Background: s/Aims: Given the high mortality associated with gallbladder cancer (GBC), the efficacy of adjuvant therapy (AT) remains controversial. We audited our data over an 11-year period to assess the impact of AT. Methods: This study included all patients who underwent curative resection for GBC from 2007 to 2017. Analyses were conducted of clinicopathological characteristics, surgical details, and postoperative therapeutic records. The benefits of adjuvant chemotherapy (CT) or chemoradiotherapy (CTRT) were evaluated against surgery alone using SPSS version 20 for statistical analysis. Results: The median age of patients (n = 142) was 50 years. The median overall survival (OS) was 93, 34, and 30 months with CT, CTRT, and surgery alone respectively (p = 0.612). Multivariate analysis indicated that only disease stage and microscopically involved margins significantly impacted OS and disease-free survival (DFS). CT showed increased effectiveness across all prognostic subsets, except for stage 4 and margin-positive resections. Following propensity score matching, median DFS and OS were higher in the CT group than in the CTRT group, although the differences were not statistically significant (p > 0.05). Conclusions Radically resected GBC patients appear to benefit more from adjuvant CT, while CTRT should be reserved for cases with high-risk features.

Background: s/Aims: Given the high mortality associated with gallbladder cancer (GBC), the efficacy of adjuvant therapy (AT) remains controversial. We audited our data over an 11-year period to assess the impact of AT. Methods: This study included all patients who underwent curative resection for GBC from 2007 to 2017. Analyses were conducted of clinicopathological characteristics, surgical details, and postoperative therapeutic records. The benefits of adjuvant chemotherapy (CT) or chemoradiotherapy (CTRT) were evaluated against surgery alone using SPSS version 20 for statistical analysis. Results: The median age of patients (n = 142) was 50 years. The median overall survival (OS) was 93, 34, and 30 months with CT, CTRT, and surgery alone respectively (p = 0.612). Multivariate analysis indicated that only disease stage and microscopically involved margins significantly impacted OS and disease-free survival (DFS). CT showed increased effectiveness across all prognostic subsets, except for stage 4 and margin-positive resections. Following propensity score matching, median DFS and OS were higher in the CT group than in the CTRT group, although the differences were not statistically significant (p > 0.05). Conclusions Radically resected GBC patients appear to benefit more from adjuvant CT, while CTRT should be reserved for cases with high-risk features.

Background: s/Aims: Given the high mortality associated with gallbladder cancer (GBC), the efficacy of adjuvant therapy (AT) remains controversial. We audited our data over an 11-year period to assess the impact of AT. Methods: This study included all patients who underwent curative resection for GBC from 2007 to 2017. Analyses were conducted of clinicopathological characteristics, surgical details, and postoperative therapeutic records. The benefits of adjuvant chemotherapy (CT) or chemoradiotherapy (CTRT) were evaluated against surgery alone using SPSS version 20 for statistical analysis. Results: The median age of patients (n = 142) was 50 years. The median overall survival (OS) was 93, 34, and 30 months with CT, CTRT, and surgery alone respectively (p = 0.612). Multivariate analysis indicated that only disease stage and microscopically involved margins significantly impacted OS and disease-free survival (DFS). CT showed increased effectiveness across all prognostic subsets, except for stage 4 and margin-positive resections. Following propensity score matching, median DFS and OS were higher in the CT group than in the CTRT group, although the differences were not statistically significant (p > 0.05). Conclusions Radically resected GBC patients appear to benefit more from adjuvant CT, while CTRT should be reserved for cases with high-risk features.

Itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules by inhibiting CD6 leading to lower levels of interferon-γ, interleukin-6, and tumor necrotic factor-α and reduced T-cell infiltration at inflammatory sites. This study aims to compare the effects of tocilizumab and itolizumab in the management of severe coronavirus disease 2019 (COVID-19). Methods: The study population was adults (>18 years) with severe COVID-19 pneumonia admitted to the intensive care unit receiving either tocilizumab or itolizumab during their stay. The primary outcome was clinical improvement (CI), defined as a two-point reduction on a seven-point ordinal scale in the status of the patient from initiating the drug or live discharge. The secondary outcomes were time until CI, improvement in PO2 /FiO2 ratio, best PO2 /FiO2 ratio, need for mechanical ventilation after administration of study drugs, time to discharge, and survival days. Results: Of the 126 patients included in the study, 92 received tocilizumab and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was not statistically significant (P=0.134). The PO2 /FiO2 ratio was significantly better with itolizumab compared to tocilizumab (median [interquartile range]: 315 [200–380] vs. 250 [150–350], P=0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab compared to tocilizumab (14.7% vs. 3.3%, P=0.032). Conclusions: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

Itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules by inhibiting CD6 leading to lower levels of interferon-γ, interleukin-6, and tumor necrotic factor-α and reduced T-cell infiltration at inflammatory sites. This study aims to compare the effects of tocilizumab and itolizumab in the management of severe coronavirus disease 2019 (COVID-19). Methods: The study population was adults (>18 years) with severe COVID-19 pneumonia admitted to the intensive care unit receiving either tocilizumab or itolizumab during their stay. The primary outcome was clinical improvement (CI), defined as a two-point reduction on a seven-point ordinal scale in the status of the patient from initiating the drug or live discharge. The secondary outcomes were time until CI, improvement in PO2 /FiO2 ratio, best PO2 /FiO2 ratio, need for mechanical ventilation after administration of study drugs, time to discharge, and survival days. Results: Of the 126 patients included in the study, 92 received tocilizumab and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was not statistically significant (P=0.134). The PO2 /FiO2 ratio was significantly better with itolizumab compared to tocilizumab (median [interquartile range]: 315 [200–380] vs. 250 [150–350], P=0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab compared to tocilizumab (14.7% vs. 3.3%, P=0.032). Conclusions: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

Itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules by inhibiting CD6 leading to lower levels of interferon-γ, interleukin-6, and tumor necrotic factor-α and reduced T-cell infiltration at inflammatory sites. This study aims to compare the effects of tocilizumab and itolizumab in the management of severe coronavirus disease 2019 (COVID-19). Methods: The study population was adults (>18 years) with severe COVID-19 pneumonia admitted to the intensive care unit receiving either tocilizumab or itolizumab during their stay. The primary outcome was clinical improvement (CI), defined as a two-point reduction on a seven-point ordinal scale in the status of the patient from initiating the drug or live discharge. The secondary outcomes were time until CI, improvement in PO2 /FiO2 ratio, best PO2 /FiO2 ratio, need for mechanical ventilation after administration of study drugs, time to discharge, and survival days. Results: Of the 126 patients included in the study, 92 received tocilizumab and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was not statistically significant (P=0.134). The PO2 /FiO2 ratio was significantly better with itolizumab compared to tocilizumab (median [interquartile range]: 315 [200–380] vs. 250 [150–350], P=0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab compared to tocilizumab (14.7% vs. 3.3%, P=0.032). Conclusions: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

Itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules by inhibiting CD6 leading to lower levels of interferon-γ, interleukin-6, and tumor necrotic factor-α and reduced T-cell infiltration at inflammatory sites. This study aims to compare the effects of tocilizumab and itolizumab in the management of severe coronavirus disease 2019 (COVID-19). Methods: The study population was adults (>18 years) with severe COVID-19 pneumonia admitted to the intensive care unit receiving either tocilizumab or itolizumab during their stay. The primary outcome was clinical improvement (CI), defined as a two-point reduction on a seven-point ordinal scale in the status of the patient from initiating the drug or live discharge. The secondary outcomes were time until CI, improvement in PO2 /FiO2 ratio, best PO2 /FiO2 ratio, need for mechanical ventilation after administration of study drugs, time to discharge, and survival days. Results: Of the 126 patients included in the study, 92 received tocilizumab and 34 received itolizumab. CI was seen in 46.7% and 61.7% of the patients in the tocilizumab and itolizumab groups, respectively and was not statistically significant (P=0.134). The PO2 /FiO2 ratio was significantly better with itolizumab compared to tocilizumab (median [interquartile range]: 315 [200–380] vs. 250 [150–350], P=0.043). The incidence of serious adverse events due to the study drugs was significantly higher with itolizumab compared to tocilizumab (14.7% vs. 3.3%, P=0.032). Conclusions: The CI with itolizumab is similar to tocilizumab. Better oxygenation can be achieved with itolizumab and it can be a substitute for tocilizumab in managing severe COVID-19.

Background: Opioids administered as bolus doses or continuous infusions are widely used by anesthesiologists worldwide for major and day care surgeries. Opioid-free anesthesia is a multimodal anesthesia and analgesia technique that does not use opioid drugs, thereby benefitting patients from opioid-related adverse effects. In this study, we compared the postoperative analgesic requirements of patients scheduled for elective laparoscopic cholecystectomy under opioid-free and opioid-based anesthesia. Methods: This study included 88 patients aged 18–60 years with American Society of Anesthesiologists physical status 1 and 2 who underwent elective laparoscopic cholecystectomy. Participants were randomly divided into two groups with forty-four participants in each group. The opioid-free anesthesia group was administered an intravenous bolus of ketamine and dexmedetomidine, whereas the opioid-based group was administered fentanyl with conventional general anesthesia. The primary outcome was to compare the total amount of fentanyl consumed by both groups during the 6 h postoperative period following extubation. Episodes of postoperative nausea and vomiting (PONV) and vital signs were noted throughout the postoperative period to analyze the secondary outcomes. Results: Both the groups had similar demographic characteristics. The opioid-free group required less postoperative analgesia within the first 2 h (61.4 ± 17.4 vs. 79.0 ± 19.4 of fentanyl, P < 0.001), which was statistically significant. However, fentanyl consumption was comparable between the groups at the sixth postoperative hour (opioid-free group 152 ± 28.2 vs. opioid group 164 ± 33.4, P = 0.061). Compared with 4.5% of the participants in the opioid-free group, 34% of those in the opioid-based group developed moderate PONV. Conclusions The opioid-free anesthesia technique in patients undergoing laparoscopic cholecystectomy reduced the requirement of analgesia in the first two hours of the postoperative period and was associated with decreased PONV.

Transmasculine individuals, considering whether to undergo total hysterectomy with bilateral salpingectomy, have the option to have a concomitant oophorectomy. While studies have evaluated hormone changes following testosterone therapy initiation, most of those patients have not undergone oophorectomy. Data are currently limited to support health outcomes regarding the decision to retain or remove the ovaries. We performed a retrospective chart review of transmasculine patients maintained on high-dose testosterone therapy at a single endocrine clinic in Vancouver, British Columbia, Canada. Twelve transmasculine individuals who underwent bilateral oophorectomy and had presurgical and postsurgical serum data were included. We identified 12 transmasculine subjects as controls, who were on testosterone therapy and did not undergo oophorectomy, but additionally matched to the first group by age, testosterone dosing regimen, and body mass index. There was a statistically significant decrease in the estradiol levels of case subjects postoophorectomy, when compared to presurgical estradiol levels (P = 0.02). There was no significant difference between baseline estradiol levels between control and case subjects; however, the difference in estradiol levels at follow-up measurements was significant (P = 0.03). Total testosterone levels did not differ between control and case subjects at baseline and follow-up (both P > 0.05). Our results demonstrate that oophorectomy further attenuates estradiol levels below what is achieved by high-dose exogenous testosterone alone. Correlated clinical outcomes, such as impacts on bone health, were not available. The clinical implications of oophorectomy versus ovarian retention on endocrinological and overall health outcomes are currently limited.
Female ; Humans ; Testosterone/therapeutic use* ; Retrospective Studies ; Ovariectomy ; Hysterectomy/methods* ; Estradiol

ABSTRACT The oral microbiome comprises several hundreds of bacterial species that contribute to periodontitis, the most complex polymicrobial inflammatory disorder. Porphyromonas gingivalis is a prominent periodontitis pathogen that produces gingipains as a major virulent factor. Gingipain facilitates P. gingivalis survival, pathogenicity, and growth. Several genes were identified to have a role in the regulating of P. gingivalis pathogenesis. Studies suggest that gingipains inhibition is key for the successful treatment of periodontitis. As of now, several gingipain inhibitors have been developed, some exhibit high inhibition activity against gingipains. However, most inhibitors offer unknown toxicity and undesirable side effects. Hence, the development of highly potent and safe gingipain inhibitor is a major concern for periodontitis treatment. The present review highlights the connectivity between P. gingivalis, virulent factors, and its gene, periodontitis, and gingipain inhibitors. Development of gingipains inhibitors would not only treat periodontitis but would also assist in the treatment of other associated systemic diseases, for example: rheumatoid arthritis, cardiovascular diseases, diabetes, and Alzheimer's disease.
Porphyromonas gingivalis--pathogenicity ; Gingipain Cysteine Endopeptidases