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Introduction: Pressurized intraperitoneal aerosol chemotherapy-oxaliplatin (PIPAC-OX) induces direct DNA damage and immunogenic cell death in patients with gastric cancer peritoneal metastases (GCPM). Combining PIPAC-OX with immune checkpoint inhibition remains untested. We conducted a phase I first-in-human trial evaluating the safety and efficacy of PIPAC-OX combined with systemic nivolumab (NCT03172416)., Methods: Patients with GCPM who experienced disease progression on at least first-line systemic therapy were recruited across three centers in Singapore and Belgium. Patients received PIPAC-OX at 90 mg/m 2 every 6 weeks and i.v. nivolumab 240 mg every 2 weeks. Translational studies were carried out on GCPM samples acquired during PIPAC-OX procedures., Results: In total, 18 patients with GCPM were prospectively recruited. The PIPAC-OX and nivolumab combination was well tolerated with manageable treatment-related adverse events, although one patient suffered from grade 4 vomiting. At second and third PIPAC-OX, respectively, the median decrease in peritoneal cancer index (PCI) was -5 (interquartile range: -12 to +1) and -7 (interquartile range: -6 to -20) and peritoneal regression grade 1 or 2 was observed in 66.7% (6/9) and 100% (3/3). Translational analyses of 43 GCPM samples revealed enrichment of immune/stromal infiltration and inflammatory signatures in peritoneal tumors after PIPAC-OX and nivolumab. M2 macrophages were reduced in treated peritoneal tumor samples while memory CD4+, CD8+ central memory and naive CD8+ T-cells were increased., Conclusions: The first-in-human trial combining PIPAC-OX and nivolumab demonstrated safety and tolerability, coupled with enhanced T-cell infiltration within peritoneal tumors. This trial sets the stage for future combinations of systemic immunotherapy with locoregional intraperitoneal treatments., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Germline genetic testing is traditionally carried out in patients suspected with hereditary cancer syndrome for enhanced cancer surveillance and/or preventive strategies, but is increasingly carried out for therapeutic indications., Materials and Methods: We conducted a retrospective review of patients who underwent germline genetic testing at our centre to determine the prevalence of actionable pathogenic germline variants (PGV) and their clinical utility., Results: From 2000 to 2022, 1154 cancer patients underwent germline testing, with the majority (945/1154) tested with multi-gene panels. Four hundred and eleven (35.6%) patients harboured a PGV and 334 (81%) were clinically actionable. BRCA1/2 accounted for 62.3% of actionable mutations, followed by mismatch repair (18%), and other homologous recombination repair (HRR) genes (19.7%). One hundred and fifty-two germline-positive patients have advanced cancers, and 79 received germline-directed therapies (poly ADP ribose polymerase inhibitors = 75; immunotherapy = 4). Median duration of immunotherapy and poly ADP ribose polymerase were 20.5 months (range 5-40 months) and 8 months (range 1-76 months), respectively. Among BRCA/HRR mutation carriers who received platinum-based chemotherapy, pathological complete response rate in the neoadjuvant setting was 53% (n = 17 breast cancers) and objective response rate was >80% in the advanced setting (n = 71)., Conclusions: One-third of cancer patients tested carried a PGV and ∼80% were clinically actionable. Three-quarters of germline-positive advanced cancer patients received germline-directed therapies in the real world, underscoring the practical utility of germline testing to guide cancer therapeutics., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Molecular profiling of metastatic breast cancer (MBC) through the widespread use of next-generation sequencing (NGS) has highlighted actionable mutations and driven trials of targeted therapy matched to tumour molecular profiles, with improved outcomes reported using such an approach. Here, we review NGS results and treatment outcomes for a cohort of Asian MBC patients in the phase I unit of a tertiary centre., Methods: Patients with MBC referred to a phase I unit underwent NGS via Ion AmpliSeq Cancer Hotspot v2 (ACH v2, 2014-2017) prior to institutional change to FoundationOne CDx (FM1; 2017-2022). Patients were counselled on findings and enrolled on matched therapeutic trials, where available. Outcomes for all subsequent treatment events were recorded to data cut-off on January 31, 2022., Results: A total of 215 patients were enrolled with successful NGS in 158 patients. The PI3K/AKT/PTEN pathway was the most altered with one or more of the pathway member genes PIK3/AKT/PTEN affected in 62% (98/158) patients and 43% of tumours harbouring a PIK3CA alteration. Tumour mutational burden (TMB) was reported in 96/109 FM1 sequenced patients, with a mean TMB of 5.04 mt/Mb and 13% (12/96) with TMB ≥ 10 mt/Mb. Treatment outcomes were evaluable in 105/158 patients, with a pooled total of 216 treatment events recorded. Matched treatment was administered in 47/216 (22%) events and associated with prolonged median progression-free survival (PFS) of 21.0 weeks [95% confidence interval (CI) 11.7, 26.0 weeks] versus 12.1 weeks (95% CI 10.0, 15.4 weeks) in unmatched, with hazard ratio (HR) for progression or death of 0.63 (95% CI 0.41, 0.97; p = 0.034). In the subgroup of PIK3/AKT/PTEN -altered MBC, the HR for progression or death was 0.57 (95% CI 0.35, 0.92; p = 0.02), favouring matched treatment. Per-patient overall survival (OS) analysis (n = 105) showed improved survival for patients receiving matched treatment versus unmatched, with median OS (mOS) of 30.1 versus 11.8 months, HR = 0.45 (95% CI 0.24, 0.84; p = 0.013). Objective response rate (ORR) in the overall population was similar in matched and unmatched treatment events (23.7% versus 17.2%, odds ratio of response 1.14 95% CI 0.50, 2.62; p = 0.75)., Conclusions: Broad-panel NGS in MBC is feasible, allowing therapeutic matching, which was associated with improvements in PFS and OS., Competing Interests: RW reported serving on the advisory board of Pfizer and Novartis and receiving honoraria from Pfizer, AstraZeneca, Novartis, and Merck MSD and travel funding from Merck MSD outside the submitted work. NN reported honoraria from Merck, MSD, AstraZeneca, and ASGO; research funding from Cyclacel and iOnctura; and travel funding from AstraZeneca and JSGO. SO reported honoraria and consulting with Astra Zeneca, Pfizer, Novartis, Eli Lilly, and Roche. AW reported advisory board membership and/or speaker activity with honoraria with AstraZeneca, Novartis, Eisai, DKSH, Pfizer, and Roache and research funding from Otsuka Pharmaceuticals. VH reported consultancy/advisory activity with DKSH, AstraZeneca, Novartis, MSD, and Pfizer. RS reported serving on the advisory board of Bristol Myers Squibb, Merck, Eisai, Bayer, Taiho, Novartis, MSD, DKSH, and GSK; receiving honoraria from MSD, Eli Lilly, Bristol Myers Squibb, Roche, Taiho, AstraZeneca, Ipsen, and DKSH; and receiving grants from Roche, AstraZeneca, Taiho, Eisai, DKSH, Paxman Coolers, Natera, and MSD outside the submitted work. RAS reported honoraria from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Novartis, Pfizer, Roche/Genentech, Takeda, Yuhan, Amgen, Bayer, Merck, Merck Serono, and Puma Biotechnology; consulting or advisory role with AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Novartis, Pfizer, Roche/Genentech, Taiho Pharmaceutical, Yuhan, Takeda, Amgen, Lilly, Merck, Janssen, Puma Biotechnology, Merck Serono, Bayer, and Thermo Fisher Scientific; and research funding from AstraZeneca and Boehringer Ingelheim. WY reported consulting or advisory role with AbbVie/Genentech, Amgen, Bristol Myers Squibb, Ipsen, Novartis, and AstraZeneca; speakers’ bureau with Lilly, Sanofi/Aventis, Taiho Pharmaceutical, Eisai, Bayer, and MSD Oncology; and travel and accommodation expenses from Pfizer. SCL reports honoraria and consulting activity with AstraZeneca, Pfizer, Novartis, Eli Lilly, Roche, ACT Genomics, and Eisai and research funding from Taihi, Eisai, Pfizer, and ACT Genomics. JL reported advisory activity with AstraZeneca, Novartis, Roche, DKSH, Pfizer, and MSD; receiving honoraria from AstraZeneca, Novartis, Roche, DKSH, MSD, Eisai, and Pierre Fabre; receiving research funding from CTI BioPharma, Daiichi Sankyo, and Synthon Pharmaceuticals; and receiving travel grant from AstraZeneca and MSD outside the submitted work. DT is an employee of the National University Health System Singapore and reports personal fees for advisory board membership from AstraZeneca, Bayer, BioNTech Boehringer Ingelheim, Eisai, Genmab, GSK, MSD, PMV Pharma, and Roche; personal fees as an invited speaker from AstraZeneca, Eisai, GSK, Merck Serono, MSD, Roche, and Takeda; ownership of stocks/shares of Asian Microbiome Library AMiLi; institutional research grants from AstraZeneca, Bayer, Karyopharm Therapeutics, and Roche; institutional funding as coordinating PI from AstraZeneca, MSD, Eisai, Roche, and Bergen Bio; institutional funding as local PI from Roche, BioNTech, PMV Pharma, GSK, Sutro Pharma, Bayer, Byondis B.V., and Zeria Pharmaceutical Co., Ltd.; a previous non-renumerated role as Chair of the Asia Pacific Gynecologic Oncology Trials Group APGOT; a previous non-renumerated role as the Society President of the Gynecologic Cancer Group Singapore; non-renumerated membership of the Board of Directors of the GCIG; research funding from the National Medical Research Council NMRC Clinician Scientist Award Senior Investigator Grant CSASI21jun-0003, the Pangestu Family Foundation Gynaecological Cancer Research Fund; and product samples from AstraZeneca, Eisai, and MSD non-financial interest for research trials. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Walsh, Ong, Cheo, Low, Jayagopal, Lee, Ngoi, Ow, Wong, Lim, Lim, Heong, Sundar, Soo, Chee, Yong, Goh, Lee, Tan and Lim.)

Chronic kidney disease (CKD), a common clinical problem in primary care, can be defined as any abnormality of the kidney structure and/or function that has been present for at least 3 months. Over the past 20 years, the incidence and prevalence of CKD have been increasing in Malaysia in line with the rising number of non-communicable diseases. At present, CKD has no cure. The treatment of CKD is very much dependent on early diagnosis and prevention of CKD progression. In this article, we aim to illustrate a practical approach to CKD in primary care, including diagnosis, evaluation, and management of CKD., (© Academy of Family Physicians of Malaysia.)

Gout is a commonly treated inflammatory arthritis that is often managed in the primary care setting. This disease is prevalent among the multi-ethnic Malaysian population. Unfortunately, gout is still frequently managed sub-optimally, even in the hospital and primary care settings. Gout should be considered a major disease since it can potentially lead to multiple disabilities from joint destruction, nephropathy and increased cardiovascular morbidity and mortality. The objectives of this review are to summarise the latest updated information and management of gout in the primary care setting., (© Academy of Family Physicians of Malaysia.)

Dengue fever (DF) is an important public health problem, and it is now endemic in more than 100 countries worldwide. Dengue associated neurological complication is estimated to be affecting 0.5 to 6.2% of patients. Even though this is rare, neurological manifestation of DF is an increasingly recognized entity in recent years due to significant mortality and morbidity reported/seen. Reported central nervous system manifestations due to dengue include encephalitis, encephalopathy, myelitis, myositis, acute disseminated encephalomyelitis, Guillain-Barré syndrome, stroke and etc. We report here a case of acute necrotizing encephalopathy secondary to DF in a previously healthy 12-year-old girl.

Chest radiograph is one of the most commonly employed imaging modalities in primary care. It may be done for symptomatic patients or routine health screening. Hence, it is important for a primary care physician to be able to interpret chest radiograph systematically in relation to patient's clinical history. Here, we would like to illustrate a case of abnormal chest radiograph detected during health screening., (© Academy of Family Physicians of Malaysia.)

Introduction: Excessive ultraviolet light (UV) can cause premature skin aging and potentially skin cancer. Currently there is a lack of awareness among health care professionals and the public on sun protection. The objectives of this study were to determine knowledge on sunscreen and skin cancer among health care professionals, to evaluate the knowledge, attitude, practice and perception of doctors and pharmacists toward the usage of sunscreen as protection against UV radiation., Materials and Methods: This is a cross-sectional study conducted among doctors and pharmacists in Hospital Sultanah Nora Ismail, Batu Pahat, Johor, Malaysia. Questionnaires were used in this study., Results: A total of 384 participants completed the questionnaires. The participants consisted of 323 doctors (84.1%) and 61 pharmacists (15.9%). The age group of the participants ranged between 25 till 55 years old. Ninety doctors (27.9%) and thirty-one pharmacists (51.0%) reported used sunscreen daily (p<0.001). This finding showed that there was a deficit in the practice of sun protection. Pharmacists scored a higher knowledge score of median 12 (IQR=3.0) while the doctors scored 11 (IQR=2.0). This study showed a significant association between ethnicity and skin cancer knowledge (p<0.05)., Conclusion: This study demonstrated a lack of knowledge of sunscreen and skin cancer prevention among health care practitioners. This finding supports better medical education program on this topic.

Dengue fever is one of the commonest tropical disease in the tropics. It can present with mild acute febrile illness to severe organ failure. Reported neurological complications of dengue include dengue encephalopathy, encephalitis, transverse myelitis and intracranial haemorrhage. Intracranial haemorrhage in dengue can present as subdural haematoma, extradural haematoma, intracerebral haemorrhage and subarachnoid haemorrhage. We report here a case of subarachnoid haemorrhage in a patient with severe dengue. Our patient was a 30-year-old man who presented with acute febrile illness. He subsequently developed plasma leakage and upper gastrointestinal bleeding. He then had reduced conscious level. Computed tomography of his brain showed subarachnoid haemorrhage. He eventually succumbed to his illness.

Hodgkin lymphoma is a form of malignant lymphoid neoplasm. It can have various clinical presentations such as prolonged fever, night sweats, weight loss and asymptomatic lymphadenopathy. It has a distinct fever pattern known as Pel Ebstein fever. However, in some instances, its clinical presentation can mimic some tropical infections. Here, we present a case of primary splenic lymphoma masquerading as splenic abscess in a 53-yearold man with underlying dyslipidemia.

Background: Cardiac tamponade is a medical emergency. This study was carried out to determine the etiologies of cardiac tamponade and review the management and outcomes., Methods: We retrospectively analysed case records of patients who underwent pericardiocentesis for cardiac tamponade during the two consecutive years (1 January 2018 to 31 December 2019) at Hospital Sultanah Nora Ismail, Batu Pahat, in Johor, Malaysia., Results: There were ten patients (eight males, two females; age range 20 to 70 years old, mean age 36 years old) who underwent pericardiocentesis for cardiac tamponade during the said period. Malignancy (40%), tuberculosis (30%), idiopathic (20%), and bacterial (10%) were among the common causes of the pericardial effusion in this center. The commonest symptoms were breathlessness (90%), chest pain (60%), cough (50%), and unexplained fever (20%). Pulsus paradoxus was the most speciÿ c sign (100%) for the presence of echocardiographic feature of cardiac tamponade. Two of the patients with tuberculous pericarditis had retroviral disease; one patient had bacterial pericarditis due to salmonella typhi., Conclusion: This study has conÿ rmed that there are many etiologies and presentation of cardiac tamponade; clinicians should be alert as urgent pericardiocentesis is lifesaving., Competing Interests: No conflict of interests declared

Stroke is a debilitating disease as it carries significant morbidity especially when it affects the younger population. There are various etiologies of young stroke, namely arterial dissection, cardioembolism, thrombophilia, inherited genetic disorder and vasculitis. Young patient with stroke should undergo complete evaluation to identify the underlying etiology in order to prevent recurrence of stroke. Here, we would like to illustrate a case of Takayasu arteritis presenting as young stroke in a 17-years-old lady with no known medical illness.

Methaemoglobinaemia is an uncommon but potentially serious condition. It can be caused by congenital or acquired cause. Drug-induced methaemoglobinaemia is the commonest cause of acquired methaemoglobinaemia. The clinical signs and symptoms of methaemoglobinaemia include dyspnoea, desaturation, presence of saturation gap, headache, nausea and seizures depending on level of serum methaemoglobinaemia. We illustrate a case of dapsone-induced methaemoglobinaemia and its successful treatment by intravenous methylene blue., (© Royal College of Physicians 2020. All rights reserved.)

Mesenchymal chondrosarcoma is a malignant neoplasm arising from cartilaginous bone or soft tissue. It is uncommon yet devastating. Our patient was a 21-year-old man who presented with pleuritic chest pain and weight loss. His chest radiograph showed left pleural effusion. His pleural effusion analysis was consistent with exudative pleural effusion. Tuberculosis workup was negative. Pleural fluid cytology did not yield malignant cells. Subsequently, his computed tomography of thorax showed left rib sclerotic lesion with soft tissue component. Biopsy of the soft tissue eventually confirmed the diagnosis of mesenchymal chondrosarcoma. He succumbed to his illness before the diagnosis was confirmed. We hope that through this case report, we are able to provide some insight into this rare condition.

Malaria is a parasitic disease that is caused by the Plasmodium parasite. Worldwide, it remains a significant public health problem especially in the Africa region where it contributes to more than 90% of cases and malaria death. However, zoonotic (simian) Plasmodium knowlesi parasite is a widely prevalent cause of malaria in the South East Asian countries. It is known to cause severe human disease due to its 24hour erythrocytic cycles. Thus far, cases of severe falciparum malaria have been reported in asplenic patients. Here, we report a case of severe P.knowlesi malaria in a 51-year-old man who is a postsplenectomy patient.

There are increasing reports of methanol poisoning (MP) incidence worldwide. In Malaysia, the largest first methanol poisoning was reported in Selangor in 2013 with a total of 41 patients and cluster of cases been reported from the country since then. Often MP involved adulterated alcohol containing more than the legal permissible concentration of methanol. Methanol is rapidly absorbed and metabolised into formic acid which causes variable symptoms of the central nervous system such as blindness, seizure, coma and gastrointestinal disturbances. Mortality could reach up to 83% as reported using the coma state, pH and pCO2 level in the worst-case scenario.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited cardiomyopathy characterised by right ventricular dysfunction, ventricular arrhythmias and increased risk of sudden cardiac death. Due to the replacement of myocardium with fibro-fatty and fibrous tissue, patients with ARVC are prone to develop ventricular tachycardia. Histologically, it is often reported as the 'triangle of dysplasia' involving the inflow tract, outflow tract and apex of the right ventricle.2 We describe a 20-years-old patient who collapsed during a futsal match and was subsequently diagnosed to have ARVC with a right ventricular thrombus from cardiac magnetic resonance imaging.

Neuromyelitis optica spectrum disorder (NMOSD) is a rare inflammatory disorder of the nervous system which can be potentially debilitating. Its prevalence is estimated to be around 0.5-10 per 100,000 population with predilection towards Asians and females. It can be diagnosed based on core clinical characteristics, serum aquaporin antibodies and neuroimaging features. It is important to pick up the diagnosis of NMOSD as the treatment is different from other demyelinating disease. Here, we illustrate a case of NMOSD presented with intractable vomiting., (© Royal College of Physicians 2020. All rights reserved.)

Catamenial pneumothorax is a rare condition. We report a case of a 36-year-old female who presented with dyspnoea every time before she had her regular menses. Further investigation confirmed that she had catamenial pneumothorax. With this case we wish to highlight this rare diagnostic entity that every clinician should keep in mind.

Systemic lupus erythematosus (SLE) is a common autoimmune disease that we see in our daily clinical practice. It can involve almost every organs in the body. Cardiac manifestations of SLE include pericarditis, myocarditis, heart block, coronary artery disease and others. Here, we report a case of SLE with an uncommon presentation of massive pericardial effusion as initial presentation. Here we also highlight that massive pericardial effusion can also be associated with other complications of SLE such as heart failure and lupus nephritis.

Haemothorax refer to the bleeding in the pleural space. It is commonly due to iatrogenic, blunt or penetrating chest trauma. Non-traumatic haemothorax is a rare entity that can potentially lead to life threatening complications. The initial management of both traumatic and non-traumatic haemothorax includes resuscitation and stabilisation of the patient. We would like to present two cases of non-traumatic haemothorax secondary to an avulsed bullae vessel.