Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder caused by uncontrolled terminal complement activation, which leads to intravascular hemolysis (IVH), thromboembolism (TE), renal failure, and premature mortality. Methods: We performed a secondary analysis of data collected from patients enrolled in the Korean National PNH Registry to assess the relative importance of risk factors, specifically lactate dehydrogenase (LDH) and hemoglobin (Hb), in predicting the incidence of TE, impaired renal function, and death in complement inhibitor-naïve patients with PNH. Results: Multivariate regression modeling indicated that LDH ≥ 1.5 × upper limit of normal (ULN), male sex, and pain were associated with increased risk of TE (P = 0.016, 0.045, and 0.033, respectively), hemoglobinuria and pain were associated with an increased risk of impaired renal function (P = 0.034 and 0.022, respectively), and TE was associated with an increased incidence of death (P < 0.001). Hb < 8 g/dL was not a predictor of TE, impaired renal function, or death in multivariate regression analyses. Standardized mortality ratio analysis indicated that LDH ≥ 1.5 × ULN (P < 0.001), Hb < 8 g/dL (P < 0.001), and Hb ≥ 8 g/dL (P = 0.004) were all risk factors for death; in contrast, patients with LDH < 1.5 × ULN had similar mortality to the general population. Conclusion In complement inhibitor-naïve patients with PNH, LDH ≥ 1.5 × ULN was a significant predictor of TE, and TE was a significant predictor of death. Hb was not a significant predictor of TE, impaired renal function, or death. Therefore, controlling IVH will improve clinical outcomes for patients with PNH.

Purpose: Targeted next-generation sequencing (NGS) is widely used for simultaneously detecting clinically informative genetic alterations in a single assay. Its application in clinical settings requires the validation of NGS gene panels. In this study, we aimed to validate a targeted hybridization capture-based DNA panel (ONCOaccuPanel) using the Illumina MiSeq sequencing platform. The panel allows the simultaneous detection of single-nucleotide variants (SNVs), insertions, deletions, and copy number changes of 323 genes and fusions of 17 genes in solid tumors. Materials and Methods: We used 16 formalin-fixed paraffin-embedded (FFPE) tumor samples with previously known genetic mutations and one reference material (HD827) for validation. Moreover, we sequenced an additional 117 FFPE tumor samples to demonstrate the clinical utility of this panel. Results: Validation revealed a 100% positive percentage agreement and positive predictive value for the detection of SNVs, insertions, deletions, copy number changes, fusion genes, and microsatellite instability–high types. We observed high levels of reproducibility and repeatability (R2 correlation coefficients=0.96-0.98). In the limit of detection assessment, we identified all clinically relevant genes with allele frequencies > 3%. Furthermore, the clinical application of ONCOaccuPanel using 117 FFPE samples demonstrated robust detection of oncogenic alterations. Oncogenic alterations and targetable genetic alterations were detected in 98.2% and 27.4% cases, respectively. Conclusion ONCOaccuPanel demonstrated high analytical sensitivity, reproducibility, and repeatability and is feasible for the detection of clinically relevant mutations in clinical settings.

Among the three subtypes of neurofibromatosis are type 1 and 2 neurofibromatosis and schwannomatosis, von Recklinghausen disease also known as type 1 neurofibromatosis has an autosomal dominant inheritance. It is the commonest form as and presents with numerous café-au-lait macules and neurofibromas. Giant congenital melanocytic nevus (CGMN) on the other hand is characterized by a melanocytic proliferation that present at birth. CGMN develops due to a defective embryonic pigment cell (melanocyte) precursors development and are often present at birth. Giant congenital melanocytic nevus (CGMN) and type 1 neurofibromatosis may occur together rarely. Clinicians should be aware of the rare presentation of both CGMN and type 1 neurofibromatosis in a patient.

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.

Primary care providers should be alert to travel-related infections. Around 10-40% of returning travelers from all destinations and 15-70% of travelers from tropical settings experience ill health, either overseas or upon returning home.1 A systematic approach concentrating on possible infections should be undertaken based on the patient’s travel location, immunization history, presence of malaria chemoprophylaxis at the destination, other potential exposures, incubation period, and clinical presentation.2-3 The World Health Organization (WHO) website is constantly being updated on specific travel-related infections and recent geographical outbreaks. In this paper, we report a case of severe falciparum malaria in a returned traveler.

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.

A 49-year-old gentleman presented with epigastric pain for one day associated with one episode of vomiting and dyspnoea. Respiratory examination showed reduced breath sound over his left lower zone. He was treated as left spontaneous pneumothorax and left lung empyema requiring left chest tube insertion and intravenous antibiotics. His left pleural fluid biochemistry result was exudative while its centrifuge showed empyema. In ward, we noticed food material draining from his left chest tube during feeding. An urgent contrast enhanced computed tomography (CECT) thorax showed a left oesophageal-pleural fistula with possible broncho-oesophageal fistula. During oesophagogastroduodenoscopy (OGDS), air bubbles were seen in his left under-water chest drainage during air-insufflation of the oesophagus. The revised diagnosis was Boerhaave syndrome. He was treated with an esophageal stent to cover the perforation and a left lung decortication via video assisted thoracoscopic surgery (VATS) for his left empyema. He improved and was discharged well.

Emerging evidence has suggested that cytoreductive prostatectomy (CRP) allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer (mPCa) has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer (PCa). Urinary incontinence was defined as the use of any pad. CRP had longer operative times (200 min vs 140 min, P < 0.0001) and higher estimated blood loss (250 ml vs 125 ml, P < 0.0001) compared to the control group. However, both overall (8.82% vs 5.85%) and major complication rates (4.41% vs 2.17%) were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group (57.4% vs 90.8%, P < 0.0001). Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model (OR: 1.18; 95% CI: 1.02-1.37; P = 0.025) and surgery type-adjusted model (OR: 1.17; 95% CI: 1.01-1.36; P = 0.034). In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.
Adult ; Aged ; Aged, 80 and over ; Blood Loss, Surgical ; Cytoreduction Surgical Procedures/adverse effects* ; Humans ; Male ; Middle Aged ; Neoplasm Grading ; Postoperative Complications/epidemiology* ; Predictive Value of Tests ; Prostatectomy/adverse effects* ; Prostatic Neoplasms/surgery* ; Retrospective Studies ; Urinary Incontinence/etiology*

BACKGROUNDFamilial cerebral cavernous malformations (CCMs), characterized by hemorrhagic stroke, recurrent headache and epilepsy, are congenital vascular anomalies of the central nervous system. Familial CCMs is an autosomal dominant inherited disorder and three CCM genes have been identified. We report a Chinese family with CCMs and intend to explore clinical, pathological, magnetic resonance imaging (MRI) features and pathogenic gene mutation of this family.

METHODSTotally 25 family members underwent brain MRI examination and clinical check. Two patients with surgical indications had surgical treatment and the specimens were subjected to histopathological and microstructural examination. In addition, polymerase chain reaction (PCR) and direct sequencing were performed with genomic DNA extracted from 25 family members' blood samples for mutation detection.

RESULTSBrain MRI identified abnormal results in seven family members. All of them had multiple intracranial lesions and four cases had skin cavernous hemangioma. T2-weighted sequence showed that the lesions were typically characterized by an area of mixed signal intensity. Gradient-echo (GRE) sequence was more sensitive to find micro-cavernous hemangiomas. There was a wide range in the clinical manifestations as well as the age of onset in the family. The youngest patient was an 8-year-old boy with least intracranial lesions. Histopathological and microstructural examination showed that CCMs were typically discrete multi-sublobes of berry-like lesions, with hemorrhage in various stages of illness evolution. They were formed by abnormally enlarged sinusoids and the thin basement membranes. A novel T deletion mutation in exon 14 of CCM1 gene was identified by mutation detection in the seven patients. But unaffected members and healthy controls did not carry this mutation.

CONCLUSIONSThe clinical manifestations were heterogenic within this family. We identified a novel mutation (c.1396delT) was the disease-causing mutation for this family and extended the mutational spectrum of CCMs.

Adult ; Animals ; Female ; Hemangioma, Cavernous, Central Nervous System ; diagnosis ; genetics ; Humans ; KRIT1 Protein ; Magnetic Resonance Imaging ; Male ; Microtubule-Associated Proteins ; genetics ; Middle Aged ; Mutation ; Pedigree ; Proto-Oncogene Proteins ; genetics