High tumor infiltrating lymphocytes are significantly associated with pathological complete response in triple negative breast cancer treated with neoadjuvant KEYNOTE-522 chemoimmunotherapy.

INTRODUCTION: For patients with locally advanced triple negative breast cancer (TNBC), the standard of care is to administer the KEYNOTE-522 (K522) regimen, including chemotherapy and immunotherapy (pembrolizumab) given in the neoadjuvant setting. Pathological complete response (pCR) is more likely in patients who receive the K522 regimen than in patients who receive standard chemotherapy. Studies have shown that pCR is a strong predictor of long-term disease-free survival. However, factors predicting pCR to K522 are not well understood and require further study in real-world populations. METHODS: We evaluated 76 patients who were treated with the K522 regimen at our institution. Twenty-nine pre-treatment biopsy slides were available for pathology review. Nuclear grade, Nottingham histologic grade, Ki-67, lymphovascular invasion, and tumor infiltrating lymphocytes (TIL) were evaluated in these 29 cases. For the cases that did not have available slides for review from pre-treatment biopsies, these variables were retrieved from available pathology reports. In addition, clinical staging, race, and BMI at the time of biopsy were retrieved from all 76 patients' charts. Binary logistic regression models were used to correlate these variables with pCR. RESULTS: At the current time, 64 of 76 patients have undergone surgery at our institution following completion of K522 and 31 (48.4%) of these achieved pCR. In univariate analysis, only TIL was significantly associated with pCR (p = 0.014) and this finding was also confirmed in multivariate analysis, whereas other variables including age, race, nuclear grade, Nottingham grade, Ki-67, lymphovascular invasion, BMI, pre-treatment tumor size, and lymph node status were not associated with pCR (p > 0.1). CONCLUSION: Our real-world data demonstrates high TIL is significantly associated with pCR rate in the K522 regimen and may potentially serve as a biomarker to select optimal treatment. The pCR rate of 48.4% in our study is lower than that reported in K522, potentially due to the smaller size of our study; however, this may also indicate differences between real-world data and clinical trial results. Larger studies are warranted to further investigate the role of immune cells in TNBC response to K522 and other treatment regimens.

Twelve tips to revitalise problem-based learning.

The role of the problem-based learning (PBL) facilitator has seen different interpretations ever since PBL first gained widespread use. What has remained unchanged is the challenge for facilitators to use their knowledge and expertise sparingly and to use their interpersonal skills to improve group dynamics. Medical undergraduates attending PBL sessions have also changed in their skill sets, expectations and the use of technology. Based on the published literature and a recent faculty workshop, we provide PBL facilitators and institutions with 12 tips on how to make PBL more vibrant and interesting. We discuss our tips with reference to published literature and International Academy of Medical Education (AMEE) guidance. Our tips help students to engage with PBL, avoid monotony and make this teaching format more vibrant and fun for all involved. Introducing greater variety to the PBL process may also help with group dynamics by catering for a broader audience with different learning styles.

Melanosis of the Bladder: Possible Pathogenetic Mechanisms.

Melanin accumulation within the bladder urothelium and/or macrophages in the lamina propria (melanosis of the bladder) is a very rare phenomenon of unknown pathogenesis. Its rarity argues for a complex, likely multifactorial, causation. We describe bladder melanosis developing after Botox therapy in an elderly woman with a history of overactive bladder, treated grade 2 uterovaginal prolapse, and episodes of urinary tract infection and speculate that one factor (probably of many) in its pathogenesis may be a derangement of local neurourothelial interactions.

Impact of Short Bowel Syndrome on Quality of Life and Family: The Patient's Perspective.

BACKGROUND: Short bowel syndrome (SBS) has an impact on children and their families not only physically, but also emotionally, mentally, and socially. This study aimed to evaluate quality of life and family impact in patients with SBS, using the Pediatric Quality of Life Inventory (PedsQL) measurement model. MATERIALS AND METHODS: PedsQL questionnaires were administered to patients with SBS followed at the Pediatric Surgery of Royal Manchester Children's Hospital. The scores were compared between two groups differing in age (children <5 y vs. >5 y) and with known-groups from literature published by Varni et al. RESULTS: Forty-three patients were sent the questionnaires, and 30 (70%, 17 < 5 and 13 > 5) responded. Family Impact Module failed to distinguish between families of children younger and older than 5 years of age. In contrast, it distinguished between families with SBS children and the ones with children in a long-term care facility. Healthcare satisfaction was worse in families of children over 5 years regarding information received, inclusion of the family, and communication. When compared with normal population, SBS children scored worse on Generic Core Scales for all domains except for emotional functioning. CONCLUSION: Although advances have been made on the treatment of children with SBS, and improvements have been reached on home PN, this condition is still significantly affecting the quality of life of children and their families. The future quality control of medical care must have greater focus on psychosocial and emotional functioning, aiming for the best possible quality of life.

A challenging abdomino-scrotal hydrocele-successful resolution with the help of interventional radiology guided sclerosis.

Abdomino-scrotal hydrocele is a rare condition that presents in male infants. There is no consensus in the literature over treatment. We present the case of a 4-year-old boy with what was thought to be a straight forward congenital hydrocele that persisted despite ligation of a patent processus vaginalis and a Jaboulay procedure. A subsequent Magnetic Resonance Imaging scan identified a large intra-abdominal component connecting to the scrotum. Laparoscopic excision of the intra-abdominal component was performed successfully, but the hydrocele persisted. The hydrocele resolved without complication following two episodes of image intensifier guided sclerotherapy carried out by the interventional radiology team.

High-volume forced diuresis with matched hydration using the RenalGuard System to prevent contrast-induced nephropathy: A meta-analysis of randomized trials.

BACKGROUND: Contrast-induced nephropathy (CIN) is a well-recognized complication of coronary angiography that is associated with poor outcomes. Several small randomized controlled trials (RCTs) have recently shown that in patients with chronic kidney disease (CKD), furosemide-induced forced diuresis with matched hydration using the RenalGuard system can prevent its occurrence. However, individual studies have been underpowered and thus cannot show significant differences in major clinical endpoints. HYPOTHESIS: Forced diuresis with matched hydration using the RenalGuard system improves clinical outcomes in patients undergoing coronary angiography. METHODS: Scientific databases and websites were searched for relevant RCTs. The pooled risk ratios were calculated using random-effects models. The primary endpoint was CIN, and the secondary endpoints were major adverse clinical events (MACEs) and the need for renal replacement therapy. RESULTS: Data from 3 trials including 586 patients were analyzed. High-volume forced diuresis with matched hydration using the RenalGuard system decreased risk of CIN by 60% (risk ratio: 0.40, 95% confidence interval: 0.25 to 0.65, P < 0.001), MACE rate by 59%, and the need for renal replacement therapy by 78%, compared with the standard of care. CONCLUSIONS: In patients with CKD undergoing coronary angiography, high-volume forced diuresis with matched hydration using the RenalGuard system significantly reduces the risk of CIN, MACE rate, and the need for renal replacement therapy. Larger RCTs with sufficient power are needed to confirm these findings.

Gastroschisis and the risk of short bowel syndrome: outcomes and counselling.

BACKGROUND: Gastroschisis can be associated with short bowel syndrome (SBS). We present 4 cases with significant bowel shortening with very different ante- and postnatal presentations. CASES: Three of the cases demonstrated 'vanishing' gastroschisis with progressively worsening antenatal intra-abdominal bowel dilatation with no defect present at birth. The fourth case followed an uneventful course antenatally but developed SBS considered secondary to gastroschisis-related atresia and necrosis. All 4 cases were classified as having SBS and were enrolled within the paediatric Intestinal Rehabilitation Programme. This involves autologous gastrointestinal reconstruction following a period of bowel expansion with concomitant parenteral and enteral nutrition. DISCUSSION: These cases demonstrate that the serious complication of significant bowel loss cannot always be anticipated. Early multidisciplinary discussion with the parents enables a shared understanding of potential outcomes. It can aid the recognition of 'vanishing' gastroschisis enabling expedient investigations and early intervention, minimising morbidity and maximising bowel length.

Granular hemostat deposits mimicking disseminated malignancy.

Hemostatic matrices are a part of the surgeon's armamentarium against profuse intraoperative bleeding. Granular deposits may form after the use of a liquid hemostat which can be mistaken for tumor recurrence or metastatic disease in the setting of neoplasia. We present two cases that highlight the importance of full knowledge of product usage during previous operations and the need for histological examination of these lesions.

Nematode infection mimicking paratesticular malignancy.

Paratesticular swellings pose a diagnostic dilemma due to concerns over malignancy. We present a case of paratesticular swelling in a 13-year-old boy as a result of Dirofilaria immitis infection. The boy presented with a 2-month history of right testicular discomfort associated with an irregular mass within the scrotum.

The physiotherapy management of muscle haematomas.

Muscle haematomas may present in athletes following a muscle tear or contusion injury. The objective of this literature review was to examine the literature pertaining to the physiotherapeutic management of muscle haematomas. An electronic literature search was performed of the databases AMED, Cinahl, Embase, PEDro and Ovid Medline from their inception to April 2006. Human and animal subject, clinical trials, written in English, which could assist in the assessment of this topic, were included. Seventeen (of 7794) papers met the inclusion criteria and were reviewed. The review concluded that few clinical trials have been published assessing the efficacy of these strategies. Furthermore, since numerous methodological weaknesses plagued the limited evidence-base, it was not possible to support or refute the application of different physiotherapy modalities, for the treatment of muscle haematomas. Further study is recommended to identify the best therapeutic interventions to treat muscle haematomas.