Atovaquone-Proguanil: A Promising Therapy for Persistent Relapsing Babesiosis.

We report a challenging case of persistent relapsing babesiosis in an immunocompromised host that was successfully managed with atovaquone-proguanil (Malarone). Malignant B-cell transformation and immunosuppressants, such as rituximab, deplete normal B-cells which normally produce antibodies to combat Babesia infection. Treatment can be prolonged and challenging in immunocompromised hosts. Atovaquone-proguanil (Malarone) is a novel therapy that can be used as part of a salvage regimen in case antimicrobial resistance or failure exists. Weighing the risks and benefits of continuing cancer therapy treatment or reducing the level of immunosuppression may aid in treatment. These are just as important as the choice of antimicrobial therapy for effective treatment and eradication of Babesia infection, especially in immunocompromised hosts.

A practical stress-based test method for evaluating reversible stress limit for critical current degradation in rare-earth barium copper oxide (REBCO) tapes.

The superior electromechanical properties of second-generation high-temperature superconducting rare-earth barium copper oxide (REBCO) coated conductor tapes make them viable candidates for high magnetic field applications. To characterize their electromechanical properties (EMPs) under operating conditions, the critical current degradation behavior of the REBCO tapes should be evaluated. Conventional evaluation methods for EMPs usually rely on a strain-based test method that utilizes an extensometer to measure the deformation induced on the coated conductor tape. This study aims to establish a practical stress-based test method that determines the reversible stress limit for critical current (Ic) degradation in REBCO tapes without using extensometers under uniaxial tension. For an efficient test procedure, Ic measurements were initially performed with broad stress intervals and then changed to narrow stress intervals before the critical current degraded irreversibly. Four commercially available REBCO tape samples were used to validate the reliability of the proposed stress-based test method. It was then assessed by comparing them with those obtained using the conventional strain-based test method. Statistical estimations were used to determine the reproducibility of the results. These results provide a basis for an international round-robin test guideline to establish a test method for measuring the electromechanical properties of high-temperature superconducting tapes at cryogenic temperatures.

PALB2 germline mutations in a large cohort of Middle Eastern breast-ovarian cancer patients.

The PALB2 gene is a breast cancer (BC) and ovarian cancer (OC) predisposition gene involved in the homologous recombination repair pathway. However, the prevalence and clinicopathological association of PALB2 pathogenic/likely pathogenic (PV/LPV) variants in Middle East is still not fully explored. Total 918 BC/OC patients from Saudi Arabia were selected for PALB2 mutations screening using capture sequencing technology. Five heterozygous PVs or LPVs were identified in six cases, accounting for 0.65% (6/918) of entire cohort. Two cases (33.3%) harbored PVs and four cases (66.7%) carried LPVs. Four PVs/LPVs (80%) were frameshift along with one novel splicing LPV (c.2835-2_2835-1delinsTT). One recurrent LPV (c.3425delT: p.L1142fs) was identified in two cases. All six affected carriers have breast cancer diagnosis with median age of 39.5 years (range 34-49 years). Only two cases (33%) have documented family history of cancer. Breast cancer phenotype was invasive ductal unilateral cancer in all cases with 66.7% of hormone receptor positive and 16% of triple negative tumors. Germline PVs/LPVs in the PALB2 gene were observed in low frequency of 0.65% in Saudi BC and/or OC. Our study confirms one recurrent LPV and one novel LPV in Saudi breast cancer patients.

Lynch Syndrome Identification in Saudi Cohort of Endometrial Cancer Patients Screened by Universal Approach.

Lynch syndrome (LS) is the most common cause of inherited endometrial cancer (EC). The prevalence and molecular characteristic of LS in Middle Eastern women with EC have been underexplored. To evaluate the frequency of LS in a cohort of EC patients from Saudi Arabia, a total of 436 EC cases were screened utilizing immunohistochemistry (IHC), MLH1 promoter methylation analysis and next-generation sequencing technology. A total of 53 of 436 (12.2%) ECs were classified as DNA mismatch repair-deficient (dMMR). MLH1 promoter hypermethylation was detected in 30 ECs (6.9%). Three ECs (0.7%) were found to be LS harboring germline pathogenic variants (PVs)/likely pathogenic variants (LPVs): two in the MSH2 gene and one in the MSH6 gene. Three ECs (0.7%) were Lynch-like syndrome (LLS) carrying double somatic MSH2 PVs/LPVs. Seven cases were found to have variants of uncertain significance in cancer-related genes other than MMR genes. Our results indicate that LS prevalence is low among Saudi EC patients and LLS is as common as LS in this ethnicity. Our findings could help in better understanding of the prevalence and mutational spectrum of this syndrome in Saudi Arabia, which may help in defining best strategies for LS identification, prevention and genetic counseling for EC patients.

Addressing Medicine's Dark Matter.

In the 20th century, the models used to predict the motion of heavenly bodies did not match observation. Investigating this incongruity led to the discovery of dark matter-the most abundant substance in the universe. In medicine, despite years of using a data-hungry approach, our models have been limited in their ability to predict population health outcomes-that is, our observations also do not meet our expectations. We believe this phenomenon represents medicine's "dark matter"- the features with have a tremendous effect on clinical outcomes that we cannot directly observe yet. Advancing the information science of health care systems will thus require unique solutions and a humble approach that acknowledges its limitations. Dark matter changed the way the scientific community understood the universe; what might medicine learn from what it cannot yet see?

Photo-Controlled [4+4] Cycloaddition of Anthryl-Polymer Systems: A Versatile Approach to Fabricate Functional Materials.

The reversible photo-induced [4+4] cycloaddition reaction of anthracene enables multiple cycles of dimerization and scission, allowing phototunable linkage of molecular fragments for the synthesis of polymer scaffolds. New functional materials ranging from hydrogels to shape-memory polymers were designed from anthryl-polymer systems because of their diverse photochemical reactivity and responsiveness. Light as an external stimulus allows for the remote and precise spatiotemporal control of materials without the need for additional reagents. Depending on how the photoreactive anthracene moieties were introduced, the interaction of anthryl-polymer systems with light results in various processes such as polymerization, cyclization, and cross-linking. Structural modifications of anthracene derivatives could shift their absorption from the ultraviolet to the visible light region, widening their range of applications including biologically relevant studies. These applications are further diversified and enhanced by the reversibility of the dimerization reaction using light and heat as stimuli. In this review, current developments in the synthesis and photodimerization of anthracene-containing polymers and their emerging applications in the fabrication of new materials are discussed.

Recurrent Somatic MAP2K1 Mutations in Papillary Thyroid Cancer and Colorectal Cancer.

Mitogen-activated protein kinase kinase 1 (MAP2K1) is a dual specificity protein kinase that phosphorylates both threonine and tyrosine residues in ERK. MAP2K1 mutations have been identified in several cancers. However, their role in Middle Eastern papillary thyroid cancer (PTC) and colorectal cancer (CRC) is lacking. In this study, we evaluated the prevalence of MAP2K1 mutations in a large cohort of Middle Eastern PTC and CRC using whole-exome and Sanger sequencing technology. In the discovery cohort of 100 PTC and 100 CRC cases (comprising 50 MAPK mutant and 50 MAPK wildtype cases each), we found one MAP2K1 mutation each in PTC and CRC, both of which were MAPK wildtype. We further analyzed 286 PTC and 289 CRC MAPK wildtype cases and found three MAP2K1 mutant PTC cases and two MAP2K1 mutant CRC cases. Thus, the overall prevalence of MAP2K1 mutation in MAPK wildtype cases was 1.1% (4/336) in PTC and 0.9% (3/339) in CRC. Histopathologically, three of the four MAP2K1 mutant PTC cases were follicular variant and all four tumors were unifocal with absence of extra-thyroidal extension. All the three CRC cases harboring MAP2K1 mutation were of older age (> 50 years) and had moderately differentiated stage II/III tumors located in the left colon. In conclusion, this is the first comprehensive report of MAP2K1 somatic mutations prevalence in PTC and CRC from this ethnicity. The mutually exclusive nature of MAP2K1 and MAPK mutations suggests that each of these mutation may function as an initiating mutation driving tumorigenesis through MAPK signaling pathway.

The Possibility and Cause of Relapse After Previously Recovering From COVID-19: A Systematic Review.

The severe acute respiratory distress syndrome coronavirus-2 (SARS-Cov-2) is a novel coronavirus that is believed to be mainly transmitted via droplet and contact transmission. While research is focusing on epidemiology, transmission, vaccine development, and therapeutics for coronavirus disease 2019 (COVID-19), there is a possibility of disease relapse. There are reports of patients who tested positive for SARS-Cov-2 after clinical recovery and initial clearance of the virus. Objective This systematic review aims to identify the trends of COVID-19 relapse, the effects of co-morbidities on it, and associated mortality rates. Methods We conducted a systematic search during March and April 2020 for research articles on the relapse of COVID-19 using two primary databases, PubMed and Embase. Results A total of 13 eligible studies were screened of which 11 (case reports) were eligible for data extraction. The earliest to report relapse was after two days of discharge and the latest was 22 days after discharge. The mean number of days to relapse was 12 days and the median number was seven days. There was incomplete information about comorbidities. No mortalities were reported at the time of the study.

2019 Novel Coronavirus Pandemic: What Do We Know?

The pandemic caused by SARS-COV2 Virus/COVID-19, which was initially reported in China in December 2019, has become a major global health concern. COVID-19 can manifest with cytokine storm - an exaggerated systemic inflammatory phenomenon due to over-production of proinflammatory cytokines by immune cells that results in diffuse inflammatory lung disease and acute respiratory distress syndrome. It may be complicated by septic shock and subsequent multi-organ failure. Based on the most recently published evidence, this article will review and discuss comprehensive information on its clinical manifestations, laboratory tests, potential therapeutics, and prevention guidelines.

Coccidioides in lung transplant: case report.

A middle-aged woman was hospitalised for generalised, painful skin lesions 6 weeks after a successful double-lung transplant. She had end-stage lung disease associated with chronic obstructive pulmonary disease due to alpha-1 antitrypsin deficiency, and she had been treated with itraconazole for 16 months because of lung infection associated with Malbranchea spp. Results of a skin biopsy of the initial lesion on her arm showed non-specific dermal inflammation, presumably due to reactivation of the Malbranchea spp infection. Follow-up cervical lymph node biopsy and culture showed Coccidioides posadasii/C. immitis A detailed review of her travel history showed a 4-month stay in Arizona as a teenager that she barely remembered. Coccidioides spp were likely misidentified as Malbranchea spp owing to similar morphological characteristics. Dosages of immunosuppressive medications were reduced, and antifungal therapy was changed to posaconazole. Her skin lesions resolved.

16S rRNA Gene PCR/Sequencing of Cerebrospinal Fluid in the Diagnosis of Post-operative Meningitis.

INTRODUCTION: Post-operative meningitis (POM) is a life-threatening complication of neurosurgery. Diagnosis is often difficult due to pre-existing inflammation and antecedent antimicrobial use. Bacterial cerebrospinal fluid (CSF) cultures may reveal no growth, but empiric antibiotics are typically given due to the high morbidity and mortality associated with POM. 16S rRNA gene PCR/sequencing is a molecular methodology that can identify the presence of bacteria regardless of viability for culture. CASE PRESENTATION: A patient presented with a rapid onset of fever associated with headache, neck pain, nausea and altered mental status 11 days after undergoing laser interstitial thermal therapy for treatment of recurrent astrocytoma at another hospital. Based on clinical presentation and imaging, POM was suspected, and empiric antibacterial therapy was started. Microbiological stains and cultures of CSF were negative. Due to persistent fevers, 16S rRNA gene PCR/sequencing was done on CSF; it detected a member of the order Enterobacteriales most closely resembling Serratia species. All antimicrobials were stopped except for cefepime, which was given for 2 weeks. The patient's mental status fully recovered. CONCLUSION: The application of 16S rRNA gene PCR/sequencing in the setting of POM is of value by improving the quality of patient care and decreasing costs by antimicrobial de-escalation. Further studies regarding the positive and negative predictive values of this test are required.

Telomerase reverse transcriptase promoter mutations in cancers derived from multiple organ sites among middle eastern population.

Sanger Sequencing and immunohistochemistry was employed to investigate the TERT promoter mutations and TERT protein expression with their association to clinicopathological characteristics in over 2200 samples of Middle Eastern origin from 13 different types of cancers. The TERT promoter mutations were most frequently present in bladder cancer (68.6%), followed by central nervous system tumors (28.7%), thyroid cancer (15.4%), prostate cancer (9.3%), endometrial carcinoma (3.7%), rhabdomyosarcoma (1.4%), colorectal cancer (1%), epithelial ovarian carcinoma (0.7%) and breast cancer (0.7%). No mutations were observed in other types of cancers. In bladder cancer, we found significant inverse association with metastasis and a trend to good survival in patients with TERT mutations. In gliomas, TERT promoter mutations predicted poor prognosis. In thyroid cancer, high frequency of TERT mutation was observed in poorly differentiated carcinoma. In addition, TERT promoter mutations were associated with aggressive markers and poor outcome in follicular thyroid carcinomas.

Staphylococcus pseudintermedius catheter-related bloodstream infection after exposure to domestic dogs and a cat.

We report a case of a catheter-related bloodstream infection due to oxacillin-susceptible Staphylococcus pseudintermedius in a patient receiving haemodialysis who possibly acquired the organism from her pets. Because of persistent bacteremia and the organism's ability to form biofilm, catheter removal and antimicrobial therapy were indicated to attain source control. Both clinical and microbiological cure were confirmed. Catheter care education should include information about pet exposure and the possibility of zoonotic infections.

Nontuberculous mycobacterial infections of the lower extremities: A 15-year experience.

OBJECTIVES: Nontuberculous mycobacterial infection (NTMI), which is increasing in prevalence, is challenging to diagnose and manage despite the availability of capable laboratories because of subtle and nonspecific clinical findings and nonstandardized treatment guidelines. We aimed to present our experience with lower-extremity NTMI and to compare clinical characteristics and treatment outcomes between immunocompetent and immunocompromised patients. METHODS: To determine clinical presentations and outcomes, we reviewed electronic health records of all patients with lower-extremity NTMI treated and followed up at our institution from January 2002 through December 2017. RESULTS: Twenty-four patients were included in this study. Mean (SD) age was 58 (19) years. Eighteen patients (75%) were men; 13 (54%) were immunocompetent; and 9 (37%) had bone and joint involvement. No significant differences existed between immunocompetent and immunocompromised patients, except immunocompetent patients had significantly more infections at the hip, thigh, and toe. Bone and joint infection required significantly longer treatment time than skin and soft-tissue infection. CONCLUSIONS: Regardless of immune status, patients with lower-extremity NTMI had similar characteristics, treatments, and outcomes. However, immunosuppression can be a major risk factor in the development of disseminated NTMI and associated complications. Acid-fast bacilli culture is strongly recommended for evaluation of delayed or nonhealing lesions. Aggressive medical and surgical management can be associated with good clinical outcomes.

Tuberculosis presenting as dacryoadenitis in the USA.

A 25-year-old Filipino woman living in the USA was evaluated for a 5-month history of left eye pain and a subsequent orbital mass. Histopathological analysis of the lacrimal mass showed a mixed inflammatory process with necrotising granulomas and positive cultures for Mycobacterium tuberculosis She was treated with antituberculosis therapy, with resolution of symptoms. Tuberculosis dacryoadenitis is extremely rare in the USA and other developed countries. It requires a high degree of clinical suspicion with special attention to the patient's history to make the correct diagnosis. It can be treated successfully with antituberculosis therapy.

Mycobacterium abscessus Prosthetic Joint Infections of the Knee.

M. abscessus complex prosthetic joint infections (PJI) of the knee are rare. We present a patient with an M. abscessus subsp. massiliense, a nontuberculous mycobacterium (NTM), peri-prosthetic knee infection who presented with wound drainage followed by sepsis. The published peer-reviewed literature on knee PJIs due to this organism is reviewed to highlight its clinical presentation,symptomatology, microbiology, surgical interventions, antimicrobial regimens, and outcomes.

MRSA Spinal Epidural Abscess as a Neurosurgical and Infectious Disease Emergency with Unresolved Antimicrobial Solution.

Spinal epidural abscess caused by MRSA, a life-threatening organism resistant to methicillin and other antibiotics, is a rare but important infectious pathology due to its potential damage to the spinal cord. We present the case of a 74-year-old man who hematogenously seeded his entire epidural spinal canal from C1 to sacrum with MRSA bacteria and remained infected even after maximal treatment with vancomycin and daptomycin. Ceftaroline, a new 5th generation antibiotic with recently described clearance of widespread MRSA infection in epidural complex spine infections, was added to vancomycin as dual therapy for his MRSA infection. A 74-year-old diabetic man with prior right total knee arthroplasty and MRSA infection presented with persistent bacteremia and sepsis. He was transferred to our academic center after diagnosis of entire spine epidural abscesses from C1 to sacral levels with midthoracic MRI T2 hyperintensities of the vertebral bodies and disc concerning for osteomyelitis and discitis. Despite surgery and IV vancomycin with MIC of 1, suggesting extreme susceptibility, the patient's blood cultures remained persistently bacteremic at day 5 of treatment. After 48 hours of dual antibiotic therapy with vancomycin and ceftaroline, his blood cultures came back showing no growth. The patient's outcome was unfavorable due to the advanced nature of his infection and multiple comorbidities, but his negative blood cultures after the addition of ceftaroline to his regime require further investigation into this dual therapy. Randomized controlled trials of 5th generation or combinatorial antibiotics should be considered for this disease.

Silent myocardial infarction secondary to cardiac autonomic neuropathy in a patient with rheumatoid arthritis.

An 83-year-old female patient with rheumatoid arthritis and hypertension presented to the emergency department with fever and chills of 1 day duration. On examination, temperature was 100.9 F, heart rate 111/min and she had orthostatic hypotension. Laboratory tests showed elevated blood urea nitrogen and white cell count. The patient underwent treatment for symptomatic urinary tract infection and while her fever and leucocytosis resolved, tachycardia persisted. An EKG done showed T inversions in leads II, III, arteriovenous fistula, V2 and V3. Troponin-I was elevated. Nuclear stress test revealed apical wall motion abnormality confirming myocardial infarction. Ewing's tests were carried out at bedside and these diagnosed severe autonomic neuropathy. Rheumatoid arthritis can cause cardiac autonomic neuropathy from chronic inflammation. This case entails the importance of assessing and detecting cardiac autonomic neuropathy in chronic inflammatory conditions, and the need to be cautious of acute coronary events in these patients, even for minimal or no symptoms.

Outcomes of 1949 endoscopic procedures: performed by a Canadian rural family physician.

OBJECTIVE: To examine the outcomes of endoscopic procedures performed by a family physician trained in endoscopy. DESIGN: Quality assurance practice audit involving medical chart review. SETTING: Rural family practice in Peace River, Alta. PARTICIPANTS: All patients who had endoscopic procedures performed by a rural family physician during the period September 24, 1999, to May 31, 2007. MAIN OUTCOME MEASURES: Type of endoscopic procedure performed, indications for and results of the endoscopies, complication rates, referral to tertiary care physicians, and patient demographic information. Colonoscopy competency was determined by the reach-the-cecum rate and by time for colonoscopy completion. RESULTS: A total of 1956 endoscopic examinations were performed; complete data were verified for 1949 procedures, including 667 gastroscopies, 1178 colonoscopies, and 104 sigmoidoscopies. Endoscopic findings with gastroscopy included 50 (7.5%) cases of peptic ulcer disease, 17 (2.5%) cases of celiac disease, and 6 (0.9%) cases of upper gastrointestinal cancer; 27 (2.1%) cases of colorectal cancer and 48 (3.7%) new cases of inflammatory bowel disease were discovered with lower gastrointestinal endoscopy. The overall adenoma detection rate was 23.7% for male patients and 15.4% for female patients; for patients 50 years and older, it was 29.8% and 18.0% for male and female patients, respectively. The adjusted reach-the-cecum rate for colonoscopies was 92.3%. There was 1 colonic perforation and 1 postpolypectomy bleed. A total of 123 (6.3%) patients required referral to tertiary care physicians, half for definitive surgical intervention. CONCLUSION: A trained family physician can perform endoscopy competently with findings and complication rates consistent with current quality assurance guidelines for endoscopy.