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Orbital volume measured by a low-dose CT scanning technique.

A method for measuring orbital volume using low-dose CT with contiguous 3 mm transaxial sections is described. The accuracy of the method is 1.6%, as demonstrated by comparing CT volume measurements with those derived directly from alginate impressions and on repeat scanning the precision of the measurement was judged as 1.3%. Within the same individual, the right and left orbital volumes were observed to be within 0.6 cm3 (s.d. +/- 0.33 cm3) of each other. This study demonstrates that low-dose CT scanning is a practical method of determining orbital volume and could be used to advantage in the management of traumatic enophthalmos and blow-out fractures of the orbit.

Enophthalmos

Low-dose CT and inflammatory disease of the paranasal sinuses.

Computed tomography (CT) is the gold standard for exact delineation of inflammatory sinus disease, especially before endoscopic surgical treatment, and in cases of postoperative recurrences. In routine CT studies, the radiation dose to the patient is not negligible. Therefore, the authors evaluated prospectively the CT scans of 44 patients with inflammatory disease of the paranasal sinuses, to define the imaging ability of low-dose CT (i.e. 60 mA-3 s, 30 mA-3 s, and 30 mA-2 s), comparatively with the standard mAs settings (130 mA-3 s). In all cases, the exact extent of the disease was correctly assessed on each of the low-dose settings, with no false negative study. The increasing graininess of low mAs sections did not induce errors of interpretation, despite a less pleasant appearance to the eyes. In cases of extensive sinus disease, the thickness and integrity of the ethmoid septa were sometimes more difficult to evaluate on low-dose CT sections. The authors recommend the use of low mAs settings in the evaluation of inflammatory disease of the sinuses, complemented, if necessary, in cases of extensive abnormalities, by one or two sections obtained with standard mAs settings, focused on questionably abnormal bone septa.

Adult

A reanalysis of the Hitachi cohort study evaluating the effectiveness of low-dose CT screening for lung cancer.

The effectiveness of low-dose thoracic computed tomography (CT) screening for lung cancer for non-smokers or light smokers has been unclear. The results of the Hitachi cohort study performed by the conventional multivariable analysis suggested the reduction of lung cancer mortality by thoracic CT screening, but also revealed the lower all-cause mortality in the CT group, which indicated the existence of self-selection bias. Because the background of the subjects in the CT screening group and that in the X-ray screening group were very different, it is critical to adjust appropriately the confounding factors. In this brief report, we describe a re-evaluation of the results of the Hitachi Cohort Study performed by using more flexible methods, propensity score matching and inverse probability weighting.

epidemiology/public health

Stage shift, histological differentiation, and survival patterns of lung squamous cell carcinoma versus adenocarcinoma in low-dose CT screening.

BACKGROUND: Whether LDCT-associated stage shift translates into similar survival patterns across lung cancer histologies remains uncertain. We compared stage shift, histological differentiation, tumor characteristics, and survival between lung squamous cell carcinoma (LUSC) and adenocarcinoma (LUAD) in the National Lung Screening Trial. METHODS: Among participants diagnosed with LUSC or LUAD, stage distribution and histological differentiation were compared between LDCT and chest X-ray (CXR) arms. Survival among diagnosed cases was measured from randomization. Multivariable models tested screening arm-by-histology interactions. Screen-detected LDCT tumors were compared by histology. RESULTS: During 6.5 years of median follow-up, 498 LUAD and 249 LUSC cases were diagnosed in the LDCT arm, and 374 and 212, respectively, were diagnosed in the CXR arm. LDCT was associated with higher odds of stage I disease for LUAD (adjusted odds ratio [aOR], 2.48; 95% CI 1.88-3.28) and LUSC (aOR, 1.71; 95% CI 1.17-2.48), without significant interaction (P&#x202f;=&#x202f;0.116). LDCT was associated with lower hazard of lung cancer-specific death among diagnosed LUAD cases (adjusted hazard ratio [aHR], 0.54; 95% CI 0.43-0.66), but not among diagnosed LUSC cases (aHR, 1.04; 95% CI 0.78-1.39; P for interaction<0.001). LUSC had lower screening sensitivity, more frequent detection in annual screening rounds, greater prediagnostic tumor size increase, and fewer well-differentiated stage I tumors than LUAD. CONCLUSION: LDCT was associated with stage shift for both subtypes, but favorable survival patterns among diagnosed cases were mainly observed for LUAD. Lower screening sensitivity, greater prediagnostic tumor size increase, and poorer histological differentiation may help explain why stage shift did not translate into similar survival patterns for LUSC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00047385.

Humans

The Growth of Screening-Detected Pure Ground-Glass Nodules Following 10 Years of Stability.

BACKGROUND: It remains uncertain for how long pure ground-glass nodules (pGGNs) detected on low-dose CT (LDCT) imaging should be followed up. Further studies with longer follow-up periods are needed to determine the optimal follow-up duration for pGGNs. RESEARCH QUESTION: What is the percentage of enlarging nodules among pGGNs that have remained stable for 10 years? STUDY DESIGN AND METHODS: This was a retrospective cohort study originating from participants with pGGNs detected on LDCT scans between 1997 and 2006 whose natural courses were reported in 2013. We re-analyzed all the follow-up data until July 2022. The study participants were followed up per our institutional guidelines until they were no longer a candidate for definitive treatment. The growth of the pGGNs was defined as an increase in the diameter of the entire nodule by&#xa0;&#x2265; 2&#xa0;mm or the appearance of new solid portions within the nodules. RESULTS: A total of 89 patients with 135 pGGNs were followed up for a median of 193&#xa0;months. Of 135 pGGNs, 23 (17.0%) increased in size, and the median time to the first detection of a size change was 71&#xa0;months. Of the 135 pGGNs, 122 were detected on the first LDCT scan and 13 were newly detected on the follow-up CT scan. An increase in size was observed within 5 years in 8 nodules (34.8%), between 5 and 10 years in 12 nodules (52.2%), and after 10 years in three nodules (13.0%). Fifteen nodules were histologically confirmed as adenocarcinoma by surgery. Among the 76 pGGNs stable for 10 years, 3 (3.9%) increased in size. INTERPRETATION: Among pGGNs that remained stable for 10 years, 3.9%&#xa0;eventually grew, indicating that some pGGNs can grow even following a long period of stability. We suggest that pGGNs may need to be followed up for > 10 years to confirm growth.

Humans

MULTIPREVENT: Integrated screening for smoking-related multimorbidity using low-dose chest computed tomography.

OBJECTIVES: Tobacco consumption, combined with individual genetic predispositions, contributes to an age-dependent risk not only for lung cancer but also for other non-communicable diseases (NCDs) such as cardiovascular disease (CVD), chronic obstructive pulmonary disease (COPD), osteoporosis, and diabetes. The MULTIPREVENT project aims to validate whether low-dose computed tomography (LDCT) of the chest, combined with simple biomarkers, functional tests, and genomic profiling, can serve as an effective tool for comprehensive health assessment and risk prediction of multimorbidity in adults. STUDY DESIGN: The study is based on a prospective epidemiological design involving 3000 participants from the MOLTEST-BIS lung cancer screening cohort (2016-2018). These participants, aged 50-79 years (during MOLTEST-BIS) and with a smoking history of at least 30 pack-years, will undergo two follow-up assessments in 2025-2027 and 2030-2032. METHODS: Each follow-up includes LDCT, spirometry, standardized blood pressure measurement, anthropometric evaluation, biomarker assessment (lipid profile, lipoprotein(a), glycated haemoglobin), and health-related questionnaires. Genetic profiling will be performed using the Illumina Infinium Global Screening Arrays approach to identify inherited predispositions to major NCDs. All data, clinical, imaging (including radiomics), molecular, and genetic, will be integrated through machine learning algorithms to develop AI-based risk prediction models. RESULTS: The MULTIPREVENT study is expected to generate a wide range of scientific, clinical, and infrastructural results that will serve as a foundation for future public health initiatives in integrated prevention. CONCLUSIONS: By linking imaging and biochemical markers, genetic susceptibility, and clinical parameters within a longitudinal design, MULTIPREVENT will establish data-driven, AI-supported prevention strategies aimed at reducing morbidity and mortality among adults exposed to tobacco. The project will also serve as a model for population-based multimorbidity prevention programs.

Humans

Long-term treatment results for acute megakaryoblastic leukaemia patients: a multicentre study.

The prognosis and long-term results of a group of 57 acute megakaryoblastic leukaemia (M7-AML) patients was analysed from a multicentre perspective. Ages ranged from 4 to 83 years, median 49 years; 30 were males and 27 were females. The median follow-up time was 7 months, range 1-24 months. Early exits occurred in 12 cases, their median age being 71 years. Forty-five patients were treated with combined aggressive chemotherapy (CT) (n = 26) or low-dose cytarabine (LD-AraC) (n = 19). The following results were obtained with combined CT or AraC, respectively. Complete remission (CR) rates were 73% and 84%, 12-month survival (SV) were 37% and 26%, 24-month SV were 12% and 11%, median SV 10 and 4 months, and relapse rates (RR) were 68% and 94%. These differences were not statistically significant. Irrespective of the treatment modality, the results were better for children (n = 10) than for adults (n = 35): RR rates were 90% and 74%, median SV: 7 and 5 months, 12-month SV: 40% and 22%, 24-month SV; 30% and 9%, and RR: 78% and 81%, respectively; these differences also were not statistically significant. In addition, a literature review of 42 patients from 18 previous reports is presented, including seven cases treated with allogeneic bone marrow transplantation (BMT). The best results were obtained with BMT: 12 and 24 month SV was 86% and the RR was 0%. On the above-mentioned basis, we feel that children and young adults with M7-AML should be offered BMT. In patients over 60 years old or not eligible for aggressive chemotherapy or BMT, an interesting possibility would be the use of LD-AraC which allows a high CR rate, followed by a classical consolidation regimen in order to prevent early relapses.

Adolescent

[Splenic subcapsular hematoma and long-term hemodialysis].

Uremic patients, or those on maintenance hemodialysis, are at increased risk for spontaneous bleeding. Manifestations include retroperitoneal, costal, hepatic, renal, pericardial, mediastinal and subdural hemorrhages. We describe 2 patients on chronic hemodialysis, a 45-year-old man and a 50-year-old woman. Each developed a subcapsular hematoma of the spleen, diagnosed by sonography and CT scan. They were conservatively managed by low-dose heparin, bed rest and careful monitoring. Frequently repeated ultrasound and CT scans demonstrated complete resolution of the hematomas after 2 and 4 months, respectively.

Bed Rest

Calcitonin nasal spray reduces opioid withdrawal syndrome without modification of endogenous opioid secretion.

It has been suggested that the well known analgesic effect of calcitonin (CT) may result from an enhanced secretion of opioid peptides. The purpose of this double-blind, controlled study was therefore to evaluate the effectiveness of CT on the opiate withdrawal syndrome. 20 drug addicts were randomly allocated to receive either 200 UI/day of salmon CT (n = 10) or placebo (n = 10) by nasal spray, after the abrupt withdrawal of low-dose methadone (20 mg/day). The severity of the withdrawal syndrome was evaluated by means of a score derived from a symptom check-list. Plasma beta-endorphin, glucose and insulin levels were measured before and after CT administration. The subjects treated with spray CT had significantly lower score than those treated with placebo. Beta-endorphin levels did not show any significant variation in both groups. An inhibitory action of CT on insulin secretion was observed. Our data suggested that CT might be considered a useful supportive measure for opiate withdrawal. CT action does not seem to involve the opioid system, but is probably mediated by a direct action on specific receptors or by a modulation of noradrenergic pathways.

Administration, Intranasal

[Chronic subdural hematoma with a markedly fibrous hypertrophic membrane. Case report].

A 40-year-old female, who had taken low-dose oral contraceptives for 2 months before onset, developed transient dysarthria, left hemiparesis, and left hemihypesthesia. One month later, a computed tomography (CT) scan revealed a uniformly enhanced, convex-shaped, hypertrophic membrane with a lobulated lumen in the subdural space of the right parietal region. A right parietal craniotomy was performed. The membrane, consisting of elastic-hard, hypertrophic granulation tissue and yellowish, sticky fluid in the lumen, was readily freed and totally extirpated. Subsequently, the patient recovered without persistent symptoms. Light microscopic examination detected the sinusoidal channel layer and the fibrous layer in an alternating configuration, along with intramembranous hemorrhagic foci. Such hypertrophy must have been caused by repeated intramembranous hemorrhages and reactive granulation. Such findings of hematoma membrane have never previously been reported. Thus, this is an interesting case, clearly distinguished from typical chronic subdural hematoma.

Adult

Aspirin to prevent growth of vegetations and cerebral emboli in infective endocarditis.

The incidence of stroke on cranial computed tomography (CT) and change in echocardiographic vegetation area was prospectively compared in a preliminary observational study involving nine patients with infective endocarditis randomized to either low-dose aspirin (75 mg d-1, Group I, n = 4) or no aspirin (Group II, n = 5). Two symptomatic cerebral infarcts and one myocardial infarct occurred in the controls, compared to no events in patients on aspirin during a total observation period of 343 d (range 28-49 d). The mean vegetation area decreased in the aspirin group (mean change = -0.24 cm2), compared to an increase in controls (mean change = +0.35 cm2). The platelet half-life (normal range 5-6 d), which was measured using Indium-111 radiolabelling, tended to be lower in Group II (4.6 +/- 0.2 vs. 3.9 +/- 0.5 d). No side-effects or complications attributable to aspirin were observed. A possible role for adjunctive aspirin therapy in the prevention of embolic complications in infective endocarditis is suggested, and warrants further study.

Adult

The role of radiation therapy in Hodgkin disease: experience and controversy. The 54th annual Janeway Lecture: 1989.

BACKGROUND: Beginning in 1970, a series of patients with Hodgkin disease were treated at the University of Minnesota, after staging laparotomy, with radiation therapy (RT) for Stage I, II, and IIIA Hodgkin disease. This report is an analysis of the results of the treatment and of treatment modifications. METHODS: From 1970 to 1974, all patients were treated with standard RT. In 1975, an analysis of these patients indicated that patients with large mediastinal mass (LMM) and patients with Stage IIIA spleen-positive (IIIAS+) disease had a higher recurrence rates than patients without these factors. Subsequently, a schema of radical radiation therapy (RRT) was devised, which included low-dose lung RT for patients with LMM and low-dose liver RT for patients with IIIAS+ disease. RESULTS: Analysis of the results of the two treatments indicates that the use of low-dose lung RT in patients with LMM and low-dose liver RT in patients with IIIAS+ Hodgkin disease produced survival and recurrence-free survival results equivalent to those achieved by use of combined modality treatment (CMT) or chemotherapy (CT) alone. CONCLUSIONS: The use of RT with whole lung and liver irradiation for patients with LMM and IIIAS+ Hodgkin disease, respectively, produces results that are equivalent to those of CMT or CT alone with the advantage of a decreased incidence of second malignant neoplasms. In addition, patients who do not respond to initial RT have a greater chance of being saved with chemotherapy than do patients initially treated with CMT of being saved with RT. The authors suggest that radical RT is the treatment of choice for patients with LMM and/or IIIAS+ Hodgkin disease.

Adolescent

Standard chemotherapy for myelomatosis: an area of great controversy.

L-PAM and prednisone (MP) has been challenged, almost from the start, by combination chemotherapy (CT) with its strong theoretic backing, as the standard chemotherapy for multiple myeloma. In effect, the two contestants were really evenly matched. Unfortunately, neither of them has been able to provide a satisfactory weapon against this remarkably resistant disease. This lack of an effective therapy has stimulated both the search for new strategies and an ongoing controversy. MP remains the standard induction chemotherapy for MM. Nevertheless, in several clinical conditions CT is preferable. The 18% of MM patients who show at presentation acute or chronic renal failure may be safely treated with regimens including cytotoxic drugs with a nonrenal excretion, such as doxorubin. Moreover, low-dose oral melphalan is not recommended for young patients in the event of their enrollment in high-dose programs. The standard chemotherapy for MM will continue to be an area of great controversy until a new treatment strategy proves to be clearly superior in large randomized studies.

Antineoplastic Combined Chemotherapy Protocols

[Treatment of infantile spasms with long-term low dose ACTH].

We investigated the effect of long-term, low-dose ACTH in 13 patients (10 boys and 3 girls) with infantile spasms who were treated with low-dose ACTH (mean: 0.0081 mg/kg/day). Two patients (one boy and one girl) received this therapy twice because of relapse of tonic spasms. ACTH was injected intramuscularly every morning for 30 days, after which dosage was tapered. The mean observation period was 53.9 months. Complete cessation of seizures was attained in 13 of 15 treatment trials. In one trial, complete cessation was not attained but the number of attacks decreased to less than one-third of that before treatment. In only one trial was treatment not effective. EEG showed good response to this treatment. The side-effects of this therapy were hypertension in 6 patients, hypokalemia in 7, and emotional outburst in 7. Emotional outburst appeared during the early phase of therapy, while the other two side-effects appeared in the later phase and disappeared when ACTH-tapering was begun. Brain shrinkage observed on CT scan was mild in all trials. Five patients have had no relapse. The total dose of ACTH was significantly larger in the group with good outcome than in the group with poor outcome.

Adrenocorticotropic Hormone

Complications of head injury and their therapy.

Common intracranial complications following head injury are meningitis, usually associated with a basilar skull fracture or open-depressed skull fracture; delayed hematoma; hydrocephalus; and vascular injuries. Prophylactic antibiotics are not recommended for the management of basilar skull fractures. The best means of preventing infection from open-depressed skull fractures is operative debridement and thorough irrigation, though recent evidence suggests that select cases can be safely managed without operation. Serial CT scans should be obtained in severely head-injured patients to identify delayed hematomas. CT and MRI scans obtained several weeks or months after severe head injury frequently reveal enlarged ventricles, though only a small percentage of these patients have clinical hydrocephalus. Those that do, often benefit from a shunt. Vascular injuries frequently are not detected until ischemic symptoms develop hours or days after the injury. Recommended treatment for intimal tears or dissection is full anticoagulation, but in those with cerebral contusions or other intracranial lesions, this may present an unacceptable risk for intracranial hemorrhage. Pulmonary infections frequently occur following head injury, and can be associated with admission to the ICU and intubation. A large percentage of these infections are caused by enteric gram-negative organisms, and aggressive treatment with appropriate antibiotics is necessary. Aspiration of gastric contents is common in head-injured patients and is frequently complicated by bacterial superinfection. The routine use of antacids and H2 blocking agents leads to bacterial colonization of the stomach with anaerobes and gram-negative aerobes. Thus, empiric therapy for aspiration pneumonia should include clindamycin. Sinusitis is a frequent cause of fever and leukocytosis in patients with nasotracheal or nasogastric tubes in place for several days and often subsides spontaneously with removal of the tubes. Pulmonary edema is often caused by excessive fluid administration during resuscitation of these patients, and can be avoided by monitoring central venous pressures. Pulmonary edema may also be caused by ARDS, excessive catecholamine release, or primary cardiac failure. Most of these patients will benefit from early intubation and PEEP. Pulmonary emboli most often originate from deep venous thrombi, and there is increasing evidence that prophylaxis with low-dose heparin and pulsating boots can significantly reduce the incidence of both complications. Erosive gastritis is found in the majority of severely head-injured patients and may be due to ischemia of the gastric mucosa as well as gastric hyperacidity.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Injuries

Combination treatment of high-dose pyridoxal phosphate and low-dose ACTH in children with West syndrome and related disorders.

Combination therapy of high-dose pyridoxal phosphate (PAL-P, 40-50 mg/kg/day) and low-dose ACTH beta 1-24-Z (tetracosactide acetate-Zn, Cortrosyn Z, 0.01 mg/kg/day) was instituted in 26 children suffering from West syndrome and related disorders--pretreated without success with high-dose PAL-P alone; 18 with West syndrome (14 with symptomatic and 4 with cryptogenic types), 2 with symptomatic Lennox-Gastaut syndrome, 5 with cerebral palsy with hypsarhythmia or diffuse slow spike-waves and one with myoclonic seizures (secondary generalized epilepsy). Clinical, electroencephalographic and neurochemical investigations were carried out. The results were summarized as follows. 1) Only one of 27 children with West syndrome and related disorders pretreated using high-dose PAL-P alone before ACTH showed a clinically excellent response. 2) Clinical seizures were completely suppressed in 19 of 21 children who initially had seizures (90%) after this combination therapy. 3) Twenty-one of the total 26 children (80%) had disappearance of hypsarhythmia or diffuse slow spike-waves in EEG after this therapy. 4) During PAL-P treatment alone transient increases in liver enzymes occurred in 37 percent. The brain shrinkage of CT and the significant rise in CSF NSE were seen in 95% and 78% after ACTH, respectively. 5) Twenty-three children have been followed for one to 29 months after tapering off of ACTH. No relapses were experienced in 11 of 18 who initially had seizures (61%) and 13 of 23 with hypsarhythmia or diffuse slow spike-waves (57%). 6) Postictal PRL elevations were suppressed during high-dose PAL-P. 7) No significant changes in the CSF levels of HVA and 5-HIAA were seen during this combination therapy. The CSF levels of HVA were significantly lower than the controls. 8) Daily ACTH therapy transiently suppressed the secretion of anterior pituitary hormones (GH, TSH, PRL, LH and FSH) and thyroid hormones (T3 free T3, T4 and free T4). It is recommended that the combination therapy of high-dose PAL-P and low-dose ACTH is a promising new method and should be tried in children with West syndrome and related disorders. The mechanism of action of this combination therapy remains obscure although some information has been obtained from our investigations.

Child, Preschool

[Comparison of conventional radium and high dose rate afterloading brachytherapy in cervix cancer].

The combination of intracavitary and external-beam radiation is the treatment of choice in advanced cervical cancer. Low-dose regimens using radium were widely abandoned in favour of high-dose-rate afterloading systems. We compared in this retrospective analysis of 550 patients the 2 different treatment modalities. We could observe neither in overall survival, nor in the incidence of side effects, any significant difference. Although the change from low- to high-dose-rate radiation therapy was not accompanied by a benefit in survival, the latter modality displayed several advantages e.g. a reduced exposure of personnel to radiation and shorter duration of confinement to bed. Patient survival rate was dependent mainly on parameters of tumour burden (FIGO stage), i.v. pyelogram or CT scan of paraaortic lymph nodes. On the other hand, neither the histological classification as epidermoid or adenocarcinoma nor the WHO grading, were useful predictors of patient outcome.

Adenocarcinoma

Oligodendrogliomas: the Mayo Clinic experience.

Eighty-one patients with pure supratentorial oligodendrogliomas underwent surgery alone (19 patients) or surgery plus postoperative radiation therapy (63 patients) between the years 1960 and 1982. The median survival time and the 5-, 10-, and 15-year survival rates for these 82 patients were 7.1 years, 54%, 34%, and 24%, respectively; these values were significantly different from those for an age- and sex-matched normal reference population. Univariate and multivariate survival analyses were performed on 13 possible prognostic factors including: patient age and sex; presence of seizures; site, size, side, computerized tomography (CT) enhancement, grade, and calcification of the tumor; and treatment (extent of surgical resection, lobectomy, radiation dose, and radiation field). Of these factors, tumor grade as classified by the Kernohan and St. Anne-Mayo methods was most strongly associated with survival. Patients with Grade 1 or 2 tumors by either grading method had a median survival time and 5- and 10-year survival rates of approximately 9.8 years. 75%, and 46%, respectively, compared to 3.9 years, 41%, and 20% for those with Grade 3 or 4 tumors. The extent of surgical resection was also associated with survival. The 19 patients who underwent gross total resection of their tumor had a median survival time and 5- and 10-year survival rates of 12.6 years, 74%, and 59%, compared to 4.9 years, 46%, and 23%, respectively, for the 63 who had subtotal resection. When comparing the 19 patients who underwent surgery alone with the 63 who had surgery plus postoperative radiation therapy, there did not appear to be a survival benefit to be gained from the addition of postoperative radiation therapy. However, the patients who had surgery alone tended to have gross total resections and lower tumor grades. Analysis of the subset of 63 patients who underwent subtotal resection alone or with radiation therapy showed that the median survival time and 5- and 10-year survival rates were: 2 years, 25%, and 25% for the eight patients with subtotal resection alone; 4.5 years, 39%, and 20% for the 26 patients with surgery and low-dose (less than 5000 cGy) radiation therapy; and 7.9 years, 62%, and 31% for the 29 patients receiving surgery and high-dose radiation therapy (greater than or equal to 5000 cGy), respectively.

Adolescent