Warfarin-induced skin necrosis associated with acquired protein C deficiency

A 36-year-old woman developed skin necrosis of the inner thighs following the re-introduction of warfarin after a laparoscopic cholecystectomy. She had a history of liver disease and cardiomyopathy and was on warfarin for 10 years. Warfarin-induced skin necrosis secondary to protein C deficiency was diagnosed. Although warfarin was ceased immediately, the prothrombin time measurements remained prolonged and warfarin levels remained therapeutic. Our patient, who had attached great significance to warfarin therapy, had continued the ingestion of warfarin despite our advice. She required three surgical debridements. Protein C levels, as measured 1 year later, were within normal limits, confirming the transient nature of the acquired deficiency during the acute event. This is the second reported case of warfarin necrosis associated with acquired protein C deficiency.     

Demographic and endoscopic characteristics of patients with Helicobacter pylori positive and negative peptic ulcer disease

OBJECTIVE: To identify demographic and endoscopic characteristics of patients with Helicobacter pylori positive and negative chronic peptic ulcer disease. DESIGN: Cross-sectional study of peptic ulcer disease in prospectively recruited PATIENTS undergoing gastroscopy. PATIENTS: 277 consecutive patients referred for gastroscopy in 1996-1998. MAIN OUTCOME MEASURES: Rapid urease test, culture and histological examination for H. pylori infection; anti-H. pylori IgG antibodies in serum; demographic data, intake of non-steroidal anti-inflammatory drugs (NSAIDs) in the preceding 3 months, and size, number and location of ulcers. RESULTS: 54 patients (19%) had evidence of peptic ulcer disease (34 gastric ulcer, 14 duodenal ulcer and 6 both gastric and duodenal ulcer); 45 had active chronic peptic ulcer disease and were analysed in detail. H. pylori was present in 25 (56%) of these patients; 10 (22%) had used NSAIDs and 7 of the NSAID group also had H. pylori infection. Of the patients with gastric ulcers, those with non-H. pylori, non-NSAID ulcers were significantly younger than both those with H. pylori-associated ulcers (mean age, 48 v. 65 years, P = 0.02) and those with NSAID-associated ulcers (mean age, 48 v 68 years, P = 0.02). The average size and number of gastric ulcers did not differ between patients with and without H. pylori infection. Of patients with duodenal ulcers, those with H. pylori infection had significantly fewer ulcers (1.1 v. 1.8, P = 0.04), although ulcer size was similar in the infected and uninfected groups. CONCLUSIONS: Gastric ulcers may now be more common than duodenal ulcers. Gastric ulcers associated with H. pylori infection and/or NSAID use occurred mostly in older people, while non-H. pylori, non-NSAID gastric ulcers were more common in younger patients. In the duodenum, single ulcers were associated with H. pylori infection, and multiple ulcers were more frequent in the non-H. pylori, non-NSAID group.     

Tissue polypeptide-specific antigen in pediatric patients: Assessment of normal values

Measurement of serum concentrations of tissue polypeptide-specific Antigen (TPS) has been demonstrated to be useful in diagnosis and monitoring of adult epithelial tumors. So far, no data have been available on normal or pathologic TPS values in children. Therefore, the present study was designed to evaluate the normal values of TPS in childhood. Using a commercial enzyme linked immunosorbent assay (ELISA) kit, serum TPS was determined in 361 healthy children. Median (M) TPS was found to be 107 U/l at birth (n = 124). By the end of the first week, the value rose to M = 150 U/l (n = 68) and then continuously decreased with age (1 week–1 year, n = 45, M = 88 U/l; 1–7 years, n = 75, M = 51 U/l) until reaching the adult level (8–18 years, n = 49, M = 34 U/l). Additionaly, the serum TPS values of 45 mothers right after delivery (M = 161 U/l) were assessed, and there was no correlation to the marker levels determined in the cord blood of their children. The age-dependent distribution of serum TPS in healthy children must be taken into account in the clinical application of this tumor marker. Med. Pediatr. Oncol. 29:218–221, 1997. © 1997 Wiley-Liss, Inc.     

Discovering disease-causing pathogens in resource-scarce Southeast Asia using a global metagenomic pathogen monitoring system

Understanding the regional pathogen landscape and surveillance of emerging pathogens is key to mitigating epidemics. Challenges lie in resource-scarce settings, where outbreaks are likely to emerge, but where laboratory diagnostics and bioinformatics capacity are limited. Using metagenomic next-generation sequencing (mNGS), we identified a variety of vector-borne, zoonotic, and emerging pathogens responsible for undifferentiated fevers in a periurban population in Cambodia. From March 2019 to October 2020, we enrolled 464 febrile patients (and 23 afebrile persons) aged 6 mo to 65 y presenting to a large periurban hospital in Cambodia. We collected sera and prepared sequencing libraries from extracted pathogen RNA for unbiased metagenomic sequencing and subsequent bioinformatic analysis on the global cloud-based platform, CZID (“IDseq”). We employed multivariable regression models to evaluate pathogen risk factors associated with undifferentiated febrile illness. mNGS identified vector-borne pathogens as the largest clinical category with dengue virus (124 of 489) as the most abundant pathogen. Underappreciated zoonotic pathogens, such as Plasmodium knowlesi, leptospirosis, and coinfecting HIV were also detected. Early detection of chikungunya virus presaged a larger national outbreak of more than 6,000 cases. Pathogen-agnostic mNGS investigation of febrile persons in resource-scarce Southeast Asia is feasible and revealing of a diverse pathogen landscape. Coordinated and ongoing mNGS pathogen surveillance can better identify the breadth of endemic, zoonotic, or emerging pathogens and deployment of rapid public health response.

A global pathogen surveillance network can best identify emerging and underlying pathogens if it employs pathogen-agnostic detection methods, such as metagenomic next-generation sequencing (mNGS), and is decentralized to include low-resource settings that are often biodiversity hotspots at increased risk for disease outbreaks (1–3). Lack of diagnostics in these areas makes undifferentiated febrile illnesses difficult to diagnose and treat, much less confirm and report for global public health awareness. In Southeast Asia, where a quarter of the world’s population resides, rapid but heterogeneous economic development juxtaposes low-resource and high-resource areas, causing high cross-border mobility of persons for economic opportunities. In Cambodia and Laos, laboratory testing for nonmalarial fevers is limited, particularly in rural and periurban areas where simple diagnostics like dengue rapid tests may not be available (4). In many instances, healthcare providers make diagnoses and empiric treatment decisions based on symptoms, so the responsible pathogen is rarely identified.Syndromic diagnosis is an epidemiological pitfall in Southeast Asia because the true scope of pathogen diversity remains poorly defined. From limited decade-old surveillance data of febrile Cambodians, Plasmodium infections made up more than 50% of the responsible pathogens followed by pathogenic Leptospira (9.4%), influenza virus (8.9%), and dengue virus (DENV) (6.3%) (5). In a separate serosurvey, one-third of febrile Cambodian patients had antibodies to rickettsiae that cause scrub typhus (via chiggers containing Orientia tsutsugamushi), endemic typhus (via rat fleas Xenopsylla cheopia carrying Rickettsia typhi), spotted fever (via ticks carrying Rickettsia rickettsii), and murine typhus (via cat fleas Ctenocephalides felis carrying Rickettsia felis) (6, 7). Entomological studies of field-collected ticks, mosquitos, and fleas in Cambodia have revealed high biodiversity of potential disease-carrying vectors, including underappreciated Bartonella spp. (8, 9). Other serosurveys of bats, domestic pigs, and birds in Cambodia demonstrated the presence of antibodies to other zoonotic viruses, including Nipah virus, hepatitis E, Japanese encephalitis virus, and West Nile virus with potential for spillover into the human population (10–12).In these settings of high pathogen diversity, monitoring with pathogen-agnostic tools, such as mNGS, is ideal but typically not available in-country to provide results within an actionable time frame. Examples of mNGS identifying pathogens in patients are limited to clinical research programs in developed countries (13–15). However, it is clear that broadly applied and timely mNGS in any population can lead to a better understanding of the overall pathogen landscape, which has direct implications for disease containment methods in the event of an outbreak (16, 17). Here, as an initial step in a low-resource setting in Asia, we describe implementation of mNGS surveillance using an open-source cloud-based bioinformatics tool to identify pathogens in sera from febrile individuals in periurban Cambodia.     

Expanded occipito-cervico-pectoral flap for reconstruction of burned cervical contracture

Postburn neck contracture and hypertrophic scarring can cause functional limitation and aesthetic disfigurement. Reconstruction of severe deformities and scar of neck following healing from burns confronts the surgeon with some of the most challenging problems in reconstructive surgery. Through knowledge of available reconstructive technique accurate diagnosis of tissue deficiency and secondary distortion, imaginative planning and definitive, careful execution of ones surgical plan are the bare minimum items for achieving improvement in a burned deformed neck. The aim of this article is to assess the role of expanded occipito-cervico-pectoral (o-c-p) flap for reconstruction in a series of four patients with severe burn scar of neck and involvement of shoulder back but intact anterior aspect of chest. This is an alternative method of reconstruction burn scar of neck area.