Delta Variants of SARS-CoV-2 Cause Significantly Increased Vaccine Breakthrough COVID-19 Cases in Houston, Texas.

Genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have repeatedly altered the course of the coronavirus disease 2019 (COVID-19) pandemic. Delta variants are now the focus of intense international attention because they are causing widespread COVID-19 globally and are associated with vaccine breakthrough cases. We sequenced 16,965 SARS-CoV-2 genomes from samples acquired March 15, 2021, through September 20, 2021, in the Houston Methodist hospital system. This sample represents 91% of all Methodist system COVID-19 patients during the study period. Delta variants increased rapidly from late April onward to cause 99.9% of all COVID-19 cases and spread throughout the Houston metroplex. Compared with all other variants combined, Delta caused a significantly higher rate of vaccine breakthrough cases (23.7% for Delta compared with 6.6% for all other variants combined). Importantly, significantly fewer fully vaccinated individuals required hospitalization. Vaccine breakthrough cases caused by Delta had a low median PCR cycle threshold value (a proxy for high virus load). This value was similar to the median cycle threshold value for unvaccinated patients with COVID-19 caused by Delta variants, suggesting that fully vaccinated individuals can transmit SARS-CoV-2 to others. Patients infected with Alpha and Delta variants had several significant differences. The integrated analysis indicates that vaccines used in the United States are highly effective in decreasing severe COVID-19, hospitalizations, and deaths.

Trajectory of Growth of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants in Houston, Texas, January through May 2021, Based on 12,476 Genome Sequences.

Certain genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of substantial concern because they may be more transmissible or detrimentally alter the pandemic course and disease features in individual patients. SARS-CoV-2 genome sequences from 12,476 patients in the Houston Methodist health care system diagnosed from January 1 through May 31, 2021 are reported here. Prevalence of the B.1.1.7 (Alpha) variant increased rapidly and caused 63% to 90% of new cases in the latter half of May. Eleven B.1.1.7 genomes had an E484K replacement in spike protein, a change also identified in other SARS-CoV-2 lineages. Compared with non-B.1.1.7-infected patients, individuals with B.1.1.7 had a significantly lower cycle threshold (a proxy for higher virus load) and significantly higher hospitalization rate. Other variants [eg, B.1.429 and B.1.427 (Epsilon), P.1 (Gamma), P.2 (Zeta), and R.1] also increased rapidly, although the magnitude was less than that in B.1.1.7. Twenty-two patients infected with B.1.617.1 (Kappa) or B.1.617.2 (Delta) variants had a high rate of hospitalization. Breakthrough cases (n = 207) in fully vaccinated patients were caused by a heterogeneous array of virus genotypes, including many not currently designated variants of interest or concern. In the aggregate, this study delineates the trajectory of SARS-CoV-2 variants circulating in a major metropolitan area, documents B.1.1.7 as the major cause of new cases in Houston, TX, and heralds the arrival of B.1.617 variants in the metroplex.

Apheresis medicine in the era of advanced telehealth technologies: An American Society for Apheresis position paper Part I: Understanding the basic technologies and apheresis medicine practice models.

The wide spread availability and use of sophisticated high-speed telecommunication networks coupled with inexpensive and easily accessible computing capacity have catalyzed the creation of new tools and strategies for healthcare delivery. Such tools and strategies are of value to apheresis medicine (AM) practitioners if they improve delivery of patient care, enhance safety during a therapeutic apheresis (TA) intervention, facilitate care access, advance technical capabilities of apheresis devices, and/or elevate quality performance within TA programs. In the past several years, healthcare delivery systems' adoption of telecommunication technologies has been fostered by organizational financial and quality improvement objectives. More recently, adoption of telehealth technologies has been catalyzed by the COVID-19 pandemic as these technologies enhance both patient and provider safety in an era of social distancing. These changes will also influence the delivery of TA services which now can be generally viewed in a tripartite model format comprised of traditional hospital-based fixed site locales, mobile TA operations and lately an evolving telemedicine remote management model now reffered to as telapheresis (TLA). This communication developed by the Public Affairs and Advocacy Committee of the American Society for Apheresis (ASFA) and endorsed by its Board of Directors, reviews and describes various aspects of established and evolving electronic technologies related to TLA and the practice of AM. In subsequent companion publications, additional aspects to TLA will be explored and ASFA's vision of reasonable, regulatory compliant and high-quality TLA practices will be expounded.

3q26.2/EVI1 rearrangement is associated with poor prognosis in classical Philadelphia chromosome-negative myeloproliferative neoplasms.

Classical Philadelphia chromosome-negative myeloproliferative neoplasms are a group of closely related myeloid disorders with different histologic features and clinical presentations at an early stage, but all later develop into a similar fibrotic stage with variable risk of acute transformation. The significance of 3q26.2/EVI1 rearrangement has been well recognized in acute myeloid leukemia, myelodysplastic syndrome, and chronic myeloid leukemia. However, the clinical importance of 3q26.2/EVI1 rearrangement in classical Philadelphia chromosome-negative myeloproliferative neoplasms is unknown. Here we reported 15 patients with classical Philadelphia chromosome-negative myeloproliferative neoplasms showing 3q26.2 rearrangement, including inv(3)(q21q26.2) (n=6), t(3;21)(q26.2;q22)(n=4), t(3;3)(q21;q26.2)(n=3), inv(3)(q13.3q26.2)(n=1), and t(3;12)(q26.2;p13)(n=1). In addition to 3q26.2 rearrangement, 9 of 15 cases had other concurrent karyotypical abnormalities, including -7/7q- and -5/5q-. There were 8 men and 7 women with a median age of 59 years (range, 35-79 years) at initial diagnosis of myeloproliferative neoplasms: 8 patients had primary myelofibrosis, 4 had polycythemia vera, and 3 had essential thrombocythemia. JAK2 V617F mutation was detected in 8/14 patients, including 4/4 with polycythemia vera. The median interval from the initial diagnosis of myeloproliferative neoplasms to the detection of 3q26.2 rearrangement was 44 months (range, 1-219 months). At time of emergence of 3q26.2 rearrangement, 11 patients were in blast phase and 2 patients had increased blasts (6-19%). Dyspoiesis, predominantly in megakaryocytes, were detected in all patients with adequate specimens at time of 3q26.2 rearrangement. Following 3q26.2 rearrangement, 12 patients received chemotherapy, but none of them achieved complete remission. Of 14 patients with follow-up information, all died with a median overall survival time of only 3 months (range 0-14 months) after the emergence of 3q26.2 rearrangement. In summary, 3q26.2 rearrangement in classical Philadelphia chromosome-negative myeloproliferative neoplasms is associated with other concurrent cytogenetic abnormalities, a rapid disease progression and blast transformation, a poor response to chemotherapy and a dismal prognosis.

A retrospective analysis of molecular testing in cytologically indeterminate thyroid nodules with histologic correlation: Experience at a heterogenous multihospital system.

INTRODUCTION: Thyroid malignancy is one of the most common types of cancer in developed nations. Currently, fine-needle aspiration cytology (FNAC) is the most practical screening test for thyroid nodules. However, cytologically indeterminate samples comprise approximately 15%-30% of cases. These include cases classified as atypia of undetermined significance (AUS), follicular neoplasm (FN), and suspicious for malignancy (SFM). Indeterminate cases can be sent for molecular testing for more definitive classification to help guide management and prevent overtreatment of benign thyroid nodules. We conducted a retrospective review on molecular testing of indeterminate thyroid FNAC and reviewed subsequent histologic diagnoses in resection specimens to assess how molecular testing supported a diagnosis and its effect on clinical management of patients at our institution. METHODS: A retrospective chart review was performed on all thyroid FNAC specimens, corresponding molecular testing, and subsequent surgical resection specimens over a 6-year period. RESULTS: A total of 10,253 thyroid FNAC were performed in our hospital system during our study period, of which 10% (n = 1102/10,253) had indeterminate FNAC results. Molecular testing was performed in 16% (n = 178/1102) of indeterminate cytology cases. Genetic alterations were identified in 39% (n = 69/178) of the cases sent for molecular testing. The majority of cytologically indeterminate cases sent for molecular testing were follicular-patterned lesions and their corresponding resection specimens revealed mostly low grade follicular derived neoplasms (i.e., follicular adenoma, non-invasive follicular thyroid neoplasm with papillary-like nuclear features, and follicular variant of papillary thyroid carcinoma). Of the cases with identified genetic alterations, 75% (n = 52/69) were treated surgically. In cases with no genetic alterations identified, only 18% (n = 20/109) were treated surgically. DISCUSSION/CONCLUSION: Molecular testing on cytologically indeterminate thyroid nodules can help provide a more accurate risk of malignancy assessment in patients with lesions that are difficult to diagnosis based solely on FNAC morphology. The types of genetic alterations identified in the resected thyroid lesions were consistent with what has been previously described in the literature. Additionally, we found that in the patients with indeterminate thyroid FNAC with adjunct molecular testing, more than half did not undergo surgical resection. This finding emphasizes the value of adding molecular testing in patients, particularly when attempting to reduce unnecessary surgical intervention.

Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer.

Background and Purpose: With the growing interest in total neoadjuvant treatment for locally advanced rectal adenocarcinoma (LARC) there is an urgent unmet need to identify predictive markers of response to long-course neoadjuvant concurrent chemoradiotherapy (LCRT). O6-Methylguanine (O6-MG)-DNA-methyltransferase (MGMT) gene methylation has been associated in some malignancies with response to concurrent chemoradiotherapy. We attempted to find if pathologic response to LCRT was associated with MGMT promoter hypermethylation (MGMTh). Materials and Methods: Patients were identified with LARC, available pre-treatment biopsy specimens, and at least 1 year of follow-up who received LCRT followed by surgical resection within 6 months. Biopsies were tested for MGMTh using a Qiagen pyrosequencing kit (Catalog number 970061). The primary outcome of LCRT responsiveness was based on tumor regression grade (TRG), with grades of 0-1 considered to have excellent response and grades of 2-3 considered to be non-responders. Secondary outcomes included overall survival (OS) and recurrence free survival (RFS). Results: Of 96 patients who met inclusion criteria, 76 had samples which produced reliable assay results. MGMTh corresponded with higher grade and age of the biopsy specimen. The percentage of responders to LCRT was higher amongst the MGMTh patients than the MGMTn patients (60.0% vs 27.5%, p value = 0.0061). MGMTh was not significantly associated with improved OS (2-year OS of 96.0% vs 98.0%, p = 0.8102) but there was a trend for improved RFS (2-year RFS of 87.6% vs 74.2%, p = 0.0903). Conclusion: Significantly greater tumor regression following LCRT was seen in MGMTh LARC. Methylation status may help identify good candidates for close observation without surgery following LCRT.

High-density porous polyethylene wedge implant in correction of enophthalmos and hypoglobus in seeing eyes.

INTRODUCTION: To report the results of post-traumatic enophthalmos/hypophthalmos correction with high-density porous polyethylene wedge implants in seeing eyes. METHODS: This is an interventional case series of 25 patients (25 eyes) with post-traumatic enophthalmos and hypophthalmos, who underwent orbital reconstruction to correct the enophthalmos and hypophthalmos using Medpor® wedge implant. The aim was an overcorrection of 1 mm in comparison to the other eye, intra-operatively. If needed, trimming of the wedge implant or adding Medpor® sheets were used to achieve the goal. Success was defined as achieving the globe position within 1 mm of the other eye in the last follow-up. Improvement and failure were considered as correction outside the success range of 1 mm and no change in the amount of enophthalmos/hypophthalmos, respectively. RESULTS: Patients were followed for at least 6 months (mean= 12.66, SD= 12.32). Success, improvement and failure of enophthalmos correction were: 58.3% (14/24), 37.5% (9/24) and 1 (1/24, 4.1%), respectively. Success, improvement and failure of hypophthalmos correction were 73.68% (14/19), 15.78% (3/19) and 5.26% (1/19), respectively. There was no significant difference between the success rate of enophthalmos versus hypophthalmos correction (P= 0.8). Results of 1-month follow up change in enophthalmos and hypophthalmos significantly correlated (r= 0.92, P= 0.000) with the change recorded at last follow up. CONCLUSIONS: Porous polyethylene wedge implants are useful and safe in correction of enophthalmos and hypoglobus in seeing eyes. Appropriately positioned implant yields no significant difference in correction of enophthalmos versus hypophthalmos.

Impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on fine-needle aspiration diagnoses of thyroid nodules.

In 2016, the entity of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was proposed. This study investigated the impact of NIFTP nomenclature on fine-needle aspiration (FNA) evaluation of thyroid nodules and clinical management, as well as the molecular profile of NIFTP. The study included 23 out of 275 cases diagnosed as follicular variant papillary thyroid carcinoma from 2005 to 2015 that were reclassified as NIFTP, as well as 14 cases with an original diagnosis of NIFTP from 2016 to 2019. Information on demographic characteristics, FNA diagnoses, and follow-up was collected. Before 2016, 43.5% of NIFTP surgical cases were diagnosed as malignant or suspicious for malignancy by presurgical FNA, 80% of which received total thyroidectomy. Since 2016, only 15.4% of NIFTP cases were diagnosed as malignant or suspicious for malignancy and treated with total thyroidectomy. The overall total thyroidectomy rate decreased from 56.5% to 21.4% for NIFTP cases. RAS mutations (KRASQ61R and NRASQ61R ) were present in 57.1% of NIFTP cases, with no BRAF mutations identified. Our study demonstrates a significant impact of NIFTP nomenclature on FNA diagnosis of thyroid nodules with reduced diagnoses as malignant or suspicious for malignancy, thus avoiding overdiagnosis and overtreatment of NIFTP patients. The molecular study indicates that RAS mutations play an important role in NIFTP tumorigenesis.

Decision-making in diagnosis of bronchus-associated lymphoid tissue lymphoma.

Bronchus-associated lymphoid tissue (BALT) lymphomas of the lung are uncommon, and diagnosis is often delayed due to the indolent clinical course. Often, adequate samples are difficult to obtain by bronchoscopy with transbronchial biopsy alone. This retrospective study reviewed the diagnosis and treatment of BALT lymphoma cases at our institution over the course of 19 years. Most patients were white, women, and >50 years old; the mean Charlson Comorbidity Index at the time of diagnosis was 6. Seven of 12 patients presented with solitary nodules or multiple nodules. For six cases, initial modalities were nondiagnostic; four subsequently underwent surgical biopsy, one underwent computed tomography-guided biopsy, and one underwent navigational bronchoscopy for final diagnosis of BALT lymphoma. Ultimately, 55% of cases were diagnosed with nonsurgical biopsy. One patient suffered a pneumothorax related to the initial diagnostic attempt. Ten patients received chemotherapy, radiation, and/or surgery, and 11 of the 12 are still alive. Our data confirm the previously described indolent behavior of BALT lymphomas and the challenges related to diagnosis. While previous studies have suggested surgical biopsy as the primary modality for obtaining histopathology, navigational bronchoscopy could serve as a safer alternative.

The Reemergence of Seasonal Respiratory Viruses in Houston, Texas, after Relaxing COVID-19 Restrictions.

Measures intended to limit the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus at the start of the coronavirus disease 2019 (COVID-19) pandemic resulted in a rapid decrease in other respiratory pathogens. Herein, we describe the trends of respiratory pathogens in a major metropolitan health care system central microbiology reference laboratory before and during the COVID-19 pandemic, with attention to when COVID-19 mitigation measures were implemented and relaxed. During the initial lockdown period, COVID-19 was the primary respiratory pathogen detected by multiplex respiratory panels. As COVID-19 containment measures were relaxed, the first non-COVID respiratory viruses to return to prepandemic levels were members of the rhinovirus/enterovirus family. After the complete removal of COVID-19 precautions at the state level, including an end to mask mandates, we observed the robust return of seasonal coronaviruses, parainfluenza virus, and respiratory syncytial virus. Inasmuch as COVID-19 has dominated the landscape of respiratory infections since early 2020, it is important for clinicians to recognize that the return of non-COVID respiratory pathogens may be rapid and significant when COVID-19 containment measures are removed. IMPORTANCE We describe the return of non-COVID respiratory viruses after the removal of COVID-19 mitigation measures. It is important for the public and physicians to recognize that, after months of COVID-19 being the primary driver of respiratory infection, more typical seasonal respiratory illnesses have returned, and this return is out of the normal season for some of these pathogens. Thus, clinicians and the public must now consider both COVID-19 and other respiratory illnesses when a patient presents with symptomatic respiratory illness.

A deep learning approach for predicting severity of COVID-19 patients using a parsimonious set of laboratory markers.

The SARS-CoV-2 virus has caused tremendous healthcare burden worldwide. Our focus was to develop a practical and easy-to-deploy system to predict the severe manifestation of disease in patients with COVID-19 with an aim to assist clinicians in triage and treatment decisions. Our proposed predictive algorithm is a trained artificial intelligence-based network using 8,427 COVID-19 patient records from four healthcare systems. The model provides a severity risk score along with likelihoods of various clinical outcomes, namely ventilator use and mortality. The trained model using patient age and nine laboratory markers has the prediction accuracy with an area under the curve (AUC) of 0.78, 95% CI: 0.77-0.82, and the negative predictive value NPV of 0.86, 95% CI: 0.84-0.88 for the need to use a ventilator and has an accuracy with AUC of 0.85, 95% CI: 0.84-0.86, and the NPV of 0.94, 95% CI: 0.92-0.96 for predicting in-hospital 30-day mortality.

Tissue necrosis after chemotherapy in osteosarcoma as the important prognostic factor.

OBJECTIVE: To determine the histological response to preoperative chemotherapy of the percentage of tumor necrosis, and to assess the relationship between the histological response and the oncological result. METHODS: Eighty patients with osteosarcoma were managed with preoperative and postoperative chemotherapy and operative resection at Shafa Yahyaeeyan Hospital, Tehran, Iran between 2003-2005. Sections of each operative specimen were examined, and the histological response to chemotherapy was graded. Grade 1 indicated necrosis of 50% of the tumor or less; grade 2, necrosis of more than 50% yet less than 90 percent; grade 3, necrosis of more than 90 percent. RESULTS: The mean duration of the follow-up of the surviving patients, who were continuously free from disease was 1044 days. The histological response to preoperative chemotherapy (p=0.016) was the most important predictor of event-free survival. The rate of event-free short-term survival for the 80 patients entering this study was 86 percent (69 patients) at 12 months, 50% 24 patients at 24 months, and 21% (5 patients) at 40 months, with 5 patients surviving for a median of 1096 days. CONCLUSION: The histological response to preoperative chemotherapy is an important clinical predictor of the result of operative treatment of osteosarcoma. This indicator should be used to identify patients who are at high risk for metastasis, as such patients may be candidates for more intensive or novel therapy.

Interocular differences of the Pentacam measurements in normal subjects.

PURPOSE: The aim of this study was to determine the interocular differences of the Pentacam corneal measurements in a normal population. METHODS: A retrospective analysis was performed on 550 eyes of 275 consecutive subjects evaluated for refractive surgery at the Rassoul Akram Hospital, Iran University of Medical Sciences. A Pentacam Scheimpflug camera was used for corneal measurements. Statistical analysis was performed to determine the normal levels of the difference between the two eyes. RESULTS: One hundred and four men and 171 women with a mean age of 29.1 +/- 7.73 years were evaluated. The mean (range) interocular difference was 2.17 (zero to 21) microm for maximum anterior elevation (AEmax), 3.62 (zero to 31) microm for maximum posterior elevation (PEmax), 8.42 (zero to 30) microm for minimum corneal thickness (CTmin), 0.06 (zero to 0.4) mm(3) for three millimetre corneal volume (CV3), 0.19 (zero to 1.2) mm(3) for five millimetre corneal volume (CV5), 0.44 (zero to 2.9) mm(3) for seven millimetre corneal volume (CV7), 0.24 (zero to 2.5) dioptres for the mean keratometry (Km) and 0.39 (zero to 2.5) D for measurements of the corneal dioptric power in the steepest meridian (Kmax). CONCLUSIONS: Individuals with differences greater than 17.4 microm in AEmax, 29.1 microm in PEmax, 29.6 microm in CTmin, 2 D in Km, 2.27 D in Kmax, 0.32 in CV3, 1.05 in CV5, and 2.6 in CV7 between eyes represent less than 0.5 per cent of the population. An interocular difference outside the normal range should alert the clinician to examine for other parameters that are more predictive of post-refractive surgical ectasia.