What Proportion of BRCA-Associated Breast Cancer Is Human Epidermal Growth Factor 2-Low and Eligible for Additional Targeted Therapy?

INTRODUCTION: DESTINY B04 provided clinical meaning to a new classification of human epidermal growth factor 2 (HER2) expression in breast cancer: HER2-low. Patients with germline breast cancer type 1 gene pathogenic variants (gBRCA1) often develop triple negative breast cancer (TNBC), but the proportion who could be classified as HER2-low and qualify for an additional targeted therapy option is unknown. This study aims to characterize the proportion of gBRCA1 or germline breast cancer type 2 gene pathogenic variants patients for whom these novel targeted therapies may be an option. METHODS: We performed a retrospective chart review of patients with gBRCA1/2 treated at our institution for invasive breast cancer from 2000 to 2021. Synchronous or metachronous contralateral breast cancers were recorded separately. HER2 status was determined by immunohistochemistry and fluorescence in situ hybridization. We excluded patients without complete HER2 data. RESULTS: Among the 95 breast cancers identified in our cohort of 85 gBRCA1/2 patients, 41 (43%) were TNBC, 38 (40%) were hormone receptor positive (HR+)/HER2-negative, and 16 (17%) were HER2-positive based on standard conventions. We found that 82% of the HR+/HER2-cancers and 66% of TNBCs would be reclassified as HER2-low. After stratifying by BRCA gene status, 64% of cancers in patients with gBRCA1 and 58% of cancers in patients with germline breast cancer type 2 gene pathogenic variants were HER2-low. CONCLUSIONS: A significant portion of gBRCA1/2 patients who were previously diagnosed with TNBC or HR+/HER2- breast cancer would now be classified as HER2-low and could be considered for the use of trastuzumab deruxtecan in the metastatic setting. Outcome differences from therapy changes in this cohort should now be assessed.

Multilocular Cystic Renal Neoplasm of Low Malignant Potential: A Case Report and Literature Review.

Multilocular cystic renal neoplasm of low malignant potential (MCRNLMP) is a rare subtype of renal cell carcinoma that has a favorable outcome. Most cases of MCRNLMP usually present as distinct multilocular cystic lesions; however, they may appear as small complicated cysts with hemorrhagic components. Herein, we present a case of MCRNLMP and provide a review of the literature.

Risk Factors for Renal Function Impairment Following Radiofrequency Ablation of Renal Tumors.

Purpose: To evaluate the various factors that affect renal function following percutaneous radiofrequency ablation (RFA) therapy in patients with renal tumors. Materials and Methods: Between 2010 and 2018, 91 patients diagnosed with renal tumors using ultrasonography and CT-guided RFA were enrolled. We retrospectively investigated the serum creatinine (SCr) level and estimated glomerular filtration rates immediately prior to RFA and during post-treatment follow-up. The patients were divided into two groups based on the degree of change in SCr level (0.3 mg/dL). Group comparisons were performed using univariable and multivariable logistic regression analyses to determine the factors impacting renal function. Results: Impaired renal function was associated with solitary kidney, chronic kidney disease (CKD) over stage 3, and pyeloureteral injury. Sex, age, other cancers, tumor size, location, growth pattern, and proximity to the collecting system were not significantly associated with impaired renal function. There was a difference in the overall change over time between the association with and without solitary kidney, CKD stage 3, and pyeloureteral injury. Conclusion: Among the medical conditions present prior to RFA, solitary kidney and CKD over stage 3 could be considered as risk factors for impaired renal function. Post-procedural pyeloureteral injury can also be considered a risk factor.

Factors affecting contralateral wrist surgery after one carpal tunnel release in bilateral carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) can be bilateral, with varying incidence. Carpal tunnel release (CTR) in one wrist may relieve the symptoms of the contralateral wrist, avoiding the need for second surgery; conversely, the symptoms may persist or worsen, requiring contralateral surgery in some cases. The present study investigated whether surgical treatment was finally required for the non-operated CTS wrist, and in what cases non-operative treatment was possible. We compared baseline characteristics, risk factors and electrodiagnostic data between CTS patients who underwent only unilateral CTR and those who subsequently underwent bilateral surgery at various time intervals. This single-center retrospective study included 188 patients with bilateral CTS managed between 2010 and 2020; 137 patients (group 1, 73%) underwent only unilateral CTR, and 51 (group 2, 27%) subsequently underwent contralateral CTR. In group 1, contralateral CTS symptoms were assessed in 4 categories and compared to the presenting symptoms in the index wrist. There were no significant differences in age, gender, preoperative symptom duration, body status, addictive behavior, electrodiagnostic study or comorbidities, other than a higher rate of dialysis in group 2. The contralateral wrist showed partial or complete symptom relief in 57% of patients undergoing unilateral CTR. High BMI and history of diabetes were risk factors for persistent severe CTS or subsequent contralateral CTR.

Genetic loss of function of Ptbp1 does not induce glia-to-neuron conversion in retina.

Direct reprogramming of glia into neurons is a potentially promising approach for the replacement of neurons lost to injury or neurodegenerative disorders. Knockdown of the polypyrimidine tract-binding protein Ptbp1 has been recently reported to induce efficient conversion of retinal Mϋller glia into functional neurons. Here, we use a combination of genetic lineage tracing, single-cell RNA sequencing (scRNA-seq), and electroretinogram analysis to show that selective induction of either heterozygous or homozygous loss-of-function mutants of Ptbp1 in adult retinal Mϋller glia does not lead to any detectable level of neuronal conversion. Only a few changes in gene expression are observed in Mϋller glia following Ptbp1 deletion, and glial identity is maintained. These findings highlight the importance of using genetic manipulation and lineage-tracing methods in studying cell-type conversion.

Low utility of the H-Score and HLH-2004 criteria to identify patients with secondary hemophagocytic lymphohistiocytosis after CAR-T cell therapy for relapsed/refractory diffuse large B-Cell lymphoma.

Secondary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune dysregulation disorder. Use of chimeric antigen receptor T-cell therapy (CAR-T) is associated with cytokine release syndrome (CRS), Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) and secondary HLH. However, application of HLH scoring systems (H-score, HLH-2004 criteria) are not validated in this setting. We analyzed the utility of applying the H-score and the HLH-2004 criteria to identify patients with possible HLH post-CAR-T for Relapsed/Refractory Diffuse Large B-cell Lymphoma. Only two of four patients with post CAR-T HLH met five or more of the diagnostic criteria for HLH by HLH 2004 criteria. In contrast all four post CAR-T HLH patients had a high H-score (>169); however, an additional ten patients that did not have HLH also had a high H-score. Thus, in this patient population, both scoring systems were demonstrated to have low prognostic significance in differentiating between high grade CRS and HLH.

Necrotizing sarcoid granulomatosis simulating pulmonary malignancy: A case report.

RATIONALE: Necrotizing sarcoid granulomatosis (NSG) has recently been termed "sarcoidosis with NSG pattern" for the disease entity representing nodular sarcoidosis with granulomatous pulmonary angiitis. It is characterized by sarcoid-like granulomas, vasculitis, and a variable degree of necrosis. Its rarity and nonspecific clinical symptoms can easily lead to misdiagnosis or delayed diagnosis. PATIENT CONCERNS: We report a 67-year-old female with a biopsy-confirmed sarcoidosis with NSG pattern mimicking pulmonary malignancy on initial chest computed tomography scan. DIAGNOSES: Sarcoidosis with NSG pattern. INTERVENTIONS: The patient underwent video-assisted thoracoscopic surgery with a lung biopsy. No further treatment was performed after the lung biopsy. OUTCOMES: Follow-up imaging studies revealed spontaneous regression of the disease after 2 months. LESSONS: Awareness of this rare benign disease entity and overlapping radiologic manifestations with pulmonary malignancy or other granulomatous diseases can be helpful for making a precise diagnosis with a better differential diagnosis.

Association between the initial serum phosphate level and 30-day mortality in blunt trauma patients.

BACKGROUND: Studies on patients with cardiac arrest or sepsis have reported that high initial phosphate levels are associated with poor outcomes. However, no previous study has investigated the association between initial phosphate levels and outcomes in blunt trauma patients. METHODS: This study was a retrospective observational study conducted on blunt trauma patients who had been treated at the single regional trauma center between January 2016 and December 2017. Patients' demographic data, initial vital signs, trauma scores, and laboratory parameters including phosphate levels were collected from the trauma registry. The primary outcome was set to 30-day mortality. The secondary outcomes were the total volume of blood transfused, 30-day hospital-free days, and 30-day intensive care unit-free days. RESULTS: Of the 1,907 included patients, 1,836 were in the survival group, and 71 were in the nonsurvival group. The nonsurvival group had a significantly higher phosphate level than the survival group. Patients in the hyperphosphatemia group had a higher 30-day mortality, fewer 30-day intensive care unit-free days, and higher transfusion volume than those in the other groups. In multivariable logistic regression analysis, hyperphosphatemia was independently associated with 30-day mortality. The receiver operating characteristic curve analysis showed that the area under the curve with the inclusion of phosphate in addition to Injury Severity Score, Revised Trauma Score, and age was 0.911. Area under the curve was also increased when phosphate was simply added to Injury Severity Score and Revised Trauma Score. CONCLUSION: In blunt trauma patients, hyperphosphatemia was associated with an increased 30-day mortality. LEVEL OF EVIDENCE: Prognostic, level III.

Designing Nonfullerene Acceptors with Oligo(Ethylene Glycol) Side Chains: Unraveling the Origin of Increased Open-Circuit Voltage and Balanced Charge Carrier Mobilities.

Despite the recent rapid development of organic solar cells (OSCs), the low dielectric constant (ϵr =3-4) of organic semiconducting materials limits their performance lower than inorganic and perovskite solar cells. In this work, we introduce oligo(ethylene glycol) (OEG) side chains into the dicyanodistyrylbenzene-based non-fullerene acceptors (NIDCS) to increase its ϵr up to 5.4. In particular, a NIDCS acceptor bearing two triethylene glycol chains (NIDCS-EO3) shows VOC as high as 1.12 V in an OSC device with a polymer donor PTB7, which is attributed to reduced exciton binding energy of the blend film. Also, the larger size grain formation with well-ordered stacking structure of the NIDCS-EO3 blend film leads to the increased charge mobility and thus to the improved charge mobility balance, resulting in higher JSC , FF, and PCE in the OSC device compared to those of a device using the hexyl chain-based NIDCS acceptor (NIDCS-HO). Finally, we fabricate NIDCS-EO3 devices with various commercial donors including P3HT, DTS-F, and PCE11 to show higher photovoltaic performance than the NIDCS-HO devices, suggesting versatility of NIDCS-EO3.

Hypercalcemia of Malignancy: Simultaneous Elevation in Parathyroid Hormone-Related Peptide and 1,25 Dihydroxyvitamin D in Sarcoma.

OBJECTIVE: Hypercalcemia is a common finding in patients who have an underlying malignancy. Only a few cases of hypercalcemia of malignancy have been linked to more than one mechanism of hypercalcemia. Here, we present a patient with liposarcoma and hypercalcemia of malignancy in the setting of simultaneous elevations in parathyroid hormone-related peptide (PTHrP) and 1,25 dihydroxyvitamin D [1,25(OH)2D] levels. Sarcoma-associated hypercalcemia is a rare disorder. METHODS: The patient was an 89-year-old woman with sarcoma-associated hypercalcemia. Multiple mechanisms were uncovered, and treatments were adjusted for them. Literature search for hypercalcemia of malignancy with multiple mechanisms was conducted. RESULTS: This is the first report describing dual mechanisms of sarcoma-associated hypercalcemia and only the fifth report on PTHrP and 1,25(OH)2D simultaneously causing hypercalcemia of malignancy. CONCLUSION: Based on this finding, we recommend measuring the 1,25(OH)2D levels in conjunction with the PTHrP level in patients with malignancy as this would allow for a more proactive approach to the diagnosis and treatment of hypercalcemia of malignancy.

[Urothelial Carcinoma of the Bladder: Radiologic Perspective]. / 방광 요로상피세포암: ì˜ìƒì˜í•™ì  ê´€ì .

Bladder cancer is a relatively common cancer type, with a high recurrence rate, that can be often encountered in the imaging study. Accurate diagnosis and staging have a significant impact on determining treatment and evaluating prognosis. Bladder cancer has been evaluated by transurethral resection of bladder tumor for clinical staging and treatment, but it is often understaged when compared with final pathologic result by radical cystectomy. If the location, size, presence of muscle invasion, lymph node metastasis, distant metastasis, and presence of upper urinary tract cancer can be accurately diagnosed and evaluated in an imaging study, it can be treated and managed more appropriately. For an accurate diagnosis, radiologists who evaluate the images must be aware of the characteristics of bladder cancer as well as its types, imaging techniques, and limitations of imaging studies. Recent developments in MRI with functional imaging have improved the quality of bladder imaging and the evaluation of cancer. In addition, the Vesical Imaging Reporting and Data System was published to objectively assess the possibility for muscle invasion of cancer. Radiologists need to know the types of bladder cancer treatment and how to evaluate the changes after treatment. In this article, the characteristics of bladder urothelial carcinoma, various imaging studies, and findings are reviewed.

Early and Atypical Radiologic Presentations of Pulmonary Langerhans Cell Histiocytosis: A Report of Two Cases.

Pulmonary Langerhans cell histiocytosis (PLCH) is a rare, multi-systemic disease primarily affecting young male adults with a history of smoking. The two patients with PLCH in our report showed relatively early and atypical radiologic presentations at initial evaluation. On chest CT, PLCH presents variable radiologic features depending on the evolutional stage of the disease. Atypical CT features of PLCH may render precise radiologic diagnosis difficult and usually require lung biopsy for a confirmation of the diagnosis. Our case review is aimed at raising the awareness of radiologists on the atypical CT features of PLCH, to help make accurate radiologic diagnosis and prevent unnecessary and invasive diagnostic procedures.

A single cell transcriptional atlas of early synovial joint development.

Synovial joint development begins with the formation of the interzone, a region of condensed mesenchymal cells at the site of the prospective joint. Recently, lineage-tracing strategies have revealed that Gdf5-lineage cells native to and from outside the interzone contribute to most, if not all, of the major joint components. However, there is limited knowledge of the specific transcriptional and signaling programs that regulate interzone formation and fate diversification of synovial joint constituents. To address this, we have performed single cell RNA-Seq analysis of 7329 synovial joint progenitor cells from the developing murine knee joint from E12.5 to E15.5. By using a combination of computational analytics, in situ hybridization and in vitro characterization of prospectively isolated populations, we have identified the transcriptional profiles of the major developmental paths for joint progenitors. Our freely available single cell transcriptional atlas will serve as a resource for the community to uncover transcriptional programs and cell interactions that regulate synovial joint development.

Missed Lung Cancers on Chest Radiograph: An Illustrative Review of Common Blind Spots on Chest Radiograph with Emphasis on Various Radiologic Presentations of Lung Cancers.

Missed lung cancers on chest radiograph (CXR) may delay the diagnosis and affect the prognosis. CXR is the primary imaging modality to evaluate the lungs and mediastinum in daily practice. The purpose of this article is to review chest radiographs for common blind spots and highlight the importance of various radiologic presentations in primary lung cancer to avoid significant diagnostic errors on CXR.

Methimazole-Induced Pleural Effusion in the Setting of Graves' Disease.

Methimazole is a thionamide drug that inhibits the synthesis of thyroid hormones by blocking the oxidation of iodine in the thyroid gland. We report a case of methimazole-induced recurrent pleural effusion. A 67-year-old female with recently diagnosed Graves' disease on methimazole 20mg daily was admitted with dyspnea and new onset atrial fibrillation with rapid ventricular rate. Chest X-ray revealed a unilateral right pleural effusion, which was consistent with a transudate on thoracocentesis. She was managed as a case of congestive heart failure and methimazole dose was increased to 30 mg daily. She was readmitted twice with recurrent right pleural effusion. The fluid revealed an exudative process on repeat thoracocentesis. CT scan of the chest with contrast showed mediastinal lymphadenopathy and a diffuse ground glass process involving the right lower lobe suggestive of pneumonitis. Bronchoalveolar lavage showed neutrophil predominant fluid, and cytology and adenosine deaminase were negative. Patient also had an endobronchial ultrasound guided biopsy of the lymph nodes (EBUS). She was treated empirically with steroids 40 mg for 10 days and the methimazole was also discontinued. The antinuclear antibodies (ANA) came back positive with a speckled pattern; antineutrophil cytoplasmic antibody (c-ANCA) and antimyeloperoxidase were also positive. The effusion resolved but recurred on rechallenge with methimazole. She was referred for urgent thyroidectomy. The patient's repeat chest X-ray showed complete resolution of the pleural effusion after stopping the methimazole. Few weeks later, repeat ANCA and antimyeloperoxidase antibody were both negative. Our case report highlights the importance of the recognition of a rare side effect of methimazole. Timely diagnosis would ensure that appropriate treatment is given.

Budget Impact of Switching to Biosimilar Trastuzumab (CT-P6) for the Treatment of Breast Cancer and Gastric Cancer in 28 European Countries.

BACKGROUND: As the economic burden of treating cancer patients has been soaring in European countries, performing a budget impact analysis is becoming one of the requirements for payers' application dossiers. OBJECTIVE: The objective of this study was to estimate the budgetary impact of introducing the biosimilar trastuzumab (CT-P6) from the payer's perspective and to determine the number of additional patients who could be treated with resulting savings in 28 European countries. METHODS: A budget impact model was developed to analyze the financial impact of switching from originator trastuzumab to biosimilar CT-P6 in the treatment of early and metastatic breast cancer and metastatic gastric cancer with a time horizon of 1-5 years. Budgetary savings and the number of patients potentially affected were measured based on epidemiological and sales volume data. The base-case analysis assumed that the price of CT-P6 is 70% of the originator price, the switching rate of originator to CT-P6 in the first year is 20%, and the annual growth in the switching rate for each subsequent year is 5%. RESULTS: For analyses using the base-case scenario following CT-P6 introduction, the total estimated budgetary savings over a 5-year period (depending on the scenario) ranged from €1.13 billion to €2.27 billion based on epidemiological data, or from €0.91 billion to €1.82 billion based on sales volume data. In the first year only, the projected budgetary savings ranged from €58 million to €136 million, and the number of additional patients who could be treated using the savings ranged from 3503 to 7078 by sensitivity analysis. CONCLUSIONS: The conducted budget impact analysis assessing a switch from originator trastuzumab to biosimilar CT-P6 in 28 European countries indicates that budget savings could be between €0.91 billion and €2.27 billion over the next 5 years. These savings could be used to help improve patient access to local biologics in their respective countries while simultaneously strengthening the overall public health landscape across the European Union.

Endoscopic and microscopic findings of gastrointestinal tract in Henoch-Schönlein purpura: Single institute experience with review of literature.

Asia has the highest incidence of Henoch-Schönlein purpura (HSP). Although 50% to 75% of patients with HSP manifest gastrointestinal (GI) symptoms, endoscopic, and pathologic findings of HSP have been rarely reviewed in Asia.Patients diagnosed with HSP who had undergone endoscopic biopsy from GI tract (GIT) in Soonchunhyang University Seoul Hospital from 2000 to 2018 were evaluated and 25 cases with 44 biopsies from upper GI tract (U-GIT) or lower GI tract (L-GIT) were enrolled. Their clinical and endoscopic findings and histologic findings of endoscopic biopsy were reviewed.Of the 25 patients, 15 were males and 10 were females. There were 6 children and 19 adults. The most common GI symptom was abdominal pain (20/25), followed by loose stool or diarrhea (9/25). Biopsied sites included 19 from U-GIT (9 stomach and 10 duodenum) and 25 from L-GIT (7 terminal ileum, 1 cecum, 4 ascending, 1 transverse, 2 descending, 7 sigmoid, and 3 rectum). Erythema/petechia was the most common endoscopic finding in U-GIT, while erosion/ulceration was the most common one in L-GIT. In U-GIT, extravasted red blood cell (RBC) (14/19) was the most common histologic finding, while leukocytoclastic vasculitis (LCV)/capillarities were identified in 7 specimens, including 5 duodenum samples. In endoscopic investigations of L-GIT, erosion/ulceration (9/14) was predominantly identified. The most common histologic finding was also extravasted RBC (22/25), while LCV/capillarities were noted in 10 specimens, including 5 specimens from terminal ileum.The HSP commonly involves GIT. Histologic findings of our cases were not significantly different from results of previous studies in Western countries. However, endoscopic and pathologic characteristics of HSP have been rarely reviewed in Asia. Herein, we share experience of endoscopic biopsy of GIT in patients with HSP.

Primary cardiac angiosarcoma with right atrial wall rupture: A case report.

RATIONALE: Cardiac angiosarcoma is the most common malignant tumor of the heart and a rare disease with rapid disease progression and poor prognosis. Cardiac wall rupture is an extremely rare complication. PATIENT CONCERNS: A 32-year-old woman presented with an acute onset of epigastric pain and chest discomfort at first time when she visited an emergency room. DIAGNOSES: A cardiac mass was identified on echocardiography and subsequently performed chest computed tomography and cardiac magnetic resonance imaging revealed the cardiac tumor at right atrium with right atrial wall rupture and hematogenous lung metastasis. Histopathologic diagnosis of metastatic angiosarcoma was done by open lung biopsy. INTERVENTIONS: The patient was treated with palliative chemotherapy for the primary cardiac tumor and hematogenous lung metastasis. OUTCOMES: The follow-up imaging studies revealed treatment response of the primary cardiac tumor and hematogenous lung metastasis. LESSONS: Clinical and radiologic evaluation of the cardiac angiosarcoma was well performed in our case with various diagnostic imaging modalities including echocardiography, chest computed tomography, cardiac magnetic resonance imaging, and fluorodeoxyglucose-positron emission tomography/computed tomography. This case report well demonstrates typical imaging findings of a rare cardiac tumor and emphasizes importance of early investigation for accurate diagnosis and proper management of the cardiac tumor.