Clinical best practices in optimal monitoring, early diagnosis, and effective management of antibody-drug conjugate-induced interstitial lung disease or pneumonitis: a multidisciplinary team approach in Singapore.

INTRODUCTION: Interstitial lung disease (ILD) or pneumonitis remains an important adverse event identified with treatment with antibody-drug conjugates (ADCs). Drug-induced ILD (DILD) accounts for 3%-5% of common ILD cases and is a significant problem in clinical practice. Hence, with the anticipation of the widespread use of ADCs, it will be important for guidelines and recommendations to be established to direct and standardize the management of DILD by a multidisciplinary team (MDT). AREAS COVERED: A thorough literature search was conducted using PubMed to identify relevant articles related to ADCs published between 1 January 2010 and 31 November 2022. Based on the review of the literature combined with expert opinions, this review article offers an overview of incidences of ILDs associated with the use of newer anticancer therapies, specifically ADCs, and discusses local-regional best practices in optimal monitoring, early diagnosis, and management of DILD involving an MDT. EXPERT OPINION: Multidisciplinary input and consensus are crucial in the accurate diagnosis of DILD. The core group of essential attendees in the MDT are oncologists, pulmonologists, thoracic radiologists, and pathologists. This allows for the integration of expertise from different specialists to achieve a 'best fit' diagnosis and management.

Perceptions of Singaporeans towards informed consent: a cross-sectional survey.

INTRODUCTION: In a patient-centric health system, it is essential to know patients' views about informed consent. The objective of this study was to understand the perceptions of the local population regarding informed consent. METHODS: Spanning across six weeks from January 2016 to March 2016, a cross-sectional survey of adults attending General Surgery outpatient clinics at Tan Tock Seng Hospital was performed. Sociodemographic data, lifestyle and health-related information, perception and purpose of consent forms, and decision-making preferences were studied. RESULTS: 445 adults participated in the survey. Most participants were below 40 years old (n = 265, 60.1%), female (n = 309, 70.1%) and degree holders (n = 196, 44.4%). 56.9% of participants wanted to know every possible risk, while 28.3% wanted to know common and serious risks. On multivariate analysis, age (age 61-74 years: odds ratio [OR] 11.1, 95% confidence interval [CI] 2.2-56.1, p = 0.004; age > 75 years: OR 22.2, 95% CI 1.8-279.1, p = 0.017) was a predictor of not wanting to know any risks. Age also predicted risk of disclosure for death (age 61-74 years: OR 13.4, 95% CI 4.2-42.6, p < 0.001; age > 75 years: OR 32.0, 95% CI 4.5-228.0, p = 0.001). Most participants (48.1%) preferred making shared decisions with doctors, and an important predictor was employment status (OR = 4.8, 95% CI 1.9-12.2, p = 0.001). CONCLUSION: Sociodemographic factors and educational level influence decision-making, and therefore, the informed consent process should be tailored for each patient.

Doxycycline host-directed therapy in human pulmonary tuberculosis.

BACKGROUNDMatrix metalloproteinases (MMPs) are key regulators of tissue destruction in tuberculosis (TB) and may be targets for host-directed therapy. We conducted a phase II double-blind, randomized, controlled trial investigating doxycycline, a licensed broad-spectrum MMP inhibitor, in patients with pulmonary TB.METHODSThirty patients with pulmonary TB were enrolled within 7 days of initiating anti-TB treatment and randomly assigned to receive either 100 mg doxycycline or placebo twice a day for 14 days, in addition to standard care.RESULTSWhole blood RNA-sequencing demonstrated that doxycycline accelerated restoration of dysregulated gene expression in TB towards normality, rapidly down-regulating type I and II interferon and innate immune response genes, and up-regulating B-cell modules relative to placebo. The effects persisted for 6 weeks after doxycycline discontinuation, concurrent with suppressed plasma MMP-1. Doxycycline significantly reduced sputum MMP-1, -8, -9, -12 and -13, suppressed type I collagen and elastin destruction, reduced pulmonary cavity volume without altering sputum mycobacterial loads, and was safe.CONCLUSIONAdjunctive doxycycline with standard anti-TB treatment suppressed pathological MMPs in PTB patients. Larger studies on adjunctive doxycycline to limit TB immunopathology are merited.TRIAL REGISTRATIONClinicalTrials.gov NCT02774993.FUNDINGSingapore National Medical Research Council (NMRC/CNIG/1120/2014, NMRC/Seedfunding/0010/2014, NMRC/CISSP/2015/009a); the Singapore Infectious Diseases Initiative (SIDI/2013/013); National University Health System (PFFR-28 January 14, NUHSRO/2014/039/BSL3-SeedFunding/Jul/01); the Singapore Immunology Network Immunomonitoring platform (BMRC/IAF/311006, H16/99/b0/011, NRF2017_SISFP09); an ExxonMobil Research Fellowship, NUHS Clinician Scientist Program (NMRC/TA/0042/2015, CSAINV17nov014); the UK Medical Research Council (MR/P023754/1, MR/N006631/1); a NUS Postdoctoral Fellowship (NUHSRO/2017/073/PDF/03); The Royal Society Challenge Grant (CHG\R1\170084); the Sir Henry Dale Fellowship, Wellcome Trust (109377/Z/15/Z); and A*STAR.

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.

Clinics in diagnostic imaging (195). Plantar fibromatosis.

A 46-year-old man presented with a six-month history of lumps in the sole of his left foot. Physical examination revealed two nodules, one tender and one firm, at the plantar left foot with no overlying skin changes. Although the initial radiographs were normal, magnetic resonance imaging of the left foot demonstrated two nodules along the medial band of the plantar fascia, characteristic of plantar fibromas. The patient opted for surgical excision. There was no further recurrence of symptoms after surgery. We describe the clinical and radiological features of plantar fibromatosis and briefly discuss other causes of lumps and pain in the sole of the foot.

A 67-Year-Old Man With Psoriatic Arthritis and New-Onset Dyspnea.

A 67-year-old retired air force officer presented with a 6-month history of nonproductive cough, progressive exertional dyspnea, and weight loss. He was unable to walk beyond 100 m compared with his baseline of unlimited walking distance. He denied fever, hemoptysis, myalgia, or chest pain. He had a 30-year history of chronic plaque psoriasis with arthritis, which was managed by his dermatologist with emollients and vitamin D analogues. Joint involvement had previously been controlled with methotrexate, which was discontinued 15 years ago after resolution of his symptoms. He developed a polyarthritis flare a year ago, and adalimumab was initiated with good response.

Pulmonary sclerosing hemangioma: pitfalls in management.

Pulmonary sclerosing hemangioma is a rare benign tumor for which surgical excision is curative with an excellent prognosis. It often mimics malignancy, making it a diagnostic and management challenge. We reviewed the clinical, radiological, and histopathological characteristics as well as the surgical management of our patients to assess the potential pitfalls in management. All 19 patients who underwent surgical biopsy between January 1999 and December 2009 with a final histopathological diagnosis of pulmonary sclerosing hemangioma were reviewed retrospectively. The median age was 48 years, 89.5% were female, 89.5% were Chinese, and 68.4% were asymptomatic. There were no specific diagnostic radiological characteristics; 1 of 3 patients who underwent combined positron-emission and computed tomography had a false-positive result. Preoperative attempts at establishing a diagnosis were successful in 20% of patients who had invasive procedures. Intraoperative frozen-section evaluation for pulmonary sclerosing hemangioma had an error rate of 25% and a deferred rate of 31%, resulting in nearly half of our patients undergoing unnecessary extensive surgical procedures. We hope to heighten awareness of this diagnosis, thereby increasing the index of suspicion and minimizing errors in diagnosis.

Bronchoscopic management of sarcoidosis related bronchial stenosis with adjunctive topical mitomycin C.

A 58-year-old woman with multiple proximal airway stenoses due to sarcoidosis failed to improve with steroid therapy. After bronchoscopic balloon dilation with adjunctive topical mitomycin C, there was symptomatic improvement and preserved patency of the airways one month later. However, the patient's effort tolerance gradually deteriorated subsequently, and a repeat bronchoscopy one year later showed recurrence of airway stenosis.

Tetanus in an injecting buprenorphine abuser.

INTRODUCTION: Injecting drug abusers are vulnerable to many infectious complications. We describe a case of tetanus in a Singaporean who regularly abused buprenorphine. CLINICAL PICTURE: A 49-year-old male was hospitalised for progressive generalised spasms associated with dysarthria and opisthotonus. Tetanus was diagnosed clinically. TREATMENT: Supportive management was instituted in the intensive care unit (ICU). Toxicology samples tested positive for buprenorphine. OUTCOME: He recovered rapidly and was transferred out of the ICU after 8 days. Retrospective questioning confirmed parenteral abuse of buprenorphine. CONCLUSION: This case highlights an uncommon and potentially lethal complication of parenteral drug abuse.