Background: The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of ＜10%.Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis. Methods: Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients’ ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score. Results: 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of ＜10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%. Conclusion Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an ¹⁸F-labeled MAGL inhibitor ([¹⁸F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [¹⁸F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl₄) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [¹⁸F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [¹⁸F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [¹⁸F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [¹⁸F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.

Background: and Purpose Mechanical thrombectomy (MT) is an effective treatment for patients with basilar artery occlusion (BAO) acute ischemic stroke. It remains unclear whether bridging intravenous thrombolysis (IVT) prior to MT confers any benefit. This study compared the outcomes of acute BAO patients who were treated with direct MT versus combined IVT plus MT. Methods: This multicenter retrospective cohort study included patients who were treated for acute BAO from eight comprehensive stroke centers between January 2015 and December 2019. Patients received direct MT or combined bridging IVT plus MT. Primary outcome was favorable functional outcome defined as modified Rankin Scale 0–3 measured at 90 days. Secondary outcome measures included mortality and symptomatic intracranial hemorrhage (sICH). Results: Among 322 patients, 127 (39.4%) patients underwent bridging IVT followed by MT and 195 (60.6%) underwent direct MT. The mean±standard deviation age was 67.5±14.1 years, 64.0% were male and median National Institutes of Health Stroke Scale was 16 (interquartile range, 8 to 25). At 90-day, the rate of favorable functional outcome was similar between the bridging IVT and direct MT groups (39.4% vs. 34.4%, P=0.361). On multivariable analyses, bridging IVT was not asComorbidisociated with favorable functional outcome, mortality or sICH. In subgroup analyses, patients with underlying atherosclerosis treated with bridging IVT compared to direct MT had a higher rate of favorable functional outcome at 90 days (37.2% vs. 15.5%, P=0.013). Conclusions Functional outcomes were similar in BAO patients treated with bridging IVT versus direct MT. In the subgroup of patients with underlying large-artery atherosclerosis stroke mechanism, bridging IVT may potentially confer benefit and this warrants further investigation.

Blunt traumatic tracheobronchial injury is rare, but can be potentially life-threatening. It accounts for only 0.5%-2% of all trauma cases. Patients may present with non-specific signs and symptoms, requiring a high index of suspicion with accurate diagnosis and prompt treatment. A 26-year-old female was brought into the emergency department after sustained a blunt trauma to the chest from a high impact motor vehicle accident. She presented with signs of respiratory distress and extensive subcutaneous emphysema from the chest up to the neck. Her airway was secured and chest drain was inserted for right sided pneumothorax. CT of the neck and thorax revealed a collapsed right middle lung lobe with a massive pneumothorax, raising the suspicion of a right middle lobe bronchus injury. Diagnosis was confirmed by bronchoscopy. In view of the difficulty in maintaining her ventilation and persistent pneumothorax with a massive air leak, immediate right thoracotomy via posterolateral approach was performed. The right middle lobar bronchus tear was repaired. There were no intra- or post-operative complications. She made an uneventful recovery. She was asymptomatic at her first month follow-up. A repeated chest X-ray showed expanded lungs. Details of the case including clinical presentation, imaging and management were discussed with an emphasis on the early uses of bronchoscopy in case of suspected blunt traumatic tracheobronchial injury. A review of the current literature of tracheobronchial injury management was presented.
Humans ; Female ; Adult ; Pneumothorax/surgery* ; Bronchi/injuries* ; Wounds, Nonpenetrating/diagnosis* ; Bronchoscopy ; Trachea/injuries*

Background: Ingestion of foreign bodies leading to impaction at the pharynx and oesophagus have been extensively described in English literatures. However, impactions at the gastrointestinal tract distal to the oesophagus are less commonly encountered due to the more capacious luminal diameter as it approaches the stomach. While intentional foreign body ingestions impacted distal to the oesophagus are often more complicated, literatures on the management of these distal oesophageal impactions are scarce. Case presentation: We present five cases of foreign body impaction at varying sites of gastrointestinal tract beyond the oesophagus, contrasting management approach comparing the role of endoscopy, open surgery and conservative management. Cases presented include patients aged 40 to 70 with intentional foreign bodies ingestion. The first case described a cerebral palsy patient with pica who had to undergo difficult evacuation under anaesthesia followed by colonoscopy; the second and third cases presented 2 different schizophrenic patients with 2 differing management approach. The second case was managed with multiple operations due to complications and died eventually, making the only mortality in our case series; whereas the third case was managed conservatively with acceptable outcome after multiple laparotomies prior. Fourth and fifth cases described 2 body packers who swallowed tobacco and 2 phones, respectively; the former was uneventfully managed conservatively, the latter, had to undergo surgical extraction. Individualized approach to these distal impactions of ingested foreign bodies are described with a review of available literatures which are tabulated and discussed in this case series. Conclusion Endoscopy, surgery, conservative management and sometimes a combination of approaches are utilised for the management of foreign bodies impacted distal to the oesophagus, especially in complex and recurrent cases. Decision, timing and approach of extraction must be individualised with consideration of risk weighed against the benefit of each intervention over the other

INTRODUCTION: Two strategies are available for prevention of early-onset group B streptococcal (GBS) sepsis - clinical risk factor-based screening and routine culture-based screening of pregnant women for GBS colonisation. In our hospital, we switched from the former to the latter approach in 2014. METHODS: We compared the incidence of early-onset GBS sepsis during 2001-2015 between infants born to pregnant women who were screened for GBS colonisation and those born to women who were not screened. RESULTS: Among 41,143 live births, there were nine cases of early-onset GBS sepsis. All infants with GBS sepsis were born to pregnant women who were not screened for GBS colonisation. The incidence of early-onset GBS sepsis among infants of women who were not screened was 0.41 per 1,000 live births (95% confidence interval [CI] 0.19-0.77) when compared to infants of women who were screened, for whom the sepsis incidence was zero per 1,000 live births (95% CI 0-0.19; p = 0.005). CONCLUSION Our data suggests that routine culture-based screening of pregnant women for GBS colonisation is a better preventive strategy for early-onset GBS sepsis in neonates when compared to clinical risk factor-based screening.

Background: The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. Methods: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. Results: In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. Conclusion Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Background: The occurrence of Graves’ disease and Hashimoto thyroiditis after coronavirus disease 2019 (COVID-19) raised concerns that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may trigger thyroid autoimmunity. We aimed to address the current uncertainties regarding incident thyroid dysfunction and autoimmunity among COVID-19 survivors. Methods: We included consecutive adult COVID-19 patients without known thyroid disorders, who were admitted to Queen Mary Hospital from July 21 to September 21, 2020 and had serum levels of thyroid-stimulating hormone, free thyroxine, free triiodothyronine (fT3), and anti-thyroid antibodies measured both on admission and at 3 months. Results: In total, 122 patients were included. Among 20 patients with abnormal thyroid function tests (TFTs) on admission (mostly low fT3), 15 recovered. Among 102 patients with initial normal TFTs, two had new-onset abnormalities that could represent different phases of thyroiditis. Among 104 patients whose anti-thyroid antibody titers were reassessed, we observed increases in anti-thyroid peroxidase (TPO) (P<0.001) and anti-thyroglobulin (P<0.001), but not anti-thyroid stimulating hormone receptor titers (P=0.486). Of 82 patients with negative anti-TPO findings at baseline, 16 had a significant interval increase in anti-TPO titer by >12 U, and four became anti-TPO-positive. Worse baseline clinical severity (P=0.018), elevated C-reactive protein during hospitalization (P=0.033), and higher baseline anti-TPO titer (P=0.005) were associated with a significant increase in anti-TPO titer. Conclusion Most patients with thyroid dysfunction on admission recovered during convalescence. Abnormal TFTs suggestive of thyroiditis occurred during convalescence, but infrequently. Importantly, our novel observation of an increase in anti-thyroid antibody titers post-COVID-19 warrants further follow-up for incident thyroid dysfunction among COVID-19 survivors.

Objective: Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis. Materials and Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes. Results: Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44–61%); DCR, 57% (95% CI, 49–66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31–54%]; DCR, 85% [95% CI, 63–95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11–20%]; DCR, 26% [95% CI, 21– 32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52–67%) compared to ICI monotherapy (11%; 95% CI, 8–17%) and ICI combined with radiotherapy (4%; 95% CI, 1–19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy). Conclusion ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.

Objective: Immune checkpoint inhibitor (ICI) therapy has shown activity against melanoma brain metastases. Recently, promising results have also been reported for ICI combination therapy and ICI combined with radiotherapy. We aimed to evaluate radiologic response and adverse event rates of these therapeutic options by a systematic review and meta-analysis. Materials and Methods: A systematic literature search of Ovid-MEDLINE and EMBASE was performed up to October 12, 2019 and included studies evaluating the intracranial objective response rates (ORRs) and/or disease control rates (DCRs) of ICI with or without radiotherapy for treating melanoma brain metastases. We also evaluated safety-associated outcomes. Results: Eleven studies with 14 cohorts (3 with ICI combination therapy; 5 with ICI combined with radiotherapy; 6 with ICI monotherapy) were included. ICI combination therapy {pooled ORR, 53% (95% confidence interval [CI], 44–61%); DCR, 57% (95% CI, 49–66%)} and ICI combined with radiotherapy (pooled ORR, 42% [95% CI, 31–54%]; DCR, 85% [95% CI, 63–95%]) showed higher local efficacy compared to ICI monotherapy (pooled ORR, 15% [95% CI, 11–20%]; DCR, 26% [95% CI, 21– 32%]). The grade 3 or 4 adverse event rate was significantly higher with ICI combination therapy (60%; 95% CI, 52–67%) compared to ICI monotherapy (11%; 95% CI, 8–17%) and ICI combined with radiotherapy (4%; 95% CI, 1–19%). Grade 3 or 4 central nervous system (CNS)-related adverse event rates were not different (9% in ICI combination therapy; 8% in ICI combined with radiotherapy; 5% in ICI monotherapy). Conclusion ICI combination therapy or ICI combined with radiotherapy showed better local efficacy than ICI monotherapy for treating melanoma brain metastasis. The grade 3 or 4 adverse event rate was highest with ICI combination therapy, and the CNS-related grade 3 or 4 event rate was similar. Prospective trials will be necessary to compare the efficacy of ICI combination therapy and ICI combined with radiotherapy.