The use of hyperbaric oxygen therapy in the treatment of hand crush injuries.

Hyperbaric oxygen therapy (HBOT) has been used as an adjuvant treatment for crush injury because it can improve tissue hypoxia and stimulate wound healing. However, the actual role of HBOT in crush hand injury is still unknown. This study is to assess the efficacy of HBOT for crush hand patients, as well as the impact of HBOT initiation timing. Between 2018 and 2021, 72 patients with crush hand injury were retrospectively reviewed. The patients were divided into the HBOT and control group, and each group had 36 patients. The average session of HBOT was 18.2 (5-32 sessions) per patient, and no patient had a complication related to the treatment. The two groups had similar demographics, but HBOT group had larger injured area (73.6 ± 51.0 vs. 48.2 ± 45.5 cm2 , p = 0.03). To better control the confounding factors, we performed the subgroup analysis with cut-off injured area of 50 cm2 . In the patients with smaller injured area (≦50 cm2 ), the HBOT group had shorter wound healing time (29.9 ± 12.9 vs. 41.0 ± 18.9 days, p = 0.03). The early HBOT group (first session ≤72 h post-operatively) had shorter hospital stay (8.1 ± 6.4 vs. 15.5 ± 11.4 days, p = 0.04), faster wound healing (28.7 ± 17.8 vs. 41.1 ± 18.1 days, p = 0.08) and less operations (1.54 ± 0.78 vs. 2.41 ± 1.62, p = 0.06) although the latter two didn't achieve statistical significance. HBOT is safe and effective in improving wound healing of hand crush injury. Early intervention of HBOT may be more beneficial. Future research is required to provide more evidence.

Lung ventilation distribution in patients after traditional full sternotomy and minimally invasive thoracotomy: An observational study.

BACKGROUND: The aim of the study was to examine the post-operative ventilation distribution changes in cardiac surgical patients after traditional full sternotomy (FS) or minimally invasive thoracotomy (MIT). METHODS: A total of 40 patients scheduled for FS with two-lung ventilation or MIT with one-lung ventilation were included. Ventilation distribution was measured with electrical impedance tomography (EIT) at T1, before surgery; T2, after surgery in ICU before weaning; T3, 24 hours after extubation. EIT-based parameters were calculated to assess the ventilation distribution, including the left-to-right lung ratio, ventral-to-dorsal ratio, and the global inhomogeneity index. RESULTS: The global inhomogeneity index increased at T2 and T3 compared to T1 in all patients but only statistically significant in patients with MIT (FS, P = .06; MIT, P < .01). Notable decrease in the dorsal regions (FS) or in the non-ventilated side (MIT) was observed at T2. Ventilation distribution was partially improved at T3 but huge variations of recovery progresses were found in all patients regardless of the surgery types. Subgroup analysis indicated that operation duration was significantly lower in the MIT group (240 ± 40 in FS vs 205 ± 90 minutes in MIT, median ± interquartile range, P < .05) but the incidence of atrial fibrillation/flutter was significantly higher (5% in FS vs 50% in MIT, P < .01). Other exploratory outcomes showed no statistical differences. CONCLUSIONS: Ventilation distribution was impaired after cardiac surgery. The recovery process of ventilation homogeneity was strongly depending on individuals so that MIT was not always superior in this aspect. EIT may help to identify the patients requiring further care after surgery.

The use of electrical impedance tomography for individualized ventilation strategy in COVID-19: a case report.

BACKGROUND: Clinical management of COVID-19 requires close monitoring of lung function. While computed tomography (CT) offers ideal way to identify the phenotypes, it cannot monitor the patient response to therapeutic interventions. We present a case of ventilation management for a COVID-19 patient where electrical impedance tomography (EIT) was used to personalize care. CASE PRESENTATION: The patient developed acute respiratory distress syndrome, required invasive mechanical ventilation, and was subsequently weaned. EIT was used multiple times: to titrate the positive end-expiratory pressure, understand the influence of body position, and guide the support levels during weaning and after extubation. We show how EIT provides bedside monitoring of the patient´s response to various therapeutic interventions and helps guide treatments. CONCLUSION: EIT provides unique information that may help the ventilation management in the pandemic of COVID-19.

Reduction of healthcare costs by implementing palliative family conference with the decision to withdraw life-sustaining treatments.

BACKGROUND: Evidence regarding the impact of early palliative family conferences (PFCs) and decision to withdraw life-sustaining treatment (DTW) on healthcare costs in an intensive care unit (ICU) setting is inconsistent. METHODS: We retrospectively analyzed patients who died in an ICU from 2013 to 2016. PFCs held within 7 days after ICU admission and DTWs were verified by reviewing medical records and claims data. Comparisons were first made between patients with and without DTWs, and secondly, between DTW patients with and without PFCs within 7 days. Propensity score matching methods were used to examine the difference in costs between patients with and without DTWs and PFCs within 7 days. RESULTS: Of the 579 patients included, those with DTWs (n = 73) had a longer ICU stay than those without (n = 506) (12.9 ± 7.1 vs. 8.4 ± 9.6 days, p < 0.001). The DTW patients were more likely to have a "do-not-resuscitate" order (p < 0.001) and PFCs within 7 days (p < 0.001) and had lower healthcare costs (USD 7358 ± 4116 vs. 8669 ± 9,535, p = 0.038). After matching, healthcare cost reduction for patients with DTWs, compared with those without DTWs, was USD 3467 [95% CI, 915-6019] (p < 0.001). Compared with DTW patients without PFCs within 7 days, the costs for DTW patients with PFCs within 7 days further reduced to USD 3042 [95%CI, 1358-4725] (p < 0.001). CONCLUSION: Palliative family conferences held within 7 days after ICU admission with decisions to withdraw life-sustaining treatments significantly lowered healthcare costs.

The incidence and interpretation of large differences in EIT-based measures for PEEP titration in ARDS patients.

Positive end-expiratory pressure (PEEP) can be titrated by electrical impedance tomography (EIT). The aim of the present study was to examine the performance of different EIT measures during PEEP trials with the aim of identifying "optimum" PEEP and to provide possible interpretations of largely diverging results. After recruitment (maximum plateau pressure 35 cmH2O), decremental PEEP trial with steps of 2 cmH2O and duration of 2 min per step was performed. Ventilation gain and loss, the global inhomogeneity (GI) index, trend of end-expiratory lung impedance (EELI) and regional compliance (Creg) for estimation of overdistension and collapse were calculated. Largely diverging results of PEEP selection among the measures were defined as differences ≥ 4 PEEP steps (i.e. ≥ 8 cmH2O). In 30 ARDS patients we examined so far, 3 patients showed significant differences in PEEP selections. Overdistension and collapse estimation based on Creg tended to select lower PEEP while the GI index and EELI trend suggested higher PEEP settings. Regional inspiration times were heterogeneous indicating that the assumption of a uniform driving pressure in the calculation of Creg may not be valid. Judging by the predominant ventilation distribution in the most dependent regions, these patients were non-recruitable with the applied recruitment method or pressure levels. The existence of differences in the recommended PEEP among the analyzed EIT measures might be an indicator of non-recruitable lungs and heterogeneous airway resistances. In these extreme cases, the largely diverging results may prompt the attending clinician to develop individual ventilation strategies.Clinical Trial Registration Registration number NCT03112512, https://clinicaltrials.gov/ Registered 13 April 2017.

Increased Plasma Acetylcarnitine in Sepsis Is Associated With Multiple Organ Dysfunction and Mortality: A Multicenter Cohort Study.

OBJECTIVES: Recent metabolomic studies of sepsis showed that increased circulatory acylcarnitines were associated with worse survival. However, it is unknown whether plasma carnitine and acylcarnitines can reflect the severity of sepsis, and the role of specific acylcarnitines in prognostic assessment need further confirmation. This study aimed to clarify these questions. DESIGN: Prospective multicenter cohort studies with derivation and validation cohort design. SETTING: ICUs at two medical centers and three regional hospitals in Taiwan. PATIENTS: Patients with sepsis and acute organ dysfunction were enrolled. Recruitment of the derivation (n = 90) and validation cohorts (n = 120) occurred from October 2010 through March 2012 and January 2013 through November 2014, respectively. INTERVENTIONS: Plasma samples were collected immediately after admission, and the levels of carnitine and acylcarnitines were measured by ultra-high performance liquid chromatography-mass spectrometry. MEASUREMENTS AND MAIN RESULTS: In the derivation cohort, increased plasma levels of short- and medium-chain acylcarnitines were significantly associated with hepatobiliary dysfunction, renal dysfunction, thrombocytopenia, and hyperlactatemia. However, acetylcarnitine is the only acylcarnitine significantly correlating with various plasma cytokine concentrations and also associated with blood culture positivity and 28-day mortality risk. The association between plasma acetylcarnitine and multiple organ dysfunction severity, blood culture positivity, and 28-day mortality, was confirmed in the validation cohort. Patients with high plasma acetylcarnitine (≥ 6,000 ng/mL) had significantly increased 28-day mortality compared with those with plasma acetylcarnitine less than 6,000 ng/mL (52.6% vs 13.9%; hazard ratio, 5.293; 95% CI, 2.340-11.975; p < 0.001 by Cox proportional hazard model). CONCLUSIONS: We confirm that plasma acetylcarnitine can reflect the severity of organ dysfunction, inflammation, and infection in sepsis and can serve as a prognostic biomarker for mortality prediction.

Comparable clinical outcomes in patients with HER2-mutant and EGFR-mutant lung adenocarcinomas.

HER2 is a major proliferative driver in lung cancer. HER2 gene aberrations impact the prognosis of lung adenocarcinoma (ADC). A one-step reverse transcription-polymerase chain reaction was performed using RNA samples from 888 Asian lung cancer patients to detect HER2, EGFR, KRAS, ALK, and ROS1 mutations. The demographic data and treatment outcomes of HER2 mutation-positive lung ADC patients were analyzed and compared to those with HER2 mutation-negative tumors. HER2 mutation was identified in 40 (4.5%) lung ADC patients. HER2 mutations tended to occur in male patients with advanced-stage disease and never-smokers. A775_G776insYVMA (n = 22, 55%) was the most prevalent HER2 mutation, followed by P780_Y781insGSP (n = 4, 10%). For patients diagnosed with stage-IIIB/IV disease, HER2-mutant patients showed clinical outcomes comparable to EGFR-mutant patients (P = 0.721, log-rank test) and a better overall survival (OS) compared to patients lacking driver mutations in the investigated genes (P = 0.033, Breslow test). Specifically, lung ADC patients with stage-IV HER2-mutant tumors treated with chemotherapy or targeted agents, even without afatinib or anti-HER2 targeted therapy, showed similar clinical outcomes to lung ADC patients harboring EGFR exon 19 deletion or L858R mutations (P = 0.870). In addition, multivariate analysis indicated that HER2 mutation status was not a major risk factor for diminished OS in stage-IV lung cancer. In conclusion, lung ADC harboring HER2 mutations showed distinct characteristics from other driver mutations, including increased chemosensitivity with in advanced stage disease.

Selection of empirical antibiotics for health care-associated pneumonia via integration of pneumonia severity index and risk factors of drug-resistant pathogens.

BACKGROUND/PURPOSE: The pneumonia severity index (PSI) both contains some risk factors of drug-resistant pathogens (DRPs) and represents the severity of health care-associated pneumonia. The aim of this study was to investigate whether the PSI could be used to predict DRPs and whether there were risk factors beyond the PSI. METHODS: A retrospective observational study enrolled 530 patients with health care-associated pneumonia who were admitted from January 2005 to December 2010 in a tertiary care hospital. RESULTS: A total of 206 patients (38.9%) had DRPs, of which the most common was Pseudomonas aeruginosa (24.3%). The incidence of DRPs increased with increasing PSI classes (6.7%, 25.5%, 36.9%, and 44.6% in PSI II, III, IV, and V, respectively). An analysis of the risk factors for DRPs by PSI classes revealed that wound care was associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in PSI V (p = 0.045). Nasogastric tube feeding (odds ratio, 3.88; 95% confidence interval, 1.75-8.60; p = 0.006), and bronchiectasis (odds ratio, 3.12; 95% confidence interval, 0.66-14.69; p = 0.007) were risk factors for DRPs in PSI III and IV. The area under the receiver operating characteristic curve progressed from 0.578 to 0.651 while integrating these risk factors with PSI classes. CONCLUSION: The findings suggested that PSI plus risk factors predicted the risk of DRPs. PSI II had a low risk of DRPs and could be treated as community-acquired pneumonia. Antibiotics of PSI III and IV with risk factors could be targeted DRPs. PSI V with wound care had a higher risk of MRSA, and empirical anti-MRSA antibiotics could be added.

Immunometabolic features of natural killer cells are associated with infection outcomes in critical illness.

Immunosuppression increases the risk of nosocomial infection in patients with chronic critical illness. This exploratory study aimed to determine the immunometabolic signature associated with nosocomial infection during chronic critical illness. We prospectively recruited patients who were admitted to the respiratory care center and who had received mechanical ventilator support for more than 10 days in the intensive care unit. The study subjects were followed for the occurrence of nosocomial infection until 6 weeks after admission, hospital discharge, or death. The cytokine levels in the plasma samples were measured. Single-cell immunometabolic regulome profiling by mass cytometry, which analyzed 16 metabolic regulators in 21 immune subsets, was performed to identify immunometabolic features associated with the risk of nosocomial infection. During the study period, 37 patients were enrolled, and 16 patients (43.2%) developed nosocomial infection. Unsupervised immunologic clustering using multidimensional scaling and logistic regression analyses revealed that expression of nuclear respiratory factor 1 (NRF1) and carnitine palmitoyltransferase 1a (CPT1a), key regulators of mitochondrial biogenesis and fatty acid transport, respectively, in natural killer (NK) cells was significantly associated with nosocomial infection. Downregulated NRF1 and upregulated CPT1a were found in all subsets of NK cells from patients who developed a nosocomial infection. The risk of nosocomial infection is significantly correlated with the predictive score developed by selecting NK cell-specific features using an elastic net algorithm. Findings were further examined in an independent cohort of COVID-19-infected patients, and the results confirm that COVID-19-related mortality is significantly associated with mitochondria biogenesis and fatty acid oxidation pathways in NK cells. In conclusion, this study uncovers that NK cell-specific immunometabolic features are significantly associated with the occurrence and fatal outcomes of infection in critically ill population, and provides mechanistic insights into NK cell-specific immunity against microbial invasion in critical illness.

Single-Center Experience of Control of Ventilator-Circuit-Transmitted Burkholderia cepacia Outbreak in an Intensive Care Unit.

Burkholderia cepacia is an emerging nosocomial pathogen frequently associated with outbreaks, but the exact transmission route of this pathogen can at times be elusive in spite of extensive environmental investigative cultures. Active surveillance for sputum cultures was performed for all patients from September 2008 to September 2009 in an intensive care unit (ICU) with B. cepacia outbreak. With evidence of persistent positive conversion of sputum cultures (colonization) and infections among patients, discontinuing re-usable ventilator circuits was introduced. A total of 689 patients were admitted to this unit for a mean duration of 8.7 ± 7.5 days. There were 489 patients (71.0%) with a stay for one to ten days; 161 (23.4%) patients for 11 to 20 days; and 39 (5.7%) with over 20 days. In the first group, 13.5% of patients had cultures converting from negative to positive, in contrast to 66.7% in the last group (p < 0.01). With intervention of using disposable ventilator circuits since June 2009, the incidence of isolated B. cepacia decreased gradually. The estimated 30-day isolation-free probabilities of the groups before, during, one month (August 2009) after, and two months (September 2009) after this intervention were 38.5%, 47.3%, 66.5%, and 96.0%, respectively (p < 0.01). Furthermore, the effect of discontinuing reusable ventilator circuit persisted in the following 6 years; both total isolates of B. cepacia and the infection caused by it were much lower compared to the outbreak period. In summary, this six-year outbreak in a medical ICU persisted until reusable ventilator circuits were discontinued in 2009. The effect of disposable circuits on the decreased incidence of B. cepacia infection maintained in the following years.

Mortality in patients with COVID-19 versus non-COVID-19- related acute respiratory distress syndrome: A single center retrospective observational cohort study.

The pathophysiology of coronavirus disease-2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) varies from other pneumonia-related ARDS. We evaluated whether the mortality rates differed for COVID-19 and non-COVID-19-related ARDS in the Asian population in 2021. This single center retrospective observational cohort study included patients with COVID-19 and non-COVID-19-related ARDS that required invasive mechanical ventilation. The primary outcome was all-cause in-hospital mortality. The secondary outcomes included hospital length of stay, ICU length of stay, duration of mechanical ventilation, and ventilator-free days (VFDs) during the first 28 days. A 1:1 propensity score matching was performed to correct potential confounders by age, obesity or not, and ARDS severity. One-hundred-and-sixty-four patients fulfilled the inclusion criteria. After 1:1 propensity score matching, there were 50 patients in each group. The all-cause in-hospital mortality of all patients was 38 (38%), and no significant differences were found between COVID-19 and non-COVID-19-related ARDS (17 [34%) vs. 21 [42%], p = 0.410). Both groups had length of stay (30.0 [20.0-46.0] vs. 27.0 [13.0-45.0] days, p = 0.312), ICU length of stay (19.0 [13.0-35.0] vs. 16.0 [10.0-32.0] days, p = 0.249), length of mechanical ventilation (19.0 [10.0-36.0] vs. 14.0 [9.0-29.0] days, p = 0.488), and ventilator-free days during the first 28 days (5.5 [0.0-17.0] vs. 0.0 [0.0-14.0] days, p = 0.320). Immunocompromised status (Hazard ratio: 3.63; 95% CI: 1.51-8.74, p = 0.004) and progress to severe ARDS (Hazard ratio: 2.92; 95% CI: 1.18-7.22, p = 0.020) were significant in-hospital mortality-related confounders. There were no significant difference in mortality among both groups. Immunocompromised status and progression to severe ARDS are two possible risk factors for patients with ARDS; COVID-19 is not a mortality-related risk exposure.

Ocular surface reconstruction of Steven Johnson syndrome / toxic epidermal necrolysis affected eye - A case report.

Introduction: Toxic epidermal necrolysis (TEN), also known as Steven Johnson syndrome (SJS), is a devastating disease. Patients develop blindness and symblepharon despite multiple reconstructive surgeries. We report a case of SJS/TEN with ocular involvement where treatment with hyperbaric oxygen therapy (HBOT) resulted in a significant improvement in the visual acuity after surgery. Case presentation: A woman with SJS/TEN with severe ocular complication (SOC) had limbal stem cell deficiency and symblepharon of the superior and inferior fornix. Pannus grew over her cornea, reducing the vision to counting finger. The symblepharon produced shortening of the fornix, causing entropion. The in-turned eyelid caused her eyelashes to rub against the cornea, causing great damage to the ocular surface. Limbal stem cell deficiency led to the loss of normal corneal morphology and invasion of the pannus onto the central visual axis, resulting in poor vision. She experienced ocular inflammation for 3 months before transfer to our hospital for admission. Ophthalmic examination showed bilateral corneal opacity with conjunctivalization, and inferior and superior fornix shortening. Symblepharon-lysis with amniotic membrane transplantation was attempted but the outcome was poor, with recurrence of superior scaring and symblepharon. She finally underwent major reconstructive surgery with allogeneic limbal stem cell transplantation with her sister as the donor, autologous minor salivary gland transplantation, and oral buccal mucosa flap transplant. HBOT was given daily post-surgery for supporting the grafts and suppressing inflammation. After 17 HBOT sessions and 3 months of autoserum drops, her left eye vision increased from the initial counting finger to 0.4 due to the successful growth of the corneal epithelium from the donor corneal limbal cell line. When a scleral contact lens which vaulted over the corneal limbal area was fitted, her vision improved to 0.8 due to redressal of high order aberration and astigmatism from the cornea scar. Conclusion: After major reconstruction of the ocular surface with multiple cell type transplants, including limbal stem cells, minor salivary gland acinar cells, and oral mucosa cells, HBOT proved useful in supporting the graft uptake and oxygenation of the donor tissues, enabling fast recovery of the grafts and cell functioning, with eventual return of the working vision of the patient.

Effect of the Timing of Hyperbaric Oxygen Therapy on the Prognosis of Patients with Idiopathic Sudden Sensorineural Hearing Loss.

This study aimed to evaluate the effects of hyperbaric oxygen therapy (HBOT) on the hearing recovery of patients with idiopathic sudden sensorineural hearing loss (ISSNHL). The clinical data of 79 patients diagnosed with ISSNHL and treated with HBOT between January 2017 and December 2019 were retrospectively reviewed. The pure tone audiometry (PTA) scores before and after HBOT were recorded. The associations of HBOT efficacy with demographic and clinical characteristics and the duration from disease onset to HBOT administration were determined. The average PTA score was 80.06 ± 25.94 dB before and 60.75 ± 21.26 dB after HBOT; the difference was significant. HBOT improved the hearing of 55.7% of the patients with ISSNHL (defined as an average PTA ≥ 11dB or a final average PTA score below 29 dB). There was a significant inverse relationship between the duration from symptom onset to HBOT administration and PTA score reduction after HBOT, which was adjusted for factors including age, sex, laterality of hearing loss, initial PTA score, reception of intratympanic steroid injections, tinnitus, dizziness, vertigo, diabetes, hypertension, and coronary artery disease. Commencing HBOT at an earlier stage is closely linked to greater improvements in hearing for patients with ISSNHL.

Hyperbaric oxygen therapy as rescue therapy for pediatric frosted branch angiitis with Purtscher-like retinopathy: A case report.

Introduction: Frosted branch angiitis (FBA) is an uncommon uveitis characterized by fulminant retinal vasculitis. Purtscher-like retinopathy (PuR) is a rare retinal angiopathy associated with a non-traumatic etiology. Both FBA and PuR can cause profound visual impairments. Case report: We describe the case of a 10-year-old male who presented with sudden bilateral painless visual loss due to FBA with concurrent PuR, with notable viral prodrome 1 month prior to presentation. Systemic investigations revealed a recent herpes simplex virus 2 infection with a high titer of IgM, positive antinuclear antibody (ANA) (1:640), and abnormal liver function tests. After administration of systemic corticosteroids, anti-viral agents, and subsequent immunosuppressive medications, the FBA was gradually alleviated. However, fundoscopy and optical coherence tomography (OCT) revealed persistent PuR and macular ischemia. Hence, hyperbaric oxygen therapy was administered as a rescue strategy, which resulted in gradual bilateral visual acuity improvement. Conclusion: Hyperbaric oxygen therapy may be a beneficial rescue treatment for retinal ischemia secondary to FBA with PuR.

Compliance and barriers to implementing the sepsis resuscitation bundle for patients developing septic shock in the general medical wards.

BACKGROUND/PURPOSE: This two-part study aimed to investigate compliance with the sepsis resuscitation bundle (SRB) and the barriers to its implementation for patients developing septic shock in the general medical wards. METHODS: In the first part, medical records of patients who were admitted to the intensive care unit from the general medical wards due to septic shock were reviewed. Compliance rates with the six SRB components were assessed. In the second part, responsible junior physicians (first-year and second-year residents) in the general wards and senior physicians (third-year residents and fellows) were randomly invited for questionnaire-based interviews. RESULTS: In the first part, during the 6-month study period, 40 patients were included. Overall compliance with the SRB within 6 h was only 2.5%, mainly due to femoral catheterization (42.5%) and the lack of measuring central venous oxygen saturation (ScvO2). Delayed completion of SRB components contributed little to the low compliance rate. In the second part, based on the questionnaire results of 71 junior physicians and 64 senior physicians, the junior physicians were less familiar with the SRB guidelines, particularly regarding the meaning of ScvO2 (p = 0.01) and management of low ScvO2 (p = 0.04). Junior physicians were also more reluctant to measure the central venous pressure (CVP; p = 0.04) and the ScvO2 (p = 0.01), and were also less confident with internal jugular vein or subclavian vein catheterization (p < 0.001). CONCLUSION: Compliance with the SRB for patients developing septic shock in the general medical wards is very low. Besides providing educational programs to improve awareness and acceptance of the SRB, measures to help in central venous catheterization and completion of SRB may be considered.

Rapid response of a medical center upon the surge of COVID-19 epidemic in Taiwan.

A surge of coronavirus disease (COVID-19) cases emerged in northern Taiwan in mid-May 2021. In spite of over one-year preparedness, the medical system in this area suffered from the crisis. Far Eastern Memorial Hospital (FEMH) responded quickly with decreased total hospitalization cases (about 50%) to free manpower and space. With simple construction work, the in-hospital service capacity increases from 11 negative-pressure ward (1 unit) and 2 negative-pressure ICU (1 unit) beds to over 130 ward (5 units) and 58 ICU beds (4 units) without negative-pressure design within 3 weeks. For a period of time, FEMH takes care of 10% of all intensive care services in Taiwan. The vaccination rate of workers reaches 90% since mid-May. The amount of testing performed during the period, including PCR and rapid tests, comprised of more than 20% of tests performed in New Taipei City. Two hotels for mild/asymptomatic COVID patients were handled by FEMH workers. By mid-July, about one-fifth of COVID-19 cases in New Taipei City received services from the FEMH system. With determined leadership and concerted efforts, combined interventions can increase the capacity of medical care within weeks and help society against the COVID-19 epidemic.

Early-Onset Pulmonary Events with Combined Brigatinib and Afatinib Treatment of L858/cisT790M/cisC797S NSCLC: A Case Report.

BACKGROUND Brigatinib is used for anaplastic lymphoma kinase (ALK)-positive lung cancer treatment, and some research showed it was useful in treating triple-mutant epidermal growth factor receptor lung cancer. Clinical trials have shown some potential pulmonary toxicities of brigatinib. The early-onset pulmonary events (EOPEs) of brigatinib are associated with high dosage and older age. The successful treatment of EOPEs with steroids was reported. We present the case of a patient with epidermal growth factor receptor L858R/cis-T790M/cis-C797S triple mutations who developed EOPEs after using brigatinib together with afatinib, and the patient was successfully treated with high-dose steroids. CASE REPORT A 54-year-old woman with underlying stage IV lung adenocarcinoma, ECOG score of 0, was treated with brigatinib and afatinib due to disease progression secondary to L858R/cis-T790M/cis-C797S triple mutations. After starting brigatinib and afatinib, she developed dyspnea and dry cough within 2 days and was intubated due to hypercapnic respiratory failure. The chest X-ray showed bilateral interstitial infiltrates while chest computed tomography (CT) showed bilateral ground-glass opacities. EOPEs were suspected and methylprednisolone was prescribed. The oxygenation of the patient improved and her chest CT showed complete resolution after 2 weeks of steroid treatment. CONCLUSIONS This is the first reported case in which brigatinib combined with afatinib induced EOPEs in a patient with triple-mutant epidermal growth factor receptors of lung cancer. Use of doubled tyrosine kinase inhibitors may result in increased risk of pulmonary toxicities that require high alertness, and the respiratory symptoms should be monitored closely after prescription. The early treatment of EOPEs with high-dose steroids resulted in remarkable improvement.