Recommendations and guidelines for the diagnosis and management of Coronavirus Disease-19 (COVID-19) associated bacterial and fungal infections in Taiwan.

Coronavirus disease-19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2 that has rapidly evolved into a pandemic to cause over 600 million infections and more than 6.6 million deaths up to Nov 25, 2022. COVID-19 carries a high mortality rate in severe cases. Co-infections and secondary infections with other micro-organisms, such as bacterial and fungus, further increases the mortality and complicates the diagnosis and management of COVID-19. The current guideline provides guidance to physicians for the management and treatment of patients with COVID-19 associated bacterial and fungal infections, including COVID-19 associated bacterial infections (CABI), pulmonary aspergillosis (CAPA), candidiasis (CAC) and mucormycosis (CAM). Recommendations were drafted by the 7th Guidelines Recommendations for Evidence-based Antimicrobial agents use Taiwan (GREAT) working group after review of the current evidence, using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations in March 2022, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes the epidemiology, diagnostic methods and treatment recommendations for COVID-19 associated infections. The aim of this guideline is to provide guidance to physicians who are involved in the medical care for patients with COVID-19 during the ongoing COVID-19 pandemic.

Using a Knowledge-Based Clinical Decision Support System to Reduce the Time to Appropriate Antimicrobial Therapy in Hospitalized Patients With Bloodstream Infections: A Single-Center Observational Study.

Background: Inappropriate antimicrobial use is a crucial determinant of mortality in hospitalized patients with bloodstream infections. Current literature reporting on the impact of clinical decision support systems on optimizing antimicrobial prescription and reducing the time to appropriate antimicrobial therapy is limited. Methods: Kaohsiung Veterans General Hospital implemented a hospital-wide, knowledge-based, active-delivery clinical decision support system, named RAPID (Real-time Alert for antimicrobial Prescription from virtual Infectious Diseases experts), to detect whether there was an antimicrobial agent-pathogen mismatch when a blood culture result was positive. Once RAPID determines the current antimicrobials as inappropriate, an alert text message is immediately sent to the clinicians in charge. This study evaluated how RAPID impacted the time to appropriate antimicrobial therapy among patients with bloodstream infections. Results: During the study period, 633 of 11 297 recorded observations (5.6%) were determined as inappropriate antimicrobial prescriptions. The time to appropriate antimicrobial therapy was significantly shortened after the implementation of RAPID (1.65 vs 2.45 hours, P < .001), especially outside working hours (1.24 vs 6.43 hours, P < .001), in the medical wards (1.40 vs 2.14 hours, P < .001), in participants with candidemia (0.74 vs 5.36 hours, P < .001), and for bacteremia due to non-multidrug-resistant organisms (1.66 vs 2.49 hours, P < .001). Conclusions: Using a knowledge-based clinical decision support system to reduce the time to appropriate antimicrobial therapy in a real-world scenario is feasible and effective. Our results support the continued use of RAPID.

Recommendations and guidelines for the treatment of infections due to multidrug resistant organisms.

Antimicrobial drug resistance is one of the major threats to global health. It has made common infections increasingly difficult or impossible to treat, and leads to higher medical costs, prolonged hospital stays and increased mortality. Infection rates due to multidrug-resistant organisms (MDRO) are increasing globally. Active agents against MDRO are limited despite an increased in the availability of novel antibiotics in recent years. This guideline aims to assist clinicians in the management of infections due to MDRO. The 2019 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, comprising of infectious disease specialists from 14 medical centers in Taiwan, reviewed current evidences and drafted recommendations for the treatment of infections due to MDRO. A nationwide expert panel reviewed the recommendations during a consensus meeting in Aug 2020, and the guideline was endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline includes recommendations for selecting antimicrobial therapy for infections caused by carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and vancomycin-resistant Enterococcus. The guideline takes into consideration the local epidemiology, and includes antimicrobial agents that may not yet be available in Taiwan. It is intended to serve as a clinical guide and not to supersede the clinical judgment of physicians in the management of individual patients.

Repairing Facial Fractures with Interrupted Maxillary-mandibular Arches by Computer-assisted Reverse Planning Model Surgery.

BACKGROUND: Management of comminuted facial fractures with maxillary-mandibular arch interruption is difficult, resulting in inadequate bone reduction and malocclusion. Traditionally, a good quality dental splint is helpful, but difficult to obtain in acute trauma. We apply a computer-assisted design and three-dimensional printing technology to improve splint fabrication and utilization, thus facilitating restoration of dental occlusion and facial fracture. METHODS: We retrospectively reviewed patients who suffered from facial fractures with interruption of the maxillary-mandibular arches. We developed the "computer-assisted reverse planning and three-dimensional printing model surgery" algorithm and applied it in selected patients. An occlusal splint was created as a surgical guide to enhance the maxilla-mandibular unit repair by taking care of the bone reduction and occlusion. All included patients were followed up to assess the functional outcome and patients suitable for this method. RESULTS: From Jan 2015 to Aug 2020, 10 patients (eight men and two women) with comminuted facial fractures were included. The average time of surgery was 9.2 days. The average follow-up time was 8.6 months. There was no patient who needed major revision to correct malocclusion or facial asymmetry. CONCLUSIONS: A computer-assisted design splint decreases intraoperative inaccuracies and difficulty in comminuted maxillo-mandibular fractures. It is a useful and reliable alternative. Collaboration with an experienced engineer and patient selection are indispensable in delivering successful outcomes. Patients who have more than three bone fragments in a single dental arch or more than four bone fragments in the entire maxillary-mandibular unit appear to be excellent candidates for this method.

Ultrasound Acupuncture for Oxaliplatin-induced Peripheral Neuropathy in Patients With Colorectal Cancer: A Pilot Study.

BACKGROUND: Oxaliplatin is frequently used in the treatment of metastatic colorectal cancer. However, peripheral neuropathy is a severe adverse effect of oxaliplatin that may persist and impact quality of life. OBJECTIVE: To assess the potential effects of ultrasound acupuncture for the alleviation of symptoms related to oxaliplatin-induced peripheral neuropathy (OIPN) among patients with metastatic colorectal cancer. DESIGN: Prospective cohort pilot study. SETTING: Education and research hospital. PARTICIPANTS: Patients with a diagnosis of stage II-IV colorectal cancer undergoing oxaliplatin-based treatment regimens who experienced OIPN symptoms (n = 17). INTERVENTIONS: Pulsed therapeutic ultrasound (1 MHz) at bilateral acupuncture points of PC6, PC7, BL60, and KI1 was administered for 5 minutes per point daily for 12 days. MAIN OUTCOME MEASUREMENTS: Pain Quality Assessment Scale (PQAS), Chemotherapy-induced Neurotoxicity Questionnaire (CINQ), quantitative touch-detection threshold, cold-trigger pain withdrawal latency, and quality of life (EORTC QLQ-C30) were measured at baseline (day 0), pre-intervention (day 12, post wash-out period), post-intervention (day 24), and final follow-up (day 54). A P value of less than .05 was considered statistically significant. RESULTS: Scores of PQAS and CINQ significantly improved after ultrasound acupuncture at post-intervention and follow-up compared to both baseline and pre-intervention. Similar trends were also observed for the quantitative sensory testing, where touch-detection threshold significantly decreased and cold-trigger pain withdrawal latency significantly increased after ultrasound acupuncture. Patients also showed an improvement on quality of life outcomes as measured by QLQ-C30 post-intervention and at follow-up. CONCLUSIONS: Ultrasound acupuncture could be an effective intervention for OIPN symptoms for patients with colorectal cancer. However, larger and randomized clinical trials with placebo controls are needed to confirm such effects.

Recommendations and guidelines for the treatment of Clostridioides difficile infection in Taiwan.

Clostridioides difficile infection (CDI) is a major enteric disease associated with antibiotic use and a leading cause of hospital-acquired infections worldwide. This is the first guideline for treatment of CDI in Taiwan, aiming to optimize medical care for patients with CDI. The target audience of this document includes all healthcare personnel who are involved in the medical care of patients with CDI. The 2018 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group was formed, comprising of infectious disease specialists from 13 medical centers in Taiwan, to review the evidence and draft recommendations using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations during a consensus meeting in March 2019. The recommendation is endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline describes the epidemiology and risk factors of CDI, and provides recommendations for treatment of CDI in both adults and children. Recommendations for treatment of the first episode of CDI, first recurrence, second and subsequent recurrences of CDI, severe CDI, fulminant CDI, and pediatric CDI are provided.

The free inverted omega-shaped flap for circumferential hypopharyngeal reconstruction with simultaneous neck skin defect.

BACKGROUND: Circumferential hypopharyngeal defect with simultaneous skin defect can pose complicated reconstructive challenge for reconstructive microsurgeons. Our experience with the versatile inverted-omega flap tubing design is proposed to accommodate such problem. METHODS: From 2012 to 2015, 13 anterolateral thigh (ALT) flaps and one anteromedial thigh (AMT) flap were harvested for reconstruction of circumferential hypopharyngeal defects with skin defects in 14 patients. All patients were males except one. Patient age ranged from 42 to 67 years (average, 53.1 years). Fifty-seven percent were recurrent cases. All but one patient received preoperative chemoradiotherapy. RESULTS: The average flap size was 29 × 8 cm (range: 25-31 × 6-10 cm2 ). An average of 2.6 perforators was included in each flap (2-4 perforators/flap). All flaps survived. One venous thrombosis was noted and salvaged after thrombolectomy and vein graft. The mean follow-up period was 25 months. The fistula rate was 21.4% (three patients). One fistula never healed because of early recurrence; one fistula healed after surgical intervention; and one fistula need a loco-regional flap for secondary reconstruction. Three postoperative strictures were noted (21.4%). CONCLUSION: For the circumferential hypopharyngeal defect with simultaneous neck skin defect, this inverted-omega ALT tubing design offers an alternative choice for such complicated reconstruction. © 2016 Wiley Periodicals, Inc. Microsurgery, 38:51-59, 2018.

Analgesic Effects of Transcutaneous Ultrasound Nerve Stimulation in a Rat Model of Oxaliplatin-Induced Mechanical Hyperalgesia and Cold Allodynia.

This study investigated the effects and underlying mechanisms of therapeutic ultrasound (TUS) in a rat model of oxaliplatin-induced peripheral neuropathy. Animals received a total of eight injections with oxaliplatin (4 mg/kg), administered at 3-d intervals. TUS intervention (1 MHz, 0.5 W/cm2) started on the fifth oxaliplatin administration and continued for 10 consecutive d. Sensory behavioral examinations, protein levels of transient receptor potential channels (TRPM8 and TRPV1) in dorsal root ganglia (DRG) and substance P (SP) in spinal dorsal horn were examined. Results indicated that TUS can reduce mechanical and cold hyper-responsive behaviors caused by repeated administration of oxaliplatin. Oxaliplatin-related increases in protein levels of TRPM8 in DRG and SP in the dorsal horn were also reduced after TUS. Taken together, the results revealed beneficial effects of TUS on oxaliplatin-induced mechanical hyperalgesia and cold allodynia and suggested involvement of TUS biochemicals in suppressing TRPM8 in DRG and SP in spinal cords.

Laser acupuncture attenuates oxaliplatin-induced peripheral neuropathy in patients with gastrointestinal cancer: a pilot prospective cohort study.

BACKGROUND: Oxaliplatin is a platinum compound that is widely used in the treatment of some solid tumours. Oxaliplatin-induced peripheral neuropathy (OIPN) in the upper and lower extremities is the major adverse side effect and represents the main dose-limiting factor of this drug. The aim of this single-arm study was to evaluate the feasibility and effects of laser acupuncture (LA) in the treatment of OIPN in patients with advanced gastrointestinal cancers. METHODS: 17 gastrointestinal cancer survivors (14 colorectal and 3 gastric cancers), who had been treated with oxaliplatin-based chemotherapies, were recruited. Low-level laser stimulation (50 mW) bilaterally at PC6, PC7, PC8, P9, LU11, SP6, KI3, BL60, KI1, and KI2 was administered for 20 min/point for 12 sessions over 4 weeks. The pain quality assessment scale (PQAS), chemotherapy-induced neurotoxicity questionnaire (CINQ), oxaliplatin-specific neurotoxicity scale (OSNS), quantitative touch-detection threshold (using von Frey filaments), and cold-triggered pain withdrawal latency (using the cold-water immersion test) were measured before and after completion of the 12 treatment sessions. RESULTS: PQAS, CINQ, and OSNS scores, as well as touch-detection threshold and cold-trigger pain withdrawal latency all improved significantly after LA in the cancer patients with OIPN (p<0.05). LA significantly relieved both oxaliplatin-induced cold and mechanical allodynia and also decreased the incidence and severity of neurotoxicity symptoms in the patients' upper and lower extremities and impact on their daily activities (all p<0.05). CONCLUSIONS: Following treatment with LA, neurotoxicity symptoms were significantly improved in cancer patients with OIPN. Further randomised controlled trials are needed to evaluate the role of LA as a therapeutic option in the management of OIPN.

Surgical site infections among high-risk patients in clean-contaminated head and neck reconstructive surgery: concordance with preoperative oral flora.

BACKGROUND: Salivary contamination of surgical wounds in clean-contaminated head and neck surgery with free flap reconstruction remains a major cause of infection and leads to significant morbidity. This study investigates the correlation between intraoral flora and surgical site infections (SSIs) among high-risk head and neck cancer patients undergoing resection and free flap reconstruction. METHODS: One hundred twenty-nine patients were identified as being at high risk for infective complications based on cancer stage, tumor size, comorbid factors, and extent of reconstruction. All patients had intraoral swab cultures before surgery. Patients with culture-confirmed SSI after surgery were chosen for analysis, using the κ index and its 95% confidence interval for concordance analysis. All patients received clindamycin and gentamicin for antibiotic prophylaxis for 5 days. Antibiotic susceptibility testing of all isolates was obtained and analyzed. RESULTS: Thirty-seven patients experienced SSI, or an infection rate of 28.3%, occurring at a mean of 9.3 postoperative days. The overall concordance between oral flora and SSI was fair to moderate (κ index of 0.25), but detailed analysis shows a higher concordance for known and opportunistic pathogens, such as Pseudomonas aeruginosa and Enterococcus faecalis, compared to typical oral commensals. Antibiotic susceptibility tests show rapid and significant increases in resistance to clindamycin, indicating a need for a more effective alternative. CONCLUSIONS: Predicting pathogens in SSI using preoperative oral swabs did not demonstrate a good concordance in general for patients undergoing clean-contaminated head and neck surgery, although concordance for certain pathogenic species seem to be higher than for typical intraoral commensals. The rapid development of resistance to clindamycin precludes its use as a prophylactic agent.

An ideal method for pressure sore reconstruction: a freestyle perforator-based flap.

BACKGROUND: Pressure sore reconstruction is quite difficult for plastic surgeons because of long-term high recurrence rates. We designed a freestyle perforator-based flap for pressure sore reconstruction considering pressure sore recurrence and further reconstruction. METHODS: We used a handheld Doppler device to locate a perforator position just adjacent to the pressure ulcer. In a series of 34 patients, we used 37 perforator-based flaps to reconstruct 25 sacral, 5 ischial, and 4 trochanteric ulcers. RESULTS: Twenty-eight of 37 flaps healed uneventfully without complication. One patient had a flap that totally necrosed, 3 had partial flap necrosis, 3 had wound dehiscence, 1 died 3 days postoperatively, and recurrence developed in 1 patient. CONCLUSIONS: We used the freestyle perforator-based fasciocutaneous flap for pressure sore management with good success. These flaps are easy to design and provide good versatility for coverage. Cooperation of surgical skills and good postoperative care also contributed to the lower recurrence rates and satisfactory results.

Signal transducer and activator of transcription 1 in breast cancer: analysis with tissue microarray.

BACKGROUND: Constitutively activated signal transducer and activator of transcription (STAT) proteins are found in various types of tumors. However, there is still very limited information about the role of STATs in breast cancer. The power of the tissue microarray analysis (TMA) technique is the capability of performing a series of analyses of thousands of specimens in a parallel fashion with minimal damage to the original blocks. This study was designed to use TMA in determing the STAT1 status in breast cancer tissues. MATERIALS AND METHODS: Archival tissue specimens from 102 patients with primary invasive breast cancer were selected and STAT1 expression was analyzed using immunohistochemical staining with tissue microarray. The data of primary tumor staging, age, estrogen receptor status, lymph node status, histological grading and TNM staging were also collected. RESULTS: There were 18 patients (17.6%) with 0 expression in STAT1, 29 patients (28.4%) with 1 expression in STAT1, 21 patients (20.6%) with 2 expression in STAT1 and 34 patients (33.4%) with 3 expression in STAT1. There was no significant relationship between STAT1 expression and age (p = 0.203), estrogen receptor status (p = 0.221), histological grading (p = 0.861), primary tumor staging (p = 0.918), lymph node status (p = 0.53), or TNM staging (p = 0.826). There was no survival difference noted among the four groups with different STAT1 expression (p = 0.859). CONCLUSION: Immuno-histochemical staining with tissue microarray analysis was convenient and feasible for the analysis of STAT1 expression status in breast cancer. STAT1 expression did not show significant correlation with the overall survival rate.