Clinical severity of COVID-19 with omicron variant predominance in relation to vaccination status, age, comorbidities- a single center in Selangor, Malaysia.

INTRODUCTION: Recently, the rapid surge of reported COVID-19 cases attributed to the Omicron variant of severe acute respiratory syndrome coronavirus (SARS-CoV-2) created an immediate concern across nations. Local information pertaining to the new variant of concern (VOC) is lacking. We aimed to determine the clinical characteristics of COVID-19 during a period of Omicron prevalence among patients hospitalised from February 1 to 21, 2022 at Sungai Buloh Hospital and to estimate the risks of disease progression presumably caused by this variant in association with gender, age, comorbidity, and vaccination status. MATERIALS AND METHODS: In this retrospective, singlecentered, retrospective cohort study, all hospitalised adults with laboratory-confirmed COVID-19, aged 18 and above, were recruited from February 1 to 21, 2022. Clinical characteristics, investigations, and outcomes were assessed. RESULTS: A total of 2279 patients aged 18 years and above with laboratory-proven COVID-19 were recruited and analysed, excluding 32 patients owing to incomplete data. Majority of the study population had a mean age of 41.8 ± 17.7, was female-predominant (1329/2279, 58.6%), had completed a primary series of vaccination with a booster (1103/2279, 48.4%), and had no underlying medical conditions (1529/2279, 67.4%). The risk of COVID-19-related disease progression was significantly lower in hospitalised patients under the age of 50 who were female, had no comorbidity, and had completed two doses of the primary series with or without a booster. [respectively, OR 7.94 (95% CI 6.16, 10.23); 1.68 (1.34, 2,12); 2.44 (1.85, 3.22); 2.56 (1.65, 3.97), p< 0.001]. CONCLUSION: During the period of Omicron prevalence, a favourable outcome of COVID-19 was strongly associated with female gender, age below 50, a comorbidity-free condition, and having completed immunization. With this new observation, it could help improve public health planning and clinical management in response to the emergence of the latest VOC.

A quality improvement project: Reducing bloodstream infection by improving adherence to the care bundle of peripheral vascular catheters at the COVID-19 treatment centre.

INTRODUCTION: During the COVID-19 pandemic, bloodstream infection (BSI) rates were substantially rising in Sungai Buloh Hospital (HSB). It is believed that the COVID-19 pandemic has had an adverse impact on BSI incidence caused by contaminated periphery vascular catheters (PVCs). The study's objective is to reduce the BSI rates in HSB by improving adherence to the PVC care bundle via the Plan-Do-Study-Act (PDSA) approach. MATERIALS AND METHODS: A quality improvement (QI) project was employed over four months, from June to September 2021, during the COVID-19 pandemic in HSB. All adults hospitalised for COVID-19 with intravenous lines were subjected to data collection. A baseline audit was conducted to study BSI incidence from April to May 2021. Implementation was carried out by PDSA cycles and data on BSI rates per 100 admissions was described using a monthly run chart. RESULTS: At baseline, the BSI rate per 100 admissions was 5.44 before implementing our QI project. Initial changes via PDSA cycles did not bring significant improvements to BSI rates and a rising trend in BSI rates was observed after two PDSA cycles. Further audits identified the problem of noncompliance with the practice of aseptic non-touch technique (ANTT) and a lack of effective leadership in implementing the PVC care bundle. The third PDSA cycle focused on adopting practical leadership skills among senior clinicians to ensure compliance with the prevention bundle and to encourage the use of ultrasound guidance for difficult line insertion. After the third PDSA cycle, the BSI rate per 100 admissions was reduced from 6.41 to 4.34 (p < 0.05). The BSI rates continued to decline down the line for another five months. CONCLUSION: Through QI initiatives, the risk of BSI can be significantly reduced.

Genetic alterations in primary melanoma in Taiwan.

BACKGROUND: Acral melanoma (AM) is the most common histopathological subtype of malignant melanoma in Asians. However, differences in the mutational profiles underlying AM and nonacral cutaneous melanoma (NAM) in Asians are not well understood. OBJECTIVES: To augment the understanding of the prevalence, patterns and associations of various mutations between different subtypes of melanoma. METHODS: We performed comprehensive genomic profiling of 409 cancer-associated genes, using next-generation sequencing, in 66 primary melanomas comprised of 45 AMs and 21 NAMs. RESULTS: Most of the AMs (n = 27/45; 60%), but only five of 21 (24%) NAMs, were triple wild-type (triple-WT) tumours. Compared with AMs, NAMs exhibited a significantly higher frequency of BRAF mutations. The frequencies of NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and gains of receptor tyrosine kinase genes were significantly higher in AMs. Ulceration was found at significantly higher rates in the AMs and NAMs with cell-cycle aberrations and gains of receptor tyrosine kinase genes. Notably, cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival in the 66 patients with melanoma and especially in the 45 patients with AM. Multivariate analysis showed that lymph node metastasis and cell-cycle aberrations were independent prognostic factors of melanoma-specific survival. CONCLUSIONS: This study strengthens our understanding of the patterns and clinical associations of oncogenic mutations in AMs and NAMs in Asians. What's already known about this topic? Mutation frequencies of driver genes vary between melanoma subtypes. Acral melanoma is the most common subtype of melanoma in Asians. KIT mutations and copy number variations occur more frequently in the acral subtype of melanoma than in the nonacral subtype What does this study add? NRAS/KRAS mutations, cell-cycle aberrations, copy number gains in BIRC2, BIRC3 and BIRC5, and amplifications of receptor tyrosine kinase genes were significantly enriched in acral melanoma and could be potential targets for treatment. Melanomas with cell-cycle aberrations and gains in receptor tyrosine kinase genes were significantly more likely to contain ulceration. What is the translational message? Cell-cycle aberrations and copy number gains in BIRC2, BIRC3 and BIRC5 were significantly associated with poor melanoma-specific survival. These observations should be explored further for future drug development.

Does Tumour Contrast Retention on CT Immediately Post Chemoembolization Predict Tumour Metabolic Response on FDG-PET in Patients with Hepatic Metastases from Colorectal Cancer?

PURPOSE: The exact mechanism of action of chemoembolization with drug eluting beads loaded with irinotecan (DEBIRI) in colorectal cancer is undetermined. Posttreatment tumour contrast retention often seen on CT immediately post procedure is of indeterminate significance. This study is aimed at assessing if metabolic response on PET-CT can be related to posttreatment tumour contrast retention. MATERIALS AND METHODS: In this retrospective study, a total of 17 patients with a total of 55 marker lesions were recruited. RESULTS: The area of tumour contrast retention can be matched to a hypometabolic area on subsequent PET-CT in over 36 lesions (65.5%). Out of the 55 lesions, a total of 38 marker lesions in 11 patients who also had pre-DEBIRI PET-CT were analyzed for disease response. 10 out of 10 lesions that had a complete response on PET-CT were found to demonstrate contrast retention throughout the tumour. 12 out of 13 (92.3%) tumours that had a partial metabolic response on PET-CT were found to demonstrate contrast uptake in the hypometabolic area only. In the 15 lesions that had progression/no response, 13 (86.6%) demonstrated no relationship between tumour contrast retention and tumour response. There was a significant correlation between contrast retention and disease response (P < 0.001). CONCLUSION: Our study showed that PET-CT response can be associated with post embolization contrast retention. The data suggests blood stasis, for which tumour contrast retention is a surrogate marker, is important for the PET-CT metabolic response. The authors propose that tumour contrast retention is an important embolization endpoint in DEBIRI.

Real-Time Quantitative Measurements of Foot Perfusion in Patients With Critical Limb Ischemia.

INTRODUCTION: Current methods of evaluating adequacy of endovascular procedures are imperfect and do not always predict which patients will do well. The purpose of this study was to evaluate the role of real-time quantitative measurements of perfusion among patients with critical limb ischemia. MATERIALS AND METHODS: Thirty-four patients with critical limb ischemia undergoing endovascular treatment were recruited. Perfusion Images of the foot were obtained pre and post successful angioplasty using an SPY Elite System (Novadaq Technologies, Ontario, Canada). Patients were followed for 6 months. Subsequently a logistic regression was performed to determine whether intraprocedural perfusion parameters predicted the odds of wound healing. RESULTS: Twenty-nine patients had successful angioplasty. Median age was 69.5% ± 8.3; 75% were men and 64% were diabetic. Rutherford stages were (4%-39%, 5%-57%, 6%-4%), and the average target limb ankle-brachial index (ABI) was 0.58 (SD 2.24). There was no significant correlation between the ABI and perfusion parameters. Inflow perfusion rate correlated significantly with Rutherford stage (Spearman rho 0.398, P = .036). After successful angioplasty 39% had a decrease in inflow rate and 57% had a decreased total inflow. In all, 25 patients completed 6 months of follow-up. Resolution of rest pain and/or healing of the ischemic wound occurred in 10 (40%) patients at 1 month, 4 (16%) at 3 months, and 2 (8%) at 6 months. One patient underwent a major amputation at 2 months. Eight (32%) patients never healed or had persistent rest pain. None of the real-time perfusion variables were significant predictors of wound healing. CONCLUSION: Many patients experience a paradoxical decrease in perfusion following successful angioplasty suggesting perfusion may not correlate with angiographic outcome, possibly due to microemboli, microvascular disease, or vasospasm. Real-time perfusion imaging following intra-arterial infusion of indocyanine green does not predict the odds of wound healing.

Which G-Tube to Use in Pullers: Assessment of Pull Pressures on Skin Models to Determine Optimal Catheter Choice in Patients with Recurrent Pulled Gastrostomy Tubes.

INTRODUCTION: Pulled or dislodged gastrostomy catheters represent a common complication associated with percutaneous gastrostomy and are a common cause of recurrent visits in patients with altered mental status. We intended to perform an experiment to compare the pull forces required to dislodge different commonly used gastrostomy catheters. MATERIALS AND METHODS: We used a digital force gauge device to measure the pull forces required to dislodge three types of 20 French gastrostomy catheters in double-layer skin models. These included the Flow 20 Pull Method (Cook Medical, Bloomington, IN, USA), Entuit Gastrostomy BR Balloon Retention feeding tube (Cook Medical, Bloomington, IN, USA), and Ponsky Non-Balloon Replacement Gastrostomy Tube (CR Bard Inc, Salt Lake City, Utah, USA). The catheters were inserted into the skin model using the same technique as would be utilized in a patient. RESULTS: The mean forces measured to dislodge the per-oral Flow 20 Pull Method, Entuit Thrive Balloon Retention, and button-type retention Ponsky replacement catheters were 35.6, 22.8, and 20.6 Newtons, respectively. The pull method per-oral gastrostomy catheter required significantly more pull force to dislodge than both the Ponsky button-type retention catheter and the Entuit balloon retention catheters. There was no significant difference in the pull force required to dislodge the Ponsky replacement catheter and the Entuit balloon retention catheter. CONCLUSIONS: Per-oral image-guided gastrostomy with pull-method button-type retention catheters may be the ideal choice in patients at high risk of tube dislodgment.

A case of pulmonary tuberculosis masquerading as lung carcinoma.

Tuberculosis is a nimble chameleon. It can manifest itself in various ways with atypical clinical and radiographic findings. In this report we discuss the importance of radiographic findings (nodular or mass-like forms) requiring a correlation with microbiological and histopathological results to differentiate lung cancer from TB.

A diatomic elastic metamaterial for tunable asymmetric wave transmission in multiple frequency bands.

Unidirectional/asymmetric transmission of acoustic/elastic waves has recently been realized by linear structures. Research related to unidirectionality of wave propagation has received intense attention due to potentially transformative and unique wave control applications. However, asymmetric transmission performance in existing devices usually occurs only in a narrow frequency band, and the asymmetric frequencies are always within ultrasound range (above 20 kHz). In this work, we design and propose a linear diatomic elastic metamaterial using dual-resonator concept to obtain large asymmetric elastic wave transmission in multiple low frequency bands. All of these frequency bands can be theoretically predicted to realize one-way wave propagation along different directions of transmission. The mechanisms of multiple asymmetric transmission bands are theoretically investigated and numerically verified by both analytical lattice and continuum models. Dynamic responses of the proposed system in the broadband asymmetric transmission bands are explored and analyzed in time and frequency domains. The effect of damping on the asymmetric wave transmission is further discussed. Excellent agreements between theoretical results and numerical verification are obtained.

Ordering of mutations in acute myeloid leukemia with partial tandem duplication of MLL (MLL-PTD).

Partial tandem duplication of MLL (MLL-PTD) characterizes acute myeloid leukemia (AML) patients often with a poor prognosis. To understand the order of occurrence of MLL-PTD in relation to other major AML mutations and to identify novel mutations that may be present in this unique AML molecular subtype, exome and targeted sequencing was performed on 85 MLL-PTD AML samples using HiSeq-2000. Genes involved in the cohesin complex (STAG2), a splicing factor (U2AF1) and a poorly studied gene, MGA were recurrently mutated, whereas NPM1, one of the most frequently mutated AML gene, was not mutated in MLL-PTD patients. Interestingly, clonality analysis suggests that IDH2/1, DNMT3A, U2AF1 and TET2 mutations are clonal and occur early, and MLL-PTD likely arises after these initial mutations. Conversely, proliferative mutations (FLT3, RAS), typically appear later, are largely subclonal and tend to be unstable. This study provides important insights for understanding the relative importance of different mutations for defining a targeted therapeutic strategy for MLL-PTD AML patients.

Numerical investigation of band gaps in 3D printed cantilever-in-mass metamaterials.

In this research, the negative effective mass behavior of elastic/mechanical metamaterials is exhibited by a cantilever-in-mass structure as a proposed design for creating frequency stopping band gaps, based on local resonance of the internal structure. The mass-in-mass unit cell model is transformed into a cantilever-in-mass model using the Bernoulli-Euler beam theory. An analytical model of the cantilever-in-mass structure is derived and the effects of geometrical dimensions and material parameters to create frequency band gaps are examined. A two-dimensional finite element model is created to validate the analytical results, and excellent agreement is achieved. The analytical model establishes an easily tunable metamaterial design to realize wave attenuation based on locally resonant frequency. To demonstrate feasibility for 3D printing, the analytical model is employed to design and fabricate 3D printable mechanical metamaterial. A three-dimensional numerical experiment is performed using COMSOL Multiphysics to validate the wave attenuation performance. Results show that the cantilever-in-mass metamaterial is capable of mitigating stress waves at the desired resonance frequency. Our study successfully presents the use of one constituent material to create a 3D printed cantilever-in-mass metamaterial with negative effective mass density for stress wave mitigation purposes.

Prediction of margin involvement and local recurrence after skin-sparing and simple mastectomy.

UNLABELLED: Skin-sparing mastectomy (SSM) facilitates immediate breast reconstruction. We investigated locoregional recurrence rates after SSM compared with simple mastectomy and the factors predicting oncological failure. METHODS: Patients with early breast cancer that underwent mastectomy between 2000 and 2005 at a single institution were studied to ascertain local and systemic recurrence rates between groups. Kaplan-Meier curves and log-rank test were used to evaluate disease-free survival. RESULTS: Patients (n = 577) underwent simple mastectomy (80%) or SSM (20%). Median follow up was 80 months. Patients undergoing SSM were of younger average age, less often had involved lymph nodes (22% vs 44%, p < 0.001), more often had DCIS present (79% vs 53%, p < 0.001) and involved margins (29% vs 15%, p = 0.001). Involved surgical margins were associated with large size (p = 0.001). The 8-year local recurrence (LR) rates were 7.9% for SSM and 5% for simple mastectomy respectively (p = 0.35). Predictors of locoregional recurrence were lymph node involvement (HR 8.0, for >4 nodes, p < 0.001) and involved surgical margins (HR 3.3, p = 0.002). In node negative patients, SSM was a predictor of locoregional recurrence (HR 4.8 [1.1, 19.9], p = 0.033). CONCLUSION(S): Delayed reconstruction is more appropriate for node positive early breast cancer after post-mastectomy radiotherapy. Re-excision of involved margins is essential to prevent local recurrence after mastectomy.

Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential.

Internal Iliac Aneurysm Repair Outcomes Using a Modification of the Iliac Branch Graft.

OBJECTIVES: Iliac branch grafts (IBGs) are a validated option for the treatment of aorto-iliac aneurysms preserving internal iliac artery (IIA) flow. IIA aneurysm (IIAA) is a relative contraindication to IBG placement. The goal of this study was to review experience in managing aorto-iliac aneurysms with concomitant IIAAs with extension of the IIA branch stent graft into the superior gluteal artery (SGA). METHODS: This retrospective study between May 2009 and November 2014 includes consecutive patients who underwent placement of an IBG (Cook, Bloomington, IN, USA) with extension of the internal iliac component of the branch stent graft into the SGA because of aneurysmal IIA (>15 mm). The stent grafts used were Viabahn (Gore, Karlsruhe, Germany), Fluency (Bard, Flagstaff, AZ, USA), or iCast (Atrium, Hudson, NH, USA) proximally. Imaging follow up was with computed tomography angiography (CTA) within 30 days of device insertion and then annually. RESULTS: The procedure was performed on 15 patients with a mean age of 76.8 years (SD 6.1 years). Twenty IIAAs were treated with a mean IIA and common iliac artery (CIA) diameter of 33 mm (SD 13 mm) and 35 mm (SD 11 mm) respectively. Technical success rate was 100%. One patient who underwent simultaneous IBG and three vessel fenestrated endovascular aneurysm repair died of mesenteric ischemia 2 days after the procedure. Mean imaging follow up with CTA was 18.3 months (SD 15.1 months). Primary patency of the SGA stent grafts was 100%. There was one case of type II endoleak. All patients were free from buttock claudication at follow up (mean: 19.7 months). Two patients who had IIA embolization contralateral to the IBG placement suffered from unilateral lower limb monoparesis. CONCLUSIONS: Extension of the internal iliac component of IBGs into the SGA for distal seal is feasible and safe in the endovascular treatment of aorto-iliac aneurysms with concomitant IIAs. Long-term results are needed to further validate this technique.

Consensus statement: the 16th Annual Western Canadian Gastrointestinal Cancer Consensus Conference; Saskatoon, Saskatchewan; September 5-6, 2014.

The 16th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Saskatoon, Saskatchewan, September 4-5, 2014. The Consensus Conference is an interactive, multidisciplinary event attended by health care professionals from across western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) involved in the care of gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancer.

Bedside Continuous Irrigation and Drainage as an Interim Local Treatment for Septic Arthritis of the Knee in the Medically Unstable Patient: A Case Report.

Septic arthritis is a surgical emergency. Prompt diagnosis and immediate treatment reduce the destruction of articular cartilage and give better outcome. We describe a simple, minimally invasive closed tube irrigation system for the initial treatment of septic arthritis of the knee in a patient with complex medical problems who was unfit to undergo surgery.

A randomised controlled trial of ultrasound-assisted spinal anaesthesia.

Pre-procedural ultrasound scanning has been used to facilitate spinal anaesthesia in patients with difficult anatomical landmarks and shown to improve first-attempt success rates in some studies. We studied whether pre-procedural ultrasound scanning improved first-attempt success rate and decreased time taken for the procedure in the general adult population. In this prospective, randomised controlled trial, 170 American Society of Anesthesiologists 1 to 3 patients aged between 21 and 80 years were recruited. Informed consent was obtained. Patients were randomised into two groups, ultrasound-guided identification of landmarks (Ultrasound Group) and manual palpation of landmarks (Manual Palpation Group). The primary outcome was first-attempt success rate and secondary outcomes were time taken to perform procedure, number of needle redirections, patient satisfaction and complications. The first-attempt success rate was 64% in the Ultrasound Group and 52% in the Manual Palpation Group (P=0.16). Time taken for procedure was shorter in the Ultrasound Group compared to the Manual Palpation Group (2.9±3.6 minutes versus 3.9±3.7 min, P= 0.007). Patient satisfaction was higher in the Ultrasound Group. There were no differences in complications. As there was no statistically significant difference in first-attempt success rates between the two groups, existing evidence for routine pre-procedural scanning for all patients is inadequate. The current use of pre-procedural ultrasound scanning will probably be limited to selected patients where spinal anaesthesia may be technically challenging with conventional methods.