Preliminary Analysis on Efficacy of Ritonavir-Boosted Nirmatrelvir on Disease Progression among High-Risk Hospitalised Covid-19 Patients: A Retrospective Case-Control Study

Intro: Ritonavir-boosted nirmatrelvir has shown efficacy in reducing the rate of hospitalisation and 28-day mortality among unvaccinated populations with COVID-19. The role of Ritonavir-boosted nirmatrelvir among high risk hospitalised COVID-19 patients remained uncertain. Our study aimed to assess the efficacy of Ritonavir-boosted nirmatrelvir in reducing disease progression among high-risk hospitalised COVID-19 patients. Method(s): This is a retrospective case-control study (ratio 1:1) among hospitalised COVID-19 patients with mild-moderate severity, within 5 days of illness, and had at least one risk factor for severe disease. Treatment group (case) received Nirmatrelvir and Ritonavir twice daily for 5 days. Historical controls before the introduction of Ritonavir-boosted nirmatrelvir were obtained in the same hospital. Both groups received standard of care. The primary outcome was rate of clinical progression from non-hypoxia to hypoxia. Finding(s): 200 patients from January to July 2022 were included in the analysis, where 108 (54%) were male, mean age of 63.7 (SD 17.1), 95% completed primary COVID-19 vaccination and 91 (45.5%) had evidence of pneumonia (moderate severity). Most common comorbids were hypertension(65%), diabetes mellitus(40%) and overweight(36%). Clinical progression to hypoxia was significantly lower in the treatment group (4%) compared to the control group (18%) (OR=0.190, 95% CI: 0.0618 - 0.583). Comparing case to control, the rates of ICU admission were 1% vs 3%, mechanical ventilation 0% vs 2% and inpatient mortality 2% vs 2%. 97% patients completed Ritonavir-boosted nirmatrelvir in the treatment group. Conclusion(s): Among high-risk hospitalised COVID-19 patients who received ritonavir-boosted nirmatrevir, they were 81% less likely to experience desaturation. Ritonavir-boosted Nirmatrelvir remains beneficial among highly vaccinated populations during the Omicron wave in COVID-19 pandemic.Copyright © 2023

A COMPARISON OF PULSE METHYLPREDNISOLONE TO LOW-DOSE METHYLPREDNISOLONE IN CRITICALLY-ILL PATIENTS WITH SARS-COV-2 PNEUMONIA: RETROSPECTIVE, OBSERVATIONAL STUDY

Intro The RECOVERY trial showed evidence that dexamethasone given at moderate doses for a short period of time reduced mortality in comparison to standard of care in hospitalised COVID-19 patients. However, there is no evidence to demonstrate whether higher doses of steroid may improve or worsen the outcomes. This study compares the effectiveness of low-dose- methylprednisolone to pulse-methylprednisolone among the critically-ill COVID- 19 patients. Methods This is a retrospective observational study among critically-ill COVID- 19 patients whom were admitted to intensive care unit Hospital Pulau Pinang from August 2020 until February 2021. We collected the data of patients that received either methylprednisolone dose more than 2mg/kg/day or methylprednisolone dose equal or less than 2mg/kg/day. Both groups received standard of care. The primary outcome is all-cause mortality within 30 days from symptoms onset. The secondary outcomes are duration of mechanical ventilation, length of ICU stays and rate of complications such as acute kidney injury, sepsis, bleeding tendency and diabetic ketoacidosis. Findings A total of 100 patients were included in the analysis, whom 64% were male, mean age of 56.6 (SD 13.4) and 53% have at least one comorbidity. The survival analysis revealed that 30 days survival rate were 91.2% in the low-dose- methylprednisolone group and 81.8% in the pulse-methylprednisolone group (p = 0.226) and showed no significant differences after adjustment for covariates such as the doses of methylprednisolone, gender, requirement of mechanical ventilation and absence or presence of comorbidity. However, age more than 60 years old does increase the risk of mortality (p value 0.018). Comparing the low- dose-methylprednisolone to pulse-methylprednisolone, the duration of mechanical ventilation were 15.7 days vs 13.8 days (p 0.572), length of ICU stay were 14.9 days vs 15 days (p 0.875) and rate of complications were not significantly differences. Conclusion The use of pulse-methylprednisolone in critically-ill COVID-19 patients does not improve the survival rate.

Pedicled Infrahyoid Flap Reconstruction for Head and Neck Cancers - an Early Experience in Hong Kong

Aim: Head and neck cancer surgeries often result in defects requiring reconstruction. When compared to free flaps, local flaps are associated with shorter operation time, which is preferred in patients with comorbidities and during COVID pandemic with local attrition of anesthetists. Submental flap has a theoretical risk of compromising oncological outcome in level I neck dissection. Alternatively, infrahyoid flap harvest is confined to the central compartment, which is a rare region for lymph node spread. To our knowledge, infrahyoid flap reconstruction has not been reported in Hong Kong. This study aims to evaluate the surgical outcome in patients underwent infrahyoid flap reconstruction at our unit. Method(s): 6 patients (median age 67) who had received infrahyoid flap reconstruction from May2018 to May2022 were retrieved. The primary lesion sites included tongue (4 patients), concomitant retromolar and buccal mucosa (1 patient) and submandibular region (1 patient). The blood supply, dimension of flap skin paddle, flap survival and complications were evaluated. Result(s): The dimension of flap skin paddle was 25 cm2 (range 20- 28). Blood supply was all via superior thyroid vessels. 100% flap survival was achieved in 5 out of 6 patients. Only one patient developed superficial skin necrosis which was treated conservatively. One patient had mild dehiscence of donor site. One patient suffered from disease recurrence and succumbed one year after operation. The other patients are alive up to today. Conclusion(s): In our experience, pedicled infrahyoid flap is a safe and reliable procedure for reconstruction of medium-sized defects after head and neck cancer surgeries.

Hong Kong poison information centre: Annual report 2020

Background: The Hong Kong Poison Information Centre has provided consultation service to healthcare professionals and collected epidemiological data on poisoning in Hong Kong since 2005. Objective(s): To analyse and report the poisoning data of Hong Kong Poison Information Centre in 2020 during the COVID-19 pandemic. Method(s): A retrospective review of all poisoning cases recorded in the Poison Information and Clinical Management System of Hong Kong Poison Information Centre in 2020. Result(s): A total of 3633 poisoning cases were analysed. Compared to 2019 (pre-COVID era), there was a reduction of ~10% of total poisoning cases recorded (383 cases), with a majority (> 90%) of reduction from poisoning cases with no clinical effect (353 cases). A greater proportion of reduction was observed among the children (0-12 years), patients with general unintentional poisoning, poisoning due to therapeutic error and food poisoning. An increased number of cases was noted from abusive use, adverse herb/proprietary Chinese medicine reaction and poisoning related to household bleaches. Teenage (13-19 years) poisoning seemed to be unaffected by the COVID-19 pandemic and the previously observed increasing trend continued (up to 11.8% of total poisoning cases this year). Despite a total reduction in poisoning cases recorded, the number of deaths increased by 37% from 35 in 2019 to 48 in 2020 (mortality rate 1.5%). A total of seven interesting cases were discussed. Conclusion(s): This 15th annual report provides updated epidemiological information on poisoning patterns in Hong Kong during the COVID-19 pandemic. It also highlighted important changes and possible effects of the COVID-19 pandemic on poisoning in Hong Kong in comparison with our previous reports. Copyright © The Author(s) 2022.

PATIENT WITH COVID-19 RELATED COLLAPSING GLOMERULOPATHY

We present a case of Collapsing Glomerulopathy (CG) in a patient with Coronavirus disease 2019 (COVID-19). A 53-year-old African American female with history of diabetes mellitus type II and hypertension presented with 7 days of fevers, cough, worsening dyspnea, diarrhea and oliguria. She was found to have severe AKI with serum creatinine of 6.2 mg/dL, up from a baseline of 0.8mg/dL, and nephrotic-range proteinuria (>2000 mg/dL), hematuria, pyuria, hypoalbuminemia, elevated LDH, leukocytosis, metabolic acidosis, and elevated inflammatory markers. COVID-19 PCR was positive;an extensive serologic work up to explain AKI was negative. Renal imaging revealed bilaterally increased echogenicity with normal arterial and venous Doppler flow, nonspecific left perinephric stranding concerning for pyelonephritis, and an obstructing 3 mm calculus with right hydronephrosis. Fluid resuscitation, empiric antibiotics, and dexamethasone were initiated. Scant urine output and worsening creatinine (peak of 9.3 mg/dL) continued, and hemodialysis was started on hospital day 2. Kidney biopsy on hospital day 10 showed podocyte hyperplasia and "collapse" of the underlying capillary lumens, and CG was diagnosed. The patient's symptoms improved after dialysis and steroid treatment. She was discharged requiring dialysis, now twice weekly, and renal function monitoring. Limited data on COVID-19-associated renal dysfunction exist. Hemodynamic instability may cause AKI in patients with COVID-19;however, this does not explain the severe proteinuria and hematuria sometimes observed. Both proteinuria and AKI are associated with increased mortality in these patients. Though electron microscopy did not prove the presence of COVID-19 in podocytes in our patient, possible mechanisms include direct viral toxicity on tubular cells that also harbor angiotensin-converting enzyme 2 or cytokine-mediated tubular damage. Treatment of CG secondary to infections includes antimicrobials and non-immunosuppressive therapy with renin-angiotensin-aldosterone blockers and statins. Steroid use is controversial. Currently, there is no proven treatment for COVID-19 infection, but it is reasonable to initiate steroids in these patients who have AKI and glomerular injury.

PROSTATE SBRT BOOST RADIOTHERAPY (PBS TRIAL): A RANDOMIZED PHASE II TRIAL OF SBRT VERSUS CONVENTIONALLY-FRACTIONATED RADIOTHERAPY BOOST FOLLOWING PELVIC RADIOTHERAPY IN HIGH-RISK PROSTATE CANCER

Purpose: Curative therapy for high-risk prostate cancer (HR-PrCa) includes androgen deprivation therapy (ADT) and a long course of pelvic and prostate boost radiotherapy (RT), which adds a significant burden on patients. Several non-randomized studies in the past 10 years suggested that 3-fraction Stereotactic body radiotherapy (SBRT) regimens provide promising rates of disease control and may be able to replace the conventionally fractionated (CF) External Beam RT (EBRT) boost, improving significantly the convenience of RT treatment. To address the deficit in randomized data, we opened a regional Prostate Boost irradiation with SBRT (PBS) randomized controlled trial at Juravinski and Walker Family Cancer Centres, in 2019. Materials and Methods: Men with localized HR-PrCa receive ADT for a total duration of three years, pelvic CF-EBRT (45-46Gy in 23-25 fractions) and are randomized to either CF-EBRT boost (32-33Gy in 15-16 fractions) or SBRT boost (19.5-21Gy in 3 fractions) to prostate and seminal vesicles. All patients receive fiducial (gold seed) implants and planning margins compatible with SBRT, regardless of treatment arm. SBRT boost is delivered with a Cyberknife unit at the Juravinski Cancer Centre or with LINACbased VoluMetric Arc Therapy (VMAT) at the Walker Family Cancer Centre) and, therefore, cases are stratified per treatment centre. Primary endpoint is quality of life (based on EPIC), and secondary endpoints include treatment-related toxicity and biochemical control. Biospecimens are collected for future analysis. Salient methodological differences between our study and a 2-fraction randomized phase II trial reported very recently (HYPO-PROST, Nov.2020) include fiducial-guided SBRT-based boost treatment and higher dose weekly fractions of boost RT. Results: We have completed nearly 50% of our target accrual of 100 patients. The mean age at enrollment was 73 (IQR 71-78) with a mean PSA of 12.7, IPSS score of 8.4 (IQR 4-13). 62.5% of the accrued patients had Gleason scores of 8 or higher, 23% had a PSA of 20 or higher, and 10% had findings consistent with cT3a or higher on DRE. Interim safety analysis of this trial will be completed in August 2021 and presented. To date, no Grade 3 or higher toxicity has been reported in either treatment arm. No biochemical failure has been noted. Conclusions: Despite interruption due to the COVID-19 pandemic, accrual on this study is progressing well with no unexpected toxicity or treatment failures detected. This study provides a formal evaluation of SBRT as a boost RT technique in HR-PrCa in a randomized setting. It is an important endeavour given the potential to develop a safe and convenient treatment for HR-PrCa.

Space-Time Cluster's Detection and Geographical Weighted Regression Analysis of COVID-19 Mortality on Texas Counties.

As COVID-19 run rampant in high-density housing sites, it is important to use real-time data in tracking the virus mobility. Emerging cluster detection analysis is a precise way of blunting the spread of COVID-19 as quickly as possible and save lives. To track compliable mobility of COVID-19 on a spatial-temporal scale, this research appropriately analyzed the disparities between spatial-temporal clusters, expectation maximization clustering (EM), and hierarchical clustering (HC) analysis on Texas county-level. Then, based on the outcome of clustering analysis, the sensitive counties are Cottle, Stonewall, Bexar, Tarrant, Dallas, Harris, Jim hogg, and Real, corresponding to Southeast Texas analysis in Geographically Weighted Regression (GWR) modeling. The sensitive period took place in the last two quarters in 2020 and the first quarter in 2021. We explored PostSQL application to portray tracking Covid-19 trajectory. We captured 14 social, economic, and environmental impact's indices to perform principal component analysis (PCA) to reduce dimensionality and minimize multicollinearity. By using the PCA, we extracted five factors related to mortality of COVID-19, involved population and hospitalization, adult population, natural supply, economic condition, air quality or medical care. We established the GWR model to seek the sensitive factors. The result shows that adult population, economic condition, air quality, and medical care are the sensitive factors. Those factors also triggered high increase of COVID-19 mortality. This research provides geographical understanding and solution of controlling COVID-19, reference of implementing geographically targeted ways to track virus mobility, and satisfy for the need of emergency operations plan (EOP).