Do athletic ECG changes predict athletic performance in Gurkha recruits?

INTRODUCTION: ECG changes are associated with regular long-term intensive exercise due to electrical manifestations of increased vagal tone, increased ventricular wall thickness and enlarged chamber size. The aim of this study was to further understand the relationship of athletic ECG changes and athletic performance in an athletic population. METHODS: A retrospective cohort study was performed in 195 Nepali civilian males undergoing selection to the Gurkhas. V̇O2max (maximal oxygen consumption) was estimated from a 1.5-mile run time using Cooper's formula and correlated with athletic ECG adaptations. Variables were explored with univariable and multivariable linear regression. RESULTS: The median number of athletic changes on ECG was 2 (IQR 1-2). There was no significant correlation (p=0.46) between the number of ECG adaptations and the degree of cardiovascular fitness by estimated V̇O2max (estV̇O2max). We found a negligible but significant correlation between the presence of inferior T wave inversion (TWI) and estV̇O2max (R2=0.03, p=0.02). The multivariable-fitted regression model was: estV̇O2max~Intercept+presence of RVH (right ventricular hypertrophy) voltage criteria+absence of sinus arrhythmia+T wave axis+inferior TWI. The overall regression was statistically significant: R2=0.10, F(df=4, df=189)=[5.4], p=0.0004). All variables in the multivariable model significantly predicted estV̇O2max (p<0.04). CONCLUSION: ECG changes of athleticism negligibly predict and differentiate athletic performance in our athletic population. The most predictive ECG markers being voltage criteria for left ventricular hypertrophy and RVH. Markers of increased vagal tone were not predictive. TWI, being a marker for disease, was also a marker for athletic performance in this cohort. The number of athletic ECG adaptations did not predict increased athletic performance.

Evaluation and 1-year follow-up of patients presenting at a Lyme borreliosis expertise centre: a prospective cohort study with validated questionnaires.

OBJECTIVES: To describe the course of symptoms reported by patients with symptoms attributed to Lyme borreliosis (LB) without being subsequently diagnosed with LB. METHODS: We performed a prospective cohort study with patients presenting at the outpatient clinic of two clinical LB centres. The primary outcome was the prevalence of persistent symptoms, which were defined as clinically relevant fatigue (CIS, subscale fatigue), pain (SF-36, subscale bodily pain), and cognitive impairment (CFQ) for ≥ 6 months and onset < 6 months over the first year of follow-up. Outcomes were compared with a longitudinal cohort of confirmed LB patients and a general population cohort. Prevalences were standardised to the distribution of pre-defined confounders in the confirmed LB cohort. RESULTS: Participants (n = 123) reported mostly fatigue, arthralgia, myalgia, and paraesthesia as symptoms. The primary outcome could be determined for 74.8% (92/123) of participants. The standardised prevalence of persistent symptoms in our participants was 58.6%, which was higher than in patients with confirmed LB at baseline (27.2%, p < 0.0001) and the population cohort (21.2%, p < 0.0001). Participants reported overall improvement of fatigue (p < 0.0001) and pain (p < 0.0001) but not for cognitive impairment (p = 0.062) during the follow-up, though symptom severity at the end of follow-up remained greater compared to confirmed LB patients (various comparisons p < 0.05). CONCLUSION: Patients with symptoms attributed to LB who present at clinical LB centres without physician-confirmed LB more often report persistent symptoms and report more severe symptoms compared to confirmed LB patients and a population cohort.

The primary prevention of pancreatic fistula using a vascularised rectus abdominis muscle flap - A porcine model.

Background: A pancreatic fistula is one of the most devastating complications following a Whipple's procedure. Fistula rates remain high despite various modifications to surgical techniques. We propose the use of a vascularised muscle flap in the primary prevention of pancreatic fistulas. Method: A distal pancreatectomy was performed on 5 pigs in our porcine model. A pancreaticojejunal (PJ) anastomotic leak was simulated. The pigs were divided into treatment (4 pigs) and control groups (1 pig). A left pedicled rectus abdominis flap was wrapped around the PJ anastomosis for the treatment group and omitted for the control group. Serum and drain amylase levels were recorded. The PJ-rectus abdominis flap complex was evaluated histologically. Results: There was no biochemical evidence of anastomotic leak in the treatment group. The drain-serum amylase ratio was less than 1.5 in the treatment group (p=0.006). Microscopically, the muscle adjacent to the anastomotic leak showed mild necrotic changes with an affected muscle depth of less than 10%. Conclusion: The vascularised rectus abdominis muscle is a durable flap to withstand proteolytic pancreatic enzymes. It is able to provide a water-tight seal around the PJ anastomosis and mitigate intraperitoneal haemorrhage and infection caused by erosion from the pancreatic fistula.

BOLD: Blood-gas and Oximetry Linked Dataset - Open Source Research.

Pulse oximeters measure peripheral arterial oxygen saturation (SpO 2 ) noninvasively, while the gold standard (SaO 2 ) involves arterial blood gas measurement. There are known racial and ethnic disparities in their performance. BOLD is a new comprehensive dataset that aims to underscore the importance of addressing biases in pulse oximetry accuracy, which disproportionately affect darker-skinned patients. The dataset was created by harmonizing three Electronic Health Record databases (MIMIC-III, MIMIC-IV, eICU-CRD) comprising Intensive Care Unit stays of US patients. Paired SpO 2 and SaO 2 measurements were time-aligned and combined with various other sociodemographic and parameters to provide a detailed representation of each patient. BOLD includes 49,099 paired measurements, within a 5-minute window and with oxygen saturation levels between 70-100%. Minority racial and ethnic groups account for ∼25% of the data - a proportion seldom achieved in previous studies. The codebase is publicly available. Given the prevalent use of pulse oximeters in the hospital and at home, we hope that BOLD will be leveraged to develop debiasing algorithms that can result in more equitable healthcare solutions.

Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

BACKGROUND: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T. PATIENTS AND METHODS: Patients with HR+ HER2-negative MBC with activating HER2 mutation(s) and prior cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) therapy received N + F + T (oral neratinib 240 mg/day with loperamide prophylaxis, intramuscular fulvestrant 500 mg on days 1, 15, and 29 of cycle 1 then q4w, intravenous trastuzumab 8 mg/kg then 6 mg/kg q3w) or F + T or fulvestrant alone. Those whose disease progressed on F + T or fulvestrant could cross-over to N + F + T. Efficacy endpoints included investigator-assessed objective response rate (ORR), clinical benefit rate (RECIST v1.1), duration of response, and progression-free survival (PFS). Plasma and/or formalin-fixed paraffin-embedded tissue samples were collected at baseline; plasma was collected during and at end of treatment. Extracted DNA was analyzed by next-generation sequencing. RESULTS: ORR for 57 N + F + T-treated patients was 39% [95% confidence interval (CI) 26% to 52%); median PFS was 8.3 months (95% CI 6.0-15.1 months). No responses occurred in fulvestrant- or F + T-treated patients; responses in patients crossing over to N + F + T supported the requirement for neratinib in the triplet. Responses were observed in patients with ductal and lobular histology, 1 or ≥1 HER2 mutations, and co-occurring HER3 mutations. Longitudinal circulating tumor DNA sequencing revealed acquisition of additional HER2 alterations, and mutations in genes including PIK3CA, enabling further precision targeting and possible re-response. CONCLUSIONS: The benefit of N + F + T for HR+ HER2-mutant MBC after progression on CDK4/6is is clinically meaningful and, based on this study, N + F + T has been included in the National Comprehensive Cancer Network treatment guidelines. SUMMIT has improved our understanding of the translational implications of targeting HER2 mutations with neratinib-based therapy.

Microplastics pollution in the rivers of a metropolitan city and its estimated dependency on surrounding developed land.

The spatial distribution and abundance of suspected microplastics (SMPs) in the surface water of a metropolitan city, as represented by four Hong Kong rivers, was studied during the dry season. Shing Mun River (SM), Lam Tsuen River (LT), and Tuen Mun River (TM) are located in urbanized areas, and SM and TM are tidal rivers. The fourth river, Silver River (SR) is situated in a rural area. TM had a significantly higher SMP abundance (53.80 ± 20.67 n/L) than the other rivers. The SMP abundance increased from upstream to downstream in non-tidal rivers (LT and SR), but not in tidal rivers (TM and SM), probably due to the tidal influence and a more homogeneous urban development along the tidal rivers. Inter-site differences in the SMP abundance were strongly correlated with the built area ratio (defined as the percentage of surrounding developed land area), human activities, and the nature of the river. About half (48.72 %) of the SMPs were <250 µm. Fibers and fragments were most abundant (>98 %), with most of them being transparent (58.54 %), black (14.68 %), or blue (12.12 %). Polyethylene terephthalate (26.96 %) and polyethylene (20.70 %) were the most common polymers. However, the MP abundance could be overestimated due to the presence of natural fibers. By contrast, an underestimation of the MP abundance could result from a smaller volume of water samples collected, due to a low filtration efficiency caused by high organic content and particle concentrations in the water. A more effective solid waste management strategy and upgrading of the sewage treatment facilities for removing microplastics are recommended to ameliorate the microplastic pollution in local rivers.

Brain Metastasis Growth Kinetics: A Novel Prognosticator for Stereotactic Radiotherapy.

AIMS: The rate of size change in brain metastasis may have clinical implications on tumour biology and prognosis for patients who receive stereotactic radiotherapy (SRT). We analysed the prognostic value of brain metastasis size kinetics and propose a model for patients with brain metastases treated with linac-based SRT in predicting overall survival. MATERIALS AND METHODS: We analysed the patients receiving linac-based SRT between 2010 and 2020. Patient and oncological factors, including the changes in sizes of brain metastasis between the diagnostic and stereotactic magnetic resonance imaging, were collected. The associations between prognostic factors and overall survival were assessed using Cox regression with least absolute selection and shrinkage operator (LASSO) checked by 500 bootstrap replications. Our prognostic score was calculated by evaluating the most statistically significant factors. Patients were grouped and compared according to our proposed score, Score Index for Radiosurgery in Brain Metastases (SIR) and Basic Score for Brain Metastases (BS-BM). RESULTS: In total, 85 patients were included. We developed the prognostic model based on the most important predictors of overall survival: growth kinetics, i.e. percentage change in brain metastasis size per day between the diagnostic and stereotactic magnetic resonance imaging (hazard ratio per 1% increase, 1.32; 95% confidence interval 1.06-1.65), extracranial oligometastatic diseases (≤5 involvements) (hazard ratio 0.28; 95% confidence interval 0.16-0.52) and the presence of neurological symptoms (hazard ratio 2.99; 95% confidence interval 1.54-5.81). Patients with scores 0, 1, 2 and 3 had a median overall survival of 44.4 (95% confidence interval 9.6-not reached), 20.4 (95% confidence interval 15.6-40.8), 12.0 (95% confidence interval 7.2-22.8) and 2.4 (95% confidence interval 1.2-not reached) years, respectively. The optimism-corrected c-indices for our proposed model, SIR and BS-BM were 0.65, 0.58 and 0.54, respectively. CONCLUSIONS: Brain metastasis growth kinetics is a valuable metric for survival outcomes of SRT. Our model is useful in identifying patients with brain metastasis treated with SRT with different overall survival.

Predictors of glaucoma in patients with uveitis and scleritis.

BACKGROUND: To examine risk factors for development of glaucoma in a large cohort of subjects with uveitis and scleritis. METHODS: Retrospective review of subjects diagnosed with uveitis or scleritis between 2006 and 2019 at Auckland District Health Board. Subjects were excluded if they had glaucoma due to another cause. Main outcome measure was development of glaucoma. Data for local steroid use was not available. RESULTS: 3462 eyes of 2414 subjects were included in the study. Mean follow-up was 5.7 years (total follow-up time 19,897 eye years). Median age was 44.3 years and 1189 (49.3%) were female. Glaucoma developed in 222 eyes (6.3%) during the follow-up. Five-year cumulative risk of glaucoma was 6.2% (CI 5.0-7.5%) for anterior uveitis, 5.4% (CI 3.2-9.0%) for intermediate uveitis, 1.6% (CI 0.4-6.7%) for posterior uveitis, 8.7% (CI 6.5-11.7%) for panuveitis, and 3.2% (CI 1.0-9.5%) for scleritis. Five-year cumulative risk of glaucoma was lowest in HLA-B27 uveitis at 0.9% (CI 0.4-2.1%) and highest in viral uveitis 15.1% (CI 10.1-22.3%), sarcoidosis 9.9% (CI 6.1-15.9%) and tuberculosis 9.7% (CI 5.4-17.0%). On multivariate analysis, risk factors for development of glaucoma were older age at presentation, higher presenting intraocular pressure, chronic inflammation, and cystoid macular oedema. CONCLUSIONS: Glaucoma is a common complication of uveitis and scleritis and was more frequent in older subjects, high presenting IOP, chronic inflammation and those with cystoid macular oedema. Local steroid therapy contributes to this, but is not quantifiable in this study. Targeted screening is required to avoid irreversible progression of glaucomatous optic neuropathy.

A two-ward acute care hospital outbreak of SARS-CoV-2 delta variant including a point-source outbreak associated with the use of a mobile vital signs cart and sub-optimal doffing of personal protective equipment.

BACKGROUND: The arrival of the Delta variant of SARS-CoV-2 was associated with increased transmissibility and illness of greater severity. Reports of nosocomial outbreaks of Delta variant COVID-19 in acute care hospitals have been described but control measures varied widely. AIM: Epidemiological investigation of a linked two-ward COVID-19 Delta variant outbreak was conducted to elucidate its source, risk factors, and control measures. METHODS: Investigations included epidemiologic analysis, detailed case review serial SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing of patients and healthcare workers (HCWs), viral culture, environmental swabbing, HCW-unaware personal protective equipment (PPE) audits, ventilation assessments, and the use of whole genome sequencing (WGS). FINDINGS: This linked two-ward outbreak resulted in 17 patient and 12 HCW cases, despite an 83% vaccination rate. In this setting, suboptimal adherence and compliance to PPE protocols, suboptimal hand hygiene, multi-bedded rooms, and a contaminated vital signs cart with potential fomite or spread via the hands of HCWs were identified as significant risk factors for nosocomial COVID-19 infection. Sudden onset of symptoms, within 72 h, was observed in 79% of all Ward 2 patients, and 93% of all cases (patients and HCWs) on Ward 2 occurred within one incubation period, consistent with a point-source outbreak. RT-PCR assays showed low cycle threshold (CT) values, indicating high viral load from environmental swabs including the vital signs cart. WGS results with ≤3 SNP differences between specimens were observed. CONCLUSION: Outbreaks on both wards settled rapidly, within 3 weeks, using a `back-to-basics' approach without extraordinary measures or changes to standard PPE requirements. Strict adherence to recommended PPE, hand hygiene, education, co-operation from HCWs, including testing and interviews, and additional measures such as limiting movement of patients and staff temporarily were all deemed to have contributed to prompt resolution of the outbreak.

A single-center comparison of our initial experiences in treating penile and urethral cancer with video-endoscopic inguinal lymphadenectomy (VEIL) and later experiences in melanoma cases.

Background: Video-endoscopic inguinal lymphadenectomy (VEIL) is a minimally invasive approach that is increasingly indicated in oncological settings, with mounting evidence for its long-term oncological safety. Objectives: To present our single-center experience of treating penile and urethral cancer with VEIL, as well as its more recent application in melanoma patients. Methods: We prospectively recorded our experiences with VEIL from September 2010 to July 2018, registering the patient primary indication, surgical details, complications, and follow-up. Results: Twenty-nine patients were operated in one (24) or both (5) groins; 18 had penile cancer, 1 had urethral cancer, and 10 had melanoma. A mean 8.62 ± 4.45 lymph nodes were removed using VEIL and of these, an average of 1.00 ± 2.87 were metastatic; 16 patients developed lymphocele and 10 presented some degree of lymphedema; there were no skin or other major complications. The median follow-up was 19.35 months; there were 3 penile cancer patient recurrences in the VEIL-operated side. None of the melanoma patients presented a lymphatic inguinal recurrence. Conclusions: VEIL is a minimally invasive technique which appears to be oncologically safe showing fewer complications than open surgery. However, complications such as lymphorrhea, lymphocele, or lymphedema were not diminished by using VEIL.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of prostate cancer was published in 2020. It was therefore decided, by both the ESMO and the Singapore Society of Oncology (SSO), to convene a special, virtual guidelines meeting in November 2021 to adapt the ESMO 2020 guidelines to take into account the differences associated with the treatment of prostate cancer in Asia. These guidelines represent the consensus opinions reached by experts in the treatment of patients with prostate cancer representing the oncological societies of China (CSCO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter were discussed when appropriate. The aim is to provide guidance for the optimisation and harmonisation of the management of patients with prostate cancer across the different regions of Asia.

Back-translating GWAS findings to animal models reveals a role for Hgfac and Slc39a8 in alcohol and nicotine consumption.

Alcohol and tobacco are the most commonly used addictive substances, with high comorbidity rates between alcohol use disorder and tobacco use disorder. Risk for alcohol and nicotine addiction is highly heritable, and they share common genetic factors. A GWAS in over 1 million individuals has revealed 566 genetic variants in 406 loci associated with multiple stages of alcohol and tobacco use. Three novel genes-SLC39A8, GRK4 and HGFAC-within loci associated with altered alcoholic drinks per week (ADW) or cigarettes per day (CPD) were selected to further study their role in alcohol and tobacco use disorder. The role of these genes was assessed using the two-bottle choice addiction paradigm in transgenic mice for each of the genes. We found significant decreases in chronic alcohol consumption and preference in female Hgfac knockout (KO) mice, and decreased nicotine preference in male Hgfac KO compared with wild-type (WT) mice. Additionally, male Slc39a8 hypomorph mice showed greater overall nicotine preference compared with WT mice, while no differences were detected for Grk4 KO mice in alcohol or nicotine consumption and preference in either sex. Thus, this study implicates Hgfac and Slc39a8 in alcohol and tobacco use in a sex-specific manner.

Complete Genome Sequence of Staphylococcus arlettae AHKW2e, Isolated from a Dog's Paws in Hong Kong.

Staphylococcus arlettae is commonly found on the skin of animals. Here, we describe the complete genome sequence of S. arlettae AHKW2e (2,649,260 bp; GC content, 33.6%), isolated from a dog's paws in Hong Kong, established through hybrid assembly and representing the second complete genome sequence of this species.

Patient acceptance of transvaginal sonographic endometrial thickness assessment compared with hysteroscopy and biopsy for exclusion of endometrial cancer in cases of postmenopausal bleeding.

INTRODUCTION: Available examinations for women with postmenopausal bleeding include transvaginal sonography to measure endometrial thickness (TVS-ET), and invasive endometrial assessment using hysteroscopy/endometrial biopsy. However, selection of the examination method seldom involves consideration of patient preferences. The aim of this study was to examine patient preferences for the method used to investigate postmenopausal bleeding. METHODS: Women were asked to complete an interviewer-administered structured survey before they underwent clinical investigations at a university gynaecology unit from June 2016 to June 2017. Using the standard gamble approach, women were asked to choose between invasive assessment by hysteroscopy/endometrial biopsy (gold standard) or TVS-ET with a risk of missing endometrial cancer. The risk of missing endometrial cancer during TVS-ET was varied until each woman was indifferent to either option. RESULTS: The median detection rate for endometrial cancer required using TVS-ET was 95% (interquartile range=80%-99.9%). In total, 200 women completed the survey, and 77 (38.5%) women required TVS-ET to have a 99.9% detection rate for endometrial cancer. Prior hysteroscopy experience was the only factor that influenced the women's decisions: a significantly higher detection rate was required by this patient group than by patients without previous hysteroscopy experience (P=0.047). CONCLUSION: A substantial proportion of women would accept TVS-ET alone for the investigation of postmenopausal bleeding. In the era of patientcentred care, clinicians should incorporate patient preferences and enable women to make informed choices concerning the management of postmenopausal bleeding.

Human Bone Marrow Stromal Cell Exosomes Ameliorate Periodontitis.

Human bone marrow stromal cell (hBMSC)-derived exosomes are promising therapeutics for inflammatory diseases due to their unique microRNA (miRNA) and protein cargos. Periodontal diseases often present with chronicity and corresponding exuberant inflammation, which leads to loss of tooth support. In this study, we explored whether hBMSC exosomes can affect periodontitis progression. hBMSC exosomes were isolated from cell culture medium through sequential ultracentrifugation. miRNAs and proteins that were enriched in hBMSC exosomes were characterized by RNA sequencing and protein array, respectively. hBMSC exosomes significantly suppressed periodontal keystone pathogen Porphyromonas gingivalis-triggered inflammatory response in macrophages in vitro. Transcriptomic analysis suggested that exosomes exerted their effects through regulating cell metabolism, differentiation, and inflammation resolution. In vivo, weekly exosome injection into the gingival tissues reduced the tissue destruction and immune cell infiltration in rat ligature-induced periodontitis model. Collectively, these findings suggest that hBMSC-derived exosomes can potentially be used as a host modulation agent in the management of periodontitis.

Effects of Tissue Temperature and Injury on ADC during Therapeutic Hypothermia in Newborn Hypoxic-Ischemic Encephalopathy.

BACKGROUND AND PURPOSE: ADC changes are useful in detecting ischemic brain injury, but mechanisms other than tissue pathology may affect the kinetic movement and diffusion of water molecules. We aimed to determine the effects of brain temperature on the corresponding ADC in infants undergoing therapeutic hypothermia. MATERIALS AND METHODS: Brain temperature and ADC values in the basal ganglia, thalamus, cortical GM, and WM were analyzed during and after therapeutic hypothermia. The study cohort was categorized as having no-injury or injury. Among infants without injury, the correlation between ADC values and temperature was analyzed using the Pearson correlation. Intrasubject comparison of ADC changes during and after therapeutic hypothermia were analyzed, excluding patients who had an MR image interval of >5 days to minimize the effects of injury evolution. RESULTS: Thirty-nine infants with hypoxic-ischemic encephalopathy were enrolled (23 no-injury; 16 injury). The median ADC was significantly lower during therapeutic hypothermia (837; interquartile range, 771-928, versus 906; interquartile range, 844-1032 ×10-6mm2/s; P < .001). There was no difference in the ADC between the no-injury and injury groups during therapeutic hypothermia (823; interquartile range, 782-868, versus 842; interquartile range, 770-1008 ×10-6mm2/s; P = .4). In the no-injury group, in which ADC is presumed least affected by the evolution of injury, the median ADC was significantly lower during therapeutic hypothermia (826; interquartile range, 771-866, versus 897; interquartile range, 846-936 ×10-6mm2/s; P < .001). There was a moderate correlation between temperature and ADC in the no-injury group (during therapeutic hypothermia: Spearman ρ, 0.48; P < .001; after therapeutic hypothermia: ρ, 0.4; P < .001). CONCLUSIONS: Aside from brain injury, reduced tissue temperature may also contribute to diffusion restriction on MR imaging in infants undergoing therapeutic hypothermia.

The ethics of a work strike.

No abstract provided.