Socio-economic status and COVID-19-related cases and fatalities.

OBJECTIVES: The United States has the highest number of coronavirus disease 2019 (COVID-19) in the world, with high variability in cases and mortality between communities. We aimed to quantify the associations between socio-economic status and COVID-19-related cases and mortality in the U.S. STUDY DESIGN: The study design includes nationwide COVID-19 data at the county level that were paired with the Distressed Communities Index (DCI) and its component metrics of socio-economic status. METHODS: Severely distressed communities were classified by DCI>75 for univariate analyses. Adjusted rate ratios were calculated for cases and fatalities per 100,000 persons using hierarchical linear mixed models. RESULTS: This cohort included 1,089,999 cases and 62,298 deaths in 3127 counties for a case fatality rate of 5.7%. Severely distressed counties had significantly fewer deaths from COVID-19 but higher number of deaths per 100,000 persons. In risk-adjusted analysis, the two socio-economic determinants of health with the strongest association with both higher cases per 100,000 persons and higher fatalities per 100,000 persons were the percentage of adults without a high school degree (cases: RR 1.10; fatalities: RR 1.08) and proportion of black residents (cases and fatalities: Relative risk(RR) 1.03). The percentage of the population aged older than 65 years was also highly predictive for fatalities per 100,000 persons (RR 1.07). CONCLUSION: Lower education levels and greater percentages of black residents are strongly associated with higher rates of both COVID-19 cases and fatalities. Socio-economic factors should be considered when implementing public health interventions to ameliorate the disparities in the impact of COVID-19 on distressed communities.

Review: The Perioperative Use of Thromboelastography for Liver Transplant Patients.

Thromboelastography (TEG) is a viscoelastic test that allows rapid evaluation of clot formation and fibrinolysis from a sample of whole blood. TEG is increasingly utilized to guide blood product resuscitation in surgical patients and transfusions for liver transplant patients. Patients with severe liver failure have significant derangement of their clotting function due to impaired production of procoagulant and anticoagulant factors. Traditional coagulation studies are limited by the short time needed for the result and provide little information about the dynamics and strength of clot formation. In addition, traditional coagulation studies do not correlate well with bleeding episodes and may lead to over-transfusion of various blood products. Evidence is less robust regarding the use of TEG for transfusion management decisions in severe liver failure patients awaiting, undergoing, or immediately after liver transplant surgery. However, the available evidence suggests that systematic implementation of TEG rather than traditional coagulation studies results in the administration of fewer blood products without increased mortality or complications. The purpose of this study is to review the literature regarding the use of TEG in liver failure patients prior to liver transplant, intraoperatively, and postoperatively. Additional high-quality randomized controlled studies should be performed to evaluate the use of TEG to guide transfusion decisions, particularly in the postoperative period following liver transplantation.

Effect of heterogeneous radio sensitivity on the survival, alpha beta ratio and biologic effective dose calculation of irradiated mammalian cell populations.

It is demonstrated that the surviving fraction of a population of cells with heterogeneous radio sensitivity, like that composing most malignant tumors, conforms to a different linear quadratic survival relation for dose less than about 3-5 Gy and dose greater than about 7-9 Gy. In the intermediate range of dose the survival relation for the population, as a whole, is not linear quadratic. Consequently, the value of the alpha beta ratio and the associated biologically effective dose calculation are different for the low and high dose range for most malignant tumors. Normal tissue cell populations responsible for organ function also have heterogeneous radio sensitivity, though to less degree than most malignant tumors. Consequently, the alpha beta ratio and associated biologically effective dose calculation related to the development of some acute early and chronic late developing radiation injuries are not the same in the low and high dose range. Variance of the distribution of α of a heterogeneous cell population lowers the effective value of the quadratic survival constant ß of the population, as a whole, and increases the α/ß ratio in the low dose range. Heterogeneous appearance of tumor cells (pleomorphism) and necrosis on biopsy or imaging studies reflect heterogeneity of the radio sensitivity of the cells. Greater heterogeneity implies a tendency to higher α/ß ratio. This may furnish a clinically accessible way to estimate a value of the α/ß ratio specific to an individual patient and tumor.

Effects of beam interruption time on tumor control probability in single-fractionated carbon-ion radiotherapy for non-small cell lung cancer.

Carbon-ion radiotherapy treatment plans are designed on the assumption that the beams are delivered instantaneously, irrespective of actual dose-delivery time structure in a treatment session. As the beam lines are fixed in the vertical and horizontal directions at our facility, beam delivery is interrupted in multi-field treatment due to the necessity of patient repositioning within the fields. Single-fractionated treatment for non-small cell lung cancer (NSCLC) is such a case, in which four treatment fields in multiple directions are delivered in one session with patient repositioning during the session. The purpose of this study was to investigate the effects of the period of dose delivery, including interruptions due to patient repositioning, on tumor control probability (TCP) of NSCLC. All clinical doses were weighted by relative biological effectiveness (RBE) evaluated for instantaneous irradiation. The rate equations defined in the microdosimetric kinetic model (MKM) for primary lesions induced in DNA were applied to the single-fractionated treatment of NSCLC. Treatment plans were made for an NSCLC case for various prescribed doses ranging from 25 to 50 Gy (RBE), on the assumption of instantaneous beam delivery. These plans were recalculated by varying the interruption time τ ranging from 0 to 120 min between the second and third fields for continuous irradiations of 3 min per field based on the MKM. The curative doses that would result in a TCP of 90% were deduced for the respective interruption times. The curative dose was 34.5 Gy (RBE) for instantaneous irradiation and 36.6 Gy (RBE), 39.2 Gy (RBE), 41.2 Gy (RBE), 43.3 Gy (RBE) and 44.4 Gy (RBE) for τ = 0 min, 15 min, 30 min, 60 min and 120 min, respectively. The realistic biological effectiveness of therapeutic carbon-ion beam decreased with increasing interruption time. These data suggest that the curative dose can increase by 20% or more compared to the planned dose if the interruption time extends to 30 min or longer. These effects should be considered in carbon-ion radiotherapy treatment planning if a longer dose-delivery procedure time is anticipated.

A microdosimetric-kinetic model for the sensitization of v79 cells to radiation by incorporation of bromodeoxyuridine.

Hawkins, R. B. A Microdosimetric-Kinetic Model for the Sensitization of V79 Cells to Radiation by Incorporation of Bromodeoxyuridine. Radiat. Res. 155, 698-702 (2001). The sensitization of G(1)-phase V79 cells to killing by ionizing radiation through incorporation of bromodeoxyuridine (BrdU) in their DNA has been reported to occur exclusively through an increase in the value of the quadratic parameter of the linear-quadratic survival relationship (beta) with no change in the linear parameter (alpha). The consequence of this, as understood through the microdosimetric-kinetic model of cell survival, is discussed. It is shown that the invariance of alpha implies that sensitization is due solely to a decrease in the rate of repair of the initial (potentially lethal) lesions in DNA containing BrdU. Further, for alpha to be unchanged, the average size of the compartments into which the nucleus is partitioned (domains), as postulated in the microdosimetric-kinetic model, must vary in proportion to the reciprocal of the square root of the rate constant for repair of the DNA lesions. This implies that the domain is not a structural subunit of the nucleus. It is a surrogate representation of the consequence of lesions in DNA being restricted to a region in the vicinity of the location in the nucleus at which they are created. A lesion is confined because the distance it can diffuse by random flight to react with another lesion to form a lethal lesion is restricted because a lesion's lifetime is limited by the repair process.

A simple method of radiation treatment of craniospinal fields with patient supine.

PURPOSE: To describe a procedure for supine craniospinal radiation treatment. METHODS AND MATERIALS: The procedure is described as carried out with a 100 cm isocenter linear accelerator and compatible simulator. Treatment is with a single PA directed spinal field abutting lateral directed cranial fields. Abutment of the fields is established by placement, under direct observation, of the edges of the light fields at a mark placed on the anterior skin surface and subtraction of a calculated distance from the collimator readout length of the cranial field. RESULTS: The precision and reproducibility of field edge placement at the abutment line appears to be as good as for treatment in the prone position. This can be verified with port films. CONCLUSION: Supine craniospinal treatment is a reliable and convenient alternative to treatment in the prone position.

Survival of a mixture of cells of variable linear-quadratic sensitivity to radiation.

The experimentally observed survival of a heterogeneous mixture of cells, each component of which obeys a different linear-quadratic survival response to ionizing radiation, is examined. It is shown that the survival relationship for the mixed population approaches a linear-quadratic form for low doses. The linear parameter of the low-dose relationship approached is equal to the average of the distribution of values of the linear parameter (alpha(i)) of the various components of the mixture. The quadratic parameter of the low-dose relationship approached is equal to the average of the distribution of values of the quadratic parameter (beta(i)) of the various components of the mixture minus one-half the variance of the distribution of the values of alpha(i). A numerical example of the survival expected for an exponentially growing population of Chinese hamster V79 cells is presented. From this it can be appreciated that the apparent value of the alpha and beta parameters obtained by fitting an experimentally obtained survival curve will depend on the range of doses over which survival is determined. The apparent value of beta is decreased at higher doses, producing a straightening of the survival curve to approach the exponential decrease in survival commonly observed for the terminal high-dose portion of survival curves. Apparent exponential survival at high doses is not inconsistent with linear-quadratic survival and may not indicate a multitarget or other mechanism of cell killing.

A microdosimetric-kinetic theory of the dependence of the RBE for cell death on LET.

Experiments with cultured mammalian cells exposed to ionizing radiation of varying LET are examined in the context of a microdosimetric-kinetic (MK) model of radiation induced mammalian. cell killing similar to the site model of the theory of dual radiation action. The experimentally measured RBE, in the limit of zero dose, increases linearly with LET for LET less than a value that lies in the range of about 40-90 keV per micron. It is shown that the tendency of the RBE to increase linearly with LET can be explained as a result of the random variation of specific energy among microscopic sized domains (sites), into which the nucleus may be partitioned, and the effect of this variation on the formation of lethal lesions by pairwise combination of repairable primary lesions in DNA. the microscopic subunits corresponding to a site have diameter in the range of 0.56-0.75 microns. The linearity of RBE with increasing LET implies that value of the quadratic parameter of the linear-quadratic survival relation (beta) is constant, at least for LET low enough to be in the linear range, and this in turn implies the production of primary DNA lesion, likely double strand breaks, does not increase with LET. the experiments, interpreted with MK model, also imply that the repairability and potential for lethality of the primary DNA lesion does not change with variation of LET within the linear range. The failure of RBE to maintain its linear increase for higher values of LET, and the resulting RBE maximum at about 100 keV per micron, are likely primarily due to the departure of the distribution of lethal lesions among cells from the Poisson distribution. Some implications concerning the use of radiation to treat cancer are noted.

Treatment of adjoining field areas with electron beams of different energy using a single central axis.

The use of a single central axis causes the divergence of radiation at the abutting boundaries to be parallel, even in cases for which the abutting boundary does not coincide with the beam central axis. Lateral diffusion of scattered electrons from an area treated with one energy into the neighboring area is reciprocated to provide a smooth change from the dose at4 any given depth near the center of one area to that near the center of the other. This allows treatment of deep levels of tissue in one portion of a field, while sparing deep level structures in an adjacent portion of the field.

Disseminated epidemic Kaposi's sarcoma treated with radiation and chemotherapy.

When a 40-year-old patient with end-stage acquired immunodeficiency syndrome (AIDS) had bloating and abdominal pain, a large epidemic Kaposi's sarcoma (EKS) lesion was found obstructing the pylorus. Treatment consisted of single-agent chemotherapy for the disseminated lesions and external beam irradiation to the obstructing lesion. Within days of radiation therapy, symptoms began to resolve, and by completion of therapy, the patient was virtually asymptomatic. Although EKS is common in homosexual men infected with the AIDS virus, these patients usually succumb to overwhelming opportunistic infections. Nevertheless, palliative courses of radiation, which can produce a complete response in 50% to 100% of treated KS lesions, can substantially improve the quality of life in these patients.

A microdosimetric-kinetic model of cell death from exposure to ionizing radiation of any LET, with experimental and clinical applications.

A model of mammalian cell death and survival following exposure to ionizing radiation that combines a kinetic description of repair and injury processes with a microdosimetric description of radiation energy deposition is presented. With reduction of one of the defining kinetic equations from quadratic to linear form, relations are obtained that describe the results of commonly performed variations of the cell survival experiment. These include single-dose survival of linear-quadratic form, survival after split-dose treatment and after post-irradiation change ill culture conditions and survival after exposure to continuously administered irradiation at low constant dose-rate. The effect of the inhomogeneous deposition of radiation energy inherent in exposure to radiation of significantly non-zero LET is included in these relations which apply to radiation of any LET. The values of the kinetic rate and time constants for repair and the processes that lead to cell death postulated in the model, which compose the alpha and beta parameters of the linear-quadratic survival relation, are estimated from cell survival experiments and DNA double-strand break measurements from the literature. A relation for estimating the daily fractional dose equivalent to continuous irradiation as employed in low dose-rate brachytherapy cancer treatment is presented.

A statistical theory of cell killing by radiation of varying linear energy transfer.

A theory is presented that provides an explanation for the observed features of the survival of cultured cells after exposure to densely ionizing high-linear energy transfer (LET) radiation. It starts from a phenomenological postulate based on the linear-quadratic form of cell survival observed for low-LET radiation and uses principles of statistics and fluctuation theory to demonstrate that the effect of varying LET on cell survival can be attributed to random variation of dose to small volumes contained within the nucleus. A simple relation is presented for surviving fraction of cells after exposure to radiation of varying LET that depends on the alpha and beta parameters for the same cells in the limit of low-LET radiation. This relation implies that the value of beta is independent of LET. Agreement of the theory with selected observations of cell survival from the literature is demonstrated. A relation is presented that gives relative biological effectiveness (RBE) as a function of the alpha and beta parameters for low-LET radiation. Measurements from microdosimetry are used to estimate the size of the subnuclear volume to which the fluctuation pertains.

Arthroscopy of the hip.

Arthroscopy of the hip is a relatively new addition to the orthopedic armamentarium. Eriksson, of Sweden, has been a pioneer in studying the force needed to distract the hip joint to allow adequate arthroscopic viewing. Johnson, of Michigan, has provided information on techniques including landmarks, needle positioning and cannula entry. Glick, of California, has described the lateral position for ease of entry of arthroscopic instruments just superior to the greater trochanter. A mini-arthrotomy technique has been used to sublux the femoral head anteriorly from the acetabulum to allow anterior viewing and debridement. An initial series of such procedures in 12 patients resulted in general improvement in symptoms of younger patients with localized articular cartilage defects. Results in older patients with diffuse osteoarthritic changes involving most of the weight-bearing zone of the femoral head were unsatisfactory, however, with most of those patients requiring total hip arthroplasty, within one to two years. Recently, arthroscopy of the hip has been performed in the outpatient surgery department under general endotracheal anesthesia in the lateral decubitus position. Mechanical distraction with 9-18 kg of force has been used routinely, without postoperative neurologic symptoms. Specially adapted long arthroscopes and powered synovial resectors and abraders have been used. In addition, pressurized saline inflow with 100 mmHg of pressure has provided improved joint visualization. Especially helpful has been the availability of angled arthroscopes, including 30 degrees, 60 degrees, and 90 degrees arthroscopes. Potential complications include inadvertent cartilage scuffing, broken instruments, neovascular injury to nearby structures, and local infection. Systemic complications such as pulmonary embolus must always by considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthroscopic stapling repair for shoulder instability: a retrospective study of 50 cases.

Fifty arthroscopic stapling repairs of detached glenoid labra were done on 50 shoulders in 47 patients with chronic shoulder dislocation or subluxation. This method offers a shorter rehabilitation period and decreases the morbidity associated with traditional repair. No arthrotomies were done. The follow-up period ranged from 18 to 54 months with an average of 39.4 months. Eight shoulders in seven patients, or 16% of the series, sustained additional trauma that caused redislocation or resubluxation. We felt that this relatively high redislocation rate was due to failure to immobilize these shoulders for 3 weeks postoperatively. This resulted from the lack of instruction from the surgeon or lack of compliance by the patient. For the past 29 months, because a mandatory 3-week immobilization in a sling has been required, there have been no further redislocations. Complications were few and basically were related to the failure to use the equipment in the precise technical manner outlined by the manufacturer. All of the hardware complications were managed without undue difficulty, and although they were a source of consternation to the surgeon, they did not affect the patients adversely. A successful outcome requires good surgical technique by the surgeon and compliance and cooperation by the patient postoperatively.

Carcinoma of the nasal cavity--results of primary and adjuvant radiotherapy.

Carcinomas of the nasal cavity are uncommon and the reported experience with radiotherapy is scarce. From 1969-1984, 62 patients with carcinoma of the nasal cavity received radiotherapy as all or part of initial treatment at the Mallinckrodt Institute of Radiology, Washington University Medical Center. Epidermoid carcinoma was the most common histologic subtype, occurring in 46 cases (73%), undifferentiated carcinoma in 10 cases (16%), and adenoid cystic carcinoma in 6 cases (10%). Minimum follow-up was 2.1 years, maximum 16.9 years, and the median was 6.9 years. Relapse-free survival and overall actuarial survival at 5 years were 47% and 52%, respectively; at 10 years, they were 42% and 32%, respectively. Of 35 recorded deaths, 16 were due to the nasal cavity carcinoma, 17 to intercurrent disease, 2 to postoperative complications. Survival was not significantly affected by histology (epidermoid vs undifferentiated), site, nodal status or treatment (radiotherapy alone vs radiotherapy + surgery). Local control was correlated significantly with tumor extent (p less than 0.04) and marginally with treatment (p = 0.15). Elective neck irradiation was not given. Nodal failure occurred in 10/52 patients (19%) with initially N0 necks. Of four patients presenting with N1 disease, one failed in the untreated contralateral neck.

Arthroscopic treatment of sports-related anterior osteophytes in the ankle.

Osteophytes on the anterior aspect of the tibia and anterior talus are common in athletes such as dancers, runners, and high jumpers who impact with quick and forceful dorsiflexion to this area. This pathology is often confirmed easily on lateral x-ray films. Excision, debridement, and/or abrasion arthroplasty can be performed arthroscopically to remove osteophytic bone. The joint space is easily approached and managed using small joint or even regular-sized arthroscopic instruments. Care is taken to reshape the anterior tibia and/or talus to its original contour, thus avoiding impingement of the joint space and scuffing of adjacent articular cartilage. Proper abrasion depths and punch lesions may be needed to expose bleeding capillary bone. This allows a regeneration of a fibrocartilage covering that not only decreases pain but also permits a return to functional and athletic activities. Postoperative treatment, including physical therapy, is described. Three case studies are presented that adequately demonstrate this problem, along with the corrective measures taken. Each case concludes with a brief summary of follow-up.

Arthroscopic stapling repair for chronic lateral instability.

We have presented a preliminary report on a limited number of patients with chronic lateral instability of the ankle treated with arthroscopic stapling reconstruction. As stated, the longest follow-ups are about 5 years, so the results over the long term are not yet known. Early adults have been quite encouraging, however, with improved functional stability of the ankle. Only one patient in more than two dozen has had recurrent instability that required more surgery. He returned with a history of additional sports trauma. The principle of secure fixation of ligaments to exposed bone surfaces with staples is a well-accepted and effective technique familiar to surgeons for many years. What is changing is that microsurgical techniques can be adapted to common orthopedic problems. Ankle arthroscopy is expanding continually to meet the needs of many patients. Discomfort is minimal, and many patients do not even fill their prescriptions for analgesic medication. The period of disability is relatively short and rehabilitation is rapid. Because most patients prefer arthroscopy to an open procedure, we must continue to explore all avenues of surgical technique. New tools and developments are constantly on the horizon. As in most arthroscopic surgical procedures, instruments of the correct size are most important, as is precise surgical technique. The key to successful arthroscopic surgery is careful forethought, meticulous planning, constant education, and a dependable team.