at the General Hospital of Ningxia Medical University between January 2005 and March 2015, were retrospectively analysed. Clinical manifestations, American Spinal Injury Association grades, states of bone fusion and lesion healing, deformity correction, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and adverse drug reactions, observed before and after surgery and at the final follow-up, were assessed. Results Sixty patients were included, comprising 26 male and 34 female patients aged 16–78 years (mean, 40.85 years). Patients received postoperative chemotherapy for 3–4 months (mean, 3.61 months) and were followed for 25–129 months (mean, 70.61 months). Spinal tuberculosis recurred after surgery in one patient, who was cured by subsequent surgery. At the final follow-up, no symptoms of tuberculosis, local pain, abscess or sinus were observed. Daily life and working abilities were almost recovered in all patients. ESR and CRP levels were restored to normal, bone grafts fused, lesions healed and neurological functions were recovered. Postoperative chemotherapy-induced complications occurred in 10 patients (16.67%). Conclusions Complete debridement plus ultra-short-course chemotherapy for 3–4 months may be safe and efficacious in treating spinal tuberculosis, and requires further investigation.

The present study was aimed at looking for hematological indicators that could predict pathological complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with short-course radiotherapy (SCRT) followed by chemotherapy and immunotherapy. A total of 171 patients were enrolled in this observational retrospective study. Pretreatment values of albumin, total cholesterol, lactate dehydrogenase, neutrophil, platelet and lymphocytes were available. Univariate and multivariate logistics analyses were used to determine the prognostic factor for pCR. SCRT followed by chemotherapy and immunotherapy was demonstrated to double the pCR rate (50.5%) compared with long-course chemoradiotherapy. For the former group, baseline high platelet to lymphocyte ratio (P=0.047), high cholesterol (P=0.026) and low neutrophils (P=0.012) level were associated with high pCR rate and baseline high cholesterol (P=0.016) and low neutrophils (P=0.020) level were the independent prognostic factors for pCR. In conclusion, pretreatment high cholesterol and low neutrophils were the independent prognostic predictors of pCR in patients with LARC treated with SCRT followed by chemotherapy and immunotherapy. Clinical trial no. NCT04928807, June 16, 2021.

IntroductionPreoperative radiotherapy followed by total mesorectal excision with adjuvant chemotherapy has been recommended as the preferred treatment method for locally advanced rectal cancer (LARC). Similar rates of local control, survival and toxicity were observed in preoperative long-course chemoradiotherapy (LCRT) (45–50.4 Gy in 25–28 fractions) and in short-course radiotherapy (SCRT) with 25 Gy over five fractions. Both regimens lower the local recurrence rates compared with that of surgery followed by postoperative radiotherapy. With the simplicity and lower cost of SCRT, a growing number of patients have been receiving SCRT as preoperative radiotherapy. However, the currently established SCRT (25 Gy over five fractions) followed immediately by surgery resulted in poor downstaging and sphincter preservation rate. The pathological complete response (pCR) rate is also markedly lower with SCRT than with LCRT (0.7%vs16%). Several studies recommended SCRT with delayed surgery for more than 4 weeks with expectation of improved pathological outcomes and fewer postoperative complications. While a number of clinical trials demonstrated a persistently better overall local control with SCRT than with LCRT, overall survival advantage has not been observed. Since survival is mainly depended on distant metastases, efforts should be made towards more effective pathological response and systemic treatment. Given the apparent advantages of SCRT, we aimed to establish a dose escalation of SCRT and sequential modified FOLFOX6 (mFOLFOX6) as preoperative therapy for LARC with objectives of achieving an optimal balance of safety, cost effectiveness and clinical outcome, and to support further investigation of this regimen in a phase II/III setting.MethodsIn this phase I study, three dose levels (6Gy×5F, 7Gy×5F, 8Gy×5F to gross tumour volume, while keeping the rest of irradiated volume at 5Gy×5) of SCRT followed by four cycles of mFOLFOX6 chemotherapy as neoadjuvant therapy will be tested by using the traditional 3+3 design. The pCR rate, R0 resection rate, sphincter preservation rate and treatment related toxicity will be assessed.Ethics and disseminationThe study protocol was approved by the Ethics Committee of Fujian Medical University Union Hospital (No. 2017YF020-02) and all participants provided written informed consent. Results from our study will be disseminated in international peer-reviewed journals. All study procedures were developed in order to assure data protection and confidentiality.Trial registration number NCT03466424; Pre-results.

Short-course radiotherapy (SCRT) of 25 Gy in five daily fractions is a recommended strategy in the neoadjuvant setting for resectable locally advanced rectal cancer (LARC), as well as in cases of metastatic disease for local control. There is scarce information regarding the use of SCRT for patients who have received nonoperative management. To describe the characteristics of patients who received treatment with SCRT for LARC and metastatic rectal cancer, toxicity, and the approach after radiation treatment. This is a retrospective analysis of all patients who underwent SCRT for rectal cancer at the Alexander Fleming Institute from March 2014 to June 2022. In total, 44 patients were treated with SCRT. The majority were male (29, 66%), with a median age of 59 years (interquartile range 46-73). Most patients had stage IV disease (26, 59.1%), followed by LARC (18, 40.9%). Most lesions were located in the middle rectum (30, 68%). The majority of LARC patients underwent SCRT followed by consolidation chemotherapy (ChT) (16/18, 89%), while most patients with metastatic disease underwent SCRT followed by consolidation ChT (14/26, 53.8%). A clinical complete response (cCR) was documented in 8/44, 18.2% of patients. Most patients with LARC and cCR were managed by a watch and wait approach (5/18, 27.7%). Local recurrence was observed in LARC cases (2/18, 11.1%). Patients who underwent SCRT following consolidation ChT were more likely to have adverse events (AEs) than those undergoing induction ChT following SCRT (11/30, 36.7% versus 3/12, 25%, = 0.02). In a subgroup of patients diagnosed with LARC and treated with SCRT followed by ChT, surgical treatment could be omitted after they achieved a cCR. Local recurrence was similar to that reported in a previous study. SCRT is a reasonable option for local disease control in stage IV disease, yielding low toxicity rates. Therefore, decisions must be made by a multidisciplinary team. Prospective studies are necessary to reach further conclusions.