Enhanced thromboprophylaxis in critically ill patients with COVID-19 infection.

Background: Patients with severe SARS-CoV-2 infection have been shown to have abnormal coagulation parameters and are at increased risk of thromboembolism. The optimal thromboprophylaxis regimen that minimizes thrombosis without increased risk of serious bleeding is uncertain. Objectives: To describe the efficacy and safety of increased intensity (enhanced) thromboprophylaxis in patients with COVID-19 admitted to the medical intensive care unit (MICU). Methods: This is a retrospective cohort analysis of patients with a diagnosis of COVID-19 admitted to the MICU of an urban safety net hospital. With the exception of patients being supported with extracorporeal membrane oxygenation or on chronic anticoagulation who received therapeutic dosing of anticoagulation, thromboprophylaxis was given as either enoxaparin or unfractionated heparin in doses higher than those recommended for standard prophylaxis, but lower than those used for therapeutic anticoagulation. Main results: Of the 120 patients managed with an enhanced thromboprophylaxis protocol, 6 (5%) experienced thromboembolism as a result of their COVID-19 disease (1 pulmonary embolus, 4 deep vein thromboses, and 1 arterial embolism). Four patients experienced major bleeding while receiving therapeutic anticoagulation. Conclusions: In critically ill patients with COVID-19, increased intensity (enhanced) thromboprophylaxis appears to be effective at preventing clinically significant thromboembolic events without an increased risk of serious bleeding.

The strength/weakness of the AJCC/UICC staging system (7th edition) for nasopharyngeal cancer and suggestions for future improvement.

BACKGROUND AND PURPOSE: To evaluate the current AJCC/UICC staging system (7th edition) for nasopharyngeal carcinoma and to explore for future improvement. MATERIALS AND METHODS: A total of 985 patients, initially staged with preceding 5-6th edition, were retrospectively re-staged with the 7th edition. All were assessed by magnetic resonance imaging, and all 945 non-disseminated patients were irradiated with conformal/intensity-modulated technique. RESULTS: Staging factors by both the 5-6th edition and the 7th edition were strongly significance for important endpoints (p<0.001). Down-staging of the previous T2a to T1 and, stages IIA to I in the 7th edition was appropriate. However, the impacts on overall stage distribution and prognostication were minimal. Further down-staging of the current T2 to T1, N2 to N1, stages II to I, and merging of N3a and N3b, stages IVA and IVB were suggested. With the 7th edition, the 5-year disease-specific survival (DSS) was 100% for stage I, 95% for II, 90% for III, 67% for IVA, 68% for IVB and 18% for IVC. The corresponding DSS for the proposed stages I, II, III and IV were 95%, 86%, 67% and 18%, respectively. CONCLUSIONS: The changes introduced in the 7th edition were appropriate, but the magnitude of improvement was minimal. With improving results by modern management, further simplification of the staging system is suggested. The proposed system could lead to more accurate prognostication, further validation is warranted.

Five-year experience with Chinese cobra (Naja atra)--related injuries in two acute hospitals in Hong Kong.

OBJECTIVE: To review the clinical features and management of patients with injuries related to the Chinese cobra (Naja atra). DESIGN: Retrospective study. SETTING: Two acute hospitals in Hong Kong. MAIN OUTCOME MEASURES: The nature of injuries, envenoming features, complications, response to antivenom therapy, and outcome. RESULTS: Eighteen patients were recruited during the 5-year study period. Fifteen of them were snake-bitten, the remaining three suffered ocular injuries. Of the 15 patients with cobra bites, 14 (93%) presented with local swelling. No patient developed severe neurotoxic symptoms. Two patients had laboratory features of haemolysis. Fourteen patients received antivenom therapy and five of them subsequently underwent surgical interventions for extensive local tissue damage and necrosis. There was no fatality. CONCLUSION: Bites from Chinese cobra result in serious local complications with extensive tissue necrosis and minimal neurotoxic symptoms. There is an apparent trend of favourable outcomes following the early administration of antivenom to patients without early signs of irreversible tissue damage. Further research is needed to evaluate the effectiveness of early antivenom use in Chinese cobra bites in order to minimise extent of tissue damage.

Prevalence of smoking and environmental tobacco smoke exposure, and attitudes and beliefs towards tobacco control among Hong Kong medical students.

OBJECTIVES: To investigate the prevalence of active smoking and environmental tobacco smoke (ETS) exposure among medical students in Hong Kong, and their attitudes and beliefs towards tobacco control. STUDY DESIGN: A cross-sectional survey with a self-administrated questionnaire. METHODS: All medical students from a university in Hong Kong were invited to participate in this survey and completed structured questionnaires. Descriptive data analyses were performed. RESULT: In total, 313 medical students participated in this study (response rate 44.7%). Only 7.2% [95% confidence interval (CI) 4.3-10.1] reported having ever smoked and 0.7% (95% CI 0-1.6%) were current smokers. ETS exposure at home was reported by 19.3% (95% CI 14.9-23.8) of students, but the proportion of ETS exposure in public places was much higher (61.6%, 95% CI 56.2-67.1%). More than 85% of students had positive attitudes towards tobacco control, but 30.8% (95% CI 25.6-36.0) disagreed with banning smoking in disco/bars/pubs. Although the majority (93.1%, 95% CI 90.3-96.0) of students thought that health professionals should receive specific training for counselling on smoking cessation, only 38.0% (95% CI 32.5-43.5) reported having received any formal training in this area. CONCLUSIONS: This study suggests that a specific professional training programme, including counselling on smoking cessation and actions on legislation and tobacco tax policy, should be built into the undergraduate medical curriculum.

Oxidative stress is the master operator of drug and chemically-induced programmed and unprogrammed cell death: Implications of natural antioxidants in vivo.

ROS, RNS, BRIs and ROS-RNS hybrids are produced during drug or chemical metabolism in vivo. These reactive species are instrumental to the culmination of cellular oxidative stress (OS). OS, once turned on, does not spare any vital intracellular macromolecule, such as glutathione, DNA, RNA, proteins, enzymes, lipids and ATP. Since concentration gradients of such components are very delicately balanced for normal cellular functioning, a gross perturbation leads to cell injury and cell death. Abundant evidence now suggests that intracellular antioxidants keep OS in check and maintain homeostasis. Our laboratory has focused on the role of OS in orchestrating various forms of cell death during drug and chemically-induced target organ toxicity and their counteraction by various natural or synthetic antioxidants in in vivo models. Despite complexity of the in vivo models, results show that metabolism of xenobiotics are invariably associated with different degrees of OS and natural antioxidants such as grape seed extract, bitter melon extract (Momordica charantia) and N-acetylcysteine (NAC) which were very effective in counteracting organ toxicities by minimizing events linked to OS (lipid peroxidation and total glutathione), and CAD-mediated DNA fragmentation. Phytoextract exposure rescued cells from toxic assaults, protected genomic integrity, and minimized apoptotic, necrotic and apocrotic (oncotic necrosis) cell deaths. Pre-exposure mode was more effective than post-exposure route. Overall scenario suggests that OS may have been the prime modulator of death and/or survival programs, whereas, antioxidants may have imparted a dual role in either erasing death signals or reviving survival signals, and a combination of antioxidants may be more beneficial than a single entity to influence a number of intracellular events operating simultaneously to neutralize chaotic toxicological consequences.

A case of partial trisomy 13 presenting with hyperinsulinaemic hypoglycaemia.

We report on a newborn baby with partial trisomy 13 who presented with multiple dysmorphic features and hyperinsulinaemic hypoglycaemia. Cytogenetic study on peripheral blood lymphocytes showed 47,XY,+mar in all cells analysed; fluorescent in situ hybridisation showed that the marker was solely derived from chromosome 13. The final karyotype was 47,XY,+del(13)(q14q32). Milk formula through a nasogastric drip and intravenous glucose infusion were given to prevent further hypoglycaemia. However, the baby developed occasional episodes of hypoglycaemia during bolus feeding. Hence, diazoxide was given, at a dosage of 10 mg/kg per day from day 24. Thereafter, no hypoglycaemic episodes were detected. Subsequent follow-up revealed satisfactory growth, global developmental delay, and left divergent squint.

DiGeorge syndrome: clinical variability in a family with submicroscopic deletion at 22q11.2.

DiGeorge syndrome is a developmental field defect involving the third and fourth branchial arches and pouches. It is characterised by conotruncal heart defect, thymic hypoplasia/aplasia, hypocalcemia secondary to hypoparathyroidism and dysmorphic facies. Most of the cases are associated with interstitial deletion of chromosome 22 which can be detected by fluorescent in situ hybridisation study. The clinical presentation of DiGeorge syndrome is highly variable, in both interfamilial and intrafamilial situations. Apart from DiGeorge syndrome, velocardiofacial syndrome and other conditions are also associated with the same interstitial deletion. Here we reported a Chinese family with the same submicroscopic deletion of chromosome 22 as evident by fluorescent in situ hybridisation, but with different clinical presentation; the two brothers had DiGeorge syndrome and velocardiofacial syndrome respectively whereas the mother was asymptomatic.

A cytogenetic study of 514 Chinese couples with recurrent spontaneous abortion.

OBJECTIVE: To study the role of chromosomal aberration in the causation of recurrent spontaneous abortion (RSA) in Chinese population. METHODS: A total of 514 Chinese couples with 2 or more spontaneous abortions at less than 24 weeks of gestation were included. For each proband, a minimum of 13 metaphases were analyzed by G-banding. Additional cells (usually 50-100 cells) were screened when mosaicism was suspected. Chi 2 test was used to compare the number and frequency of couples with and without balanced translocation with respect to whether liveborn was present or absent. Chi 2 test for trend was used to show whether a correlation existed between the occurrence of balanced translocation and the number of spontaneous abortions at ascertainment. RESULTS: The overall incidence of chromosome anomaly was 51 out of 514 (9.92%). Chi 2 test for trend analysis showed that the chance of one member of a couple being a balanced carrier increased with the number of spontaneous abortions. The chance of finding translocation in couples with liveborn was higher than that in couples without liveborn, but the difference was not statistically significant. We also found that pericentric inversion 9 did not play an important role in the causation of recurrent abortion. CONCLUSIONS: Cytogenetic analysis is indicated in couples with 2 or more spontaneous abortions and the chance of finding chromosomal aberration increases with the number of abortions at the time of ascertainment.

Effect of NaF and okadaic acid on the subcellular distribution of CTP: phosphocholine cytidylyltransferase activity in rat liver.

The effect of preincubation of rat liver post-mitochondrial supernatant with NaF and okadaic acid on the subcellular distribution of CTP: phosphocholine cytidylyltransferase activity was investigated. NaF (20 mM) inhibited the time-dependent activation of cytidylyltransferase activity in post-mitochondrial supernatant. Subcellular fractionation of the post-mitochondrial supernatant revealed that cytidylyltransferase activity in the microsomal fraction was decreased and activity in the cytosolic fraction increased with time of preincubation with NaF compared to controls. Okadaic acid is a specific and potent inhibitor of type 1 and 2A phosphoprotein phosphatases. Preincubation of cytosol with 5 microM okadaic acid inhibited the time-dependent activation of cytosolic cytidylyltransferase activity. Preincubation of post-mitochondrial supernatants with 5 microM okadaic acid inhibited the time-dependent activation of cytidylyltransferase activity by 13% at 45 min and 16% at 60 min of preincubation compared to controls. Microsomal cytidylyltransferase activity was decreased 27% at 45 min and 31% at 60 min with a corresponding retention of cytosolic cytidylyltransferase activity of 21% at 45 min and 37% at 60 min of preincubation with okadaic acid compared to controls. We postulate that the activity of the type 1 and/or type 2A phosphoprotein phosphatases affect the subcellular distribution of CTP: phosphocholine cytidylyltransferase activity in rat liver.

Energy metabolism in fracture healing. Measurement of adenosine triphosphate in callus to monitor progress.

We measured the adenosine triphosphate (ATP) content of callus at various intervals during healing in 78 fractured tibiae in 10- to 12-week-old rabbits. The results, compared with the level in normal tissues, showed a high rate of energy metabolism in the early phase of fracture healing, which persisted until the callus was corticalised and remodelling had started. The ATP content could provide a more sensitive index to monitor fracture healing in animal studies. Our findings lend support to the need for nutritional supplements for patients with multiple fractures.

Spontaneous hepatitis B e antigen to antibody seroconversion and reversion in Chinese patients with chronic hepatitis B virus infection.

Five hundred twelve (373 men, 139 women) patients, aged 1-75 yr, with chronic hepatitis B virus infection seen during a 5-yr period were analyzed. Of these, 43.8% were hepatitis B e antigen (HBeAg)-positive, 49.2% were positive for hepatitis B e antibody, and 7% were negative for both HBeAg and hepatitis B e antibody at presentation. The cumulative probability of clearing HBeAg at the end of the first, second, and third years was 17%, 30%, and 34%, respectively. The probability of clearing HBeAg increased with the age of the patients. Reversion to HBeAg occurred in 7.8% of patients who were HBeAg-negative at presentation and 32.3% of HBeAg-positive patients who cleared HBeAg. In 70.6% of these patients, serum hepatitis B virus-deoxyribonucleic acid was persistently positive or became detectable at the time of HBeAg reversion. Most reversions occurred during the "e-window" phase. The reversions were transient in 31.8% of the cases. Recognition of the dynamics of these serologic changes is important in the evaluation of therapeutic regimens aimed at suppression of HBV replication and call for controlled trials with adequate duration of follow-up. Biochemical exacerbation of liver disease accompanied 38.7% of HBeAg to hepatitis B e antibody seroconversions and 34.8% of reversions. Such exacerbations may be mistaken for acute attacks of hepatitis B in patients not previously recognized to be hepatitis B surface antigen carriers and, in the absence of serial serologic data, are indistinguishable from superimposed non-A, non-B hepatitis.

Control of connective tissue metabolism by lasers: recent developments and future prospects.

Various laser modalities are currently in extensive use in dermatology and plastic surgery, particularly for treatment of vascular and pigmented lesions. A relatively new area of laser utilization involves the possible biologic effects of the lasers. In this overview, we are summarizing our recent studies, which indicate that lasers at specific wavelengths and energy densities modulate the connective tissue metabolism by skin fibroblasts both in vitro and in vivo. Specifically, the neodymium-yttrium-aluminum-garnet (Nd: YAG) laser was shown to selectively suppress collagen production both in fibroblast cultures and in normal skin in vivo, thus suggesting that this laser modality may be useful for the treatment of fibrotic conditions such as keloids and hypertrophic scars. Furthermore, two low-energy lasers, helium-neon (He-Ne) and gallium-arsenide (Ga-As), were shown to stimulate collagen production in human skin fibroblast cultures, suggesting that these lasers could be used for enhancement of wound healing processes. These experimental approaches illustrate the future possibilities for applying lasers for the modulation of various biologic functions of cells in tissues and attest to the potential role of lasers in the treatment of cutaneous disorders.