Removal of Spinal Instrumentation Is Not Required to Successfully Treat Postoperative Wound Infections in Most Cases.

INTRODUCTION: Controversy exists regarding whether spinal implants need to be removed to treat postoperative deep wound infections (DWIs). This retrospective study aimed to determine whether the removal or retention of implants impacts the successful treatment of a DWI after spine surgery. METHODS: Postoperative spine surgery patients presenting with signs of infection who underwent irrigation and debridement (I&D) at Twin Cities Spine Surgeons at Abbott Northwestern Hospital, Minnesota, USA, were studied. First, the persistence of infection when implants were retained or removed was assessed. Second, we analyzed the persistence of infection with respect to the number of I&D, the use of vacuum-assisted closure (VAC) treatment, pseudoarthrosis status, and functional outcomes. RESULTS: One hundred thirty-five patients were included. Treatment of infection with retention of implants occurred in 64% (87/135); of these, 7% (6/87) had a persistent infection. Of patients with implant removal (36%, 48/135), 6% (3/48) had a persistent infection. Thus, we observed no difference between treatment with implants present compared to implants removed (p = 1.0). Fifty of the 135 patients (37%) received I&D and primary wound closure, and 85 (63%) patients received I&D and VAC treatment. There was no statistical difference between primary wound closure and VAC treatment (p = 0.15) with respect to persistence. Repeat I&D with VAC (three or more times) had a significantly lower rate of recurrence than those with two I&Ds. Pseudoarthrosis and persistent infection were unrelated. At minimum one-year follow-up, achieving a minimum clinically important difference in functional outcome was independent of persistent infection status. CONCLUSION: Persistent infection was unrelated to the retention of implants. When VAC treatment was deemed necessary, more than two I&Ds resulted in a significantly better cure for infection. Those with a persistent infection were no more likely to exhibit pseudoarthrosis than those with no persistent infection. All patients showed improvement in functional outcomes at minimum one-year follow-up.

The Ozaki Procedure: Standardized Protocol Adoption of a Complex Innovative Procedure.

Background: The Ozaki procedure using autologous pericardium is an interesting but complex alternative for aortic valve replacement. We present a standardized approach to minimize the learning curve and confirm reproducibility. Methods: After careful preparation, from May 2015 to February 2021, an Ozaki procedure was performed on 46 patients age 51 ± 14 years. Seven had unicuspid (15%), 29 bicuspid (63%), and 10 tricuspid (22%) aortic valves, and 2 patients had endocarditis. Endpoints were operative learning curves, perioperative outcomes, intermediate-term valve hemodynamics, reintervention, health-related quality of life (MacNew Heart Disease Health-Related Quality of Life questionnaire), and mortality. Results: Cardiopulmonary bypass and aortic clamp times decreased from 145 to 125 â€‹minutes and 120 to 100 â€‹minutes, respectively, over the first 20 cases, reflecting the learning curve. There was no major perioperative morbidity or mortality. Median postoperative stay was 6.9 days. Aortic regurgitation was mild or less in all but 2 patients who developed moderate aortic regurgitation. Mean aortic valve gradient was 7.9 mmHg postoperatively, 9.2 mmHg by 6 months, and constant thereafter. Left ventricular ejection fraction was 58% preoperatively, 60% at 6 months, and remained stable thereafter. One patient developed infective endocarditis 7 months postoperatively, failed medical management, and underwent valve replacement at 14 months. Two-year survival was 96%, with 1 noncardiac death at 16 months. Health-related quality of life in mental, physical, and emotional domains was better than matched norms, global 6.2 vs. 5.0 (p < 0.0001). Conclusions: Using a well-prepared standardized approach, the Ozaki procedure is reproducible with a short learning curve, excellent hemodynamic performance, and good quality of life.

Association of molecular subgroups with pathological parameters in endometrial carcinomas.

BACKGROUND: The integration of molecular features into the already existing pathological classification of endometrial carcinomas will offer significant prognostic information. As the literature search reveals, there are no studies from India that have classified these carcinomas based on molecular subtypes. The aim of the study was to classify endometrial carcinomas into four subtypes based on their molecular and immunohistochemical features and to find out the association of each of these molecular subtypes with the other pathological parameters. METHODS: A prospective study was done on 37 consecutive cases of fresh hysterectomy specimens, biopsy-proven as endometrial carcinomas between November 2019 and August 2020. Three immunohistochemical markers (p53, mismatch repair proteins,MutS homolog6 and Postmeiotic seggregation 2 respectively[MSH6, and PMS2]), along with DNA (deoxyribonucleic acid) sequencing of selected regions of the POLE gene was performed in each of the 37 cases. Endometrial carcinomas were subclassified into four subtypes, and the association of each of these four subtypes with the other pathological parameters was also explored. Statistical analysis was done using the IBM Statistical Package for the Social Science (SPSS) Version 20.0 software (IBM SPSS, USA). RESULTS: Among the 37 cases studied, eight (21.6%) cases were p53 abnormal, eight (21.6%) cases showed MMR-D (mismatch repair deficient), one case (2.7%) showed mutation of POLE, and 21 cases (56.8%) were assembled under p53 wild-type. Higher grade endometrial carcinomas showed more (80.0%) p53 abnormal (P < 0.001). All the p53 wild-type (100%) were of Type 1 endometrial carcinoma subtype (P = 0.001) and low-grade type (90.5%; P = 0.005). CONCLUSION: Our study confirms that the type of carcinoma and grade correlates with p53 expression, p53 abnormal being associated with higher grade and type 2 endometrial carcinomas, whereas p53 wild-type is associated with low-grade and type 1 endometrial carcinoma. There was only one case of the POLE subtype identifiable in our study.

Imaging spectrum, associations and outcomes in acute invasive fungal rhino-ocular-cerebral sinusitis in patients with COVID-19 pneumonia.

Background: Coronavirus Disease 2019 (COVID-19) has been speculated to enhance mucormycosis infection due to its immune-altering pathophysiology. Early identification of high-morbidity conditions is crucial for optimal treatment and improved outcomes. Methods: A retrospective study was conducted on 63 patients with clinical and microbiological evidence of rhino-ocular-cerebral mucormycosis, who had a history of COVID-19 infection. The clinical, demographic, and imaging data were retrieved and analyzed. Descriptive statistics (mean [SD] and frequency [%]) were used to describe important characteristics across audit cycles. Results: Out of 63 patients, 54 (85.71%) patients had associated comorbidities, with diabetes mellitus being common comorbidity and all patients had received injectable and/or oral corticosteroids. Imaging showed nasal and paranasal sinus, perisinus, maxillary alveolar arch, and hard palate involvement in 62 (98.41%), 33 (52.38%), 5 (7.94%) and 5 (7.94%) patients, respectively. Orbital involvement was seen in 24 (38.10%) patients. Skull base involvement was seen in 11 (17.46%) patients, and intracranial extension of disease was present in 11 (17.46%) patients. A total of 16 patients were on mechanical ventilation, of whom 3 succumbed. The mean (standard deviation [SD]) intensive care unit (ICU) stay was 13.2 days (6.8) for 5 patients who succumbed and 6.4 days (4.6) for 30 patients who survived (P value = 0.008). Conclusion: Cross-sectional imaging not only provides the extent of disease spread but also plays a vital role in providing a surgical roadmap to treating surgeons and in predicting prognosis in patients with invasive fungal infections.

Impact of Faculty Incentivization on Resident Evaluations.

INTRODUCTION: In the Program Requirements for Graduate Medical Education in Emergency Medicine, the Accreditation Council for Graduate Medical Education requires frequent and routine feedback. It is a common challenge for program leadership to obtain adequate and effective summative evaluations. METHODS: This is a retrospective, case-crossover, interventional study conducted in an academic medical center. This study occurred over a two-year period, with an intervention between years one and two. Throughout year two of the study, faculty incentive compensation was linked to completion of end-of-shift evaluations. We compared pre- an post-implementation data using paired sample t-tests with the significance level P < .05 applied. RESULTS: After implementation of the incentive metric there was an increase in the number of total evaluations by 42% (P = .001). The mean number of evaluations submitted by each faculty per shift increased from 0.45 to 0.86 (SD 0.56, P < .001). Overall, 32 of the 38 faculty members (84.2%) had an increase in the number of evaluations submitted per shift during the intervention period with an average increase of 0.5 evaluations per shift (range 0.01-1.54). CONCLUSION: Incentivizing faculty to submit resident evaluations through use of bonus compensation increased the number of evaluations at our institution. This information may be applied by other programs to increase resident evaluations.

A Practical Approach to the Diagnosis of Lymphedema: A Narrative Review.

INTRODUCTION: Lymphedema often presents as progressive, unremitting swelling and skin changes that are extremely distressing to patients. Hereditary lymphedema (HL) constitutes a type of primary lymphedema that is passed down through generations. OBJECTIVES: The primary aims of this narrative review are to illustrate a framework to distinguish lymphedema from other causes of swelling and to differentiate the hereditary lymphedemas from each other. RESULTS: A literature search was undertaken using relevant search terms. The articles were evaluated to generate a diagnostic algorithm to approach the swelling of an extremity using clinical and laboratory data. First, the stemmer sign should be evaluated. If it is negative, other causes should be considered. History and additional physical exam findings suggest either a primary or secondary cause of lymph-edema. CONCLUSIONS: The hereditary lymphedemas have been classified by age of onset and then stratified by clinical criteria and genetic testing.

Etiologies and Predictors of 30-Day Readmission in Heart Failure: An Updated Analysis.

Background and Objectives: Readmissions in heart failure (HF), historically reported as 20%, contribute to significant patient morbidity and high financial cost to the healthcare system. The changing population landscape and risk factor dynamics mandate periodic epidemiologic reassessment of HF readmissions. Methods: National Readmission Database (NRD, 2019) was used to identify HF-related hospitalizations and evaluated for demographic, admission characteristics, and comorbidity differences between patients readmitted vs. those not readmitted at 30-days. Causes of readmission and predictors of all-cause, HF-specific, and non-HF-related readmissions were analyzed. Results: Of 48,971 HF patients, the readmitted cohort was younger (mean 67.4 vs. 68.9 years, p≤0.001), had higher proportion of males (56.3% vs. 53.7%), lowest income quartiles (33.3% vs. 28.9%), Charlson comorbidity index (CCI) ≥3 (61.7% vs. 52.8%), resource utilization including large bed-size hospitalizations, Medicaid enrollees, mean length of stay (6.2 vs. 5.4 days), and disposition to other facilities (23.9% vs. 20%) than non-readmitted. Readmission (30-day) rate was 21.2% (10,370) with cardiovascular causes in 50.3% (HF being the most common: 39%), and non-cardiac in 49.7%. Independent predictors for readmission were male sex, lower socioeconomic status, nonelective admissions, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, anemia, and CCI ≥3. HF-specific readmissions were significantly associated with prior coronary artery disease and Medicaid enrollment. Conclusions: Our analysis revealed cardiac and noncardiac causes of readmission were equally common for 30-day readmissions in HF patients with HF itself being the most common etiology highlighting the importance of addressing the comorbidities, both cardiac and non-cardiac, to mitigate the risk of readmission.

Errors encountered in the diagnostic pathway: A prospective single-institution study.

BACKGROUND: Biopsy specimens go through a diagnostic pathway before a pathology report is rendered for the clinician. Errors can occur at any step in this pathway. METHODS: A 1-year prospective study was conducted at a single academic institution to identify and characterize errors that occurred in the diagnostic pathway from the clinic to the dermatopathology lab. RESULTS: A total of 25 662 specimens were processed and 190 errors were recorded (an error rate of 0.7%). The most common errors were an incorrect biopsy site (n = 65), incorrect data entry of a correct diagnosis (n = 25), and specimen mix-up (n = 23). There were 17 diagnostic errors. Errors most often occurred in the pre-analytical phase (n = 128). The clinician was responsible for 34.2% of errors, the dermatopathologist for 23.7%, and the histotechnician for 18.9%. Slips were the most common type of human error (n = 156). CONCLUSION: The most common error involved an incorrect biopsy site at the clinical stage. Over two-thirds of errors occurred before the slide reached the dermatopathologist. Diagnostic errors (analytical phase) rarely occurred, and when they did occur, the clinician was most likely to discover the error. Examining and addressing common laboratory errors help to reduce their incidence and lead to quality improvement in dermatopathology.

Keratosis pilaris: an update and approach to management.

Keratosis pilaris (KP) is a common, hyperkeratotic skin condition characterized by small, folliculocentric papules with variable perifollicular erythema. We provide an updated review on the pathogenesis, clinical manifestations, and management of this common, and often annoying, finding. KP represents a family of follicular disorders, of which KP simplex is by far the most common. Other variants and rare subtypes include keratosis pilaris rubra, erythromelanosis follicularis faciei et colli, and the spectrum of keratosis pilaris atrophicans. Inherited mutations of the FLG gene and ABCA12 gene have been implicated etiologically. KP may be associated with ichthyosis vulgaris and palmar hyperlinearity, but less likely atopic dermatitis. Some potential differential diagnoses for KP include lichen spinulosus, phrynoderma, ichthyosis vulgaris, and trichostasis spinulosa. General cutaneous measures such as hydrating skin, avoiding long baths or showers, and using mild soaps or cleansers should be recommended. Topical keratolytic agents are first-line therapy, followed by topical retinoids and corticosteroids. Recent options include a variety of lasers and microdermabrasion if the patient is refractory to topical therapy.

Life-threatening hemoptysis in patients with metastatic kidney cancer.

Hemoptysis is a complication of intrathoracic tumors, both primary and metastatic, and the risk may be increased by procedural interventions as well as Stereotactic Ablative Radiation (SAbR). The risk of hemoptysis with SAbR for lung cancer is well characterized, but there is a paucity of data about intrathoracic metastases. Here, we sought to evaluate the incidence of life-threatening/fatal hemoptysis (LTH) in patients with renal cell carcinoma (RCC) chest metastases with a focus on SAbR. We systematically evaluated patients with RCC at UT Southwestern Medical Center (UTSW) Kidney Cancer Program (KCP) from July 2005 to March 2020. We queried Kidney Cancer Explorer (KCE), a data portal with clinical, pathological, and experimental genomic data. Patients were included in the study based on mention of "hemoptysis" in clinical documentation, if they had a previous bronchoscopy, or had undergone SAbR to any site within the chest. Two hundred and thirty four patients met query criteria and their records were individually reviewed. We identified 10 patients who developed LTH. Of these, 4 had LTH as an immediate procedural complication whilst the remaining 6 had prior SAbR to ultra-central (UC; abutting the central bronchial tree) metastases. These 6 patients had a total of 10 lung lesions irradiated (UC, 8; central 1, peripheral 1), with a median total cumulative SAbR dose of 38 Gray (Gy/ lesion) (range: 25-50 Gy). Other risk factors included intrathoracic disease progression (n = 4, 67%), concurrent anticoagulant therapy (n = 1, 17%) and concurrent systemic therapy (n = 4, 67%). Median time to LTH from first SAbR was 26 months (range: 8-61 months). Considering that 130 patients received SAbR to a chest lesion during the study period, the overall incidence of LTH following SAbR was 4.6% (6/130). The patient population that received SAbR (n = 130) was at particularly high risk for complications, with 67 (52%) having two or more chest metastaes treated, and 29 (22%) receiving SAbR to three or more lesions. Overall, the risk of LTH following SAbR to a central or UC lesion was 10.5% (6/57). In conclusion, SAbR of RCC metastases located near the central bronchial tree may increase the risk of LTH.

Impact of hypothermia alert device (BEMPU) on improvement of duration of Kangaroo Mother Care (KMC) provided at home: parallel-group randomized control trial.

The objective of the study was to determine if using the hypothermia-detecting bracelet (named BEMPU) improves the duration of Kangaroo Mother Care (KMC) at home by one hour. This parallel-group randomized controlled trial was conducted at a step-down nursery of a teaching hospital. Neonates between 1000 and 2000 g were randomized to BEMPU and control groups at the time of discharge. BEMPU was applied at the wrist of each newborn in the BEMPU (intervention) group. Parents were advised to keep the BEMPU in place till 4 weeks post-discharge. The BEMPU generates a beep sound as an alarm when a newborn's temperature drops below 36.5 °C. Parents in both groups were trained to provide KMC at home. Parents in the BEMPU group received the "KMC chart" and "BEMPU beep chart," while the control group received the "KMC chart" only. In the "KMC chart," parents entered information about KMC hours on a real-time basis, and in the "BEMPU beep chart," they entered information about alarm beeps from BEMPU on a real-time basis till 4 weeks post-discharge. Independent samples t-test was used to compare mean KMC hours between the two groups. A total of 128 neonates participated in the study (64 in BEMPU and 64 in Control groups). The mean(SD) gestational age for the BEMPU group was 34.04(2.84) weeks vs 34.75(2.70) weeks for the control group. In BEMPU group, mean(SD) daily time spent doing KMC was significantly higher in 1st week [4.78(2.93) vs. 3.22(2.44) h, p = 0.003], in 2nd week [4.52(3.43) vs. 2.84(2.95) h, p = 0.008], in 3rd week [4.23(3.71) vs. 2.30(2.70) h, p = 0.003], in 4th week [3.72(3.30) vs. 1.95(2.65) h, p = 0.003] as compared to control group. BEMPU improved the daily duration of KMC hours at home compared to the control group over four weeks. Clinical Trial Registration: This trial is registered at Clinical Trials Registry India with registration number: CTRI/2018/08/015154 and accessible at http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=27600&EncHid=&modid=&compid=%27,%2727600det%27 Registered on 01/08/2018.

Midterm postoperative outcomes of different types of surgical reconstruction of sinus venosus atrial septal defects with anomalous pulmonary venous connection: The Results of Prospective Cohort Study.

Background and Aims: Sinus venosus atrial septal defects (SVASDs) constitute a substantial part of atrial septal defects and are usually characterized by anomalous pulmonary venous connection (APVC), causing complications like sinus node dysfunction and arrhythmias. Several surgical approaches are used for treating SVASDs in pediatric patients, including single- and two-patch techniques. The study aimed to prospectively evaluate and compare the safety and efficacy of these two methods with different follow-up periods. Methods: Ten patients aged 1-8 years with SVASDs and partial APVC were enrolled in the study at Bhanubhai and Madhuben Patel Cardiac Centre, Karamsad, India, between December 2018 and October 2021. The single-patch (sandwich-patch) technique was used in two patients, whereas the two-patch (dual-patch) technique with autologous pericardium was used in seven. Safety was assessed as the absence of complications in the follow-up periods of 6 months, 1, and 2 years, whereas efficacy was estimated by the preserved sinus rhythm and the development of arrhythmias. Electrocardiographic and echocardiographic methods were used to evaluate both parameters. Results: No deaths, reoperations, pulmonary vein, and superior vena cava (SVC) stenosis or phrenic nerve palsy were observed among the 10 patients in the three follow-up periods. Sinus rhythm was arrested in two of the seven patients who underwent two-patch repair, whereas no rhythm disturbances occurred in those who underwent single-patch repair. Conclusion: Both techniques used in SVASD repair with autologous pericardium proved to cause the smaller rate of complications in midterm postsurgical phase. However, there is a potentially great risk of the development of sinus node malfunction after the application of the two-patch technique. Therefore, methods avoiding sinus node interference are preferred in patients with partial APVC involving SVC.

Role of MRCP to determine the etiological spectrum, level and degree of biliary obstruction in obstructive jaundice.

Context: Obstructive jaundice as a result of hepatocellular disease many a times is indistinguishable from jaundice due to extrahepatic biliary obstruction based on just clinical and biochemical examinations. It is one of the most frequent and grave form of hepatobiliary disease which may lead to complications like ascending cholangitis, malabsorption and hepatorenal syndrome, thus demanding urgent surgical intervention. Thus not only early diagnosis but also accurate identification of level and cause of obstruction is crucial in managing these patients. Aims: The aim of this study is to evaluate the role of MRCP in the determination of the etiological spectrum, to evaluate level and degree of biliary obstruction in cases of obstructive jaundice, and to correlate MRCP findings with surgical/histopathology/ERCP findings where possible. Methods and Material: It is an observational study done after the Institutional Ethics Committee (I.E.C.)- 2 approval. (IEC no: IEC/HMPCMCE/122/Faculty/8/186/20) Outdoor and indoor patients referred to radiodiagnosis department of Shree Krishna Hospital, Karamsad, for MRCP with clinical and laboratory parameters suggesting obstructive jaundice were included in the study. Patients less than 10 years of age, those with contraindications to MRI and patients with clinico-laboratory evidence of perihepatic/hepatic jaundice were excluded. Methodology: A total of 50 patients were included after taking an informed consent from each patient. Demographic data, clinical details were recorded and collated along with MRI findings. Descriptive statistics was used to explore MRI findings and findings were correlated with surgical/histopathology/ERCP findings whichever applicable. The MRI scan was performed with 5 mm thick axial T1W, T2W and STIR, 5 mm thick coronal T1W, T2W and STIR TRUFIS, Thin coronal T2 FS, Thick coronal T2 FS, T2W coronal respiratory trigger sequences, 3-5 mm thick T2 weighted Haste and 3D sequence. Statistical Analysis Used: Analysis was performed using STATA (14.2). Descriptive statistics was used of study population. Sensitivity and specificity value was used to compare the modality and individually calculated for various causative factors of jaundice. Results: Of the 50 patients, 9 had CBD stones, it is observed that MRCP has sensitivity and specificity of 100% and 100%, respectively, in detecting Bile duct stones, whereas sensitivity and specificity of ERCP was 87.5% each. About 11 patients had CBD strictures, which were seen as narrowing of CBD with upstream dilatation. It was observed in our study that the sensitivity of MRCP was 93% and specificity was 95% in detecting CBD strictures while ERCP had 100% sensitivity and specificity. About 12 patients had CBD tumor for sensitivity and specificity of MRCP and ERCP was 100%. Out of 50 patients, 36% had gall bladder stones in whom MRCP sensitivity and specificity was 88.89% and 100% and was found to comparable with ERCP. Only three patients in our study had ampullary carcinoma out of which the sensitivity and specificity came 100% for MRCP. One patient, in whom MRCP and HPE detected ampullary carcinoma, ERCP detected no ampullary carcinoma thus favoring MRCP. However, owing to inadequate study population results are inconclusive. There is significant difference between MRCP and ERCP accuracy rate in detection of ampullary carcinoma. Therefore, our study which is more in favor of MRCP. There were 78% patients who were detected with biliary duct dilatation in ERCP, which was equally detected in MRCP. Thus MRCP had 100% sensitivity and specificity in detecting biliary duct dilatation compared to ERCP. Pancreatic dilatation was detected in four patients and there were two patients who were detected with ampullary stones and its sensitivity, specificity came up to 100% compared to ERCP. Conclusion: Thus to conclude, MRCP has high sensitivity for CBD such as stones, strictures and malignancies therefore to avoid unnecessary diagnostic ERCP; in cases with suspicion (clinical/CBD-IHBR dilatation on USG) of choledocholithiasis/ampullary stone, MRCP is recommended.

Development and implementation of optimized chest CT protocol in COVID-19: A clinical audit.

Background: Several studies have justified use of chest computed tomography (CT) in diagnosis, evaluation of severity, treatment response, and complications of coronavirus disease 2019 (COVID-19) pneumonia. Increased utilization of CT in patients with known or suspected COVID-19 pneumonia has resulted in concerns of overuse, lack of protocol optimization, and radiation exposure. Aims: The study was conducted to develop and implement optimized protocol for chest CT for reducing radiation dose in adult patients suspected or diagnosed to have COVID-19 infection. Setting and Design: The study was conducted in the department of radiology of a rural tertiary care teaching hospital in western India. Clinical audit was used as a tool to impart and assess the impact of optimized chest CT protocol. Methods and Material: The pre-intervention audit included radiation dosimetry data, number of phases and length of scan of 50 adult patients, undergoing non-contrast chest CT scans in March 2021. A brief educational intervention outlining the parameters of optimized protocol was conducted on April 1, 2021.The post-intervention audit consisted of two cycles for 109 and 67 chest CT scans in the months April and May 2021. Results: The optimized protocol was found clinically adequate with a good inter-rater reliability. The compliance to the optimized protocol was weak in audit cycle 2, which improved significantly in audit cycle 3 after reinforcement. The mean (SD) per scan Computed Tomography Dose Index-Volume (CTDI-vol) reduced significantly across audit cycles [22.06 (12. 31) Vs. 10.58 (7.58) Vs. 4.51 (2.90) milli Gray, respectively, P < 0.001]. Similar findings were noted for Dose Length Product (DLP). Conclusion: Clinical audit of chest CT protocol and resultant radiation doses provided adequate feedback for dose optimization. A simple educational intervention helped achieve dose optimization.

Invasive fungal sinusitis-A neglected but important association with COVID 19 infection and a ticking bomb.

A retrospective analysis of severe acute respiratory syndrome (SARS) and influenza data worldwide has concluded that fungal coinfections associated with global SARS-coronavirus 2 (CoV-2) are likely to be missed or misdiagnosed. The coronavirus disease-2019 (COVID)-19 patients, especially those who are severely ill or immunocompromised, are more likely to suffer from invasive mycoses which require early detection and treatment. We report two such cases, one of which is a case of aspergillosis of unilateral orbit and maxilla and another case is of mucormycosis infection of the paranasal sinuses and bilateral orbits.

Discovery, Characterization, and Structure-Based Optimization of Small-Molecule In Vitro and In Vivo Probes for Human DNA Polymerase Theta.

Human DNA polymerase theta (Polθ), which is essential for microhomology-mediated DNA double strand break repair, has been proposed as an attractive target for the treatment of BRCA deficient and other DNA repair pathway defective cancers. As previously reported, we recently identified the first selective small molecule Polθ in vitro probe, 22 (ART558), which recapitulates the phenotype of Polθ loss, and in vivo probe, 43 (ART812), which is efficacious in a model of PARP inhibitor resistant TNBC in vivo. Here we describe the discovery, biochemical and biophysical characterization of these probes including small molecule ligand co-crystal structures with Polθ. The crystallographic data provides a basis for understanding the unique mechanism of inhibition of these compounds which is dependent on stabilization of a "closed" enzyme conformation. Additionally, the structural biology platform provided a basis for rational optimization based primarily on reduced ligand conformational flexibility.