Serologic response to COVID-19 infection and/or vaccine in cancer patients on active treatment.

BACKGROUND: It was shown that immunocompromised patients have significantly reduced immunologic responses to COVID-19 vaccines. The immunogenicity of COVID-19 vaccine/infection in patients with solid tumors is reduced. We evaluated the immunologic response to COVID-19 and/or the BNT162b2 mRNA COVID-19 vaccine among cancer patients on active treatments and reviewed previous literature to identify subgroups that may require third vaccination. PATIENTS AND METHODS: Anti-SARS-CoV-2 S1/S2 antibodies were measured in a cohort of 202 cancer patients on active treatment with chemotherapy (96), immunologic (52), biologic (46), and hormonal (12) treatments for early (n = 66, 32.7%) or metastatic disease (n = 136, 67.3%). Of those, 172 had received two vaccine doses, and 30 had COVID-19 infection (20/30 also received one dose of vaccine). Specific anti-S receptor-binding domain antibodies were further measured in patients with equivocal anti-S1/S2 results. RESULTS: Among cancer patients, the SARS-CoV-2 antibody response rate was 89.1% (180/202) after COVID-19 vaccination or infection and 87.2% (150/172) in patients after vaccination without a history of COVID-19, compared with 100% positive serologic tests in a control group of 30 health care workers (P < 0.001). Chemotherapy treatment was independently associated with significantly reduced humoral response to infection or vaccination, with an 81.3% response rate, compared with 96.2% in patients on other treatments (P = 0.001). In vaccinated patients on chemotherapy, the positive response rate was 77.5%. In a multiple regression model, a neutralizing antibody titer (>60 AU/ml) was more likely with immunotherapy (odds ratio 2.44) and less likely with chemotherapy (odds ratio 0.39). CONCLUSIONS: Overall, both COVID-19 vaccine and natural infection are highly immunogenic among cancer patients. Our study, however, identifies those under chemotherapy as significantly less responsive, and with lower antibody levels. These findings justify close virological and serological surveillance along with consideration of these patients for booster (third dose) vaccine prioritization, as new highly spreading SARS-CoV-2 variants emerge.

Parathyroid cell resistance to fibroblast growth factor 23 in secondary hyperparathyroidism of chronic kidney disease.

Although fibroblast growth factor 23 (FGF23) acting through its receptor Klotho-FGFR1c decreases parathyroid hormone expression, this hormone is increased in chronic kidney disease despite an elevated serum FGF23. We measured possible factors that might contribute to the resistance of parathyroid glands to FGF23 in rats with the dietary adenine-induced model of chronic kidney disease. Quantitative immunohistochemical and reverse transcription-PCR analysis using laser capture microscopy showed that both Klotho and FGFR1 protein and mRNA levels were decreased in histological sections of the parathyroid glands. Recombinant FGF23 failed to decrease serum parathyroid hormone levels or activate the mitogen-activated protein kinase signaling pathway in the glands of rats with advanced experimental chronic kidney disease. In parathyroid gland organ culture, the addition of FGF23 decreased parathyroid hormone secretion and mRNA levels in control animals or rats with early but not advanced chronic kidney disease. Our results show that because of a downregulation of the Klotho-FGFR1c receptor complex, an increase of circulating FGF23 does not decrease parathyroid hormone levels in established chronic kidney disease. This in vivo resistance is sustained in parathyroid organ culture in vitro.

A modified ambulatory arterial stiffness index is independently associated with all-cause mortality.

Dependence of the ambulatory arterial stiffness index (AASI) on data scattering interferes with its potential clinical relevance. We assessed the correlates and all-cause mortality associations of a modified AASI (s-AASI). AASI was derived from the 24-h diastolic vs. systolic blood pressure linear regression line, whereas s-AASI was derived by symmetric regression (bisecting the line of diastolic vs systolic and systolic vs. diastolic). Of 2918 patients 55% were women; age was 56 +/- 16 years and body mass index was 27.3 +/- 4.5 kg/m(2). Average 24-h ambulatory blood pressure was 138 +/- 16/78 +/- 10 mm Hg. Applying the modified method for calculating AASI yielded a different measure: the negative correlation between AASI and blood pressure dipping (r = -0.304, P < 0.0001) was abolished (r = +0.223, P < 0.0001), s-AASI was more dependent on age (r = 0.266 vs. r = 0.089 for AASI), and prediction of all-cause mortality was enhanced; hazard ratio (95% confidence intervals) 1.17 (1.00-1.36) per 1 s.d. increase in s-AASI in the fully adjusted model as compared with 1.15 (0.97-1.36) for AASI.

Alterations of microRNAs throughout the malignant evolution of cutaneous squamous cell carcinoma: the role of miR-497 in epithelial to mesenchymal transition of keratinocytes.

Skin carcinogenesis is known to be a multi-step process with several stages along its malignant evolution. We hypothesized that transformation of normal epidermis to cutaneous squamous cell carcinoma (cSCC) is causally linked to alterations in microRNAs (miRNA) expression. For this end we decided to evaluate their alterations in the pathologic states ending in cSCC. Total RNA was extracted from formalin fixed paraffin embedded biopsies of five stages along the malignant evolution of keratinocytes towards cSCC: Normal epidermis, solar elastosis, actinic keratosis KIN1-2, advanced actinic keratosis KIN3 and well-differentiated cSCC. Next-generation small RNA sequencing was performed. We found that 18 miRNAs are overexpressed and 28 miRNAs are underexpressed in cSCC compared to normal epidermis. miR-424, miR-320, miR-222 and miR-15a showed the highest fold change among the overexpressed miRNAs. And miR-100, miR-101 and miR-497 showed the highest fold change among the underexpressed miRNAs. Heat map of hierarchical clustering analysis of significantly changed miRNAs and principle component analysis disclosed that the most prominent change in miRNAs expression occurred in the switch from 'early' stages; normal epidermis, solar elastosis and early actinic keratosis to the 'late' stages of epidermal carcinogenesis; late actinic keratosis and cSCC. We found several miRNAs with 'stage specific' alterations while others display a clear 'gradual', either progressive increase or decrease in expression along the malignant evolution of keratinocytes. The observed alterations focused in miRNAs involved in the regulation of AKT/mTOR or in those involved in epithelial to mesenchymal transition. We chose to concentrate on the evaluation of the molecular role of miR-497. We found that it induces reversion of epithelial to mesenchymal transition. We proved that SERPINE-1 is its biochemical target. The present study allows us to further study the pathways that are regulated by miRNAs along the malignant evolution of keratinocytes towards cSCC.

Normal ambulatory blood pressure: a clinical practice-based comparison of two recently published definitions.

The European Society of Hypertension (ESH) has issued guidelines for the detection and treatment of hypertension. According to these guidelines, normal 24-h ambulatory blood pressure (ABP) is defined as lower than 125/80 mmHg. Another publication of ESH recommendations for blood pressure (BP) measurement defines normal awake and asleep blood pressure as lower than 135/85 and 120/70 mmHg, respectively. Our aim was to investigate the compatibility of these two recently proposed ABP cutoffs in clinical practice. We analysed 1495 consecutive ABP measurements. In all, 56% of the subjects were female; age 58 +/- 16 years; body mass index 27 +/- 4 kg/m(2); clinic BP 151+/-22/84 +/- 13 mmHg. Two-thirds were treated for hypertension, and 11% for diabetes. Subjects were classified as having normal 24-h BP if the corresponding value was <125/80 mmHg. Normal awake-sleep BP was diagnosed if awake BP was <135/85 mmHg and sleep BP was <120/70 mmHg. Concordance between the cutoffs was found in 93% of the subjects. Among the 7% discordant subjects, 4.5% were hypertensive applying the 24 h, but not awake-sleep, BP values, whereas only 2.5% were hypertensive according to awake-sleep, but not 24 h, BP values (P < 0.005). In Conclusion, in real-life ABP measurement, a good agreement was found between two recently issued ABP normality definitions. However, some subjects are classified as hypertensive only according to one of these methods, more often by the 24-h cutoff of 125/80. This discordance may be significant in large-scale clinical BP monitoring.

Poststreptococcal neprhitis and acute rheumatic fever in two adults.

In two adult subjects who suffered acute episodes of rheumatic fever, sever kidney involvement developed with proteinuria and renal insufficiency. The clinical and histologic picture was typical of poststreptococcal (infectious) glomerulonephritis. During a follow-up period of more than three years, no clinical or biochemical abnormalities have been detected; thus, it is likely that both patients have recovered from their renal diseases. The coexistence of rheumatic fever and acute glomerulonephritis, which is uncommon even in your age groups, may be observed in adult subjects.

Kidney transplantation unraveling Wolfram syndrome: a case report.

BACKGROUND: In Wolfram syndrome insulin-dependent diabetes is associated with a multisystem neurodegenerative disorder. There are no prior reports of kidney transplantation in patients with Wolfram syndrome. METHODS: Kidney transplantation was undertaken in a child with dysplastic kidneys, sensorineural hearing impairment and bilateral optic atrophy-a combination of features insufficient to define Wolfram syndrome. RESULTS: After the procedure diabetes mellitus, diabetes insipidus and urinary bladder dysfunction emerged, thereby revealing Wolfram syndrome. CONCLUSIONS: We discuss the etiology of our patient's postoperative events, and conclude that kidney transplantation may expose dormant manifestations-or aggravate existing manifestations-of Wolfram syndrome.

Acute rheumatic fever in adults over the age of 45 years: an analysis of 23 patients together with a review of the literature.

The natural history of acute rheumatic fever (ARF) in adults has been studied from an analysis of 23 patients together with a review of a further 466 published cases. In contrast to the picture in juvenile ARF, in our patients (average age 55 yr), only arthritis (83%) and carditis (35%) were major criteria for the diagnosis. All patients had at least 3 minor criteria. To summarize, 39% of the patients, average age 56 yr were seen in their initial attack of ARF. In those patients with a previous history of rheumatic fever, the mean interval between the index attack and the first illness was 20.5 yr. Contact with young children appeared to be an important predisposing factor. None had an ESR of less than 50 mm in the first hour, even in the presence of cardiac failure. Findings in the acute illness included anemia (70%), hyperglobulinemia (70%), urinary sediment (66%), and hypercalcemia in 7 out of 12 cases. The response to treatment was good and only 1 patient of 13 followed-up developed a new valvular lesion. A survey of the literature shows that attacks of ARF may occur at any age; death in the acute episode is rare and occurs only in patients with severe preexisting valvular disease with congestive failure. The problem of diagnosing active carditis in the presence of rheumatic heart disease (RHD) is discussed. While juvenile ARF may be overdiagnosed, the diagnosis may be missed in the adult rheumatic patient whose cardiac state inexplicably deteriorates. In such patients evidence for a preceding streptococcal infection should be sought. Patients with a high risk of developing ARF include those with carditis in previous attacks, with preexistent RHD, and with several children in the family. These factors should be considered when advising on the duration of antibiotic prophylaxis.

Effect of venous obstruction of lower extremities on exercise tolerance.

The effect of venous obstruction on effort tolerance is not well appreciated. We studied a patient with severe lower body venous obstruction (with near normal heart and lung function) who had marked exercise intolerance. Peak O2 uptake for leg exercise was reduced, but peak O2 uptake for upper extremities was normal. This difference indicates that severe venous obstruction can lead to exercise limitation.

Dynamics of oxygen uptake for submaximal exercise and recovery in patients with chronic heart failure.

STUDY DESIGN AND OBJECTIVES: Attainment of a steady state for oxygen uptake (VO2) during constant work rate exercise has been reported to take longer for patients with chronic heart failure (CHF) compared with normal. The steady state is also delayed in normal subjects during high-intensity exercise compared with moderate exercise, however, and the delay correlates with the degree of associated lactic acidosis. To determine whether prolonged kinetics of VO2 are attributable solely to the reduction of exercise capacity in CHF, VO2 kinetics were compared for patients with CHF and normal subjects, both for exercise of matched absolute work rate and for matched relative work intensity. SUBJECTS: Eighteen men with CHF and 10 normal men. METHODS AND RESULTS: Subjects performed 6 min of constant work rate cycle ergometry with breath-by-breath measurement of VO2. Patients were studied using 25 W, and a work rate midway between the lactic acidosis threshold and maximal capacity (50 percent delta). Normal subjects were tested similarly, and also at a work rate matched to the patients' average 50 percent delta work rate. The VO2 kinetics were characterized by the mean response time (MRT) to attain the 6 min VO2 value. Rates of recovery of VO2 were analyzed for 2 min following exercise. For the same absolute work rate, VO2 MRTs were significantly longer for patients than controls (25 W, 67 +/- 26 vs 37 +/- 25 s; approximately 60 W, 87 +/- 20 vs 54 +/- 27 s), but there was no significant difference in VO2 MRT between the two groups at a matched intensity of 50 percent delta (87 +/- 20 vs 81 +/- 18 s). However, the decrease in VO2 during 2 min of recovery was slower for the patients on all comparisons, even for matched exercise intensity. CONCLUSION: The VO2 dynamics for submaximal exercise are slowed in CHF. The slower dynamics are not entirely accounted for by the relatively higher intensity of a given work rate, since delayed recovery is evident even at a matched relative work intensity. Exercise intolerance in CHF is characterized not only by decreased maximal exercise capacity, but also by slower adaptations to and from submaximal levels of exercise.

Comparison of PY 108-068, a new calcium antagonist, with nifedipine in exercise-induced asthma.

Several calcium antagonists, each with significantly different chemical structures, have demonstrated variable attenuation of exercise-induced asthma. Quantitative comparisons have been hampered by differences in the intensity of challenge and the severity of the underlying disease between groups of patients. In 12 asthmatic adults with relatively severe exercise-induced asthma, we compared the effect of a new calcium antagonist, PY 108-068, in doses of 75 mg and 150 mg with nifedipine (30 mg) and placebo on resting flow rates and flow rates after exercise. Over a three-week period, each patient completed a four-day, randomized, double-blind Latin-square study. After receiving one of four oral drugs, spirometry was repeated every 30 minutes for two hours, followed by a six-minute treadmill exercise test breathing dry air. The exercise tests were well matched for work rate, ventilation, heart rate, and oxygen uptake. Spirometry was then repeated seven times over the next 30 minutes after exercise. Though both 150 mg of PY 108-068 and nifedipine were associated with mild bronchodilation before exercise, only the latter was significant (p less than 0.05). Exercise-induced asthma (expressed as maximal percent fall in the forced expiratory volume in one second from before baseline) was significantly attenuated only by 150 mg of PY 108-068 compared to placebo (24 +/- 13 vs 40 +/- 16; p less than 0.05). Headache, which occurred in six subjects after nifedipine, five after 150 mg of PY 108-068, one after 75 mg of PY 108-068, and none after placebo, was subjectively more severe after nifedipine. We conclude that in these patients, there was a tendency for mild bronchodilation before exercise with both 150 mg of PY 108-068 and nifedipine, but only the 150-mg dose provided significant protection against exercise-induced asthma two hours after the drug.

Endobronchial actinomycosis simulating bronchogenic carcinoma. Diagnosis by bronchial biopsy.

Five cases of actinomycosis of the main bronchi or trachea which were suggestive clinically of bronchogenic carcinoma are described. In four patients the correct diagnosis was made by a bronchial biopsy or wash, or both. Three of them recovered following antibiotic treatment, and one died a few days after bronchoscopy. In one case the Actinomyces were found in the bronchial wash retrospectively following diagnosis of pulmonary actinomycosis in the lobectomy specimen. A concomitant endobronchial lipoma was found in one of the patients. The diagnosis of pulmonary actinomycosis by bronchial biopsy may save the patient major surgical intervention.

Prolonged pyrexia and lung metastases. A rare presentation of an occult epithelioid sarcoma.

A 31-year-old patient presenting with fever of unknown origin, night sweats and weight loss, associated later with pulmonary nodules, is described. Multiple invasive diagnostic procedures, including exploratory laparotomy and open-lung biopsy, suggested a benign inflammatory granulomatous disease. Metastatic epithelioid sarcoma was ultimately diagnosed after biopsy of an enlarging groin mass. Epithelioid sarcoma should be considered in the differential diagnosis of prolonged fever, associated with granulomas of obscure etiology.

O2 uptake kinetics in response to exercise. A measure of tissue anaerobiosis in heart failure.

Oxygen uptake (VO2) reflects the rate of aerobic regeneration of high-energy phosphate compounds (primarily adenosine triphosphate [ATP]). Since lactate increase is thought to result from an inadequate rate of aerobic ATP regeneration, it might be expected that lactate increase would be associated with a delayed attainment of steady state for VO2 in response to constant load exercise. Similarly if mitochondrial ATP regeneration during exercise is inadequately supported by O2 transport mechanisms, adenosine diphosphate (ADP) and purine nucleotide by-products, such as hypoxanthine, should increase. This study investigated the relationship between VO2 kinetics during exercise and accompanying changes in blood lactate and hypoxanthine values in heart failure patients, as a model of compromised O2 transport. Twenty-five patients with chronic heart failure performed cycle ergometry for 6 min at 25 W and at a work rate midway (50 percent delta) between their lactic acidosis threshold (LAT) and peak VO2. Ventilation and gas exchange were measured breath by breath, and venous lactate, hypoxanthine, norepinephrine, and epinephrine were determined at rest and 2 min after each test. The slow component of VO2 kinetics was quantified as the rise in VO2 from the third to the sixth minute of exercise (delta VO2 [6-3]). Ten age- and size-matched normal subjects served as control subjects. delta VO2 (6-3) was correlated with the increase in lactate (r = 0.71, p < 0.001), hypoxanthine (r = 0.61, p < 0.001), and norepinephrine (r = 0.41, p < 0.01) but not epinephrine in response to exercise in the heart failure patients. The delta VO2 (6-3) and delta lactate were both greater in the patients than in the control subjects at similar absolute work rates (54 +/- 20 and 60 W, respectively). However, the slope of the relationship between delta La and delta VO2 (6-3) for the patient and normal groups was indistinguishable. The lactate increase was correlated with hypoxanthine increase (r = 0.66, p < 0.001), but not norepinephrine or epinephrine. In summary, VO2 kinetics in response to exercise reflects delayed attainment of the steady state in heart failure patients, which is correlated with increases in lactate and hypoxanthine, markers of increased anaerobic metabolism.

Marked weight reduction lowers resting and exercise blood pressure in morbidly obese subjects.

Obesity and high blood pressure (BP) often coexist. Weight reduction lowers resting BP but its effect on BP during exercise (a predictor of target organ damage) has not been evaluated. Blood pressure was measured at rest and during cycling, before and after weight reduction induced by gastric restriction. Nineteen subjects (4 male), 41 +/-2 (SEM) years of age and body mass index (BMI) of 43 +/- 0.9 kg/m2, were studied. On each occasion BP was measured at rest, at a steady state of 0 and 25 watts, at peak exercise and 1 min into recovery. Body weight was reduced by 28% +/- 6% and BMI decreased from 43.3 +/- 0.9 to 31.5 +/- 0.7 kg/m2 (P < .01). Both BP and heart rate, at rest and at all exercise intensities, were significantly lower after weight reduction. Resting BP decreased from 133 +/-4/87 +/- 3 mm Hg to 115 +/- 4/77 +/- 2 mm Hg (P < .001), and BP at peak exercise decreased from 181 +/- 8/98 +/- 4 to 162 +/- 6/83 +/- 5 mm Hg (P < .001). The change in resting systolic BP did not correlate with the change in body weight or with the change in heart rate, but it correlated with the baseline systolic BP (R = 0.61; P < .005). It is concluded that marked weight reduction reduces BP at rest and at all exercise intensities. Gastroplasty should be considered as an option in morbidly obese hypertensive patients who are not well controlled with conventional treatment, and who fail to lose or to maintain a reduced weight by calorie restriction alone.

Effect of endurance training on possible determinants of VO2 during heavy exercise.

When moderate exercise begins, O2 uptake (VO2) reaches a steady state within 3 min. However, with heavy exercise, VO2 continues to rise beyond 3 min (VO2 drift). We sought to identify factors contributing to VO2 drift. Ten young subjects performed cycle ergometer tests of 15 min duration for each of four constant work rates, corresponding to 90% of the anaerobic threshold (AT) and 25, 50, and 75% of the difference between maximum VO2 (VO2 max) and AT for that subject. Time courses of VO2, minute ventilation (VE), and rectal temperature were recorded. Blood lactate, norepinephrine, and epinephrine were measured at the end of exercise. Eight weeks of cycle ergometer endurance training improved average VO2 max by 15%. Subjects then performed four tests identical to pretraining studies. For the above AT tests, training reduced VO2 drift substantially; reduction in each of the possible mediators we measured was also demonstrated. The training-induced decrease in VO2 drift was well correlated with decreases in end exercise lactate and less well correlated with the drift in VE seen at above AT work rates. The training-induced reduction in VO2 drift was not significantly correlated with attenuation of rectal temperature rise or decrease in end-exercise level of the catecholamines. Thus the slow rise in VO2 during heavy exercise seems linked to lactate, though a component dictated by the work of breathing cannot be ruled out.

Photochemically-activated electrodes: application in design of reversible immunosensors and antibody patterned interfaces.

Antigen monolayers assembled onto Au electrodes associated with a quartz crystal act as electrochemical or microgravimetric quartz-crystal-microbalance (QCM) sensing interfaces for the complementary antibody. Electrochemical analysis of the antibody (Ab) is based on the insulation of the antigen monolayer electrode by the associated Ab towards a redox probe in the electrolyte solution. Ferrocene-modified glucose oxidase (Fc-GOx) and glucose are employed as redox probes for the amperometric transduction of the Ab association to the electrode. Bioelectrocatalyzed oxidation of glucose provides an electrochemical route to amplify the antigen-Ab complex formation. Electrochemical analysis of the dinitrophenyl antibody, DNP-Ab, by a dinitrophenyl-lysine monolayer electrode is presented. QCM analysis of the Ab is based on the frequency changes of the quartz crystal resulting from the association of the Ab to the crystal assembly. This method is discussed with the analysis of the fluorescein antibody, Flc-Ab, using a fluorescein monolayer-modified quartz crystal. A novel method to tailor reversible immunosensor devices by the application of photoisomerizable antigen monolayers on electrodes is presented. The antigen is modified by photoactive units exhibiting reversible photoisomerizable properties. In one photoisomer state, the antigen exhibits affinity for the Ab and enables its electrochemical or QCM analysis. Photoisomerization to the complementary state perturbs the antigen structure and the monolayer lacks affinity for the Ab. This enables the washing-off of the Ab and the regeneration of the actively sensing interface by a second illumination process that restores the antigen monolayer-modified surface. This method is exemplified by the development of a reversible DNP-Ab sensing electrode. N-Mercaptobutyl dinitrospiropyran was assembled as a photoisomerizable monolayer on a Au electrode. The dinitrospiropyran monolayer, SP-state, exhibits affinity for the DNP-Ab and enables the amperometric detection of the Ab using Fc-GOx and glucose as redox probe. The complementary photoisomerized protonated dinitromerocyanine monolayer, MRH(+)-state, lacks affinity for the DNP-Ab. By photoisomerization of the DNP-Ab associated with the SP-monolayer electrode to the MRH(+)-monolayer state, the DNP-Ab is washed-off, and by a second illumination process, the MRH(+)-monolayer is re-isomerized to the SP-monolayer assembly, which is the active interface for further analysis of the DNP-Ab. Cyclic amperometric detection of the DNP-Ab by the photoisomerizable dinitrospiropyran monolayer is demonstrated. The association of the DNP-Ab to the SP-monolayer electrode and the dissociation of the Ab from the MRH(+)-monolayer electrode are confirmed by QCM experiments using a dinitrospiropyran monolayer-modified quartz crystal. The insulating features of an antigen-Ab complex on a conductive surface and the photochemically controlled association of an antibody to a photoisomerizable monolayer assembled onto the surface were used to develop means for micropatterning of surfaces by the antibody. A dinitrospiropyran antigen monolayer was assembled onto conductive ITO glass. A DNP-Ab solution was used as 'ink solution' to pattern the surface. The Ab-pattern was imaged by electrochemical copper deposition onto the Ab-lacking surface domains. The dinitrospiropyran monolayer assembled onto ITO or Pyrex glass surfaces was employed as an active interface for the photolithographic patterning of the surface with the DNP-Ab. (ABSTRACT TRUNCATED)

Drug-resistant pulmonary tuberculosis in Israel, a society of immigrants: 1985-1994.

SETTING AND OBJECTIVES: Drug-resistant tuberculosis was uncommon in Israel until 1985, when the waves of immigration began. We studied the incidence and clinical course of resistant pulmonary tuberculosis nationwide. DESIGN: Isolates of Mycobacterium tuberculosis between 1985 and 1994 were surveyed. Data on 150 patients with resistance and 110 patients with drug-sensitive disease were reviewed. Ethnic origin, type of resistance, radiological findings and outcome were analysed. RESULTS: In total, 16.7% of the isolates showed resistance to at least one drug; 58% had resistance to multiple drugs. In 67% of the patients the resistance was primary. Most patients were immigrants from the former USSR and from Ethiopia; none were Israeli-born Jews. Mortality with resistance was 10%, and was highest (14%) with multiple drug resistance. Mortality among drug-resistant cases was lowest (3%) among Ethiopian Jews. Cavities and extensive disease were more common with drug resistance. CONCLUSION: Drug resistance has become relatively common in Israel due to immigration from the former USSR and Ethiopia. It is more extensive radiologically and carries a poorer outcome.

Inaccuracies in estimates of life expectancies of patients with bronchial cancer in clinical decision making.

Approximations of life expectancy in clinical decision making frequently assume constant disease-specific ("excess") mortality hazards over age at diagnosis and over time from diagnosis. This assumption is inconsistent with the longer relative survival of younger patients with bladder cancer and with the declines in mortality hazards from bladder and breast cancers over time from diagnosis. To estimate the error that may result from these assumptions, the authors derived excess mortality hazards from the Surveillance, Epidemiology and End Result (SEER) tumor registry for bronchial cancers stratified by age at diagnosis and time from diagnosis. They compared the life expectancies calculated by a model using an average constant annual cancer-specific mortality hazard over time from diagnosis with those calculated using data-derived cancer-specific annual mortality hazards that varied as a function of time from diagnosis. For younger patients with less advanced disease, the constant-average-mortality model underestimated life expectancies by up to 50% relative to those predicted by the time-variant model. For those over 75 years old at diagnosis, and for all patients with advanced disease, the constant-average-mortality model overestimated life expectancies by up to 65% relative to those predicted by the time-variant model. The authors conclude that predictions of life expectancy with bronchial cancer, and probably with other neoplasms, are limited by the widespread use of oversimplified methods of calculation and by the lack of data describing mortality hazards as a function of time from diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Post-partum isolated ovarian abscess in an asplenic host.

A 23-yr-old splenectomized female developed an isolated ovarian abscess, a very rare complication, following a normal delivery. Apart from the palpated 'cyst', findings on pelvic examination were unremarkable, as is often the case with ovarian abscess. The patient recovered after conservative 'cystectomy'. We suggest that the asplenic state plays a role in the development of this very rare complication.