Emerging therapeutics in the management of COVID-19

The severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) pandemic has placed a tremendous burden on healthcare systems globally. Therapeutics for treatment of the virus are extremely inconsistent due to the lack of time evaluating drug efficacy in clinical trials. Currently, there is a deficiency of published literature that comprehensively discusses all therapeutics being considered for the treatment of COVID-19. A review of the literature was performed for articles related to therapeutics and clinical trials in the context of the current COVID-19 pandemic. We used PubMed, Google Scholar, and Clinicaltrials.gov to search for articles relative to the topic of interest. We used the following keywords: “COVID-19”, “therapeutics”, “clinical trials”, “treatment”, “FDA”, “ICU”, “mortality”, and “management”. In addition, searches through the references of retrieved articles was also performed. In this paper, we have elaborated on the therapeutic strategies that have been hypothesized or trialed to-date, the mechanism of action of each therapeutic, the clinical trials finished or in-process that support the use of each therapeutic, and the adverse effects associated with each therapeutic. Currently, there is no treatment that has been proven to provide significant benefit in reducing morbidity and mortality. There are many clinical trials for numerous different therapeutic agents currently underway. By looking back and measuring successful strategies from previous pandemics in addition to carrying out ongoing research, we provide ourselves with the greatest opportunity to find treatments that are beneficial.     

Thelohanellus niloticus sp. nov. (Myxozoa: Myxosporea), a parasite of the Nile carp Labeo niloticus from the River Nile, Egypt

In the present study, the morphology and morphometric characterization of Thelohanellus niloticus sp. nov., a new myxozoan belonging to genus Thelohanellus Kudo, 1933 (Myxosporea, Bivalvulida) infecting the gills of Labeo niloticus (Osteichthyes, Cyprinidae), were described for the first time from the River Nile at El-Minia Governorate, Egypt. Forty-one out of 78 (52.6 %) of the examined fish were infected. The infection was observed as irregular, milky whitish, cyst-like plasmodia (up to 0.8 mm in diameter) attached to the gill filaments of the host fish. These plasmodia contained tear-shaped myxospores with slightly tapering anterior and rounded posterior ends. Each spore has a single pyriform polar capsule. Spores measured about 23.3?±?0.3 (20.4–27.1) μm long and 13.4?±?0.4 (11.5–14.2) μm wide. The polar capsule was 11.7?±?0.3 (9.2–12.5) μm long and 4.7?±?0.3 (3.5–6.2) μm wide, containing a polar filament coiled perpendicular to the longitudinal axis of the spore body making eight turns. Occasionally, an oblong, irregular-shaped mass of protoplasm with a slightly oval nucleus (1.4 μm in diameter) and a small iodinophilous vacuole measured 0.85?±?0.2 μm (0.73–1.2 μm) were observed in the spore. Due to the lack of the second polar capsule characterizing Myxobolus sp., the present parasite is placed within the genus Thelohanellus. Based on morphological differences (compared with other members of Thelohanellus Kudo, 1933) and the host specificity, this species is described as a new one of the genus Thelohanellus recorded for the first time in Egypt.     

Individual Composition of Human Leukocyte Antigens and Periodontopathogens in the Background of Periodontitis

Background : Human leukocyte antigens (HLAs) are a basic precondition to induce the immune response to pathogens. Therefore, this study evaluates associations among periodontitis, five key periodontopathic bacteria, and HLAs to test their impact together with additional risk factors in multivariate analyses. Methods: Eighty‐five patients with generalized aggressive periodontitis (GAgP) and 71 patients with generalized chronic periodontitis (CP) were compared to 88 periodontitis‐free controls. HLA Class I and II typing was performed by polymerase chain reaction (PCR) with sequence‐specific primers. Subgingival plaque specimens were detected by PCR with sequence‐specific oligonucleotides. Risk‐factor analyses were performed with respect to the cofactors age, sex, smoking, and plaque level by logistic regression. Results: In the total patient group (GAgP + CP), the adjusted odds ratio (OR) of periodontitis was decreased in cases who were carriers of HLA‐B*57 (OR = 0.259, 95% confidence interval [CI] = 0.086 to 0.782), HLA‐DQB1*08 (OR = 0.404, 95% CI = 0.187 to 0.871), or the combination HLA‐DRB1*04;DRB4*;DQB1*0302 (OR = 0.407, 95% CI = 0.185 to 0.895). Moreover, individuals who expressed HLA‐DRB1*04 (OR = 0.36, 95% CI = 0.148 to 0.886) or HLA‐DRB1*04;DRB4*;DQB1*0302 (OR = 0.29, 95% CI = 0.092 to 0.884) had a decreased colonization risk with Aggregatibacter actinomycetemcomitans. Conclusions: Certain HLA markers were negatively associated to the manifestation of a generalized periodontitis and/or the individual colonization of A. actinomycetemcomitans. The underlying mechanisms have to be investigated in future studies.     

Recurrent right sublingual ranula,concomitant with ipsilateral submandibular salivary gland aplasia

INTRODUCTIONOral ranula is a retention cyst that arises from the salivary gland with recurrence rate of up to 25% after complete excision of ranula and up to 2% in case of complete excision of ranula and sublingual gland.Major salivary gland aplasia is a rare finding that is usually associated with other developmental anomalies.PRESENTATION OF CASEWe report a 15-year-old female patient presented with recurrent intraoral cystic swelling that was documented to be sublingual ranula. CT scan revealed also the absence of right submandibular salivary gland with persistence of its Whartons duct. This combination has never been reported previously.DISCUSSIONThe combination of recurrent sublingual ranula associated with aplasia of ipsilateral submandibular salivary gland and persistence of Whartons duct has never been reported before in the literature, a finding that may provide the base for future research.CONCLUSIONFurther research may prove similar associations between oral ranula and salivary gland aplasia, which may have clinical implications on diagnostic and management plan decisions.     

Comparative value of coronary artery calcium and multiple blood biomarkers for prognostication of cardiovascular events

The value of coronary artery calcium (CAC) scoring versus multiple biomarkers in increasing risk prediction for cardiovascular disease (CVD) remains unknown. The study group consisted of 1,286 asymptomatic participants (mean ± SD 59 ± 8 years old) with no known coronary heart disease. Mean follow-up time was 4.1 ± 0.4 years with the primary outcome of combined CVD (cardiac death, myocardial infarction, stroke, and late target vessel revascularization). CAC was calculated by the method of Agatston. Biomarkers measured were C-reactive protein, interleukin-6, myeloperoxidase, B-type natriuretic peptide, and plasminogen activator-1. During follow-up 35 participants developed CVD events including cardiac deaths (6%), myocardial infarction (23%), strokes (17%), and late revascularizations (54%). In Cox proportional-hazards models adjusted for Framingham Risk Score (FRS), presence of log CAC beyond FRS was associated with increased hazards for CVD events (hazard ratio 1.7, 95% confidence interval [CI] 1.4 to 2.0, p <0.001). Multiple biomarkers score was also associated with increased risk beyond FRS (hazard ratio 2.1, p = 0.02) per 1-U increase in score; however, the c-statistic did not increase significantly (0.75, 95% CI 0.68 to 0.84, p = 0.32). The c-statistic increased when log CAC was incorporated into FRS without or with multiple biomarkers score (c-statistic 0.84, p = 0.003 and p = 0.008 respectively). Addition of CAC to risk factors showed significant reclassification (net reclassification improvement 0.35 (95% CI 0.11 to 0.58, p = 0.007; integrated discrimination index 0.076, p = 0.0001), whereas addition of multiple biomarkers score did not show significant reclassification. In conclusion, in this study of asymptomatic subjects without known CVD, addition of CAC but not biomarkers substantially improved risk reclassification for future CVD events beyond traditional risk factors.     

Prognostic Impact of Lymph Node Retrieval and Ratio in Gastric Cancer: a U.S. Single Center Experience

Introduction

Increased lymph node (LN) retrieval for gastric cancer has been associated with improved overall survival (OS). This study examines the impact of number of examined LN (eLN) and lymph node ratio.

Methods

Patients referred for surgical care of gastric cancer were stratified by number of eLN, positive LNs (LN+), and lymph node ratio (LN+/eLN). Clinicopathologic factors were compared; OS and disease-free survival (DFS) were the primary endpoints.

Results

From 1997 to 2012, 222 patients, median age 67 (range, 17–92)?years, were analyzed. Of 220 (99 %) explored, 164 (74 %) underwent resection. Median OS was 22 (range, 0.3–140)?months. Perineural and lymphovascular invasion and poor differentiation adversely affected OS, p?<?0.05. A median 14 eLN (range, 0–45), with median 1 LN+ (range, 0–31), was observed. There were no OS or DFS differences when comparing the eLN groups. Both OS and DFS were impacted by LN+. Lymph node ratio demonstrated worse median OS with increasing ratio: 49 months (0) to 37 months (0.01–0.2), 27 months (0.21–0.5), and 12 months (>0.5), p?<?0.0001. DFS was similar: 35 months (0), decreasing to 22 months (0.01–0.2), 13 months (0.21–0.5), and 7 months (>0.5), p?<?0.0001.

Conclusion

Number of eLN did not impact survival, while LN+ adversely affected survival. Lymph node ratio may predict prognosis better than number of eLN or LN+ in gastric cancer.     

Osteitis of the Fourth Metatarsal Caused by a Date Palm Thorn in a Child: Why the Dorsum of the Foot Is the Most Commonly Injured Site

The palms are frequent in the region of eastern Morocco. An insidious onset of a lytic lesion in the base of the fourth metatarsal caused by a date palm thorn in a 20-year-old patient is presented. An untreated embedded thorn can cause late complications, including periostitis or osteomyelitis. In most cases, removal of the foreign body is easy, and no surgical care is needed. If detected, these injuries can be treated without complications. In children, however, the diagnosis can be very easily missed, especially if the child has aphasia and deafness, which was present in our patient. These can influence communication between the child and family, such that the patient is unable to inform the family about what object pricked him (e.g., date palm thorn, toothpick, insect) and is unable to tell the family that the foreign object remains embedded. This major communication issue between the child and family can result in potentially avoidable complications such as osteitis. No other issues were present in our patient that could have caused a delay in diagnosis, such as fear of punishment or fear of medical treatment. We present a case of date palm thorn-induced periostitis of the base of the fourth metatarsal. Surgical exploration revealed a 2.5-cm palm tree thorn embedded in granulation tissue, forming an abscess. The lesion was successfully treated by curettage of the lesion and removal of the thorn embedded in the periosteum of the metatarsal base. The purpose of the present report was to explain the mechanism of this rare entity and the frequency of this lesion on the dorsal aspect of the foot rather than on the plantar. Despite the absence of a definite history of trauma, organic foreign material should be in the differential diagnosis of a lytic lesion of the bone, especially in patients who have a problem with deafness or aphasia.