Intravenous Tocilizumab versus Standard of Care in the Treatment of Severe and Critical COVID-19-related Pneumonia: A Single-center, Double-blind, Placebo-controlled, Phase 3 Trial.

Background: Severe and critical COVID-19 disease is characterized by hyperinflammation involving pro-inflammatory cytokines, particularly IL-6. Tocilizumab is a monoclonal antibody that blocks IL-6 receptors. Objectives: This study evaluated the efficacy of tocilizumab in Filipino patients with severe to critical COVID-19 disease. Methods: This phase 3 randomized double-blind trial, included patients hospitalized for severe or critical COVID-19 in a 1:1 ratio to receive either tocilizumab plus local standard of care or placebo plus standard of care. Patients were eligible for a repeat IV infusion within 24-48 hours if they deteriorated or did not improve. Treatment success or clinical improvement was defined as at least two categories of improvement from baseline in the WHO 7-point Ordinal Scale of patient status, in an intention-to-treat manner. Results: Forty-nine (49) patients were randomized in the tocilizumab arm and 49 in the placebo arm. There was no significant difference in age, comorbidities, COVID-19 severity, need for mechanical ventilation, presence of acute respiratory distress syndrome, or biomarker levels between groups. Use of adjunctive therapy was similar between groups, with corticosteroid used in 91.8% in tocilizumab group and 81.6% in the placebo group, while remdesivir was used in 98% of participants in both groups.There was no significant difference between groups in terms of treatment success in both the intention-to-treat analysis (relative risk=1.05, 95% CI: 0.85-1.30) and per-protocol analysis (relative risk=0.98, 95% CI: 0.80 to 1.21). There was no significant difference in time to improvement of at least two categories relative to baseline on the 7-point Ordinal Scale of clinical status. Conclusion: The use of tocilizumab on top of standard of care in the management of patients with severe to critical COVID-19 did not result in significant improvement as defined by the WHO 7-point Ordinal Scale of patient status, nor in significant improvement in incidence of mechanical ventilation, incidence of ICU admission, length of ICU stay, and mortality rate.

Qualities of Role Models of Internal Medicine Residents in a Tertiary National University Hospital in the Philippines.

Background: Teachers in medicine do not only teach scientific facts about health and disease to their learners but they are also looked up to as role models. Little is known about the qualities of consultant-faculty members who are regarded as role models by Filipino internal medicine residents. Objective: This study aimed to determine the reasons why consultant-faculty members are considered role models by Filipino internal medicine residents. Methods: A cross-sectional survey was conducted among internal medicine residents at a tertiary national university hospital in the Philippines. Participants were asked to give the reasons for citing consultant-faculty members who they consider as role models. Results: There were 81 residents who participated (93% response rate) who gave a total of 332 qualities as reasons for citing them as role models. The most commonly cited quality category was those of personal qualities (35.84% of all responses). This was followed by academic, clinical, teaching, leadership and research qualities. Physical qualities were the least cited (0.30% of all responses). Across the four batches of residents, personal qualities were consistently cited the most number of times, while physical qualities were consistently cited the least. Conclusion: Filipino internal medicine residents identified personal qualities as the most frequent reason for considering their consultant-faculty as role models.

Evaluation of Fine Needle Biopsy (FNB) for Endoscopic Ultrasound (EUS)-guided Tissue Acquisition of Pancreatic Masses to Negate the Need for Rapid On-site Evaluation: A Randomized Control Trial.

Background and Objectives: The benefits of rapid on-site evaluation (ROSE) of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid masses have not been convincingly shown in large, randomized trials. New equipment using EUS-guided fine needle biopsy (FNB) allows for more material to be acquired that may obviate the need for ROSE. This study aimed to evaluate if EUS-FNB without ROSE was non-inferior to EUS-FNA with ROSE in solid pancreatic masses (SPMs). Methods: Patients with SPMs requiring tissue sampling were randomly assigned to undergo either EUS-FNA with ROSE or EUS-FNB without ROSE. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy and secondary endpoints were specimen quality, complication rates, and procedure time. Results: Seventy-eight patients were randomized and analyzed (39 EUS-FNA with ROSE and 39 EUS-FNB without ROSE). Non-significantly different diagnostic accuracies were noted in both groups (97% with ROSE and 100% without ROSE, P < 0.371). The bloodiness of histologic samples and complication rates were not significantly different between groups. A significantly shorter mean sampling procedural time was noted for EUS-FNB over EUS-FNA with ROSE (30.4 ± 10.4 vs 35.8 ± 9.8 minutes, P < .02). Conclusions: EUS-FNB demonstrated equal diagnostic accuracy with shorter procedure times in evaluating SPMs compared to EUS-FNA with ROSE. These new-generation FNB needles may obviate the need for ROSE.

Evaluation of Fine Needle Biopsy (FNB) for Endoscopic Ultrasound (EUS)-guided tissue acquisition of pancreatic masses to negate the need for rapid on-site evaluation: A randomized control trial

Background and Objectives@#The benefits of rapid on-site evaluation (ROSE) of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of solid masses have not been convincingly shown in large, randomized trials. New equipment using EUS-guided fine needle biopsy (FNB) allows for more material to be acquired that may obviate the need for ROSE. This study aimed to evaluate if EUS-FNB without ROSE was non-inferior to EUS-FNA with ROSE in solid pancreatic masses (SPMs). @*Methods@#Patients with SPMs requiring tissue sampling were randomly assigned to undergo either EUS-FNA with ROSE or EUS-FNB without ROSE. The touch-imprint cytology technique was used to perform ROSE. The primary endpoint was diagnostic accuracy and secondary endpoints were specimen quality, complication rates, and procedure time. @*Results@#Seventy-eight patients were randomized and analyzed (39 EUS-FNA with ROSE and 39 EUS-FNB without ROSE). Non-significantly different diagnostic accuracies were noted in both groups (97% with ROSE and 100% without ROSE, P < 0.371). The bloodiness of histologic samples and complication rates were not significantly different between groups. A significantly shorter mean sampling procedural time was noted for EUS-FNB over EUS-FNA with ROSE (30.4 ± 10.4 vs 35.8 ± 9.8 minutes, P < .02). @*Conclusions@#EUS-FNB demonstrated equal diagnostic accuracy with shorter procedure times in evaluating SPMs compared to EUS-FNA with ROSE. These new-generation FNB needles may obviate the need for ROSE.

Intravenous tocilizumab versus standard of care in the treatment of severe and critical COVID-19-related pneumonia: A single center, double-blind, placebo controlled, phase 3 trial

Background@#Severe and critical COVID-19 disease is characterized by hyperinflammation involving pro-inflammatory cytokines, particularly IL-6. Tocilizumab is a monoclonal antibody that blocks IL-6 receptors. @*Objectives@#This study evaluated the efficacy of tocilizumab in Filipino patients with severe to critical COVID-19 disease. @*Methods@#This phase 3 randomized double-blind trial, included patients hospitalized for severe or critical COVID-19 in a 1:1 ratio to receive either tocilizumab plus local standard of care or placebo plus standard of care. Patients were eligible for a repeat IV infusion within 24-48 hours if they deteriorated or did not improve. Treatment success or clinical improvement was defined as at least two categories of improvement from baseline in the WHO 7-point Ordinal Scale of patient status, in an intention-to-treat manner. @*Results@#Forty-nine (49) patients were randomized in the tocilizumab arm and 49 in the placebo arm. There was no significant difference in age, comorbidities, COVID-19 severity, need for mechanical ventilation, presence of acute respiratory distress syndrome, or biomarker levels between groups. Use of adjunctive therapy was similar between groups, with corticosteroid used in 91.8% in tocilizumab group and 81.6% in the placebo group, while remdesivir was used in 98% of participants in both groups. There was no significant difference between groups in terms of treatment success in both the intention-to-treat analysis (relative risk=1.05, 95% CI: 0.85-1.30) and per-protocol analysis (relative risk=0.98, 95% CI: 0.80 to 1.21). There was no significant difference in time to improvement of at least two categories relative to baseline on the 7-point Ordinal Scale of clinical status. @*Conclusion@#The use of tocilizumab on top of standard of care in the management of patients with severe to critical COVID-19 did not result in significant improvement as defined by the WHO 7-point Ordinal Scale of patient status, nor in significant improvement in incidence of mechanical ventilation, incidence of ICU admission, length of ICU stay, and mortality rate.

Adenoma detection rate and polyp detection rate among gastroenterology fellows and consultants in a tertiary hospital in the Philippines: A cross-sectional study

Background and Objective@#Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the fourth leading cause of cancer mortality worldwide. Likewise in the Philippines, the prevalence of CRC has shown to be increasing. Colonoscopy, a screening procedure for CRC, has parameters to gauge quality of detection. One of which is the Adenoma Detection Rate (ADR). Higher ADR has been linked to improved cancer detection. This study aimed to determine the ADR and Polyp Detection Rate (PDR) among Gastroenterology practitioners in a tertiary government university hospital in the Philippines, estimate ADR from PDR, and identify factors associated with ADR.@*Methods@#An analytical, cross-sectional study among patients who underwent colonoscopy for the years 2021 and the first half of 2022 at the Central Endoscopy Unit (CENDU) of the Philippine General Hospital. Demographic data of fellows and consultants were collected through an online form, while those from patients were obtained from electronic records. Colonoscopy details and histopathology results were accessed through the hospital’s Open Medical Record System (MRS). ADR, PDR, and estimated ADR were computed using established formulas. To evaluate the strength of the relationship between the estimated and actual ADR, Pearson’s correlation coefficient was used. Chi-square analysis, Mann-Whitney U test, and Kruskal-Wallis H test were performed to identify the factors that might influence the ADR. A cut-off of p < 0.05 was considered statistically significant.@*Results@#The total computed ADR of consultants and fellows combined is 22%. The difference between the ADRs of Gastroenterology consultants and Fellows-in-Training is statistically significant at 31.6% and 18.7%, respectively (p= 0.017). The total Polyp Detection Rate is 57.6% while the weighted group average Adenoma to Polyp Detection Rate Quotient (APDRQ) is 0.4085 or 40.85%. The estimated ADR has a moderate degree of correlation with the actual ADR when an outlier was excluded (r=0.521 (95% CI, 0.072-0.795, p=0.0266). Significant factors related to ADR include endoscopists’ years of practice (p=0.020), number of colonoscopies done (p=0.031), and patient tobacco use (p=0.014).@*Conclusion@#The overall ADR among consultants and fellows is at par with the standard guidelines. A moderate degree of correlation exists between actual and estimated ADR when an outlier is excluded; however, more studies are needed to determine the APDRQ in the wider local setting. Longer years in practice, total number of colonoscopies performed, and patient tobacco use are associated with increased ADR.

Clostridioides difficile infection following procalcitonin-guided antibiotic therapy for COVID-19

@#We present a case of a 50-year-old man with chronic kidney disease (CKD) presenting with acute diarrhea and fever. He was admitted a month prior for COVID-19, where he received antibiotics for radiographic findings of pneumonia and elevated procalcitonin. In the emergency department, his stool sample tested positive for Clostridioides difficile antigen and toxin. He was given oral vancomycin and intravenous metronidazole for fulminant C. difficile infection and was discharged with resolution of symptoms. This case documents a potential risk associated with routine antibiotic use during the pandemic and the pitfalls in interpreting procalcitonin, especially in patients with COVID-19 and CKD.

Metformin extended-release versus metformin immediate-release for adults with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials.

AIM: To compare the efficacy and tolerability of metformin extended-release (MXR) and the conventional metformin immediate-release (MIR) formulations in adults with type 2 diabetes mellitus (T2DM) METHODS: PubMed, the Cochrane Library, ClinicalTrials.gov and other sources were searched until 19 March 2021 for randomized controlled trials (RCTs) that compared equal daily doses of MXR and MIR in adults with T2DM. Random-effects model meta-analysis was performed to obtain pooled mean difference (MD) of change from baseline for continuous outcomes and risk ratio (RR) for dichotomous outcomes. Primary outcomes considered were HbA1c and key gastrointestinal (GI) symptoms (abdominal discomfort or pain, diarrhea, dyspepsia, and nausea & vomiting). RESULTS: Nine RCTs that randomized a total of 2609 adults revealed that MIR was statistically associated with better HbA1c lowering (MD 0.09% [95% confidence interval or CI, 0.01%, 0.17%]), MXR only reduced dyspepsia (RR 0.58 [95% CI, 0.34, 0.98]), and both formulations were associated with similar cumulative incidence of other key GI symptoms. CONCLUSIONS: MXR was associated with statistically worse but likely clinically similar HbA1c lowering and minimal improvement of GI intolerance compared to MIR. Protocol Registration: PROSPERO (CRD42019148008).

Palmar fasciitis and arthritis syndrome associated with metastatic ovarian cancer: a paraneoplastic syndrome.

Palmar fasciitis and polyarthritis syndrome (PFPA) is an uncommon syndrome that affects predominantly elderly women and characterized by symmetrical polyarthritis followed by flexioncontracture of the hands. It is usually associated with a metastatic malignant neoplasm, and therefore implies a poor prognosis. We report a case of a 54-year old woman presented with palmar fasciitis and polyarthritis six months before the diagnosis of a metastatic adenocarcinoma of the ovary. Surgical excision of the tumor and adjuvant chemotherapy caused remission of the polyarthritis.

Prevalence of angiotensin-converting enzyme gene insertion-deletion polymorphism in patients with primary knee osteoarthritis.

OBJECTIVE: Angiotensin converting enzyme (ACE) plays an important role in a number of inflammatory and immune related disorders. This study was undertaken to investigate an association between Angiotensin converting enzyme (ACE) gene insertion- deletion (I/D) polymorphism and primary knee osteoarthritis (OA) in Kuwait and to explore a correlation between clinical subgroups of OA and ACE I/D polymorphism genotypes. PATIENTS AND METHODS: The prevalence of ACE gene I/D polymorphism was determined in 115 patients with primary knee OA and 111 ethnically matched healthy controls by using polymerase chain reaction (PCR) of the genomic DNA. The association of ACE gene I/D polymorphism genotypes was also studied with age of disease onset, function and radiological grading. RESULTS: No significant difference was detected in the frequency of ACE gene I/D polymorphism genotypes and alleles between knee OA patients and the controls. The frequency of ACE gene polymorphism genotypes was also studied in subgroups on the basis of clinical parameters of age of onset of disease, function and radiological grading and no significant difference was detected between subgroups of OA patients and the controls. This is in sharp contrast to a previous report from Korea in which a significant association has been reported between ACE gene polymorphism and knee OA. CONCLUSION: This study did not find an association between ACE gene I/D polymorphism genotypes in Kuwaiti patients with primary knee osteoarthritis and the onset or severity of the disease, which is very different from Korean knee OA patients in which an association has been reported.

Angiotensin-converting enzyme gene polymorphism in Kuwaiti patients with systemic lupus erythematosus.

OBJECTIVE: To investigate the frequency of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism genotypes in patients with systemic lupus erythematosus (SLE), and to study the correlation between I/D polymorphism of the ACE gene and the clinical manifestations of SLE, especially vascular involvement, lupus nephritis and disease severity. METHODS: The frequency of ACE gene I/D polymorphism genotypes was determined in 92 patients with SLE from Kuwait, and compared to that in 100 ethnically matched healthy controls using the polymerase chain reaction. RESULTS: The distribution of ACE I/D polymorphism and allele frequencies in SLE patients was not significantly different from controls. Further analyses of SLE patients showed that there was a significant association between DD genotype and Raynaud's phenomenon (p=0.008, odd ratio=5.4, 95% confidence interval: 1.6-18.6). However, there was no significant association between the ACE genotype and lupus nephritis or disease severity. CONCLUSION: No difference was found between the distribution of the ACE genotype in SLE patients and the general pop-ulation in Kuwait. However, the presence of the DD genotype may confer susceptibility to the development of vascular morbidity.

Secondary hypertrophic osteoarthropathy: new insights on pathogenesis and management.

Hypertrophic osteoarthropathy is a syndrome that includes finger clubbing, periostitis with new subperiosteal bone formation of long bones and arthritis. It is often related to an intrathoracic neoplasms or chronic infections; hence called hypertrophic pulmonary osteoarthropathy. A primary or idiopathic form, also known as Pachydermoperiostosis, also exist. It is commonly seen in children and young adults and has not been found associated with underlying disease. Platelet derived growth factors has been recently recognized to have a key role in the pathogenesis of this disorder. Hypertrophic osteoarthropathy may cause disabling symptoms. Cure of neoplasia may result in regression of the hypertrophic osteoarthropathy.