DNA Damage and Its Role in Cancer Therapeutics.

DNA damage is a double-edged sword in cancer cells. On the one hand, DNA damage exacerbates gene mutation frequency and cancer risk. Mutations in key DNA repair genes, such as breast cancer 1 (BRCA1) and/or breast cancer 2 (BRCA2), induce genomic instability and promote tumorigenesis. On the other hand, the induction of DNA damage using chemical reagents or radiation kills cancer cells effectively. Cancer-burdening mutations in key DNA repair-related genes imply relatively high sensitivity to chemotherapy or radiotherapy because of reduced DNA repair efficiency. Therefore, designing specific inhibitors targeting key enzymes in the DNA repair pathway is an effective way to induce synthetic lethality with chemotherapy or radiotherapy in cancer therapeutics. This study reviews the general pathways involved in DNA repair in cancer cells and the potential proteins that could be targeted for cancer therapeutics.

Comparison of survival rates between total knee arthroplasty after a previous anterior cruciate ligament reconstruction and primary total knee arthroplasty via propensity score matching.

INTRODUCTION: Although the survival rate of total knee arthroplasty (TKA) in patients treated with anterior cruciate ligament reconstruction (ACLR) is not as favorable as that in patients treated with primary TKA without ligament reconstruction, the exact survival rates and complications associated with these procedures are still controversial. Therefore, the purpose of the current study was to compare the revision rates of TKA in patients with knee osteoarthritis (OA) with a previous ACLR and those of patients with primary TKA with no history of knee surgery by using propensity score matching analysis. MATERIALS AND METHODS: A list of patients who underwent TKA from January 1, 2008 to May 31, 2019 was obtained from the Korean National Health Insurance database. Among these, 460 patients underwent TKA in a knee with a previous ACLR and 569,766 patients who underwent primary TKA due to degenerative OA. We performed propensity scoring matching to compare the revision rates including septic revision due to prosthetic joint infection after TKA and perioperative complication rates within 90 days after revision TKA between the two groups. RESULTS: Matched patients were assigned to one of the two groups (group A: 2,201 patients who underwent TKA due to primary OA, group B: 448 patients who underwent TKA in a knee with a previous ACLR) based on the propensity score. The total number of revisions per 1000 person-years was significantly higher in group B than in group A (10.16 vs 4.66, respectively). Group B showed a higher risk of revision than group A at 10 years post-TKA (hazard ratio: 2.49, 95% confidence interval: 1.30-4.77). However, group B showed a similar risk of septic revision as group A (p = 0.44). Perioperative complications within 90 days after TKA showed no significant differences between the groups. CONCLUSIONS: Surgeons should be aware of the relatively higher revision rate of TKA in patients who had previously undergone an ACLR compared to that in patients who underwent primary TKA.

Aerosol transmission of severe fever with thrombocytopenia syndrome virus during resuscitation.

We investigated potential nosocomial aerosol transmission of severe fever with thrombocytopenia syndrome virus (SFTSV) with droplet precautions. During aerosol generating procedures, SFTSV was be transmitted from person to person through aerosols. Thus, airborne precautions should be added to standard precautions to avoid direct contact and droplet transmission.

Comparable Efficacy of Tigecycline versus Colistin Therapy for Multidrug-Resistant and Extensively Drug-Resistant Acinetobacter baumannii Pneumonia in Critically Ill Patients.

Tigecycline has in vitro activity against multidrug-resistant and extensively drug-resistant Acinetobacter baumannii (MDR/XDRAB), and may constitute an alternative therapy for treating pneumonia caused by MDR/XDRAB. The aim of this study was to compare the efficacy of tigecycline-based therapy with colistin-based therapy in patients with MDR/XDRAB pneumonia. Between January 2009 and December 2010, patients in the intensive care unit who were diagnosed with MDR/XDRAB pneumonia and treated with either tigecycline or colistin mono-/combination therapy were reviewed. A total of 70 patients were included in our analysis. Among them, 30 patients received tigecycline-based therapy, and 40 patients received colistin-based therapy. Baseline characteristics were similar in the two groups. Clinical success rate was 47% in the tigecycline group and 48% in the colistin group (P = 0.95). There were no differences between the groups with regard to other clinical outcomes, with the exception that nephrotoxicity was observed only in the colistin group (0% vs. 20%; P = 0.009). Clinical and microbiological success rates were numerically higher, and mortality rates were numerically lower in combination therapy group than in the monotherapy group. Multivariate analysis indicated that monotherapy was independently associated with increased clinical failure (aOR, 3.96; 95% CI, 1.03-15.26; P = 0.046). Our results suggest that tigecycline-based therapy was tolerable and the clinical outcome was comparable to that of colistin-based therapy for patients with MDR/XDRAB pneumonia. In addition, combination therapy may be more useful than monotherapy in treatment of MDR/XDRAB pneumonia.

Malignant Mesothelioma Diagnosed by Bronchoscopic Biopsy.

Malignant mesothelioma is a rare malignant neoplasm that arises from mesothelial surfaces of the pleural cavity, peritoneal cavity, tunica vaginalis, or pericardium. Typically, pleural fluid cytology or closed pleural biopsy, surgical intervention (video thoracoscopic biopsy or open thoracotomy) is conducted to obtain pleural tissue specimens. However, endobronchial lesions are rarely seen and cases diagnosed from bronchoscopic biopsy are also rarely reported. We reported the case of a 77-year-old male who was diagnosed as malignant mesothelioma on bronchoscopic biopsy from obstructing masses of the endobronchial lesion.

Clinical significance of circulating endothelial cells in patients with severe sepsis or septic shock.

BACKGROUND: Endothelial damage developing in severe sepsis or septic shock results in multiorgan dysfunction. An increased circulating endothelial cell (CEC) count represents a novel marker of endothelial damage, which has been reported in cases of severe sepsis or septic shock. The aim of this study was to evaluate the clinical significance of CECs in patients with severe sepsis or septic shock. METHODS: CECs were evaluated and quantified by flow cytometry using plasma collected from patients with severe sepsis or septic shock who were admitted to a medical intensive care unit from February 2011 to August 2011. RESULTS: During the study period, 77 patients were enrolled. The median CEC count was 350 cells/ml (range 0-15 984 cells/ml). There was no significant difference between cases of severe sepsis and septic shock [163 cells/ml (0-15 984 cells/ml) vs 363 cells/ml (0-7884 cells/ml), p = 0.507]. There were no correlations between the number of CECs and inflammatory markers. CEC counts were significantly increased in non-survivors compared to survivors [588.5 cells/ml (1-15 984 cells/ml) vs 292 cells/ml (0-12 882 cells/ml), p = 0.044] within 28 days. The sequential-related organ failure assessment score, CEC counts ≥ 500 cells/ml and blood lactate levels were significantly associated with 28 day mortality. CONCLUSIONS: CEC counts were higher in non-survivors of severe sepsis or septic shock and could be used as a biomarker to predict the prognosis in these patients.

Progression-free survival: an important prognostic marker for long-term survival of small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is an extremely aggressive tumor with a poor clinical course. Although many efforts have been made to improve patients' survival rates, patients who survive longer than 2 years after chemotherapy are still very rare. We examined the baseline characteristics of patients with long-term survival rates in order to identify the prognostic factors for overall survivals. METHODS: A total of 242 patients with cytologically or histologically diagnosed SCLC were enrolled into this study. The patients were categorized into long- and short-term survival groups by using a survival cut-off of 2 years after diagnosis. Cox's analyses were performed to identify the independent factors. RESULTS: The mean patient age was 65.66 years, and 85.5% were males; among the patients, 61 of them (25.2%) survived longer than 2 years. In the multivariate analyses, CRP (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.25-6.06; p=0.012), TNM staging (HR, 3.29; 95% CI, 1.59-6.80; p=0.001), and progression-free survival (PFS) (HR, 11.14; 95% CI, 2.98-41.73; p<0.001) were independent prognostic markers for poor survival rates. CONCLUSION: In addition to other well-known prognostic factors, this study discovered relationships between the long-term survival rates and serum CRP levels, TNM staging, and PFS. In situations with unfavorable conditions, the PFS would be particularly helpful for managing SCLC patients.

Acetabular Central Fracture Dislocation after Generalized Seizure during Lumbar Myelography with Iohexol.

Fracture is a less common complication in seizure patients, and fractures as a consequence of convulsive seizures without direct trauma occur in 0.3% of cases. Acetabular fractures after convulsions are even more rare, and only a few cases of acetabular fracture dislocations, purely caused by convulsive activity, have been reported. Therefore, we report a case of unilateral acetabular central fracture dislocation after a seizure episode, with relevant literature review. The seizure attack occurred after contrast media (Iohexol) injection for checking the myelography.

Minimum Two-year Results of Revision Total Knee Arthroplasty Following Infectious or Non-infectious Causes.

PURPOSE: To compare clinical outcome of revision total knee arthroplasty (TKA) between the infected and non-infected groups. MATERIALS AND METHODS: This study compared the clinical and radiographic results of 21 infected and 15 non-infected revision TKAs at a minimum 2-years follow-up. Clinical evaluations were assessed using the range of motion (ROM), Hospital for Special Surgery (HSS) score, Knee Society Knee Score (KSKS), Knee Society Function Score (KSFS), and Western Ontario and McMaster Universities (WOMAC) score. Radiologic evaluations were assessed using the radiographic results of the American Knee Society and joint line change. RESULTS: Patients operated for non-infectious causes had significantly better postoperative ROM than the infected group (infected group, 101.7°; non-infected group, 117.8°). The infected group achieved significantly poor HSS (79.2 vs. 85.5), KSKS (75.5 vs. 86.6), KSFS (76.9 vs. 85.5), WOMAC (30.3 vs. 21.2) scores than the non-infected group. Postoperative joint line elevation was lower in the infected versus non-infected group (0.5 mm vs. 2.1 mm), but there was no significant difference. CONCLUSIONS: Revision TKA is an effective treatment that can provide successful results in the infected as well as non-infected patients. The overall results of non-infected revision were more satisfactory than infected revision.

Outcomes of proximal chevron osteotomy for moderate versus severe hallux valgus deformities.

BACKGROUND: Proximal chevron osteotomy with a distal soft tissue procedure has been widely used to treat moderate to severe hallux valgus deformities. However, there have been no studies comparing the results of proximal chevron osteotomy between patients with moderate and severe hallux valgus. We compared the results of this procedure among these groups. METHODS: A retrospective review of 95 patients (108 feet) that underwent proximal chevron osteotomy and distal soft tissue procedure for moderate and severe hallux valgus was conducted. The 108 feet were divided into two groups: moderate hallux valgus (Group A) and severe hallux valgus (Group B). Group A was composed of 57 feet (52 patients) and Group B of 51 feet (43 patients). Average followup was 45 months. RESULTS: Mean American Orthopedic Foot and Ankle Society hallux metatarsophalangeal-interphalangeal scores were 54.1 points in Group A and 53.0 points in Group B preoperatively, and these improved to 90.8 and 92.6, respectively, at the last followup. Mean hallux valgus angles in Groups A and B reduced from 32.3 and 40.8 degrees, preoperatively to 10.7 and 13.2 degrees, postoperatively. Similarly, mean first intermetatarsal angles in Groups A and B reduced from 15.0 and 19.2 degrees, preoperatively to 9.0 and 9.2 degrees, postoperatively. CONCLUSION: The clinical and radiographic outcomes of proximal chevron osteotomy with a distal soft tissue procedure were found to be comparable for moderate and severe hallux valgus. Accordingly, our results suggest that this procedure provides an effective and reliable means of correcting hallux valgus regardless of severity of deformity.

Oral muscle relaxant may induce immediate allergic reactions.

Eperisone and afloqualone act by relaxing both skeletal and vascular smooth muscles to improve circulation and suppress pain reflex. These drugs are typically prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) as painkillers. However, there have been no reports on serious adverse reactions to oral muscle relaxants; and this is the first report to describe three allergic reactions caused by eperisone and afloqualone. All three patients had histories of allergic reactions after oral intake of multiple painkillers, including oral muscle relaxants and NSAIDs, for chronic muscle pain. An open-label oral challenge test was performed with each drug to confirm which drugs caused the systemic reactions. All patients experienced the same reactions within one hour after oral intake of eperisone or afloqualone. The severity of these reactions ranged from laryngeal edema to hypotension. To confirm that the systemic reaction was caused by eperisone or afloqualone, skin prick testing and intradermal skin tests were performed with eperisone or afloqualone extract in vivo, and basophil activity tests were performed after stimulation with these drugs in vitro. In one patient with laryngeal edema, the intradermal test with afloqualone extract had a positive result, and CD63 expression levels on basophils increased in a dose-dependent manner by stimulation with afloqualone. We report three allergic reactions caused by oral muscle relaxants that might be mediated by non-immunoglobulin E-mediated responses. Since oral muscle relaxants such as eperisone and afloqualone are commonly prescribed for chronic muscle pain and can induce severe allergic reactions, we should prescribe them carefully.