Invasive cerebral phaeohyphomycosis in a Chinese boy with CARD9 deficiency and showing unique radiological features, managed with surgical excision and antifungal treatment.

We report this rare case of cerebral phaeohyphomycosis in a previously healthy Chinese boy, who was found to have caspase recruitment domain family member 9 (CARD9) deficiency. Initial radiological features suggested a neoplastic cerebral lesion, while histopathological examination supplemented by internal transcribed sequencing (ITS) of cerebral tissue confirmed the diagnosis of phaeohyphomycosis. He was treated with intravenous (IV) liposomal amphotericin B and voriconazole, guided by plasma and cerebrospinal fluid (CSF) level monitoring at drug initiation. At the 1 year follow-up, the patient demonstrated near complete neurological and radiological recovery.

Characterising frailty, metrics of continuous glucose monitoring, and mortality hazards in older adults with type 2 diabetes on insulin therapy (HARE): a prospective, observational cohort study.

BACKGROUND: To our knowledge, no previous study has examined the inter-relationship between frailty, dysglycaemia, and mortality in frail older adults with type 2 diabetes who are on insulin therapy. We used continuous glucose monitors (CGMs) to profile this patient population and determine the prognostic value of CGM metrics. We hypothesised that incremental frailty was associated with increased hypoglycaemia or time below range (TBR). METHODS: HARE was a multicentre, prospective, observational cohort study with mortality hazard analysis carried out in four hospitals in Hong Kong. Eligible participants were community-living adults aged 70 years and older; had had type 2 diabetes for 5 years or more; were on insulin therapy; were frail; and were not hospitalised at the time of frailty assessment and CGM recording. Glucose control was characterised according to the Advanced Technologies and Treatments for Diabetes 2019 international consensus clinical targets. Frailty index was computed, and comprehensive frailty assessments and targeted serum metabolic profiling were performed. The Jonckheere-Terpstra test for trend was used to analyse frailty index tertiles and variables. Inter-relationships between CGM metrics and frailty, glycated haemoglobin A1c (HbA1c), and serum albumin were characterised using adjusted regression models. Survival analysis and Cox proportional hazard modelling were performed. FINDINGS: Between July 25, 2018, and Sept 27, 2019, 225 participants were recruited, 222 of whom had CGMs fitted and 215 of whom had analysable CGM data (190 were frail, 25 were not frail). Incremental frailty was associated with older age, greater HbA1c, worse renal function, and history of stroke. Eight of 11 CGM metrics were significantly associated with frailty. Decreased time in range (TIR; glucose concentration 3·9-10·0 mmol/L) and increased time above range (TAR) metrics were strongly correlated with increased frailty and hyperglycaemia, whereas TBR metrics were marginally or not different between frailty levels. Glucose-lowering agents did not significantly affect regression estimates. In patients with HbA1c of 7·5% or more, reduced serum albumin was associated with level 2 TAR (glucose concentration >13·9 mmol/L) and dysglycaemia. During a median follow-up of 28·0 months (IQR 25·3-30·4), increased level 2 TAR was predictive of mortality explainable by frailty in the absence of detectable interaction. Each 1% increment of level 2 TAR was associated with 1·9% increase in mortality hazard. INTERPRETATION: In older adults with type 2 diabetes who are on insulin therapy, incremental frailty was associated with increased dysglycaemia and hyperglycaemia rather than hypoglycaemia. Mortality hazard was increased with severe hyperglycaemia. Future clinical studies and trials targeting actionable CGM metrics highlighted in this study could translate into improved care and outcomes. FUNDING: Health and Medical Research Fund, Food and Health Bureau, The Government of the Hong Kong Special Administrative Region of China.

Treatment of Post-mastectomy Lymphedema with Herbal Medicine: An Innovative Pilot Study.

BACKGROUND: Lymphedema of the arms or legs is a difficult clinical problem yet devoid of effective treatment. Lymphedema is the result of obstructed lymphatic flow secondary to chronic infection, parasitic infestation, or postsurgical obstruction (eg, after axillary dissections). We arranged this clinical trial to investigate whether patients with limb lymphedema can benefit from a standard dose of Astragalus plus Paeoniae rubra to improve the symptomatology, functional capacity, and quality of life (QOL). METHOD: The pilot study was designed as a self-control clinical trial. Patients with post-mastectomy lymphedema were recruited. A double-herb formulation (Astragalus, Paeoniae rubra) with standard dosage was administered orally in a powdered form, 6 times per week for 6 months. Outcome measurements included standard limb volume changes measured by water displacement method; handgrip strength; and QOL for limb lymphedema questionnaire (LYMQOL). RESULTS: There were no reported adverse effects or complications; there were no episodes of infection during the period of study. There was a tendency of limb volume reduction by 6 months, which, however, did not reach statistical significance. There was a significant improvement in appearance and symptom scores as was assessed with the LYMQOL questionnaire. CONCLUSIONS: The oral herbal formula improved the symptomatology and QOL among the pilot group of patients with post-mastectomy lymphedema. Side effects were absent, and there was a trend of lymphedema reduction.

A randomized placebo controlled trial of an innovative herbal formula in the prevention of atherosclerosis in postmenopausal women with borderline hypercholesterolemia.

BACKGROUND: Danshen (Salvia miltiorrhiza) and Gegen (Radix puerariae) (D&G) are two herbs frequently used for the treatment of angina and other cardiac symptoms in Chinese materia medica. Recent studies have demonstrated their cardio-protective and anti-atherosclerosis effects. Earlier we have conducted two clinical trials in 2004 and 2007 which demonstrated such effects in extremely high risk patients. STUDY OBJECTIVE: The aim of the study was to demonstrate the safety and effectiveness of D&G in the prevention of atherosclerosis in postmenopausal women with early hypercholesterolemia. DESIGN: The study was designed as a randomized, double-blinded, placebo-controlled trial with a 12-month treatment period. SUBJECT: A population based sample of 165 postmenopausal women aged 47-65 were included in the trial. Only women who experienced menopause for more than 12 months were recruited. INTERVENTIONS: The eligible subjects were randomized to take the D&G preparation (two capsules), or image-identical placebo capsules (two capsules) daily, in a double-blind and parallel fashion for 12 month. MEASUREMENTS: The postmenopausal women with mild hypercholesterolemia (mean age 56.5 ± 4.1 of treatment group and 56.0 ± 3.8 years of placebo group) were randomized to the D&G group or placebo group for trial treatment. Carotid intima-media thickness (IMT) was used as the surrogate marker and was measured using high resolution ultrasound. Lipid profile was also tested. RESULTS: Baseline characteristics were comparable between the two groups. After 12 months, there were no significant changes in the blood pressures and general biochemical profiles in both groups, however, there was a remarkable decrease in serum low density lipoprotein (LDL) cholesterol (-6.92%) and total cholesterol (TC) (-5.85%) in the D&G group compared with the placebo group (-3.21% and -3.42%) when compared with the baseline. The carotid intima-media thickness (IMT) decreased 1.52% from baseline in the D&G group (p < 0.004) but the decrease was only 1.13% in the placebo treatment group (p = 0.009) after 12 months treatment. Twelve adverse events were reported (six in placebo group and six in D&G group) but none of them was directly relevant to the study herbal preparation. CONCLUSIONS: Postmenopausal women with early hypercholesterolemia tolerated D&G well. D&G improved the carotid intima thickness, lowered LDL and total cholesterol. D&G therefore can be recommended for the prevention of atherosclerosis in postmenopausal women with hypercholesterolemia.

Healing effect of a two-herb recipe (NF3) on foot ulcers in Chinese patients with diabetes: a randomized double-blind placebo-controlled study.

BACKGROUND: In the present study, we examined the effect of a two-herb traditional Chinese medicine (NF3), comprised of Astragali Radix and Radix Rehmanniae, on the healing of diabetic foot ulcer and the possible molecular mechanisms involved. METHODS: This was a prospective randomized double-blind placebo-controlled study. Sixteen diabetic patients were randomized to receive either placebo or NF3 for 6 months. Ulcer healing and sensory changes were examined. Molecular studies included measurement of serum tumor necrosis factor (TNF)-α and RNA microarray investigation. RESULTS: The daily rate of reduction in ulcer area was 3.55% in the NF3 group and 1.52% in the placebo group (P = 0.062). In the index limb, the number of negative tests for sensory neuropathy using monofilament was reduced from 27% to 7% in the NF3 group and from 37% to 35% in the placebo group (P < 0.001). In addition, NF3 significantly decreased serum TNF-α levels (P = 0.034). Microarray studies revealed concerted changes following NF3 treatment in the expression of genes implicated in fibroblast regeneration, angiogenesis, and anti-inflammation. CONCLUSIONS: In this proof-of-concept study, 6-month treatment with NF3 was associated with improved wound healing and sensation accompanied by concerted changes in gene expression.

Gene expression profiling on the molecular action of danshen-gegen formula in a randomized placebo-controlled trial of postmenopausal women with hypercholesterolemia.

The Danshen-Gegen formula (DG) is a traditional Chinese herbal formula which has long been used to treat cardiovascular disease. DG was found to be a cardiovascular tonic in our recent research. However, a comprehensive investigation of the molecular mechanism of DG in cardiovascular disease has not been performed. The aim of this study was to clarify the transcriptional profiling of genes modulated by DG on postmenopausal women by using DNAmicroarray technology. We obtained 29 whole blood samples both from DG-treated and placebo-treated subjects. Blood lipid profile and intima-media thickness (IMT) were measured. Affymetrix GeneChip was used to identify differentially expressed genes (DEGs), followed by validation by the real-time PCR method. The results showed that DG-treated group has a significant improvement in IMT and lipid profile as compared to placebo-treated group. For the genomic study, the DG-treated group has a higher number of DEGs identified as compared to the placebo-treated group. Two important biological processes of "regulation of systemic arterial blood pressure by hormone" and "regulation of smooth muscle proliferation" have been identified by GePS in the DG-treated group. No significant biological process and cellular components were identified in the placebo-treated group. This genomic study on the molecular action of DG in postmenopausal women gathered sufficient molecular targets and pathways to reveal that DG could improve neointima thickening and hypertension.

A herbal formula for prevention of influenza-like syndrome: a double-blind randomized clinical trial.

OBJECTIVE: To investigate the efficacy of a herbal formula in the prevention of influenza or influenza-like syndrome among elderies residing in old-people's home in Hong Kong. The secondary objectives are to investigate the quality of life (QOL) and symptomology changes among the herbal users and to evaluate the safety of this formula. METHODS: In ten old people's home or community centres in New Territories, Hong Kong, 740 eligible subjects agreed to join the study and were randomized to receive a herbal formula or a placebo on alternate days over 8 weeks. Among those 740 participants, 113 had provided blood samples for immunological assessments before and after the study drug. Assessments were done at 0, 4, 8 and 12 weeks. Participants were instructed to keep a daily record of body temperature and any symptoms as sore throat, myalgia, running nose or cough, and to report to assessor accordingly. Those reporting body temperature of 37.8 °C and above would be visited and a proper nasopharyngeal swab be taken for viral study. RESULTS: Seventy-two participants developed influenza-like-symptoms but none of them was proven influenza in their nasopharyngeal swabs, 40 of these patients belonged to the herbal group and 32 to the placebo group, without significant differences between groups. The difference on the changes in QOL between the two groups was not statistically significant. However, in the immunological study, the natural killer cell absolute count was significantly increased in the herbal group compared with the placebo group (463 ± 253 vs 413 ± 198, P<0.05). CONCLUSIONS: The herbal preparation was not effective compared with placebo in the prevention of influenza-like syndrome. It was however safe and possibly supporting immunological responses.

A randomized, double-blind, multiple-dose escalation study of a Chinese herbal medicine preparation (Dang Gui Buxue Tang) for moderate to severe menopausal symptoms and quality of life in postmenopausal women.

OBJECTIVE: This study is a phase II clinical trial that aims to investigate the dose-response relationship of a Chinese herbal medicine preparation, Dang Gui Buxue Tang (DBT), with short-term menopausal symptoms and quality of life in local postmenopausal women. METHODS: A randomized, double-blind, multiple-dose escalation trial was performed in 60 postmenopausal women experiencing severe hot flashes and night sweats. The participants were randomized to receive DBT preparations at 1.5, 3.0, or 6.0 g/day for 12 weeks. The primary outcomes were vasomotor symptoms, Greene Climacteric Scale (GCS) score, and Menopause-Specific Quality of Life (MENQOL) score. Secondary outcomes included serum hormones and lipids. RESULTS: There were between-group differences in psychological/psychosocial (P = 0.015, GCS; P = 0.013, MENQOL) and somatic/physical (P = 0.019, GCS; P = 0.037, MENQOL) domains, and improvement was significantly greatest (P < 0.05) in the 6.0 g/day dose group. The frequency and severity of hot flashes and night sweats were significantly reduced in the 3.0 g/day (14.5%-21.2%, P < 0.05, hot flashes; 28.6%-39.6%, P < 0.05, night sweats) and 6.0 g/day (34.9%-37.4.0%, P < 0.01, hot flashes; 10.1%-12.8%, P < 0.01, night sweats) dose groups. The female hormones follicle-stimulating hormone, luteinizing hormone, and 17ß-estradiol, as well as the lipids total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol, were not significantly different within groups and between groups. CONCLUSIONS: DBT preparations at 6.0 g/day significantly improve physical and psychological scores and significantly reduce vasomotor symptoms from baseline. The treatment was well tolerated, with no serious adverse events noted during the 12-week intervention period. The changes do not affect hormones and lipid profiles.

An innovative herbal product for the prevention of osteoporosis.

OBJECTIVE: To prevent the deterioration of osteopenia, a triple herb product Bo-gu Ling ( , ELP) was created for a clinical trial on post-menopausal women suffering from osteopenia. METHODS: The design of the clinical trial was of randomized, double-blind, placebo-controlled nature. A total of 150 women aged 40-60 years, who were after menopause for at least 1 year and their lumbar spine bone mineral density (BMD) must be lower than 0.891 g/cm(2), were recruited and randomly divided into the ELP group treated with ELP and the placebo group, with 75 in each group. The primary endpoint was the BMD of the lumbar spine that was assessed at baseline, 6 and 12 months after treatment. Secondary endpoints included peripheral quantitative computed tomography (pQCT) measurements of distal tibia and the changes in the quality of life (QOL). RESULTS: The spine BMD of the ELP group was increased by 0.69% in the subjects who were more than 10 years after menopause. In contrast, the placebo group of the same stratum decreased by 0.61% (P=0.067). In the subjects with more than 10 years duration of menopause, the hip BMD increased by 0.21% in the ELP group, compared with a decrease of 0.52% in the placebo group (P=0.159). The tibia strength-strain index was increased by 1.94% in the ELP group compared with 0.33% in the placebo group (P=0.047). Physical function of SF-36 QOL questionnaire was remarkably improved compared with the baseline, but did not show dominance over the placebo group. CONCLUSION: ELP showed potential benefit in improving BMD on the women who experienced over 10 years of menopause.

The effects of Boehmeria nivea (L.) Gaud. on embryonic development: in vivo and in vitro studies.

AIM OF THE STUDY: Boehmeria nivea (L.) Gaud. was commonly used to treat miscarriages clinically. The aim of this study was to examine its safety for embryonic development. MATERIALS AND METHODS: Pregnant mice were randomly assigned into 5 groups, i.e. mice were oral-treated with distilled water (G1), with Boehmeria nivea extract of 2, 8 or 32 g/kg/day (G2, G3 or G4), and with 3 doses of vitamin A of 200,000 IU/kg as positive controls (G5). Meanwhile, IC(50) values for both embryonic stem cells (ESCs) and 3T3 cells were detected by cytotoxicity assays. RESULTS: (1) The resorptions and malformed fetuses in G5 were significantly higher than G1 (P<0.001), whereas the maternal body-weight and uterus-weight were lower than G1 (P<0.05); (2) there was no difference in the fetal body-weight, maternal relative body-weight gain, liver-, kidney- or heart-weight, relative organ-weight, and histological examination among five groups; (3) there was no difference in IC(50) values between ESCs and 3T3 cells, but high concentration of Boehmeria nivea extract might significantly lower ESCs' viability (P<0.05). CONCLUSION: Boehmeria nivea extract at 32 g/kg/day did not cause significant embryotoxicity or maternal toxicity in mice, although it might cause cytotoxicity in cultured ESCs at a high dose.

Acupuncture: Complications are preventable not adverse events.

If adverse effects are understood as "something that happened unexpectedly" while receiving drug treatment, there is no difference between adverse effects and complications. However, acupuncture is a process different from the use of drugs. While acupuncture procedures should not be taken for granted as safe, complications causing harm are usually, according to the authors, the result of negligence, and should be differentiated from other adverse effects. Harmful complications noted consisted of bleeding and damage to the tissues and organs under the puncture sites. Adverse effects consisted of symptomatology like fainting and other systemic disturbances difficult to explain. In a study of acupuncture complications and adverse effects in 2000 procedures conducted by experienced professional acupuncturists in a research institution, it was found that complications did not occur, and adverse events happened infrequently. Attempts were made to explain the causes of adverse effects. Now that acupuncture is being widely incorporated into medical practice, a good understanding of adverse effects and complications would be necessary and helpful.

Treatment of perennial allergic rhinitis using Shi-Bi-Lin, a Chinese herbal formula.

AIM OF THE STUDY: Shi-Bi-Lin (SBL) is modified from the classic formula Cang-Er-Zi-San which has been used to treat chronic rhinitis, paranasal sinusitis and allergic rhinitis by herbal practitioners. The present study aimed at patients with moderate to severe perennial allergic rhinitis. SBL which has been shown effective in treating a guinea-pig model of allergic rhinitis, was evaluated for its efficacy and safety. MATERIALS AND METHODS: 126 allergic rhinitis patients were recruited in a double-blind randomized control trial. Half of the patients received SBL capsules and the others half received placebo for 4 weeks. Symptoms scores, physician's evaluation, nose examination, quality of life, adverse effects, serum cytokines were evaluated before and after treatment. RESULTS: SBL was found to be safe and effective in relieving some symptoms of perennial allergic rhinitis, improving the nose condition, and enhancing some domains of quality of life when compare to placebo, (p<0.05). In the 2 weeks follow up after treatment completion, the SBL enjoyed a prolongation of symptom control (p=0.05). CONCLUSION: SBL relieved symptoms of nose blockage among patients with perennial allergic rhinitis, and some aspects of the quality of life were also improved. The improvement was sustained for at least 2 weeks after treatment. No serious adverse events were encountered.