'PartBreCon' study. A UK multicentre retrospective cohort study to assess outcomes following PARTial BREast reCONstruction with chest wall perforator flaps.

BACKGROUND: Partial breast reconstruction with a pedicled chest wall perforator flap (CWPF) enables breast conservation in a higher tumour: breast volume ratio scenario. Since there is limited evidence, this retrospective cohort study aimed to ascertain immediate (30-days) and medium-term (follow-up duration) surgical outcomes. METHODS: STROBE-compliant protocol ascertained CWPF outcomes between March 2011-March 2021. UK centres known to perform CWPF were invited to participate if they performed at least 10 cases. Data were retrospectively collected, including patient demographics, tumour and treatment characteristics, and surgical and oncological outcomes. Statistical analysis (R™) included multivariable logistic regression and sensitivity analysis. RESULTS: Across 15 centres, 507 patients with median age (54 years, IQR; 48-62), body mass index (25.4 kg/m2, IQR; 22.5-29), tumour size (26 mm, IQR; 18-35), and specimen weight (62 g, IQR; 40-92) had following flap types: LiCAP (54.1%, n = 273), MiCAP/AiCAP (19.6%, n = 99), LiCAP + LTAP (19.8%, n = 100) and TDAP (2.2%, n = 11). 30-days complication rates were in 12%: haematoma (4.3%, n = 22), wound infection (4.3%, n = 22), delayed wound healing (2.8%, n = 14) and flap loss (0.6%, n = 3; 1 full) leading to readmissions (2.6%, n = 13) and re-operations (2.6%, n = 13). Positive margins (n = 88, 17.7%) led to 15.9% (n = 79) re-excisions, including 7.5% (n = 37) at the planned 2nd of 2-stage surgery and 1.8% (n = 9) mastectomy. At median 23 months (IQR; 11-39) follow-up, there were 1.2% (n = 6) symmetrisations; recurrences: local (1%), regional/nodal (0.6%) and distant (3.2%). CONCLUSIONS: This large multicentre cohort study demonstrates acceptable complication and margin re-excision rates. CWPF extends the range of breast conservation techniques. Further studies are required for long-term oncological outcomes.

International Variation in Criteria for Internal Mammary Chain Radiotherapy.

AIMS: Evidence has emerged that internal mammary chain (IMC) radiotherapy reduces breast cancer mortality, leading to changes in treatment guidelines. This study investigated current IMC radiotherapy criteria and the percentages of patients irradiated for breast cancer in England who fulfilled them. MATERIALS AND METHODS: A systematic search was undertaken for national guidelines published in English during 2013-2018 presenting criteria for 'consideration of' or 'recommendation for' IMC radiotherapy. Patient and tumour variables were collected for patients who received breast cancer radiotherapy in England during 2012-2016. The percentages of patients fulfilling criteria stipulated in each set of guidelines were calculated. RESULTS: In total, 111 729 women were recorded as receiving adjuvant breast cancer radiotherapy in England during 2012-2016 and full data were available on 48 095 of them. Percentages of patients fulfilling IMC radiotherapy criteria in various national guidelines were: UK Royal College of Radiologists 13% (6035/48 095), UK National Institute for Health and Care Excellence 18% (8816/48 095), Germany 32% (15 646/48 095), Ireland 56% (26 846/48 095) and USA 59% (28 373/48 095). Differences between countries occurred because in Ireland and the USA, treatment may be considered in some node-negative patients, whereas in the UK, treatment is considered if at least four axillary nodes are involved or for high-risk patients with one to three positive nodes. In Germany, treatment may be considered for all node-positive patients. CONCLUSIONS: There is substantial variability between countries in criteria for consideration of IMC radiotherapy, despite guidelines being based on the same evidence. This will probably lead to large variations in practice and resource needs worldwide.

Drivers of Mercury Cycling in the Rapidly Changing Glacierized Watershed of the High Arctic's Largest Lake by Volume (Lake Hazen, Nunavut, Canada).

Across the Arctic, glaciers are melting and permafrost is thawing at unprecedented rates, releasing not only water to downstream aquatic systems, but also contaminants like mercury, archived in ice over centuries. Using concentrations from samples collected over 4 years and calibrated modeled hydrology, we calculated methylmercury (MeHg) and total mercury (THg) mass balances for Lake Hazen, the world's largest High Arctic lake by volume, for 2015 and 2016. Glacial rivers were the most important source of MeHg and THg to Lake Hazen, accounting for up to 53% and 94% of the inputs, respectively. However, due to the MeHg and THg being primarily particle-bound, Lake Hazen was an annual MeHg and THg sink. Exports of MeHg and THg out the Ruggles River outflow were consequently very low, but erosion and permafrost slumping downstream of the lake increased river MeHg and THg concentrations significantly before entering coastal waters in Chandler Fjord. Since 2001, glacial MeHg and THg inputs to Lake Hazen have increased by 0.01 and 0.400 kg yr-1, respectively, in step with dramatic increases in glacial melt. This study highlights the potential for increases in mercury inputs to arctic ecosystems downstream of glaciers despite recent reductions in global mercury emissions.

Evaluating bone health in women with oestrogen receptor positive breast cancer (ERBC) starting aromatase inhibitors.

AIMS: There is an increase in fractures in women with oestrogen receptor positive breast cancer (ERBC) particularly those taking aromatase inhibitors (AIs). How to identify women at osteoporosis risk, assess bone health and who to treat, are questions not adequately answered by previous studies. METHODS: We present an audit of osteoporosis risk factors, bone mineral density (BMD) measurement and other data relevant to bone health (falls and laboratory tests) in 85 women with ERBC starting AIs. RESULTS: Only 9/85 (11%) women overall and only 2/13 with previous peripheral fragility fractures had osteoporosis. Of note, secondary hyperparathyroidism was present in 40% of women <60 years; 67% of women 60-69 years and 75% of women >70 years. CONCLUSIONS: Reliance on BMD alone to guide decisions for osteoporosis prevention treatment in those taking AIs would lead to few women being treated. Osteoporosis risk in women taking AIs is likely influenced by factors other than those encompassed by BMD alone.

Formation of specialized propagules resistant to desiccation and cryopreservation in the threatened moss Ditrichum plumbicola (Ditrichales, Bryopsida).

BACKGROUND AND AIMS: Successful cryopreservation of bryophytes is linked to intrinsic desiccation tolerance and survival can be enhanced by pre-treatment with abscisic acid (ABA) and sucrose. The pioneer moss Ditrichum plumbicola is naturally subjected to desiccation in the field but showed unexpectedly low survival of cryopreservation, as well as a poor response to pre-treatment. The effects of the cryopreservation protocol on protonemata of D. plumbicola were investigated in order to explore possible relationships between the production in vitro of cryopreservation-tolerant asexual propagules and the reproductive biology of D. plumbicola in nature. METHODS: Protonemata were prepared for cryopreservation using a four-step protocol involving encapsulation in sodium alginate, pre-treatment for 2 weeks with ABA and sucrose, desiccation for 6 h and rapid freezing in liquid nitrogen. After each stage, protonemata were prepared for light and electron microscopy and growth on standard medium was monitored. Further samples were prepared for light and electron microscopy at intervals over a 24-h period following removal from liquid nitrogen and re-hydration. KEY RESULTS: Pre-treatment with ABA and sucrose caused dramatic changes to the protonemata. Growth was arrested and propagules induced with pronounced morphological and cytological changes. Most cells died, but those that survived were characterized by thick, deeply pigmented walls, numerous small vacuoles and lipid droplets in their cytoplasm. Desiccation and cryopreservation elicited no dramatic cytological changes. Cells returned to their pre-dehydration and cryopreservation state within 2 h of re-hydration and/or removal from liquid nitrogen. Regeneration was normal once the ABA/sucrose stimulus was removed. CONCLUSIONS: The ABA/sucrose pre-treatment induced the formation of highly desiccation- and cryopreservation-tolerant propagules from the protonemata of D. plumbicola. This parallels behaviour in the wild, where highly desiccation-tolerant rhizoids function as perennating organs allowing the moss to endure extreme environmental conditions. An involvement of endogenous ABA in the desiccation tolerance of D. plumbicola is suggested.

Thymic carcinoma - an unusual cause for unilateral breast oedema.

An 83-year-old lady presented with oedema of the right breast with no focal masses and was found to have a tumour of thymic origin in the anterior mediastinum. We describe this interesting case along with a review of the causes of unilateral breast oedema.

Patient information on phantom limb pain: a focus group study of patient experiences, perceptions and opinions.

Educating patients about their condition is regarded as a fundamental step in pain management. This study used focus groups with patients to explore their experiences and perceptions of the information on phantom pain that they received before and after amputation, and their views on improving this information. Thirty-one patients with a lower limb amputation attended one of seven focus groups. The majority reported phantom pain although there were individual variations in character, severity and persistence. There were wide variations in what people were told from occasional reports of good information to instances of people reporting little or no information from professionals. There were strong feelings that information should be given before or soon after amputation with a preference for verbal one-to-one explanations. Professionals, particularly nurses and surgeons, were regarded as the best source of information, although peer support was seen to be important. These findings indicate that people require timely up-to-date information on phantom pain which sensitively addresses the variability of the experience and provides the foundation for ongoing pain management. We propose that the information process could be improved by ensuring that professionals use standard information for patients derived from purposefully written sections in national guidelines.

Iritis associated with intravenous cidofovir.

OBJECTIVE: To report two patients with AIDS and cytomegalovirus retinitis who developed iritis after receiving intravenous cidofovir. Both experienced recurrent symptoms upon rechallenge. CASE SUMMARIES: Two HIV-positive patients with cytomegalovirus retinitis infections previously controlled with intravenous ganciclovir or foscarnet were treated with intravenous cidofovir. Symptoms of iritis developed after the second or third dose of cidofovir. One patient experienced symptoms unilaterally, while the other patient had bilateral symptoms. In both patients, the iritis resolved with topical ophthalmic therapy, but recurred following subsequent infusions of cidofovir. Therapy with cidofovir was discontinued, and no further recurrences of iritis were noted. One patient had post-inflammatory fixed dilated pupils. CONCLUSIONS: Iritis can uncommonly occur in patients receiving intravenous cidofovir and oral probenecid. With prompt drug discontinuation and administration of topical corticosteroids and/or mydriatic agents, symptoms are usually reversible.

Predictive value of cytomegalovirus (CMV) antigenemia and digene hybrid capture DNA assays for CMV disease in human immunodeficiency virus-infected patients.

Oral ganciclovir prophylaxis decreases the incidence of cytomegalovirus (CMV) disease among persons infected with the human immunodeficiency virus (HIV), but universal prophylaxis is not cost-effective. We evaluated urine and peripheral blood mononuclear cell cultures, a qualitative and quantitative antigenemia assay, and a commercially available CMV DNA hybridization assay for their ability to predict CMV disease in 138 HIV-infected patients. During a median follow-up of 10 months, 23 patients (17%) developed CMV disease. The sensitivity, specificity, positive predictive value, negative predictive value, and mean lead times for the antigenemia assay (with use of a threshold of 8 positive cells per 10(5) peripheral blood mononuclear cells as a positive) were 74%, 91%, 63%, 95%, and 95 days, respectively. Corresponding figures for the DNA hybridization assay were 91%, 64%, 34%, 97%, and 152 days. These assays can identify patients at increased risk of CMV disease and should allow a strategy of preemptive therapy to be tested.

Case report: retinopathy and neuropathy associated with complete apolipoprotein A-I deficiency.

Genetic deficiencies of plasma high-density lipoprotein cholesterol are associated variably with diseases of the eyes and nervous system. We ascertained a proband with undetectable plasma HDL-cholesterol due to homozygosity for a DNA mutation, APOA1 Q[-2]X, which encodes premature termination of translation of apolipoprotein in HDL. This person had a unique retinopathy, ataxia, and electrophysiologic abnormalities suggesting multifocal central nervous system deficits. Other gene carriers in this family had similar neurologic features, but only the proband had the retinopathy. The presence of retinopathy and neuropathy in affected family members was highly variable. This heterogeneity might results from time-dependent interactions with other genetic or environmental factors.

Expression of FGFR2 BEK and K-SAM mRNA variants in normal and malignant human breast.

The expression of mRNA encoding alternative forms of fibroblast growth factor receptor 2 (FGFR2) differing in the carboxy terminal half of their third immunoglobulin-like domain, was investigated in 77 human breast cancer tissues, 12 non-malignant breast biopsies and 29 cell lines, using a reverse transcriptase (RT) polymerase chain reaction (PCR) method. RNA from the two tissue groups yielded PCR product corresponding to both the BEK and the K-SAM form; amounts normalised to glyceraldehyde phosphate dehydrogenase product were similar in both groups. The level of either variant or of the total FGFR2 product was essentially unrelated to prognosis or clinical status except that patients with advanced clinical T staging had a higher proportion of BEK to K-SAM (P = 0.01). RNA from 1/2 normal breast derived and 8/10 breast cancer cell lines expressed exclusively or predominantly the K-SAM form; 2/10 had significant amounts of both BEK and K-SAM mRNA. Of 12 other epithelial lines, seven expressed mainly K-SAM mRNA, four expressed BEK and one was negative. Of five non-epithelial lines, one was negative, two expressed only BEK mRNA and two had significant amounts of both variants. We conclude that tissue levels of FGFR2 mRNA are unaltered in breast cancer extracts and that the splicing mechanism for this exon selection appears not to be significantly disrupted.

Magnetisation transfer ratios and transverse magnetisation decay curves in optic neuritis: correlation with clinical findings and electrophysiology.

Conventional MRI sequences do not permit the distinction between the different pathological characteristics (oedema, demyelination, gliosis, axonal loss) of the multiple sclerosis plaque. Magnetisation transfer imaging and transverse magnetisation decay curve (tMDC) analysis may be more specific. These techniques have been applied to the optic nerves in 20 patients with optic neuritis and the results correlated with clinical and visual evoked potential (VEP) findings. tMDC analysis failed to identify separate intracellular and extracellular water compartments within the optic nerve but gave a measure of transverse relaxation time (T2) without the confounding effects of CSF in the nerve sheath. Both T2 and magnetisation transfer ratio (MTR) were abnormal after an episode of optic neuritis. T2 did not correlate with visual function or with VEP latency or amplitude. There was a significant correlation between MTR reduction and prolongation of VEP latency: this increased latency may reflect an effect of myelin loss on MTR. Longer lesions were associated with worse visual outcome, implying that the overall extent of pathological involvement is likely to influence the degree of functional deficit.

Clinical evaluation of VEPs to interleaved checkerboard reversal stimulation of central, hemi- and peripheral fields.

The VEPs of 195 patients referred for supportive evidence of multiple sclerosis or optic neuritis were studied by a new method of interleaved checkerboard reversal stimulation of different areas of the visual field. In the first group of 95 patients checks of 40' subtense reversed in the whole field (28 degrees x 20 degrees), alternatively in the left and right hemifields and alternately in the central (5 degrees radius) and peripheral fields. In the second group of 100 patients checks reversed in the whole field and in interleaved mode in 3 visual field areas, comprising the central (4 degrees radius) and left and right hemisurround fields. In the first group abnormal responses were recorded from 52 eyes and there was partial disagreement among the stimulus conditions in 10 of the 52. Abnormalities were seen uniquely to central field stimulation in 3 eyes but never to whole field stimulation alone. In the second group abnormal responses were recorded in 58 eyes, again never uniquely to whole field stimulation, while abnormalities confined to one or two areas of the visual field were seen in 24, providing evidence of peripheral field involvement alone in 8 eyes. In the first group, waveforms created from the sum of the left and right hemifield and central and peripheral field responses showed quite close conformity to the whole field VEP, although amplitudes were significantly lower and latencies significantly shorter. In 7 eyes responses would have been differently classified (normal or abnormal) using the sum as compared with the whole fields.(ABSTRACT TRUNCATED AT 250 WORDS)

Expression of 2 variant forms of fibroblast growth factor receptor 1 in human breast.

The expression of variant mRNAs encoding isoforms of fibroblast growth factor receptor (FGFR)1 with either 2 or 3 Ig-like loops in the extracellular domain was investigated in human breast tissues and cell lines using a polymerase chain reaction amplification method. Almost all tissues contained both forms of FGFR1, but cancers (n = 137) had a significantly lower proportion of the transcript that encoded the full 3-loop form compared with non-malignant biopsies (n = 34). This was confirmed using microdissected populations of normal and cancerous cells from frozen tissue sections. A high ratio of the 2- to 3-loop form was found to be predictive of reduced relapse-free survival. In both groups, however, the predominant form of FGFR1 was that encoding the 2-loop receptor. Cell lines derived from a variety of tissues, including breast, also co-expressed both variants of FGFR1, suggesting their presence within the same cell type. Again, there was a similar preponderance of the shorter isoform. Our results were confirmed at the protein level, where out of 5 cancers analysed 4 expressed more of the 2-loop form than the 3-loop form. Our findings suggest that cells may normally simultaneously express several splice variants of FGFR1, and aberrant expression or a change in their relative amounts (i.e., in malignancy) could contribute to modified responses to either autocrine or paracrine factors.

Osteoporosis in a largely self-referred population: high prevalence but low medical priority: why?

Dual photon bone density screening for osteoporosis (OP) and osteopenia of the lumbar spine was performed in 108 women aged 34-75 years of whom 91% were self-referred in a cross-sectional study. OP was present in 18.6% when defined as greater than 2 SD bone mineral density (BMD) reduction compared to young normals and in 41.6% with osteopenia (1 SD BMD reduction). Twelve percent gave an actual history of previous fractures. In those who showed reduced BMD (60%), 69.5% had a family history and 54% scalp hair loss although this was not a good prognostic sign. An Osteoporosis Risk Questionnaire was not an accurate predictor of BMD, thus bone density screening remains essential for early and accurate diagnosis. Previous oral contraceptive use appears to be protective (p = 0.004). Sex hormone replacement therapy (sHRT) taken by 20% of the postmenopausal patients had not yet provided significant protection (p = 0.15) probably due to its late introduction, short exposure and failure to optimise dose levels. Despite detailed information and questionnaires provided to their doctors, of 53 patients with OP or osteopenia 15 (28%) started sHRT without additional investigation, 19 (36%) remained untreated, while the outcome in the rest, 19 (36%), was unknown. A disturbing indifference by doctors and patients continues to the prevention and treatment of OP and low BMD, a potentially preventable and reversible condition, which signals a higher risk of future fragility fracture.

Efficacy of polyacrylamide vs. sodium hyaluronate in cataract surgery.

A prospective randomized study was conducted in 137 patients who underwent cataract surgery and implantation of a polymethylmethacrylate intraocular lens with either polyacrylamide (Orcolon) (68 patients) or sodium hyaluronate (Healon) (69 patients) as the viscoelastic material. Both viscoelastics were aspirated at the end of surgery. Patients were examined before surgery and 1 and 14 days after surgery. Endothelial cell counts were obtained before surgery and 3 months after surgery in 34 patients (16 in the polyacrylamide group and 18 in the sodium hyaluronate group). There were no reports of a flat or shallow anterior chamber intraoperatively in either group. There was no statistically significant difference between the two groups in the incidence of corneal edema or iritis on any visit or in endothelial cell loss. Although there was a significant reduction in intraocular pressure across postoperative visits for the overall sample, there was no significant difference in pressure between the polyacrylamide and sodium hyaluronate groups. The results indicate that no untoward effects on corneal edema, endothelial cell count, iritis or intraocular pressure are to be expected when polyacrylamide is used as an aid to cataract surgery.

Foscarnet therapy of cytomegalovirus retinitis in AIDS.

Cytomegalovirus (CMV) retinitis is the most common cause of blindness in AIDS. Twenty patients were treated with a 21-day course of foscarnet therapy by continuous infusion. Response to therapy was good in eight (47%) of 17 evaluable patients; partial arrest of progression was observed in eight (47%); and no response was obtained in one (6%). Foscarnet therapy did not lead to suppression of urinary excretion of CMV in four of 12 patients who nonetheless had improvement in retinal lesions. Toxic effects, especially reversible renal failure, were common, with blood creatinine increase in 50% and dialysis in two patients. Renal toxicity occurred primarily during the third week of therapy. Anemia (hemoglobin less than 80 g/L) occurred in 10 patients after a mean of 14.5 +/- 5.1 days of therapy and required transfusion. Review of this study and of data from a previous case series, however, was inconclusive regarding the additional benefit of a third week of therapy. Maintenance therapy was given to seven patients. Four had recurrence of CMV retinitis at a mean interval of 62 +/- 52 days. Only one patient has maintained prolonged remission on maintenance (greater than 24 weeks). Toxicity on the maintenance protocol included anemia (two of seven patients) and increased creatinine blood levels (one of seven patients). Zidovudine therapy in six patients did not contribute to increased toxicity of induction or maintenance therapy. Drug levels during continuous infusion were stable for individual patients but showed wide inter-patient variability. Peak levels of post-maintenance infusion varied both within and between patients.

Comparison of 2% hydroxypropyl methylcellulose and 1% sodium hyaluronate in implant surgery.

We conducted a prospective randomized clinical trial of 2% hydroxypropyl methylcellulose and 1% sodium hyaluronate (Healon) in routine extracapsular cataract surgery with implantation of a posterior chamber intraocular lens. Of the 84 patients 40 received methylcellulose and 44 received sodium hyaluronate. There was no statistically significant difference in endothelial-cell loss or induced cellular polymegathism between the two groups. The intraocular pressure before and after surgery was similar in the two groups, as was the visual acuity 8 weeks after surgery. The results suggest that 2% hydroxypropyl methylcellulose is a safe and effective alternative to 1% sodium hyaluronate in routine implant surgery.