Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Objective:To analyze early improvements in clinical indicators among patients with pre-diabetes (pre-DM), type 2 diabetes mellitus (T2DM), and hypertension (HT) participating in the Chronic Disease Co-Care (CDCC) Pilot Scheme in the Hong Kong Special Administrative Region of the People′s Republic of China (HKSAR). Methods:This longitudinal study enrolled participants with pre-DM, T2DM, and HT who participated in the CDCC Pilot Scheme between November 2023 and May 2024. Baseline clinical data was collected. All participants were managed followed standardized protocols: family doctors issued prescriptions in accordance with the Hong Kong Reference Framework by the Health Bureau of the Government of the HKSAR, District Health Centre (DHC) and DHC Express provided health education, and personalized counseling by allied health professionals (nurses, optometrists, and dietitians). During the screening phase, screening costs, including consultations and related laboratory investigations, were fully covered by the Government of the HKSAR, while partial subsidies were available during the treatment phase. Participants were followed for 6 months. Primary outcomes were glycated hemoglobin A1c (HbA1c) for pre-DM and T2DM, and blood pressure for HT. Secondary outcomes included body mass index (BMI), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and the Framingham model-based 10-year cardiovascular risk score. Changes in clinical indicators from baseline to 6 months were analyzed using a linear mixed model, with subgroup analyses by age, sex, and baseline Framingham 10-year cardiovascular disease risk score. Results:A total of 3 910 participants were included in the study, comprising 903 (23.1%) with pre-DM, 478 (12.2%) with T2DM, and 2 529 (64.7%) with HT. Pre-DM participants had an age of (61.4±7.0) years with 641 (71.0%) females; T2DM participants had an age of (60.4±7.4) years with 247 (51.7%) females; HT participants had an age of (60.8±7.9) years with 1 237 (48.9%) females. At 6 months, HbA1c levels declined in the pre-DM and T2DM groups by -0.09% (95% CI:-0.10%--0.07%) and -1.06% (95% CI:-1.21%--0.91%), respectively. In the HT group, systolic blood pressure decreased by 15.3 mmHg (1 mmHg=0.133 kPa) (95% CI:-16.0--14.6 mmHg) and diastolic blood pressure by 8.6 mmHg (95% CI:-9.0--8.1 mmHg). BMI decreased in the three groups, with the largest reduction in the T2DM group (-1.04 kg/m 2, 95% CI:-1.22--0.86 kg/m 2). TC, TG, and LDL-C levels decreased in the three groups (all P<0.05). Subgroup analysis revealed that among HT participants, individuals with a baseline Framingham 10-year cardiovascular disease risk of ≥20% experienced greater reductions in blood pressure compared to those with a risk <20% ( P<0.05). Additionally, male participants demonstrated significantly lower diastolic blood pressure than female participants ( P<0.05). Among participants with T2DM, males exhibited greater reductions in HbA1c levels than females, and participants aged 45-64 years showed significantly lower HbA1c levels compared to those aged 65 years and older (both P<0.05). Conclusions:In the early phase of the CDCC Pilot Scheme, glycemic, blood pressure, lipid, and BMI indicators improved among patients with pre-DM, T2DM, and HT. These effects were particularly pronounced in males and in individuals younger than 65 years of age.

Purpose: A small proportion of colorectal cancer (CRC) surgical patients will require an admission to an intensive care unit (ICU) within the early postoperative period. This study aimed to compare the characteristics and outcomes of patients admitted to an ICU following CRC surgery per hospital type (metropolitan vs. rural) over a decade in Australia. Methods: A retrospective cohort analysis was undertaken of all adult patients admitted to a participating Australian ICUs following CRC surgery between January 2011 and December 2021. The primary outcome was in-hospital mortality. Results: Over the 10-year period, 19,611 patients were treated in 122 metropolitan ICUs and 4,108 patients were treated in 42 rural ICUs. Rural ICUs had a lower proportion of annual admissions following CRC surgery (20 vs. 36, P<0.001). Patients admitted to a rural ICU were more likely to have undergone emergency CRC surgery compared to those admitted to a metropolitan cohort (28.5% vs. 13.8%, P<0.001). There was no difference in in-hospital mortality between metropolitan and rural hospitals (odds ratio [OR], 1.03; 95% confidence interval [CI], 0.73–1.35; P=0.500). There was a general trend for lower mortality in later years of the study with the odds of death in the final year of the study (2021) almost half that of the first study year (OR, 0.52; 95% CI, 0.34–0.80; P=0.003). Conclusion There was no difference between in-hospital mortality outcomes for CRC surgical patients requiring ICU admission between metropolitan and rural hospitals. These findings may contribute to discussions regarding rural scope of colorectal practice within Australia and globally.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

Purpose: To identify factors associated with adjacent-level ossification development (ALOD) after anterior cervical discectomy and fusion (ACDF) and associated clinical outcomes. Methods: We retrospectively reviewed records of 140 adults who underwent primary ACDF for degenerative disc disease. We compared patients with and without ALOD after ACDF. Radiographic measurements and factors associated with ALOD were assessed preoperatively and at minimum 24-month follow-up. Clinical outcomes were incidence of clinical adjacent-segment pathologies (CASP), revision surgery, and patient-reported outcomes. Results: Factors associated with both cranial and caudal ALOD were short plate-to-disc distance (PDD), adjacent-segment kyphosis, hyperlordotic ACDF causing junctional segment kyphosis, and preoperative ossification of the anterior longitudinal ligament (OALL). Mean final adjacent-segment range of motion (ROM) was less in those with cranial ALOD (6.9° ± 2.8°) than in those without cranial ALOD (12° ± 4.2°) (p < 0.01). Mean final adjacent-segment ROM was also less in those with caudal ALOD (5.5° ± 2.4º) than in those without caudal ALOD (8.2º ± 3.7º) (p < 0.01). The incidence of CASP-required surgery was higher in those with caudal ALOD (p = 0.02) but no different in those with cranial ALOD (p = 0.69) compared with those without ALOD. Conclusion Factors associated with ALOD were a kyphotic segment adjacent to ACDF, hyperlordotic fusion, preoperative OALL, and short PDD. ALOD was associated with less segmental ROM and, for those with caudal but not cranial ALOD, higher incidence of revision surgery for CASP.

Purpose: To identify factors associated with adjacent-level ossification development (ALOD) after anterior cervical discectomy and fusion (ACDF) and associated clinical outcomes. Methods: We retrospectively reviewed records of 140 adults who underwent primary ACDF for degenerative disc disease. We compared patients with and without ALOD after ACDF. Radiographic measurements and factors associated with ALOD were assessed preoperatively and at minimum 24-month follow-up. Clinical outcomes were incidence of clinical adjacent-segment pathologies (CASP), revision surgery, and patient-reported outcomes. Results: Factors associated with both cranial and caudal ALOD were short plate-to-disc distance (PDD), adjacent-segment kyphosis, hyperlordotic ACDF causing junctional segment kyphosis, and preoperative ossification of the anterior longitudinal ligament (OALL). Mean final adjacent-segment range of motion (ROM) was less in those with cranial ALOD (6.9° ± 2.8°) than in those without cranial ALOD (12° ± 4.2°) (p < 0.01). Mean final adjacent-segment ROM was also less in those with caudal ALOD (5.5° ± 2.4º) than in those without caudal ALOD (8.2º ± 3.7º) (p < 0.01). The incidence of CASP-required surgery was higher in those with caudal ALOD (p = 0.02) but no different in those with cranial ALOD (p = 0.69) compared with those without ALOD. Conclusion Factors associated with ALOD were a kyphotic segment adjacent to ACDF, hyperlordotic fusion, preoperative OALL, and short PDD. ALOD was associated with less segmental ROM and, for those with caudal but not cranial ALOD, higher incidence of revision surgery for CASP.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.

Mucoceles, commonly observed in the appendix, are mucin-filled, dilated structures arising from a range of etiologies. Cases associated with dysplastic or neoplastic epithelium can rupture and disseminate within the abdominopelvic cavity. Similar lesions in other parts of the colon are exceedingly rare, with only 16 colonic mucoceles having been reported. The first case of a colonic mucinous neoplasm with dysplasia resembling a low-grade appendiceal mucinous neoplasm involving rectal stump was described in 2016. Here, we present the second such case arising in the rectal stump, identified in a 44-year-old male with extensive surgical history. Microscopic examination revealed low-grade dysplastic epithelium lining the cyst and mucin dissecting into the stroma, without evidence of rupture or extramural mucin. The patient was followed for 16 months without recurrence or peritoneal disease. The exact etiology and outcome of these rare lesions remain unknown, requiring close follow-up.

Purpose: To identify factors associated with adjacent-level ossification development (ALOD) after anterior cervical discectomy and fusion (ACDF) and associated clinical outcomes. Methods: We retrospectively reviewed records of 140 adults who underwent primary ACDF for degenerative disc disease. We compared patients with and without ALOD after ACDF. Radiographic measurements and factors associated with ALOD were assessed preoperatively and at minimum 24-month follow-up. Clinical outcomes were incidence of clinical adjacent-segment pathologies (CASP), revision surgery, and patient-reported outcomes. Results: Factors associated with both cranial and caudal ALOD were short plate-to-disc distance (PDD), adjacent-segment kyphosis, hyperlordotic ACDF causing junctional segment kyphosis, and preoperative ossification of the anterior longitudinal ligament (OALL). Mean final adjacent-segment range of motion (ROM) was less in those with cranial ALOD (6.9° ± 2.8°) than in those without cranial ALOD (12° ± 4.2°) (p < 0.01). Mean final adjacent-segment ROM was also less in those with caudal ALOD (5.5° ± 2.4º) than in those without caudal ALOD (8.2º ± 3.7º) (p < 0.01). The incidence of CASP-required surgery was higher in those with caudal ALOD (p = 0.02) but no different in those with cranial ALOD (p = 0.69) compared with those without ALOD. Conclusion Factors associated with ALOD were a kyphotic segment adjacent to ACDF, hyperlordotic fusion, preoperative OALL, and short PDD. ALOD was associated with less segmental ROM and, for those with caudal but not cranial ALOD, higher incidence of revision surgery for CASP.

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC.Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/− bevacizumab in rGCCC. Methods DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/− bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator’s choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinumbased chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti–PD-1, anti–programmed death-ligand 1, or anti–programmed death-ligand 2 agent.The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers.