Identification of warning signs in Malaysian patients having COVID-19 infection who progress to severe form of the illness.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a novel coronavirus, now widely known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has caused 3 major pandemic waves in Malaysia. We aimed to identify the warning signs as indicators that predict the progression of disease. MATERIALS AND METHODS: This is a retrospective cohort study of adult patients more than 12 years of age presenting with laboratory-confirmed COVID-19 admitted in three separate hospitals around the country. RESULTS: Of the 228 patients initially admitted with mild illness, 47 had progressed requiring oxygen. The median time from admission to deterioration was 3 days (IQR 2 - 5). Age more than ≥50years old (median age = 42.5, IQR = 28.8 - 57.0), higher temperature (mean = 37.3, IQR 36.8 - 38.0), MEWS score >3 (9, 19.1%), Neutrophil-to-lymphocyte ratio (NLR) >3.13 , (18, 38.3%) C-reactive protein (CRP) >5. (12, 27.3%), multiple zonal involvement on the chest radiography on admission (2, IQR 1-3) were more common in the deteriorated group on admission. On multivariate analysis, multiple comorbidities (HR = 7.40, 95 percent CI 2.58-21.2, p0.001), presence of persistent fever (HR = 2.88, 95 percent CI 1.15 - 7.2, p = 0.024), MEWS scoring >3 (HR of 6.72 ;95 percent CI 2.81-16.0, p0.001) were associated with progression to severe illness. CONCLUSION: In our cohort, we found that several factors were associated with the severity of COVID19. Early detection of these factors could correctly identify patients who need more intensive monitoring, and early referral for ICU care.

Loading behavior of Pt nanoparticles on the surface of multiwalled carbon nanotubes having defects formed via microwave treatment.

We developed a simple and efficient method to load Pt nanoparticles (NPs) uniformly on defects generated in multiwalled CNTs (MWCNTs) without using reduction agents or organic reagents. Defects on the surfaces of MWCNTs were artificially generated by microwave treatment at various exposure times. Nucleation of Pt NPs occurs on the defect sites spontaneously due to an innate electropotential difference. Because of the correlation between defects and Pt NPs, we were able to control the size of Pt NPs by changing defect size, quantity and distribution, which was confirmed by Raman spectroscopy and TEM. After microwave treatment for 3 min, more uniform and smaller Pt NPs were observed. Also, the defects via microwave treatment make adhesion of Pt NPs stronger, which can be helpful to improve the reliability for applications. Finally, the methanol oxidation behavior of MWCNTs with Pt NPs was examined by cyclic voltammetry (CV).

Diagnostic significance of serum miR-26b and miR-21 expressions in ovarian cancer and their associations with clinicopathological characteristics and prognosis of patients.

OBJECTIVE: The aim of this study was to detect the expressions of serum micro-ribonucleic acid (miR)-26b and miR-21 in ovarian cancer patients, and to explore their associations with the diagnosis, clinicopathological parameters and prognosis of ovarian cancer. PATIENTS AND METHODS: A total of 86 patients diagnosed with ovarian cancer in our hospital from January 2014 to January 2015 were enrolled in the observation group. Meanwhile, another 86 subjects receiving physical examination in our hospital during the same period were enrolled in the control group. The expressions of serum miR-26b and miR-21 in both groups were detected via Real Time fluorescence-quantitative Polymerase Chain Reaction (RT-qPCR). Receiver operating characteristic (ROC) curves were plotted. Later, the clinical diagnostic value of combined detection of miR-26b and miR-21 in ovarian cancer was analyzed. Moreover, the associations of serum miR-26b and miR-21 expressions with clinicopathological characteristics and prognosis of ovarian cancer patients were explored. RESULTS: The expression of serum miR-26b in ovarian cancer patients was significantly lower than that of healthy subjects, while miR-21 expression was markedly higher in ovarian cancer patients (p<0.05). The area under the ROC curve (AUC), the sensitivity and specificity of miR-26b detection, miR-21 detection and combined detection in the diagnosis of ovarian cancer were 0.753 vs. 0.826 vs. 0.916, 47.2 vs. 76.3 vs. 87.6 and 78.5 vs. 85.6 vs. 90.4, respectively. Therefore, it could be observed that both the sensitivity and specificity of combined detection were remarkably higher than those of single detection (p<0.05). In addition, the expressions of serum miR-26b and miR-21 were associated with clinical stage and lymph node metastasis of ovarian cancer patients, whereas it was not correlated with age and histological type. The 3-year survival rate of patients with high expression of serum miR-26b was significantly higher than that in those with low expression of serum miR-26b. However, the 3-year survival rate of patients with low expression of serum miR-21 was higher than that in those with high expression. CONCLUSIONS: MiR-21 is highly expressed, while miR-26b is lowly expressed in the serum of ovarian cancer patients. Both of them may be involved in the incidence and development of ovarian cancer. Furthermore, combined monitoring of serum miR-26b and miR-21 has a certain value in the clinical diagnosis and treatment of ovarian cancer.

Superconducting and normal-state anisotropy of the doped topological insulator Sr0.1Bi2Se3.

SrxBi2Se3 and the related compounds CuxBi2Se3 and NbxBi2Se3 have attracted considerable interest, as these materials may be realizations of unconventional topological superconductors. Superconductivity with Tc ~3 K in SrxBi2Se3 arises upon intercalation of Sr into the layered topological insulator Bi2Se3. Here we elucidate the anisotropy of the normal and superconducting state of Sr0.1Bi2Se3 with angular dependent magnetotransport and thermodynamic measurements. High resolution x-ray diffraction studies underline the high crystalline quality of the samples. We demonstrate that the normal state electronic and magnetic properties of Sr0.1Bi2Se3 are isotropic in the basal plane while we observe a large two-fold in-plane anisotropy of the upper critical field in the superconducting state. Our results support the recently proposed odd-parity nematic state characterized by a nodal gap of Eu symmetry in SrxBi2Se3.

Suitable whole blood levels 2 hours after neoral in liver transplant patients: experiences at a single center.

UNLABELLED: Whole blood levels 2 hours after Neoral (C2) administration were observed to correlate better with area under the curve (AUC(0-4)) than trough levels (C0), suggesting that C2 may be the best single time point predictor of Neoral absorption. Owing to concerns about drug toxicity due to excessive immunosuppression, C2 adjustments to target blood levels may represent an advance. The present study measured C2 and levels to determine which correlated more closely with AUC(0-4). METHODS: Between August 2003 and July 2004, 40 adult liver transplantations were performed in our center. All patients received Neoral twice daily. They were maintained at a C0 level of about 200 ng/mL. C0 levels were measured daily. C2 levels were estimated on postoperative days 3, 5, 7, 14, and 28. AUC(0-4) performed on postoperative days 3, 7, and 28 was calculated using the trapezoidal rule. RESULTS: The mean AUC(0-4), C0, C1, C2, C3, and C4 were 1100.3 +/- 484.8 ng/mL, 197.1 +/- 84.7 ng/mL, 240.7 +/- 166.2 ng/mL, 307.8 +/- 162.6 ng/mL, 302.8 +/- 138.9 ng/mL, and 300.3 +/- 142.8 ng/mL, respectively. C2 correlated with AUC(0-4) (R2 = 0.868: P < .05) better than C0 (R2 = 0.245: P < .05), C1 (R2 = 0.604: P < .05), or C4 (R2 = 0.583: P < .05). CONCLUSIONS: Neoral dose monitoring according to a mean C2 range of 307.8 +/- 162.6 ng/mL correlated better with AUC(0-4). Further studies are required to determine suitable C2 levels in liver transplant patients.

Is it appropriate to offer allogeneic hematopoietic stem cell transplantation to patients with primary refractory acute myeloid leukemia?

Although continued advances have been made in the treatment of acute myeloid leukemia (AML), approximately 20-30% of patients will never achieve a remission. For these patients with primary refractory AML, the only curative option remains an allogeneic stem cell transplant. Allogeneic transplantation provides the ability to administer myeloablative doses of chemotherapy or chemoradiotherapy, as well as the advantage of a possible graft-versus-leukemia effect. Difficulty in interpreting the literature is due to selection bias, in particular, the varying definitions of primary refractory disease with respect to the morphological criteria and the number of induction regimen required before being defined as being refractory. Regardless, it is a procedure with high treatment-related mortality and risk of relapse. Most studies demonstrate an event-free survival of 10-20% at 5 years. Predictive factors of outcome include blast cell count in the marrow, karyotype, the number of prior regimen, age, performance status and availability of a related donor. These prognostic factors should be considered prior to offering allogeneic transplantation for primary refractory AML. Those patients with many favorable prognostic factors and an HLA-matched related donor available would be the best candidate for the procedure. Those with many poor prognostic factors and only an unrelated donor available may be better served by being offered palliation or being enrolled in investigational studies.

Myeloablative allografting for chronic lymphocytic leukemia: evidence for a potent graft-versus-leukemia effect associated with graft-versus-host disease.

In all, 30 patients with CLL proceeded to myeloablative allogeneic BMT using related (n=20, 67%) or unrelated (n=10) donors, at the Princess Margaret Hospital (Toronto) (n=20) or the Leukemia/BMT Program of BC (Vancouver) (n=10), from 1989 to 2001. Median (range) interval from diagnosis to BMT was 4.8 (0.3-13) years, median number of prior therapies was three and median age 48 years. The preparative regimen included total body irradiation in 15 (50%). In all, 14 of 30 patients (47%) are alive, with median (range) follow up of 4.3 (2.4-10.5) years. All are in complete remission, two following therapy for post-BMT progression. Actuarial overall (OS) and event-free survival (EFS) at 5 years is 39% (OS 48% for related donor and 20% for unrelated donor BMT); cumulative incidence of nonrelapse mortality (NRM) and relapse is 47 and 19%, respectively. Both acute (RR=0.008, P=0.01) and chronic (RR=0.006, P=0.02) Graft-versus-host disease (GVHD) were associated with markedly decreased risk of relapse. Patients receiving grafts from unrelated donors had increased NRM (RR=3.6, P=0.02) and decreased OS (RR of death=3.4, P=0.002). Allogeneic BMT has resulted in long-term EFS in approximately 40% of patients with CLL. There is evidence for a strong graft-versus-leukemia effect associated with acute and chronic GVHD, resulting in near complete protection from relapse.

Study on gelatin-containing artificial skin: I. Preparation and characteristics of novel gelatin-alginate sponge.

An absorbable sponge, composed of gelatin and alginate, was prepared by new crosslinking method that improved the efficiency of crosslinking. The crosslinking degree was characterized by trinitrobenzenesulfonic acid (TNBS) assay. A water uptake ability test, in vitro drug release and collagenase degradation tests, and an in vivo animal test were employed to confirm the applicability of this gelatin-alginate sponge as a wound dressing material. As the alginate content in the sponge increased, the porosity increased, resulting in an enhanced water uptake ability. Sponges loaded with silver sulfadiazine or gentamicin sulfate slowly released drugs for up to four days. The crosslinked sponge resisted in vitro collagenase digestion for up to three days. An in vivo animal test using witar rat showed rather good wound healing effect of gelatin-alginate sponge containing AgSD than vaseline gauze in our full-thickness skin defect model.

Study on gelatin-containing artificial skin IV: A comparative study on the effect of antibiotic and EGF on cell proliferation during epidermal healing.

Gelatin-hyaluronate sponge with and without antibiotic and epidermal growth factor (EGF) were prepared and compared. Four types of sponges were applied on the full-thickness dorsal skin defect of Wistar rat. The effects of antibiotic and EGF in gelatin-hyaluronate sponge on wound healing were investigated by light microscopy and image analyzer at postoperative days of 5, 12 and 21. An immunohistochemical technique, employing PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA) was applied to wounded tissue sections. The number of PC10-positive cells was very high for the sponge with EGF at postoperative day 5, then gradually decreased with time. Also we found that antibiotics restrained the cell proliferation during the migratory phase. The sponge with both antibiotic and EGF showed good wound healing performances on the whole for a healing period. The epithelium was regenerated fast with EGF-impregnated sponges at day 5, but each sample had nearly the same length of regenerated epithelium at day 12.

Characteristics and outcome of patients developing endocarditis following hematopoietic stem cell transplantation.

Endocarditis is an uncommon complication of hematopoietic stem cell transplantation (HSCT). A retrospective review of 1547 patients who underwent HSCT in Vancouver between January 1986 and December 2001 was performed. In all, 20 cases of endocarditis were identified (1.3% of all patients) with nine patients having received cryopreserved autologous stem cells, six stem cells from a histocompatible sibling and five patients stem cells from an unrelated donor. Five patients had endocarditis diagnosed while alive, a median of 6 months post-HSCT, by transthoracic (four patients) or transesophageal (one patient) echocardiography. The remaining 15 cases of endocarditis were only identified post mortem. The mitral valve was the most frequently involved (10 patients) followed by the aortic valve (six patients); multivalvular disease was noted in five patients. Of the 11 affected allogeneic HSCT patients, 10 had previously developed acute graft-versus-host disease (GVHD). Causative organisms were identified in 11 patients, while nine additional cases were felt to be thrombotic in origin. Of the 20 patients, 19 died with the sole survivor alive 10 years following an aortic valve replacement. Endocarditis is an uncommon complication of HSCT usually involving the cardiac valves on the left side of the heart and is associated with a high mortality rate.

Second malignancy following high-dose therapy and autologous stem cell transplantation: incidence and risk factor analysis.

To establish incidence and risk factors for development of second malignant neoplasms after high-dose chemo/radiotherapy (HDT) and autologous hematopoietic stem cell transplantation (AHSCT), the case files of 800 consecutive patients who underwent AHSCT at our institution between June 1982 and December 2000 were reviewed. In all, 26 patients developed 29 second malignancies (nine myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML), 16 solid tumors and four lymphoproliferative disorders (LPDs)) for a 15-year cumulative incidence of 11% (95% confidence interval (CI), 5-18%). These second tumors occurred at a median of 68 (range 1.5-177) months following AHSCT. The relative risk (RR) compared to the general population of developing a second malignancy following AHSCT was 3.3 (CI 2.2-4.7) P<0.001. The RR of developing MDS/AML, LPD and a solid tumor was 47.2 (CI 21.5-89.5) P<0.001, 8.1 (2.2-20.7) P=0.002 and 1.98 (1.1-3.2) P=0.009, respectively. In multivariate analysis, age >or=35 years at the time of AHSCT (P=0.001) and an interval from diagnosis to AHSCT >or=36 months (P=0.03) were associated with a greater risk of developing a second malignancy. Patients who have undergone HDT and AHSCT are at significant risk for developing a second malignancy and should receive indefinite follow-up.

Subdural hematomas during CML therapy with imatinib mesylate.

Seven of one hundred twenty-one patients with chronic myeloid leukemia (CML) treated with imatinib mesylate developed subdural hematomas. All had advanced disease and were treated initially at a dose of 600 mg per day. Three patients had thrombocytopenia (platelet < 10 x 10(9)/l), one had leukocytosis (white blood cell count > 150 x 10(9)/l) and three had neither around the time of diagnosis of the subdural hematomas. Four patients required surgical evacuation. One patient, in blast crisis, died as a consequence of the subdural hematoma. Three patients survived but died of progressive CML. The remaining three patients having recommenced imatinib, are alive and well, and one has achieved a major cytogenetic response. Subdural hematomas must be considered even in mildly symptomatic patients receiving imatinib regardless of their peripheral blood counts. Patients who survive can be cautiously restarted on imatinib. Further studies are required to study the potential relationship between imatinib mesylate and subdural hematomas.

Gamma-radiation accelerates ovarian follicular atresia in immature mice.

This study deals with the morphological degenerations of normal and atretic follicles based on artificially induced radiation apoptosis. ICR strain of 3 week-old female mice were whole body irradiated with 8.3 Gy and sacrificed by cervical dislocation. Ovaries were collected at 0 h, 6 h, 12 h, 1 d, 2 d, 4 d, and 8 d post irradiation and processed for morphological observation. Irradiated ovarian follicles showed such characteristics as faint connection between zona and cumulus thinning of granulosa layer, numerous apoptotic bodies, and increased cell debris in antrum. However, in normal ovaries about a half of the follicles were healthy. Within 6 h post irradiation, more than 95% of follicles steeply became apoptotic. At 4 d, severely damaged follicles with hypertrophed theca layer and fragmented oocytes were shown. At 8 d, normal shaped follicles were observed together with severely disrupted ones. The normal shaped follicles seemed to have grown from radioresistant ones. In conclusion, gamma-radiation had an additive or concomitant effect on atretic degeneration of mouse ovarian follicles.

Transnasal endoscopic excision of an isolated neurofibroma of the nasal septum.

Neurofibroma may occur in any parts of myelinated nerves having Schwann cells. However, it is extremely rare in the nasal septum. We have had experience with an isolated neurofibroma of the nasal septum which was successfully removed by transnasal endoscopic excision, and describe the clinical, endoscopic surgical and pathological features.

Distribution of nitric oxide in the nasal mucosa of the rat: a histochemical study.

We evaluated the distribution of nitric oxide (NO) in the rat nasal mucosa using nicotineamide adenosine dinucleotide phosphate (NADPH)-diaphorase histochemistry. The NADPH-diaphorase positive nerve fibers in the nasal mucosa were observed around blood vessels and submucosal glands and in sphenopalatine ganglions. Strong positive reactions for NADPH-diaphorase were observed in ganglions as compared with the other tissues. In septal and turbinate mucosa, positive reactions for NADPH-diaphorase were mainly seen in the anterior portion, and a few positive reactions were observed in the posterior portion. No positive reactions for NADPH-diaphorase were demonstrated in the sinus mucosa. These results suggest that NO may be related to regulation of blood flow, glandular secretion and neurotransmission, and also that NO may play an important role in the defense mechanism of the upper airway system against external environments.

Displaced intra-articular calcaneal fracture treated surgically with limited posterior incision.

The incidence of calcaneal fracture has been slowly increasing; however, the ideal treatment for displaced intra-articular fracture is not available yet, even though the fracture brings frequent complication and disability. Between April 1991 and March 1998, we treated 103 displaced intra-articular calcaneal fractures of 92 patients surgically with limited posterior incision, modified Gallie approach. There were thirty-seven tongue-type fractures, fifteen tongue-type fractures with moderate comminution, nineteen joint-depression fractures, twenty-nine joint-depression fractures with moderate comminution, and three extensively comminuted fractures. The fracture fragments were fixed mainly with partly threaded small cancellous screws or Steinmann pins without any bone graft. Ankle and subtalar motion was permitted immediately if fixation were stable enough. Otherwise, a short period of cast immobilization was utilized. With a mean follow-up of 28 months (range, 12 to 66 months), eighty six percent of feet had no pain or only occasional pain not requiring medication. Using American Orthopedic Foot and Ankle Society hindfoot score system for assessment, ninety percent of feet rated as good to excellent. We used "Circle draw test" for evaluation of subtalar motion during follow-up visitation and found eight-seven percent of feet showed good to excellent correlation with the functional recovery. We recommend a limited posterior incision for reduction and internal fixation of displaced intra-articular calcaneal fractures. For displaced intra-articular fractures with three or four large fragments without further comminution and without a displaced fracture of the calcaneal cuboid joint, this method is particularly useful. We also recommend a Circle draw test for evaluation of subtalar joint motion as well as an indicator of functional recovery after displaced calcaneal fractures.

HIV-Associated Burkitt Lymphoma: Good Efficacy and Tolerance of Intensive Chemotherapy Including CODOX-M/IVAC with or without Rituximab in the HAART Era.

Background. The outcome of HIV-associated non-Hodgkin lymphoma (NHL) has improved substantially in the highly active antiretroviral therapy (HAART) era. However, HIV-Burkitt lymphoma (BL), which accounts for up to 20% of HIV-NHL, has poor outcome with standard chemotherapy. Patients and Methods. We retrospectively reviewed HIV-BL treated in the HAART era with the Magrath regimen (CODOX-M/IVAC±R) at four Canadian centres. Results. Fourteen patients with HIV-BL received at least one CODOX-M/IVAC±R treatment. Median age at BL diagnosis was 45.5 years, CD4 count 375 cells/mL and HIV viral load (VL) <50 copies/mL. Patients received PCP prophylaxis and G-CSF, 13 received HAART with chemotherapy and 10 rituximab. There were 63 episodes of toxicity, none fatal, including: bacterial infection, n = 20; grade 3-4 hematologic toxicity, n = 14; febrile neutropenia, n = 7; oral thrush; and ifosfamide neurological toxicity, n = 1 each. At a median followup of 11.7 months, 12 (86%) patients are alive and in remission. All 10 patients who received HAART, chemotherapy, and rituximab are alive. CD4 counts and HIV VL 6 months following BL therapy completion (n = 5 patients) were >250 cells/mL and undetectable, respectively, in 4. Conclusion. Intensive chemotherapy with CODOX-M/IVAC±R yielded acceptable toxicity and good survival rates in patients with HIV-associated Burkitt lymphoma receiving HAART.

Comparison of the molecular adsorbent recirculating system and plasmapheresis for patients with graft dysfunction after liver transplantation.

BACKGROUND: Graft dysfunction after liver transplantation (OLT) is a life- threatening condition. Molecular adsorbent recirculating system (MARS) or plasmapheresis (PLP) may be effective supportive therapy of graft dysfunction for patients who cannot undergo retransplantation. The aim of this study was to compare the effects of MARS and PLP in patients with graft dysfunction after OLT. METHODS: Between January 2002 and July 2007, 31 OLT recipients who experienced graft dysfunction, defined as hyperbilirubinemia (>10 mg/dL) without bile duct obstruction and/or presence of hepatic encephalopathy, were treated with MARS or PLP. Biochemical and hemodynamic data and survival were compared in MARS and PLP groups. RESULTS: Fifteen patients were treated with 41 MARS sessions and 16 with 105 PLP sessions. After a single MARS session, patients showed significant reductions in creatinine, urea nitrogen, bilirubin, and ammonia. After a single PLP session, patients showed significant improvements in prothrombin time, bilirubin, alanine aminotransferase, alkaline phosphatase, and albumin. After the completion of treatment, Both MARS and PLP significantly improved bilirubin values. at 90 days there were no differences in overall survival rates; 53% in MARS versus 56% in PLP. CONCLUSION: Both MARS and PLP are alternative supportive treatments for graft dysfunction after OLT.

Long-term outcome after allo-SCT: close follow-up on a large cohort treated with myeloablative regimens.

We analyzed the late outcomes of 429 long-term survivors post allogeneic hematopoietic SCT (allo-HSCT) who received transplant in our center between 1981 and 2002, and were free of their primary disease for > or =2 years after allo-HSCT. Late recurrent primary malignancy was found in 58 (13.5%) patients and was the primary cause of late death. A total of 37 (8.6%) patients died of non-relapse causes at a median of 5.5 years (range, 2-15.6 years) post allo-HSCT. The major non-relapse causes of death were chronic GVHD (cGVHD), secondary malignancy and infection. The probabilities of OS and EFS were 85% (95% cumulative incidence (CI) (81-89%)) and 79% (95% CI (74-83%)) at 10 years, respectively. Long-term allo-HSCT survivors were evaluated for late complications (median follow-up, 8.6 years (range, 2.3-22.8 years)). cGVHD was diagnosed in 196 (53.1%) survivors. The endocrine and metabolic complications were hypogonadism in 134 (36.3%) patients, osteopenia/osteoporosis in 90 (24.4%), dyslipidemia in 33 (8.9%), hypothyroidism in 28 (7.6%) and diabetes in 28 (7.6%). Hypertension was diagnosed in 79 (21.4%), renal impairment in 70 (19.0%), depression in 40 (10.8%) and sexual dysfunction in 33 (8.9%) survivors. We conclude that in patients who receive allo-HSCT as treatment for hematological malignancy and who are free of their original disease 2 years post transplant, mortality is low and the probability of durable remission is high. Lifelong surveillance is recommended.