The Addition of Systemic Terbinafine to Antifungal Combination Therapy in the Treatment of Disseminated Drug-Resistant Mold Infections in a National Cancer Institute Comprehensive Cancer Center: A Six-Year Study.

Introduction Combination antifungal regimens are frequently employed in the treatment of invasive fungal infections in patients who are immunocompromised, particularly for cancer and transplant patients. Terbinafine is a potential agent of interest for combination regimens. Methods We reviewed data over a six-year period examining patient outcomes in terms of both mortality and distribution of pathogens. The total number of patients in our study was 64. The use of terbinafine versus no terbinafine in combination therapy was assessed. Of the 64 patients analyzed, only 14 received terbinafine. Mortality was calculated for both groups, and demographics were analyzed by descriptive statistics. Results There was no statistical difference in mortality outcomes in either group. The addition of terbinafine was well tolerated and did not appear to result in any undue toxicity concerns. Discussion We wish to draw greater attention to this potential agent within our armamentarium for invasive fungal infections. To our knowledge, the total number of patients in our study, while small, represents the largest reported cohort in the literature to date. Sensitivities are crucial to be obtained for fungal pathogens as this likely undermined the utility of terbinafine in our study with larger than expected numbers of multidrug-resistant Fusarium. With limited patient numbers, a multicenter trial would be beneficial to further examine terbinafine in combination regimens.

Relationships among Non-Neoplastic Histopathological Features, Kidney Function, Proteinuria, and Other Clinical Factors in Patients Undergoing Nephrectomy.

Introduction: The non-neoplastic kidney parenchyma from nephrectomies is often overlooked in routine examinations. We aimed to evaluate the associations between global glomerulosclerosis (GS), interstitial fibrosis (IF), or arteriosclerosis (AS) and estimated glomerular filtration rate (eGFR), dipstick proteinuria, and other clinical factors. Methods: We performed a cross-sectional analysis of 781 patients with nephrectomy. We used regression models with and without interaction factors. The tested exposures were GS, IF, or AS, and the outcome measures were GFR and dipstick proteinuria. Results: In multivariable analyses, increasing degrees of GS, IF, or AS were significantly associated with lower eGFR and proteinuria (p < 0.05 for each). Obesity and hypertension (HTN) modified the association between eGFR and degrees of GS, whereas proteinuria and cardiovascular disease (CVD) modified the association between eGFR and degrees of AS (p for interaction <0.05). Compared with GS <10%, GS >50% was associated with lower eGFR in patients with (-45 mL/min/1.73 m2) than without (-19 mL/min/1.73 m2) obesity, and GS >50% was associated with lower eGFR in patients with (-31 mL/min/1.73 m2) than without (-16 mL/min/1.73 m2) HTN. Compared with AS <26%, AS >50% was associated with lower eGFR in patients with (-11 mL/min/1.73 m2) than without (-6 mL/min/1.73 m2) proteinuria, and AS >50% was associated with lower eGFR in patients with (-23 mL/min/1.73 m2) than without (-7 mL/min/1.73 m2) CVD. Conclusion: Greater degrees of each GS, IF, and AS are independently associated with proteinuria and lower eGFR. Obesity, HTN, proteinuria, and CVD modify the relationship between eGFR and specific histopathological features of nephrosclerosis.

JAK inhibitor blocks COVID-19 cytokine-induced JAK/STAT/APOL1 signaling in glomerular cells and podocytopathy in human kidney organoids.

COVID-19 infection causes collapse of glomerular capillaries and loss of podocytes, culminating in a severe kidney disease called COVID-19-associated nephropathy (COVAN). The underlying mechanism of COVAN is unknown. We hypothesized that cytokines induced by COVID-19 trigger expression of pathogenic APOL1 via JAK/STAT signaling, resulting in podocyte loss and COVAN phenotype. Here, based on 9 biopsy-proven COVAN cases, we demonstrated for the first time, to the best of our knowledge, that APOL1 protein was abundantly expressed in podocytes and glomerular endothelial cells (GECs) of COVAN kidneys but not in controls. Moreover, a majority of patients with COVAN carried 2 APOL1 risk alleles. We show that recombinant cytokines induced by SARS-CoV-2 acted synergistically to drive APOL1 expression through the JAK/STAT pathway in primary human podocytes, GECs, and kidney micro-organoids derived from a carrier of 2 APOL1 risk alleles, but expression was blocked by a JAK1/2 inhibitor, baricitinib. We demonstrate that cytokine-induced JAK/STAT/APOL1 signaling reduced the viability of kidney organoid podocytes but was rescued by baricitinib. Together, our results support the conclusion that COVID-19-induced cytokines are sufficient to drive COVAN-associated podocytopathy via JAK/STAT/APOL1 signaling and that JAK inhibitors could block this pathogenic process. These findings suggest JAK inhibitors may have therapeutic benefits for managing cytokine-induced, APOL1-mediated podocytopathy.

Cohabitation, infection and breast cancer risk.

For 50 years, the effect of age at first birth (AFB) has been thought to explain the strong association between breast cancer risk and age at first marriage (AFM), which was first reported in 1926. The independent effects of AFM, AFB and number of sexual partners adjusted for parity and other risk factors were estimated in reanalysis of a large international case-control study conducted in 1979 to 1982 (2274 breast cancers, 18209 controls) by unconditional logistic regression. Respective AFB and AFM breast cancer odds ratios (ORs) for ≥31 years relative to ≤18 years were 3.01 (95% CI 2.44-3.71; P(trend) < .0001) and 3.24 (95% CI 2.62-4.01; P(trend) < .0001) in univariate analyses. Among married parous women, these ORs fell to 1.38 (95% CI 0.98-1.95; P(trend) < .03) for AFB and 1.70 (95% CI 1.17-2.46; P(trend) < .002) for AFM when fitted together in multivariate analysis including other risk factors. A similar adjusted OR for AFM ≥ 31 years relative to ≤18 years was seen among married nulliparous women (OR 1.71, 95% CI 0.98-2.98; P(trend) < .001). AFM (a surrogate for age at starting prolonged cohabitation) is thus strongly associated with breast cancer risk. This suggests an effect of close contact. Identifying the (probably infective) mechanism might lead to effective prevention of breast cancer. The independent effect of AFB is smaller and could be due to residual confounding.

Lactobacillus acidophilus Endocarditis Complicated by Pauci-Immune Necrotizing Glomerulonephritis.

Infective endocarditis (IE) is more common in patients with predisposing cardiac lesions and has many potential complications, including stroke and arterial thromboembolisms. Renal manifestations have an estimated prevalence of ∼20%. Rapidly progressive glomerulonephritis (RPGN) is a nephrological emergency manifested by autoimmune-mediated progressive loss of renal function over a relatively short period of time. Here, we report the case of a 60-year-old Caucasian male, who presented with speech impairment and was found to have multiple embolic strokes caused by aortic valve IE. His renal function declined rapidly, and his urine sediment featured hematuria and proteinuria. ANCA titer was negative by immunofluorescence (IF); however, the PR3 antibody was elevated. The renal biopsy revealed pauci-immune focally necrotizing glomerulonephritis with the presence of ∼25% cellular crescents. He was initially treated with plasmapheresis and pulse dose steroids. Hemodialysis was initiated for uremic symptoms. After four weeks of antibiotic therapy and with blood cultures remaining negative, he was treated with rituximab. Two months after discharge, his renal function showed improvement, and hemodialysis was discontinued. This case highlights several complications associated with lactobacillus endocarditis including RPGN.

The potential role of complements in cocaine-induced thrombotic microangiopathy.

Thrombotic microangiopathy (TMA) is a rare disorder characterized by microvascular injury and occlusion resulting in tissue ischemia and dysfunction. TMA occurs in a variety of settings including cocaine use. Although cocaine is widely used in the United States, cocaine-associated TMA is only rarely reported. Therefore, other factors may predispose cocaine users to the development of TMA. Emerging evidence indicates that cocaine activates complements. Therefore, complement activation may contribute to the development of cocaine-induced TMA. Here, we report a cocaine user who presented with renal failure. Renal biopsy demonstrated TMA. Laboratory tests revealed reduced serum complement C3 and normal complement C4 levels indicative of alternative complement activation. We postulate that complement activation is involved in the pathogenesis of cocaine-induced TMA.

Pharmacological and genetic inhibition of downstream targets of p38 MAPK in experimental nephrotic syndrome.

Nie X, Chanley MA, Pengal R, Thomas DB, Agrawal S, Smoyer WE. Pharmacological and genetic inhibition of downstream targets of p38 MAPK in experimental nephrotic syndrome. Am J Physiol Renal Physiol 314: F602-F613, 2018. First published November 29, 2017; doi: 10.1152/ajprenal.00207.2017 .-The p38 MAPK pathway plays a crucial role in various glomerulopathies, with activation being associated with disease and inhibition being associated with disease amelioration. We hypothesized that the downstream targets of p38 MAPK, MAPK-activated protein kinase 2 and/or 3 (MK2 and/or MK3), play an important role in mediating injury in experimental nephrotic syndrome via their actions on their downstream substrates heat shock protein B1 (HSPB1) and cyclooxygenase-2 (COX-2). To test this hypothesis, the effects of both pharmacological and genetic inhibition of MK2 and MK3 were examined in mouse adriamycin (ADR) and rat puromycin aminonucleoside (PAN) nephropathy models. MK2-/-, MK3-/-, and MK2-/-MK3-/- mice were generated in the Sv129 background and subjected to ADR-induced nephropathy. MK2 and MK3 protein expression was completely abrogated in the respective knockout genotypes, and massive proteinuria and renal histopathological changes developed after ADR treatment. Furthermore, renal cortical HSPB1 was induced in all four genotypes by day 21, but HSPB1 was activated only in the wild-type and MK3-/- mice. Expression of the stress proteins HSPB8 and glucose-regulated protein 78 (GRP78) remained unaltered across all genotypes. Finally, while MK2 and/or MK3-knockout downregulated the proinflammatory enzyme COX-2, ADR significantly induced renal cortical COX-2 only in MK2-/- mice. Additionally, pharmacological MK2 inhibition with PF-318 during PAN-induced nephropathy did not result in significant proteinuria reduction in rats. Together, these data suggest that while the inhibition of MK2 and/or MK3 regulates the renal stress response, our currently available approaches are not yet able to safely and effectively reduce proteinuria in experimental nephrotic syndrome and that other p38MAPK downstream targets should also be considered to improve the future treatment of glomerular disease.

Interstitial nephritis in melanoma patients secondary to PD-1 checkpoint inhibitor.

BACKGROUND: Immune checkpoint inhibitors have become the first line therapy in melanoma treatment and their use is extending to other malignancies. However, we are still learning about immune side effects produced by these drugs and their severity especially in patients with history of inflammatory diseases. CASE PRESENTATION: We present two cases of metastatic melanoma treated with nivolumab and pembrolizumab (anti PD-1). Both patients developed acute interstitial nephritis during immune checkpoint therapy. We emphasize the causal association between immune checkpoint inhibitors and the nephritis. The timing of drug administration and appearance of nephritis is suggestive of a causal relation between the checkpoint inhibitor therapy and this adverse event. CONCLUSIONS: Although uncommon, some side effects from checkpoint inhibitors can be severe and may need to be addressed with immunosuppression. Given the increasing frequency of immunotherapy use, awareness should be raised in regards to immune side effects and their appropriate management.

Plasma equol concentration is not associated with breast cancer and fibrocystic breast conditions among women in Shanghai, China.

Equol (a bacterial metabolite of the soy isoflavone daidzein) is produced by 30% to 50% of humans and may be associated with health outcomes. We hypothesized that plasma equol would be inversely associated with risks of fibrocystic breast conditions (FBC) and breast cancer (BC). Plasma from women in a breast self-examination trial in Shanghai with BC (n=269) or FBC (n=443), and age-matched controls (n=1027) was analyzed for isoflavones. Equol was grouped into categories (<20, 20-<45, and ≥45nmol/L) and, among women with daidzein ≥20nmol/L, the log10 equol:daidzein ratio was grouped into tertiles. Where available, non-cancerous tissue (NCT) adjacent to the carcinomas from women with BC were classified as non-proliferative or proliferative (n=130 and 172, respectively). The lesions from women with FBC were similarly classified (n=99 and 92, respectively). Odds ratios (OR) and 95% confidence intervals (CI) were calculated across equol categories and tertiles of log10 equol:daidzein ratio. Equol categories were not associated with FBC or BC (P>.05). For log10 equol:daidzein, compared to controls there were positive associations in the mid tertile for proliferative FBC (OR 2.06, 95% CI 1.08-3.93), BC with proliferative NCT (OR 2.95, 95% CI 1.37-6.35), and all BC regardless of histology (OR 2.37, 95% CI 1.43-3.95). However, trends in ORs with increasing plasma equol values or equol:daidzein ratios were not observed (P>.05). The results of this study do not provide evidence that equol plays a role in the etiology of these breast conditions. However, further work is needed to confirm or refute this conclusion.

Risk of Pancreatic Cancer in Female Textile Workers in Shanghai, China, Exposed to Metals, Solvents, Chemicals, and Endotoxin: Follow-Up to a Nested Case-Cohort Study.

OBJECTIVE: We studied associations between pancreatic cancer and occupational exposures to metals, solvents, chemicals, and endotoxin in a cohort of female textile workers in Shanghai, China. To assess the longer-term influences of these agents on pancreatic cancer we extended follow-up of this previously studied cohort. METHODS: We utilized a job exposure matrix to assess occupational exposures for 481 pancreatic cancer cases and a randomly selected sub-cohort of 3191 non-cases. We calculated hazard ratios and 95% confidence intervals using Cox proportional hazards modeling adapted for the case-cohort design. RESULTS: We observed a statistically significant trend of increasing hazard ratios associated with solvent exposure, but no associations with any of the remaining occupational exposures, including endotoxin and metals. CONCLUSIONS: Our findings of increasing risk of pancreatic cancer with solvent exposures are consistent with published literature.

Increased breast cancer screening and downstaging in Colombian women: A randomized trial of opportunistic breast-screening.

The lack of breast cancer screening in low and middle-income countries results in later stage diagnosis and worsened outcomes for women. A cluster randomized trial was performed in Bogotá, Colombia between 2008 and 2012 to evaluate effects of opportunistic breast cancer screening. Thirteen clinics were randomized to an intervention arm and 13 to a control arm. Physicians in intervention clinics were instructed to perform clinical breast examination on all women aged 50-69 years attending clinics for non-breast health issues, and then refer them for mammographic screening. Physicians in control clinics were not explicitly instructed to perform breast screening or mammography referrals, but could do so if they thought it indicated ("usual care"). Women were followed for 2-years postrandomization. 7,436 women were enrolled and 7,419 (99.8%) screened in intervention clinics, versus 8,419 enrolled and 1,108 (13.1%) screened in control clinics. Incidence ratios (IR) of early, advanced and all breast cancers were 2.9 (95% CI 1.1-9.2), 1.0 (0.3-3.5) and 1.9 (0.9-4.1) in the first (screening) year of the trial, and the cumulative IR for all breast cancers converged to 1.4 (0.7-2.8) by the end of follow-up (Year 2). Eighteen (69.2%) of 26 women with early stage disease had breast conservation surgery (BCS) versus 6 (42.5%) of 14 women with late-stage disease (p = 0.02). Fifteen (68.2%) of 22 women with breast cancer in the intervention group had BCS versus nine (50.0%) of 18 women in the control group (p = 0.34). Well-designed opportunistic clinic-based breast cancer screening programs may be useful for early breast cancer detection in LMICs.

Occupational exposures and risk of stomach and esophageal cancers: update of a cohort of female textile workers in Shanghai, China.

BACKGROUND: Associations between stomach and esophageal cancer and exposures to dusts, metals, chemicals, and endotoxin in the workplace are not very well understood, particularly in women. METHODS: We followed 267,400 female textile workers in Shanghai, China for cancer incidence from 1989 to 2006. Stomach (n = 1374) and esophageal (n = 190) cancer cases were identified and a comparison subcohort (n = 3187) was randomly selected. Cox proportional hazard modeling was used, adjusting for age and smoking. RESULTS: Increasing stomach cancer risk was observed with increasing duration of synthetic fiber dust exposure (p = 0.03), although the magnitude of effect was small (20 + years: HR = 1.2, 95% CI 1.1-1.4). Trends with endotoxin exposure were modestly inversed for esophageal cancer and increased for stomach cancer, but with little deviation from a null association. CONCLUSIONS: Our findings demonstrate that long durations of synthetic fiber dust exposure can increase stomach cancer risk in women, but provide limited support for associations with other textile industry exposures.

Night shift work and lung cancer risk among female textile workers in Shanghai, China.

In 2007, the International Agency for Research on Cancer classified shift work that involves circadian disruption as a probable human carcinogen. Suppression of the anti-neoplastic hormone, melatonin, is a presumed mechanism of action. We conducted a case-cohort study nested within a cohort of 267,400 female textile workers in Shanghai, China. Newly diagnosed lung cancer cases (n = 1451) identified during the study period (1989-2006) were compared with an age-stratified subcohort (n = 3040). Adjusting for age, smoking, parity, and endotoxin exposure, relative risks [hazard ratios (HRs)] were estimated by Cox regression modeling to assess associations with cumulative years and nights of rotating shift work. Results did not consistently reveal any increased risk of lung cancer among rotating shift work or statistically significant trends for both cumulative years (HR 0.82, 95% CI 0.66 to 1.02; P(trend) = 0.294) and nights (HR 0.81, 95% CI 0.65 to 1.00; P(trend) = 0.415). Further analyses imposing 10- and 20-year lag times for disease latency also revealed similar results. Contrary to the initial hypothesis, rotating nighttime shift work appears to be associated with a relatively reduced lung cancer risk although the magnitude of the effect was modest and not statistically significant.

Shift work and breast cancer among women textile workers in Shanghai, China.

PURPOSE: Although night-shift work has been associated with elevated risk of breast cancer in numerous epidemiologic studies, evidence is not consistent. We conducted a nested case-cohort study to investigate a possible association between shift work including a night shift and risk of breast cancer within a large cohort of women textile workers in Shanghai, China. METHODS: The study included 1,709 incident breast cancer cases and 4,780 non-cases. Data on historical shift work schedules were collected by categorized jobs from the factories, where the study subjects had worked, and then were linked to the complete work histories of each subject. No jobs in the factories involved exclusively night-shift work. Therefore, night shift was evaluated as part of a rotating shift work pattern. Hazard ratios and 95 % confidence intervals were calculated using Cox proportional hazards modeling adapted for the case-cohort design for years of night-shift work and the total number of nights worked. Additionally, analyses were repeated with exposures lagged by 10 and 20 years. RESULTS: We observed no associations with either years of night-shift work or number of nights worked during the entire employment period, irrespective of lag intervals. Findings from the age-stratified analyses were very similar to those observed for the entire study population. CONCLUSIONS: The findings from this study provide no evidence to support the hypothesis that shift work increases breast cancer risk. The positive association between shift work and breast cancer observed in Western populations, but not observed in this and other studies of the Chinese population, suggests that the effect of shift work on breast cancer risk may be different in Asian and Caucasian women.

Tobacco and alcohol in relation to male breast cancer: an analysis of the male breast cancer pooling project consortium.

BACKGROUND: The etiology of male breast cancer is poorly understood, partly due to its relative rarity. Although tobacco and alcohol exposures are known carcinogens, their association with male breast cancer risk remains ill-defined. METHODS: The Male Breast Cancer Pooling Project consortium provided 2,378 cases and 51,959 controls for analysis from 10 case-control and 10 cohort studies. Individual participant data were harmonized and pooled. Unconditional logistic regression was used to estimate study design-specific (case-control/cohort) ORs and 95% confidence intervals (CI), which were then combined using fixed-effects meta-analysis. RESULTS: Cigarette smoking status, smoking pack-years, duration, intensity, and age at initiation were not associated with male breast cancer risk. Relations with cigar and pipe smoking, tobacco chewing, and snuff use were also null. Recent alcohol consumption and average grams of alcohol consumed per day were also not associated with risk; only one subanalysis of very high recent alcohol consumption (>60 g/day) was tentatively associated with male breast cancer (ORunexposed referent = 1.29; 95% CI, 0.97-1.71; OR>0-<7 g/day referent = 1.36; 95% CI, 1.04-1.77). Specific alcoholic beverage types were not associated with male breast cancer. Relations were not altered when stratified by age or body mass index. CONCLUSIONS: In this analysis of the Male Breast Cancer Pooling Project, we found little evidence that tobacco and alcohol exposures were associated with risk of male breast cancer. IMPACT: Tobacco and alcohol do not appear to be carcinogenic for male breast cancer. Future studies should aim to assess these exposures in relation to subtypes of male breast cancer.

Amyloid A amyloidosis with subcutaneous drug abuse.

INTRODUCTION: Amyloid A (AA) amyloidosis is a systemic form of amyloidosis secondary to chronic infections and inflammatory disorders. An acute-phase protein produced by the liver, serum amyloid A (SAA) is the precursor of AA amyloid fibrils. AA amyloid deposition occurs predominantly in the kidneys, spleen, adrenal glands, liver and gastrointestinal tract. The manifestations of AA amyloidosis involving the kidneys include proteinuria, tubular dysfunction and progressive loss of renal function. CASE: We report a 47-year-old drug addict who developed AA amyloidosis as a result of recurrent suppurative skin infections secondary to subcutaneous drug injection. Elevated C-reactive protein concentrations attested to the presence of a chronic systemic inflammatory state. He suffered from the nephrotic syndrome and insidious loss of renal function. Isosthenuria and glycosuria were indicative of renal tubular dysfunction. Renal biopsy demonstrated AA amyloidosis involving the glomeruli, tubular basement membranes and blood vessel walls. CONCLUSION: Superimposed acute tubular necrosis due to concomitant endocarditis and cocaine use accelerated his renal disease. CASE presentation is followed by a brief discussion of clinical features, natural history and outcome of AA amyloidosis with a particular emphasis on AA amyloidosis as a complication of subcutaneous drug abuse.

Tubulointerstitial nephritis accompanying gamma-heavy chain deposition and gamma-heavy chain restricted plasma cells in the kidney.

Monoclonal immunoglobulin heavy chain (HC) diseases are rare proliferative disorders of B lymphocytes or plasma cells characterized by the presence of monoclonal α-, µ-, or γ-HC without associated light chains in the blood, urine, or both. We report a 59-year-old woman with a history of Hodgkin disease who developed hypercalcemia, proteinuria, and impaired kidney function. Protein electrophoresis and immunofixation displayed γ-HC without associated light chains in the serum and urine. Pathologic examination demonstrated severe tubulointerstitial nephritis associated with diffuse and strong linear staining of the glomerular and tubular basement membranes as well as Bowman capsules for γ-HC, but not for κ- or λ-light chains. Immunohistochemical examination of the kidney and bone marrow demonstrated numerous CD138+ plasma cells immunoreactive for γ-HC, but not for κ- or λ-light chains. This is the first report of tubulointerstitial nephritis associated with γ-HC deposition and γ-HC restricted plasma cells in the kidney. This report heightens awareness about tubulointerstitial nephritis as a possible manifestation of γ-HC deposition in the kidney.

Anthropometric and hormonal risk factors for male breast cancer: male breast cancer pooling project results.

BACKGROUND: The etiology of male breast cancer is poorly understood, partly because of its relative rarity. Although genetic factors are involved, less is known regarding the role of anthropometric and hormonally related risk factors. METHODS: In the Male Breast Cancer Pooling Project, a consortium of 11 case-control and 10 cohort investigations involving 2405 case patients (n = 1190 from case-control and n = 1215 from cohort studies) and 52013 control subjects, individual participant data were harmonized and pooled. Unconditional logistic regression generated study design-specific (case-control/cohort) odds ratios (ORs) and 95% confidence intervals (CIs), with exposure estimates combined using fixed effects meta-analysis. All statistical tests were two-sided. RESULTS: Risk was statistically significantly associated with weight (highest/lowest tertile: OR = 1.36; 95% CI = 1.18 to 1.57), height (OR = 1.18; 95% CI = 1.01 to 1.38), and body mass index (BMI; OR = 1.30; 95% CI = 1.12 to 1.51), with evidence that recent rather than distant BMI was the strongest predictor. Klinefelter syndrome (OR = 24.7; 95% CI = 8.94 to 68.4) and gynecomastia (OR = 9.78; 95% CI = 7.52 to 12.7) were also statistically significantly associated with risk, relations that were independent of BMI. Diabetes also emerged as an independent risk factor (OR = 1.19; 95% CI = 1.04 to 1.37). There were also suggestive relations with cryptorchidism (OR = 2.18; 95% CI = 0.96 to 4.94) and orchitis (OR = 1.43; 95% CI = 1.02 to 1.99). Although age at onset of puberty and histories of infertility were unrelated to risk, never having had children was statistically significantly related (OR = 1.29; 95% CI = 1.01 to 1.66). Among individuals diagnosed at older ages, a history of fractures was statistically significantly related (OR = 1.41; 95% CI = 1.07 to 1.86). CONCLUSIONS: Consistent findings across case-control and cohort investigations, complemented by pooled analyses, indicated important roles for anthropometric and hormonal risk factors in the etiology of male breast cancer. Further investigation should focus on potential roles of endogenous hormones.

Short report: Limited effectiveness of screening mammography in addition to clinical breast examination by trained nurse midwives in rural Jakarta, Indonesia.

Low- and middle-income countries (LMICs) are undergoing an increase in incidence of breast cancer, but have inadequate resources to implement mammographic screening. Clinical breast examination (CBE) has been suggested as an alternative to mammography in these settings. We compared the results of CBE screening by 47 midwives and 15 trained lay health workers to results of independently performed mammographic screening in an unscreened population of 1,179 women in Jakarta, Indonesia. Two hundred and eight-nine (24.5%) of the screened women had a suspicious finding on CBE and/or mammography. Sixty-nine (23.9%) of these women had both an abnormal CBE and mammogram; 98 (33.9%) had an abnormal CBE, but a normal mammogram; and 122 (42.2%) had a normal CBE and an abnormal mammogram. Fourteen breast cancers were diagnosed. Of these, 13 were identified by both mammogram and CBE. One breast cancer was identified from an abnormal mammogram, but had a normal CBE. One hundred and sixty-seven (14.2%) of the CBEs required additional work-up to diagnose 13 of the 14 cancers detected by mammography. In comparison, 191 (16.2%) of mammograms required additional work-up to diagnose the 14 cancers. Unfortunately, only 42.8% of the women diagnosed with cancer returned for treatment. In an unscreened population in LMICs such as Indonesia, CBE is nearly as effective as mammography in detecting prevalent breast cancers. However identifying and overcoming barriers to appropriate treatment of women who are identified as having breast cancer are essential to the success of any screening program.

Occupational exposure to magnetic fields and breast cancer among women textile workers in Shanghai, China.

Exposure to magnetic fields (MFs) is hypothesized to increase the risk of breast cancer by reducing production of melatonin by the pineal gland. A nested case-cohort study was conducted to investigate the association between occupational exposure to MFs and the risk of breast cancer within a cohort of 267,400 female textile workers in Shanghai, China. The study included 1,687 incident breast cancer cases diagnosed from 1989 to 2000 and 4,702 noncases selected from the cohort. Subjects' complete work histories were linked to a job-exposure matrix developed specifically for the present study to estimate cumulative MF exposure. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards modeling that was adapted for the case-cohort design. Hazard ratios were estimated in relation to cumulative exposure during a woman's entire working years. No association was observed between cumulative exposure to MFs and overall risk of breast cancer. The hazard ratio for the highest compared with the lowest quartile of cumulative exposure was 1.03 (95% confidence interval: 0.87, 1.21). Similar null findings were observed when exposures were lagged and stratified by age at breast cancer diagnosis. The findings do not support the hypothesis that MF exposure increases the risk of breast cancer.