Fungal Integrated Histomolecular Diagnosis Using Targeted Next-Generation Sequencing on Formalin-Fixed Paraffin-Embedded Tissues.

Histopathology is the gold standard for fungal infection (FI) diagnosis, but it does not provide a genus and/or species identification. The objective of the present study was to develop targeted next-generation sequencing (NGS) on formalin-fixed tissue samples (FTs) to achieve a fungal integrated histomolecular diagnosis. Nucleic acid extraction was optimized on a first group of 30 FTs with Aspergillus fumigatus or Mucorales infection by macrodissecting the microscopically identified fungal-rich area and comparing Qiagen and Promega extraction methods through DNA amplification by A. fumigatus and Mucorales primers. Targeted NGS was developed on a second group of 74 FTs using three primer pairs (ITS-3/ITS-4, MITS-2A/MITS-2B, and 28S-12-F/28S-13-R) and two databases (UNITE and RefSeq). A prior fungal identification of this group was established on fresh tissues. Targeted NGS and Sanger sequencing results on FTs were compared. To be valid, the molecular identifications had to be compatible with the histopathological analysis. In the first group, the Qiagen method yielded a better extraction efficiency than the Promega method (100% and 86.7% of positive PCRs, respectively). In the second group, targeted NGS allowed fungal identification in 82.4% (61/74) of FTs using all primer pairs, in 73% (54/74) using ITS-3/ITS-4, in 68.9% (51/74) using MITS-2A/MITS-2B, and in 23% (17/74) using 28S-12-F/28S-13-R. The sensitivity varied according to the database used (81% [60/74] using UNITE compared to 50% [37/74] using RefSeq [P = 0.000002]). The sensitivity of targeted NGS (82.4%) was higher than that of Sanger sequencing (45.9%; P < 0.00001). To conclude, fungal integrated histomolecular diagnosis using targeted NGS is suitable on FTs and improves fungal detection and identification.

Liposomal Bupivacaine Versus Continuous Nerve Block: Liposomal Bupivacaine May be Non-inferior and More Cost Effective.

BACKGROUND: Regional anesthesia with adductor canal block has become the standard of care for pain management after total knee arthroplasty (TKA). We hypothesized that liposomal bupivacaine (LB) may be noninferior to continuous nerve block with a pain pump in terms of average pain scores, 30- and 90-day readmissions, and emergency department (ED) visits while reducing cost. METHODS: A retrospective chart review was performed on primary TKA patients from 2015 to 2020 by 23 orthopaedic surgeons at a single institution. The inclusion criteria was treatment with LB or a pain pump, and exclusion criteria was receipt of both anesthetics and revision surgery. A total of 2,378 patients met the inclusion criteria with 1,640 patients treated with LB and 738 treated with the pain pump. Demographic differences were not statistically significant. Primary outcomes were average pain scores, 30- and 90-day readmissions, and ED visits. Secondary outcomes were average milligram morphine equivalents per admission, hospital lengths of stay , and costs. RESULTS: There was no significant difference in pain scores on postoperative days 0, 1, 2, or 3 (P = .77, .86, 0.08, and 0.40, respectively), 30- or 90- day readmissions (P = .527 and P = .374), ED visits (P = .129 and P = .108), milligram morphine equivalents utilizations (P = .194), or average hospital LOS (P = .348). We estimated a potential cost savings of $95 per patient and $155,800 over the course of the study. CONCLUSION: LB was found to be noninferior to a pain pump, and the transition to this medication was associated with cost savings.

Dermatoscopic and clinical features of congenital or congenital-type nail matrix nevi: A multicenter prospective cohort study by the International Dermoscopy Society.

BACKGROUND: Congenital nail matrix nevi (NMN) are difficult to diagnose because they feature clinical characteristics suggestive of adult subungual melanoma. Nail matrix biopsy is difficult to perform, especially in children. OBJECTIVE: To describe the initial clinical and dermatoscopic features of NMN appearing at birth (congenital) or after birth but before the age of 5 years (congenital-type). METHODS: We conducted a prospective, international, and consecutive data collection in 102 hospitals or private medical offices across 30 countries from 2009 to 2019. RESULTS: There were 69 congenital and 161 congenital-type NMNs. Congenital and congenital-type NMN predominantly displayed an irregular pattern of longitudinal microlines (n = 146, 64%), reminiscent of subungual melanoma in adults. The distal fibrillar ("brush-like") pattern, present in 63 patients (27.8%), was more frequently encountered in congenital NMN than in congenital-type NMN (P = .012). Moreover, congenital NMN more frequently displayed a periungual pigmentation (P = .029) and Hutchinson's sign (P = .027) than did congenital-type NMN. LIMITATIONS: Lack of systematic biopsy-proven diagnosis and heterogeneity of clinical and dermatoscopic photographs. CONCLUSION: Congenital and congenital-type NMN showed worrisome clinical and dermatoscopic features similar to those observed in adulthood subungual melanoma. The distal fibrillar ("brush-like") pattern is a suggestive feature of congenital and congenital-type NMN.

An Appraisal of Pharmacotherapy-Pertinent Literature Published in 2021 and 2022 for Clinicians Caring for Patients With Thermal or Inhalation Injury.

Studies focusing on pharmacotherapy interventions to aid patients after thermal injury are a minor focus in burn injury-centered studies and published across a wide array of journals, which challenges those with limited resources to keep their knowledge current. This review is a renewal of previous years' work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Twenty-three geographically dispersed, board-certified pharmacists participated in the review. A Medical Subject Heading-based, filtered search returned 2336 manuscripts over the previous 2-year period. After manual review, 98 (4%) manuscripts were determined to have a potential impact on current pharmacotherapy practice. The top 10 scored manuscripts are discussed. Only 17% of those reviewed were assessed to likely have little effect on current practice. The overall impact of the current cohort was higher than previous editions of this review, which is encouraging. There remains a need for investment in well-designed, high-impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries.

Evaluation of the Knowledge of Primary Care Physicians About Important Nail Diseases Before and After a Short Online Training.

INTRODUCTION: Nail diseases are often diagnosed late with a potential prognostic and functional impact. This could be partly due to knowledge gaps among primary care physicians (PCPs). OBJECTIVES: To evaluate the knowledge about diagnosis and management of ten common/important nail conditions in a population of French PCPs and its improvement after a 31-minute online training session. METHODS: We submitted 10 pre-test and post-test clinical cases and an educative online course on the diagnosis and the management of nail diseases to 138 volunteer PCPs; 73 completed the whole training path. RESULTS: Compared to pre-test, more PCPs in the post-test required an urgent second opinion to dermatologist for pigmented melanoma (100% versus 80.3%; P <0.05) and use of inappropriate/dangerous systemic treatment for trauma-induced nail changes was reduced after the training program (0% versus 6.8%; P <0.05). A lack of knowledge remained after training for amelanotic melanoma with an increase of mycological/bacteriological tests (9.6% versus 0%; P <0.05). CONCLUSIONS: Management of nail diseases by our panel of PCPs was suboptimal and was improved after a short online training.

Brentuximab-vedotin in combination with cyclophosphamide, doxorubicin, prednisolone for the treatment of aggressive CD30-positive cutaneous T-cell lymphomas.

Aggressive CD30-positive cutaneous T-cell lymphomas (CD30+CTCL) are associated with unfavorable prognosis. Anthracycline-based polychemotherapy (CHOP) and brentuximab-vedotin (BV) monotherapy are related to poor outcomes in case of extracutaneous involvement or rapidly-progressing disease. Our objective was to assess the effectiveness of BV + CHP in aggressive CD30+CTCL. We included 7 patients treated with BV + CHP from April 2015 to January 2022: 4 had mycosis fungoides with large-cell transformation, 2 had primary cutaneous anaplastic large-cell lymphoma, and 1 harbored a primary cutaneous aggressive epidermotropic CD8-positive T-cell lymphoma. After a median [IQR] follow-up of 17.2 [13.2-21.0] months, 6/7 patients achieved an ORR lasting ≥4 months. The median [IQR] duration of response was 9.5 [5.9-11.1] months and the median [IQR] progression free survival was 14.9 [11.6-16.4] months. Four patients displayed progression with a median (range) time to next treatment of 15.8 (6.5-16.3) months. Two grade-3 adverse events were reported: febrile neutropenia and thromboembolic event. BV + CHP displayed substantial antitumor activity and favorable safety profile in 7 patients with aggressive CD30+CTCL.

Impact of Bone Metastases on Patients with Renal Cell Carcinoma or Melanoma Treated with Combotherapy Ipilimumab Plus Nivolumab.

(1) Background: Ipilimumab plus nivolumab (combo-ICI) improves overall survival (OS) in patients with advanced renal cell carcinoma (RCC) or melanoma. The impact of bone metastases (BM) on survival outcomes of combo-ICI-treated patients is unknown. (2) Methods: This single-center retrospective observational study involved 36 combo-ICI-treated patients with advanced RCC and 35 with melanoma. Clinical and laboratory data preceding the initiation of combo-ICI were collected. Univariate and multivariate Cox proportional hazard models were used to assess the effect of BM on overall survival (OS) and progression-free survival (PFS). (3) Results: zNine RCC and 11 melanoma patients had baseline BM. In unadjusted analysis, baseline BM was associated with a poorer OS in the RCC cohort. Baseline BM did not have any impact on survival outcomes in melanoma patients. After adjustment on baseline performance status and on neutrophil-to-lymphocyte ratio (NLR), the impact of BM was no longer significant, but a NLR ≥ 3 was significantly associated with a poorer OS in the RCC cohort. (4) Conclusions: The presence of baseline BM seems to be associated with worse outcomes in RCC combo-ICI-treated patients, while its effect might not be independent from the inflammatory state (approximated by the NLR). BM seems to have no impact on the outcomes of melanoma combo-ICI-treated patients.

A practice game changer: Impact of tenecteplase for acute ischemic stroke in a multicenter quality improvement project.

PURPOSE: Tenecteplase is a thrombolytic that is more fibrin specific, has a longer half-life, and is easier to administer than alteplase for acute ischemic stroke (AIS). This article outlines the pharmacy experience and perspective on implementation of tenecteplase as the treatment of choice for AIS. SUMMARY: Tenecteplase has been of increasing interest for AIS and is currently being studied in several clinical trials. Although it is not indicated by the Food and Drug Administration for AIS, several published studies and an update to stroke guidelines from the American Heart Association and American Stroke Association support its use in this setting. In January 2021, Cedars-Sinai Health System made the decision to add tenecteplase to the formulary for AIS in addition to keeping alteplase for patients who met the criterion of being outside the 4.5-hour window following stroke onset. Along with the added benefits of having tenecteplase on formulary come challenges of managing multiple thrombolytics for the same indication. Identifying key stakeholders and creating an interdisciplinary team are critical to ensure safe transitions. CONCLUSION: Institutions can safely transition from alteplase to tenecteplase as a thrombolytic of choice for AIS.

Cutaneous Complications Secondary to Haemostasis Abnormalities in COVID-19 Infection.

We describe the case of a patient hospitalized for acute decompensated heart failure in a standard medical ward. During hospitalization, he was diagnosed with COVID-19 and transferred to a special unit. The clinical course was marked by worsening of the respiratory disease, the development of right parotiditis and thrombosis of the left internal jugular vein. Therapeutic anticoagulation was initiated and 2 days later, the minimal dermatoporosis lesions previously present in the upper extremities evolved to haemorrhagic bullae with intra-bullae blood clots and dissecting haematomas. Surgical management of the dissecting haematomas was difficult in the context of haemostasis abnormalities. The patient died 29 days after hospital admission. LEARNING POINTS: Single room accommodation should be preferred to double room accommodation in standard wards during the COVID-19 pandemic.Anticoagulation therapy and the presence of lupus anticoagulant may induce cutaneous complications during COVID-19 infection.The discontinuation of anticoagulation therapy did not help improve the management of cutaneous lesions.