Neutrophil-to-Lymphocyte Ratio Predicts Development of Immune-Related Adverse Events and Outcomes from Immune Checkpoint Blockade: A Case-Control Study.

The utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) utility in predicting immune-related adverse events (irAEs) and survival have not been well studied in the context of treatment with immune checkpoint inhibitors (ICIs). We performed a case-control study of cancer patients who received at least one dose of ICI in a tertiary hospital. We examined NLR and PLR in irAE cases and controls. Logistic and Cox regression models were used to identify independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). The study included 91 patients with irAEs and 56 controls. Multiple logistic regression showed that NLR < 3 at baseline was associated with higher occurrence of irAEs. Multivariate Cox regression showed that development of irAEs and reduction in NLR from baseline to week 6 were associated with longer PFS. Higher NLR values at baseline and/or week 6 were independently associated with shorter OS. A reduction in NLR from baseline to week 6 was associated with longer OS. In this study of cancer patients treated with ICIs, NLR has a bidirectional relationship with adverse outcomes. Lower NLR was associated with increased occurrence of irAEs while higher NLR values were associated with worse clinical outcomes.

Subclinical Cardiomyopathy in Miyoshi Myopathy Detected by Late Gadolinium Enhancement Cardiac Magnetic Resonance Imaging.

Dysferlin is a sarcolemmal protein present in muscle cells. It is responsible for muscle membrane repair. Dysferlin gene (DYSF) mutation, resulting in deficiency in this protein, is termed dysferlinopathy. Clinically, it manifests as early adulthood onset of muscle weakness with markedly elevated creatine kinase levels. The main phenotypes are limb-girdle muscular dystrophy type 2B (LGMD2B), affecting proximal muscles, and Miyoshi myopathy (MM), affecting distal muscles. Dysferlin is also present in cardiomyocytes, and case reports have emerged of cardiac abnormalities in dysferlinopathy. While routine methods of cardiac screening, namely, electrocardiography or echocardiography, are convenient and noninvasive, they often exhibit insufficient diagnostic sensitivity for detecting subclinical cardiac remodeling during early stages of cardiomyopathy. Cardiac magnetic resonance imaging though can provide accurate assessment of cardiac chamber sizes and function. With gadolinium administration, it can also detect areas of myocardial scarring and fibrosis. Early diagnosis of neuromuscular disease-related cardiomyopathy is of clinical significance, as appropriate treatment can retard myocardial fibrosis, delaying cardiomyopathy progression. We present a case of a patient with MM incidentally diagnosed with concomitant cardiomyopathy.

Neurology of COVID-19 in Singapore.

PURPOSE: To describe the spectrum of COVID-19 neurology in Singapore. METHOD: We prospectively studied all microbiologically-confirmed COVID-19 patients in Singapore, who were referred for any neurological complaint within three months of COVID-19 onset. Neurological diagnoses and relationship to COVID-19 was made by consensus guided by contemporaneous literature, refined using recent case definitions. RESULTS: 47,572 patients (median age 34 years, 98% males) were diagnosed with COVID-19 in Singapore between 19 March to 19 July 2020. We identified 90 patients (median age 38, 98.9% males) with neurological disorders; 39 with varying certainty of relationship to COVID-19 categorised as: i) Central nervous system syndromes-4 acute disseminated encephalomyelitis (ADEM) and encephalitis, ii) Cerebrovascular disorders-19 acute ischaemic stroke and transient ischaemic attack (AIS/TIA), 4 cerebral venous thrombosis (CVT), 2 intracerebral haemorrhage, iii) Peripheral nervous system-7 mono/polyneuropathies, and a novel group, iv) Autonomic nervous system-4 limited dysautonomic syndromes. Fifty-one other patients had pre/co-existent neurological conditions unrelated to COVID-19. Encephalitis/ADEM is delayed, occurring in critical COVID-19, while CVT and dysautonomia occurred relatively early, and largely in mild infections. AIS/TIA was variable in onset, occurring in patients with differing COVID-19 severity; remarkably 63.2% were asymptomatic. CVT was more frequent than expected and occurred in mild/asymptomatic patients. There were no neurological complications in all 81 paediatric COVID-19 cases. CONCLUSION: COVID-19 neurology has a wide spectrum of dysimmune-thrombotic disorders. We encountered relatively few neurological complications, probably because our outbreak involved largely young men with mild/asymptomatic COVID-19. It is also widely perceived that the pandemic did not unduly affect the Singapore healthcare system.

Should we treat patients with impaired consciousness and periodic patterns on EEG?

PURPOSE: The significance of periodic EEG patterns in patients with impaired consciousness is controversial. We aimed to determine if treating these patterns influences clinical outcome. METHOD: We studied all patients who had periodic discharges on their EEG recordings from January 2007 to December 2009. Patients with clinical seizures within the preceding 24h, or with unequivocal electrographical seizure activity were excluded. Logistic regression was performed to analyze for factors associated with (a) mortality (b) functional status (c) resolution of EEG pattern. RESULTS: Of the 4246 patients who had EEG, 111 (2.6%) had periodic EEG patterns. 64 met inclusion criteria. In adjusted analysis, higher mortality was associated with acute symptomatic etiology (OR 17.74, 95% CI 1.61-196.07, p=0.019), and presence of clinical seizures (OR 4.73, 95% CI 1.10-20.34, p=0.037). For each unit decrement of GCS, the odds of inpatient mortality and a poorer functional state on discharge increased by 23% (95% CI 7-37%, p=0.009) and 33% (95% CI 9-51%, p=0.011) respectively. Administration of abortive therapy was an independent risk factor for poorer functional status on discharge (adjusted OR 41.39, 95% CI 2.88-594.42, p=0.006), while patients with history of pre-existing cerebral disease appeared more likely to return to baseline functional status on discharge (unadjusted OR 5.00, 95% CI 1.40-17.86, p=0.013). CONCLUSION: Treatment of periodic EEG patterns does not independently improve clinical outcome of patients with impaired conscious levels. Occurrence of seizures remote to the time of EEG and lower GCS scores independently predict poor prognoses.

Streptococcus constellatus bacteremia causing septic shock following tooth extraction: a case report.

INTRODUCTION: Organisms of the Streptococcus milleri group consists of Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus. Though they are commonly associated with abscesses, bacteremia with subsequent septic shock and mortality is infrequent. CASE PRESENTATION: We report a case of a 27-year-old Chinese man who presented with Streptococcus constellatus bacteremia following an incomplete tooth extraction resulting in septic shock. CONCLUSION: Bacteremia from the Streptococcus milleri group is infrequent but must trigger the search for an underlying abscess. Knowledge of each member's predilection for different clinical presentations can aid in determining the location of the underlying source of infection.