Baseline factors predicting a response to neoadjuvant chemotherapy with implications for non-surgical management of triple-negative breast cancer.

BACKGROUND: Patients with triple-negative breast cancer (TNBC) and a pathological complete response (pCR) after neoadjuvant chemotherapy may be suitable for non-surgical management. The goal of this study was to identify baseline clinicopathological variables that are associated with residual disease, and to evaluate the effect of neoadjuvant chemotherapy on both the invasive and ductal carcinoma in situ (DCIS) components in TNBC. METHODS: Patients with TNBC treated with neoadjuvant chemotherapy followed by surgical resection were identified. Patients with a pCR were compared with those who had residual disease in the breast and/or lymph nodes. Clinicopathological variables were analysed to determine their association with residual disease. RESULTS: Of the 328 patients, 36·9 per cent had no residual disease and 9·1 per cent had residual DCIS only. Patients with residual disease were more likely to have malignant microcalcifications (P = 0·023) and DCIS on the initial core needle biopsy (CNB) (P = 0·030). Variables independently associated with residual disease included: DCIS on CNB (odds ratio (OR) 2·46; P = 0·022), T2 disease (OR 2·40; P = 0·029), N1 status (OR 2·03; P = 0·030) and low Ki-67 (OR 2·41; P = 0·083). Imaging after neoadjuvant chemotherapy had an accuracy of 71·7 (95 per cent c.i. 66·3 to 76·6) per cent and a negative predictive value of 76·9 (60·7 to 88·9) per cent for identifying residual disease in the breast and lymph nodes. Neoadjuvant chemotherapy did not eradicate the DCIS component in 55 per cent of patients. CONCLUSION: The presence of microcalcifications on imaging and DCIS on initial CNB are associated with residual disease after neoadjuvant chemotherapy in TNBC. These variables can aid in identifying patients with TNBC suitable for inclusion in trials evaluating non-surgical management after neoadjuvant chemotherapy.

Magic angle effect plays a major role in both T1rho and T2 relaxation in articular cartilage.

PURPOSE: To investigate the effect of sample orientation on T1rho and T2 values of articular cartilage in histologically confirmed normal and abnormal regions using a whole-body 3T scanner. MATERIALS AND METHODS: Eight human cadaveric patellae were evaluated using a 2D CPMG sequence for T2 measurement as well as a 2D spin-locking prepared spiral sequence and a 3D magnetization-prepared angle-modulated partitioned-k-space spoiled gradient echo snapshots (3D MAPSS) sequence for T1rho measurement. Each sample was imaged at six angles from 0° to 100° relative to the B0 field. T2 and T1rho values were measured for three regions (medial, apex and lateral) with three layers (10% superficial, 60% middle, 30% deep). Multiple histopathologically confirmed normal and abnormal regions were used to evaluate the angular dependence of T2 and T1rho relaxation in articular cartilage. RESULTS: Our study demonstrated a strong magic angle effect for T1rho and T2 relaxation in articular cartilage, especially in the deeper layers of cartilage. On average, T2 values were increased by 231.8% (72.2% for superficial, 237.6% for middle, and 187.9% for deep layers) while T1rho values were increased by 92% (31.7% for superficial, 69% for middle, and 140% for deep layers) near the magic angle. Both normal and abnormal cartilage showed similar T1rho and T2 magic angle effect. CONCLUSIONS: Changes in T1rho and T2 values due to the magic angle effect can be several times more than that caused by degeneration, and this may significantly complicate the clinical application of T1rho and T2 as an early surrogate marker for degeneration.

Muscle-fiber specific genetic manipulation of Drosophila sallimus severely impacts neuromuscular development, morphology, and physiology.

The ability of skeletal muscles to contract is derived from the unique genes and proteins expressed within muscles, most notably myofilaments and elastic proteins. Here we investigated the role of the sallimus (sls) gene, which encodes a structural homologue of titin, in regulating development, structure, and function of Drosophila melanogaster. Knockdown of sls using RNA interference (RNAi) in all body-wall muscle fibers resulted in embryonic lethality. A screen for muscle-specific drivers revealed a Gal4 line that expresses in a single larval body wall muscle in each abdominal hemisegment. Disrupting sls expression in single muscle fibers did not impact egg or larval viability nor gross larval morphology but did significantly alter the morphology of individual muscle fibers. Ultrastructural analysis of individual muscles revealed significant changes in organization. Surprisingly, muscle-cell specific disruption of sls also severely impacted neuromuscular junction (NMJ) formation. The extent of motor-neuron (MN) innervation along disrupted muscles was significantly reduced along with the number of glutamatergic boutons, in MN-Is and MN-Ib. Electrophysiological recordings revealed a 40% reduction in excitatory junctional potentials correlating with the extent of motor neuron loss. Analysis of active zone (AZ) composition revealed changes in presynaptic scaffolding protein (brp) abundance, but no changes in postsynaptic glutamate receptors. Ultrastructural changes in muscle and NMJ development at these single muscle fibers were sufficient to lead to observable changes in neuromuscular transduction and ultimately, locomotory behavior. Collectively, the data demonstrate that sls mediates critical aspects of muscle and NMJ development and function, illuminating greater roles for sls/titin.

Developmental and physiological impacts of pathogenic human huntingtin protein in the nervous system.

Huntington's Disease (HD) is a neurodegenerative disorder, part of the nine identified inherited polyglutamine (polyQ) diseases. Most commonly, HD pathophysiology manifests in middle-aged adults with symptoms including progressive loss of motor control, cognitive decline, and psychiatric disturbances. Associated with the pathophysiology of HD is the formation of insoluble fragments of the huntingtin protein (htt) that tend to aggregate in the nucleus and cytoplasm of neurons. To track both the intracellular progression of the aggregation phenotype as well as the physiological deficits associated with mutant htt, two constructs of human HTT were expressed with varying polyQ lengths, non-pathogenic-htt (Q15, NP-htt) and pathogenic-htt (Q138, P-htt), with an N-terminal RFP tag for in vivo visualization. P-htt aggregates accumulate in the ventral nerve cord cell bodies as early as 24 hours post hatching and significant aggregates form in the segmental nerve branches at 48 hours post hatching. Organelle trafficking up-and downstream of aggregates formed in motor neurons showed severe deficits in trafficking dynamics. To explore putative downstream deficits of htt aggregation, ultrastructural changes of presynaptic motor neurons and muscles were assessed, but no significant effects were observed. However, the force and kinetics of muscle contractions were severely affected in P-htt animals, reminiscent of human chorea. Reduced muscle force production translated to altered locomotory behavior. A novel HD aggregation model was established to track htt aggregation throughout adulthood in the wing, showing similar aggregation patterns with larvae. Expressing P-htt in the adult nervous system resulted in significantly reduced lifespan, which could be partially rescued by feeding flies the mTOR inhibitor rapamycin. These findings advance our understanding of htt aggregate progression as well the downstream physiological impacts on the nervous system and peripheral tissues.

Double complete capsulorrhexis required for cataract extraction: is it a sign of true exfoliation?

We report an 88-year-old lady who required two complete capsulorrhexis in a single cataract extraction. To our knowledge, there has been no reported case where two complete capsulorrhexis has been done for a single cataract extraction.

Psoriasis: is it the tip of the iceberg for the quality of life of patients and their families?

OBJECTIVE: To evaluate the impact of psoriasis on patients' and their relatives' quality of life (QoL). METHODS: Eighty patients with their accompanying family members were included in the study. For measuring health related QoL (HRQoL) of patients with psoriasis, two questionnaires were used: Short Form 36 Health Survey (SF-36) and EuroQol (EQ-5D). Disease-specific HRQoL was assessed by the Dermatology Life Quality Index. For measuring the quality of life of patients' relatives, a specific questionnaire for dermatological diseases was used (Family Dermatology Life Quality Index, FDLQI). RESULTS: Of our patients, 88.3% reported that their disease affects in many and different ways their QoL whereas only 11.2% reported that psoriasis does not influence at all their life. Regarding FDLQI, 90% of the participating family members, responded that their relative's psoriasis affected their own QoL. CONCLUSIONS: Psoriasis is a chronic disease that affects in a cumulative way the quality of life of both patients and their close relatives.

Description of the normal variants of the anatomical shapes of the sella turcica using plain radiographs: experience from Sokoto, Northwestern Nigeria.

BACKGROUND: The anatomy of the sella turcica is variable in size and shape. It has been classified into three types: round, oval and flat. It can also be deep or shallow in both children and adults. The floor of the sella turcica which in most cases is concave may be, flat or even convex. In both anatomical and radiological practice in Nigeria, normal data in relation to the description of the normal variants of the anatomical shapes of the sella turcica are based on Caucasian studies. METHODS: All available lateral skull radiographs of subjects over a 3-year period, from 2002 to 2004, were retrieved from the Radiology Department of the Usmanu Danfodiyo University Teaching Hospital, Sokoto for the study. Radiographs were mounted on the viewing boxes and sellae turcicae were stu died and classified. RESULTS: A total of 228 subjects were involved in this study. Of this figure, 171 (75%) were males, and 57 (25%) were females (m:f ratio = 3:1). The predominant shape of sella in the African subjects studied is oval, and the difference in frequency of oval shaped sella and that of round or flat types is highly statistically significant. (P < .001).The commonest type of sella floor in the African subjects studied is concave and the difference in frequency of concave shaped sella floor and that of flat and convex types is highly statistically significant.(P< .001). In both the various anatomical shapes of the sella turcica and the types of floor of the sella turcica in relation to sex of the subjects studied, the difference in frequency of males and females is highly statistically significant. (P < .001). CONCLUSION: It is concluded that the prevalence and the relative frequencies of the normal variants of the anatomical shapes of the sella turcica reported in this study on Nigerian subjects is similar to those reported in Caucasians. Further studies on a larger scale are needed to corroborate our findings.

Head and neck reconstruction.

Head and neck cancers are among the rarer types of cancer presenting in the UK. However, oncological resection can cause significant morbidity in these patients, so reconstruction has a crucial role in the management of such patients to improve their postoperative quality of life.

Prognosis with newly diagnosed mycosis fungoides after total skin electron radiation of 30 or 35 GY.

PURPOSE: To determine the prognosis of new patients with T1-4N0-1B0M0 mycosis fungoides treated with total skin electron beam radiation. METHODS AND MATERIALS: 25 consecutive patients received 30 Gy with 3 or 4 MeV electrons in 1977-1980; 121 received 35 Gy with 4 MeV in 1980-1992. Response rates, relapse-free survival, and overall and cause-specific survivals were assessed by explicit criteria. The relationships of T, N, gender, age, and radiation technique to prognosis were investigated by regression statistics. RESULTS: The average age was 55 years and the male:female ratio was 1:4. Forty-four percent were T1N0 and 34% were T2N0. The overall complete response rate was 82%, and lower T status, more radiation, and female gender were independently and positively associated with response. Median follow-up was 5.2 years. T1 patients who entered remission had a higher relapse-free survival compared to T2 through T4 patients. Thirty-four percent of T1 patients remained relapse-free at 6 years, compared to fewer than 20% of T2-4 patients. For all 146 patients the median overall survival was not reached at 15 years. Only 8 of 29 deaths were related to mycosis fungoides and these were significantly associated with higher T. The 54 T1N0 patients who had 35 Gy had a 10-year mycosis fungoides-specific survival of 100%. CONCLUSION: Total skin electron beam radiation gives good results with T1N0B0M0 disease. T3-4 disease is less likely to respond, it relapses more quickly, and it implies a poorer survival, but radiation offers palliation. T2 responds like T1, but relapses like T3-4. T2 also implies an intermediate survival. These results have implications for staging, informed consent, optimizing radiation treatment, and clinical trials.

Total skin electron irradiation for mycosis fungoides: failure analysis and prognostic factors.

From 1970 to 1980, 106 patients with mycosis fungoides received total skin electron irradiation to full tolerance. The majority received 30 Gy of 3 MeV electrons in 12 treatments over three weeks. Eighty-eight patients had received prior therapy. Fifty patients had cutaneous plaques only (T1-2N0), and 56 had more advanced disease. At five years, actuarial survival is 66.7% and disease-free survival 21.4%. The median time to relapse is 12 months; prolonged survival is seen only with complete response. Compared with more advanced stages, T1-2N0 patients have more frequent complete response (96% vs 71%) and better relapse-free survival at five years (32 vs 7%). Of 14 patients with T2 disease in continuous complete remission for from 45-113 months, only one has relapsed. This suggests that cure is possible in up to 26% of patients with T2 disease who achieve complete response. In advanced stages, complete response is more likely with doses over 25 Gy (80 vs 50%). First recurrences were predominently in sites of previous involvement. Death resulted mainly from extracutaneous dissemination or failure to induce remission.

An unusual complication of Vacuum Assisted Closure in the treatment of a pressure ulcer.

A patient with a non-healing sacral pressure ulcer underwent exploratory surgery. During the procedure a piece of polyurethane sponge was found to have been left in situ. This unusual case highlights the importance of vigilance at dressing changes.

Stiff fingers as an unwanted side effect of intravascular tadalafil gel abuse.

The internet provides the public with unregulated access to a wide range of medications. We present the case of a 43-year-old man who purchased oral tadalafil gel on the internet and injected it into his left radial artery. He presented 48 hours after injection with signs of ischaemia distal to the injection site requiring a combination of medical and surgical treatment. This unique case highlights the potential dangers of unregulated access to medication and the consequences of intravascular injection of oral gels.

Digital image referral for suspected skin malignancy--a pilot study of 300 patients.

Referral of suspect skin cancers as well as non malignant symptomatic skin lesions using high quality digital images transferred via a secure electronic referral system (ERS) potentially offers significant advantages regarding speed of referral, diagnosis and subsequent treatment over conventional pathways. However concerns over safety of the diagnostic process have been raised. This prospective study looks at 300 patients referred by ERS. A comparison of the diagnoses made from digital images with the diagnoses confirmed on pathology reports for lesions excised is described using a random selection of patients' images and referrals. Intra observer analysis of was also assessed. A sample group of patients with lesions deemed as benign, not requiring surgery or other treatment and therefore not seen in secondary care were revisited at a special clinic to determine the safety of the referral system. In this series of 300 patients the study concludes that digital image referral for skin malignancy and other cutaneous lesions reduced the interval between referral and diagnosis by 81% and referral to commencement of treatment in suspect lesions by 30%. Diagnostic accuracy in a random sample of 30 patients was comparable to that reported for patients seen in face to face consultations. High levels of GP and patient satisfaction were recorded. In conclusion digital image referral for skin malignancy and other cutaneous lesions is a safe and cost effective referral pathway, significantly reducing the interval between referral diagnosis and onset of treatment for skin malignancy.

Bilateral tarsometatarsal fracture-dislocations: a missed work-related injury.

Tarsometatarsal (Lisfranc) fracture-dislocation is an uncommon foot injury. Subtle injuries are more difficult to diagnose though they cause serious morbidity. Bilateral subtle tarsometatarsal injury has not been reported before. We report bilateral subtle tarsometatarsal dislocations that were caused by a work-related accident in a 25-year-old man. The injury was initially missed. Diagnosis was confirmed by computed tomography with curved reconstruction. Associated foot injuries are shown as a guide to the diagnosis.

Usefulness of different imaging modalities in the assessment of scapular fractures caused by blunt trauma.

PURPOSE: To analyze the usefulness of chest and scapular trauma radiographs, axial computed tomography (CT), and two- and three-dimensional (2D and 3D) reconstruction CT in detecting fractures of the six anatomical regions of the scapula. MATERIAL AND METHODS: Forty-four patients, with a median age (range) of 34 (16-60) years, with scapular fractures caused by blunt trauma were prospectively collected between January 2003 and December 2005. Their chest and scapula radiographs, and axial, 2D, and 3D CTs were reviewed blindly and independently by two observers. Each modality was compared with a gold standard to determine its diagnostic usefulness. Our gold standard was consensus reached by all authors together examining all modalities at the same time. We also compared 3D CTs reconstructed from chest and scapula axial views. RESULTS: Axial and 3D reconstruction tomographic studies were the only useful modalities in assessing fractures in all six anatomical scapular regions. Three-dimensional CTs reconstructed from chest and scapula axial views were equally sensitive and specific. CONCLUSION: CT scanning with 3D reconstructions is the most useful imaging modality to detect and define the extent of scapular injury, and this can be done as part of a chest trauma computed tomography protocol.

Acute plain anterioposterior radiograph of the pelvis is not useful in detecting fractures of iliac wing and os sacrum: a prospective study of 73 patients using CT as gold standard.

Conflicting opinions exist to what extent interpreters of an acute anterioposterior (AP) radiograph of the pelvis underdiagnose pelvic injury. We have prospectively evaluated the usefulness of a plain AP radiograph of the pelvis in detecting injuries, using CT as the gold standard. Seventy-three haemodynamically stable blunt trauma patients, who had an AP radiograph of the pelvis and an abdominopelvic CT as part of their initial imaging evaluation, were included. There were 14 women and 59 men, with a mean age of 30 (3-61) years. Two senior radiologists, with special interest in CT examinations evaluating trauma, reviewed the radiographs and a month later the CT scans, blinded and independently. Usefulness index of the plain AP radiograph of the pelvis in detecting specific injuries was calculated using CT as the gold standard. A radiograph is regarded as useful if the usefulness index is 0.35 or more. The usefulness index for a plain AP radiograph of the pelvis for detecting a fracture of iliac wing and os sacrum was 0.25 and 0.01, respectively. An acute AP radiograph of the pelvis is not useful in detecting a fracture of iliac wing or os sacrum.

EM-PSYCH: a training program scheduling database.

EM-PSYCH is a scheduling database for training programs. It stores scheduling records and generates schedules and letters informing students, supervisors, and advisors of deadlines. Since EM-PSYCH was originally designed for a psychoanalytic institute, the institute model is presented as well as the database model to illustrate how the database program can be applied. EM-PSYCH is very user friendly and makes scheduling and sending reminders efficient and easy. It can handle any number of trainees and can be modified for any number of years or schedule interval. It can be easily adapted for psychiatric residencies, medical student education, psychology internships, and other training programs.