Clinical features and outcomes of paediatric Spitz-type lesions.

INTRODUCTION AND OBJECTIVES: No definitive management guidelines exist for Spitz-type lesions; recommendations in the UK favour a 'safe' approach with a low threshold for excision. We aimed to describe Spitz-type lesions in children to further clarify the clinical features and outcomes. METHODS: We conducted a retrospective cohort study in Addenbrooke's Hospital, Cambridge, UK, and reviewed all patients aged ≤18 years with histologically confirmed Spitz-type lesions from November 2014 to September 2020. Information collected included patient demographics, lesion details, follow-up, outcomes and recurrence. RESULTS: Ninety-one children (male: female 42: 49; mean age at diagnosis: 9.4 years, SD: 4.6 years) were identified. Among them, 64 (70.3%) had classic Spitz or spitzoid naevi, 26 (28.6%) atypical Spitz tumours and 1 (1.1%) had spitzoid malignant melanoma based on histological features. On assessing the clinical features, where documented, we found that 22.0% (20/91) had amelanosis, 44.0% (40/91) had a raised bump, 12.1% (11/91) displayed bleeding, 25.0% (20/80) had non-uniform colour, 96.7% (88/91) were de novo lesions, 55.1% (43/78) were evolving in size and 35.9% (28/78) were evolving in colour. Fifty-nine patients (64.8%) were discharged without the need for follow-up, and the other 32 had a median follow-up time of 4 months. After confirmed excision, no incidences of local recurrence, distant metastases or mortality have been reported to date in all patients. CONCLUSIONS: The outcomes for paediatric Spitz-type lesions continue to be exceptionally good, remaining a low-risk lesion, which is more likely to be benign in children. Hence, we do not advocate aggressive management strategies for paediatric patients with clinically banal Spitz-type lesions.

Single organ metastatic sites in non-small cell lung cancer: Patient characteristics, treatment patterns and outcomes from a large retrospective Canadian cohort.

BACKGROUND: There is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). METHODS: This retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. RESULTS: Of 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47-0.66, p < 0.001). CONCLUSION: In NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.

Proteomics profiling and in silico analysis of peptides identified during Fusarium oxysporum infection in castor (Ricinus communis).

Castor is industrially important non-edible oil seeds crop severely affected by soil borne pathogen Fusarium oxysporum f. sp. ricini which causes heavy economic losses among the castor growing states in India and worldwide. The development of Fusarium wilt resistant varieties in castor is also challenging because the genes identified for resistance are recessive in nature. Unlike transcriptomics and genomics, proteomics is always a method of choice for quick identification of novel proteins expressed during biological events. Therefore, comparative proteomic approach was employed for identification of proteins released in resistant genotype during Fusarium infection. Protein was extracted from inoculated 48-1 resistant and JI-35 susceptible genotype and subjected to 2D-gel electrophoresis coupled with RPLC-MS/MS. This analysis resulted in 18 unique peptides in resistant genotype and 8 unique peptides in susceptible genotype were identified through MASCOT search database. The real time expression study showed that 5 genes namely CCR 1, Germin like protein 5-1, RPP8, Laccase 4 and Chitinase like 6 was found highly up-regulated during Fusarium oxysporum infection. Furthermore, end point PCR analysis of c-DNA showed amplification of three genes namely Chitinase 6 like, RPP8 and ß-glucanase exclusively in resistant genotype indicating that these genes may be involved in resistance phenomenon in castor. Up-regulation of CCR-1 and Laccase 4 involved in lignin biosynthesis provides mechanical strength and may help to prevent the entry of fungal mycelia and protein Germin like 5-1 helps to neutralized ROS by SOD activity. The clear role of these genes can be further confirmed through functional genomics for castor improvement and also for development of transgenic in different crops for wilt resistance.

Effect of bariatric surgery on maternal cardiovascular system.

OBJECTIVE: Bariatric surgery is a successful treatment for sustainable weight loss and has been associated with improvement in cardiovascular function. Pregnancy after bariatric surgery is becoming increasingly common; however, little is known about the maternal cardiovascular system postsurgery. The aim of this study was to investigate maternal cardiovascular adaptation to pregnancy in women with previous bariatric surgery, compared with that in women with no history of weight-loss surgery and an early-pregnancy body mass index (BMI) similar to the presurgery BMI of the postbariatric women. METHODS: This was a prospective, observational, longitudinal study conducted from April 2018 to June 2020 including 30 pregnant women who had undergone bariatric surgery and 30 who had not, matched for presurgery BMI. Participants were seen at three timepoints during pregnancy: 12-14, 20-24 and 30-32 weeks' gestation. At all visits, maternal blood pressure (BP) was measured and cardiac geometry and function were assessed using two-dimensional (2D) transthoracic echocardiography. On a subset of patients (15 in each group), 2D speckle tracking was performed to assess global longitudinal and circumferential strain. Offline analysis was performed, and multilevel linear mixed-effects models were used for all comparisons. RESULTS: Compared with the no-surgery group, and across all trimesters, pregnant women with previous bariatric surgery had lower BP, heart rate and cardiac output and higher peripheral vascular resistance (P < 0.01 for all). Similarly, the postbariatric group demonstrated more favorable cardiac geometry and diastolic indices, including lower left ventricular mass, left atrial volume and relative wall thickness, together with higher E-wave/A-wave flow velocity across the mitral valve and higher mitral velocity (E') at the lateral and medial annulus on tissue Doppler imaging (P < 0.01 for all). There was no difference in ejection fraction, although global longitudinal strain was lower in postbariatric women (P < 0.01), indicating better systolic function. CONCLUSION: Our findings indicate better maternal cardiovascular adaptation in women with previous bariatric surgery compared with presurgery BMI-matched pregnant women with no history of weight-loss surgery. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Surgical outcomes of T4b oral cancers: assessment of prognostic factors and a need to re-evaluate the current staging system.

T4b oral cancer is a broad umbrella term for all advanced oral cancers, the prognosis of which varies drastically for disease of the same stage, according to the extent of the masticator space involvement. This was a retrospective observational study including all consecutive T4b oral squamous cell carcinoma patients treated surgically between January 2015 and January 2016 and followed up until January 2020. The disease was classified as upper disease or lower disease based on the anatomical location in relation to an imaginary plane passing through the base of the retromolar trigone. The prime objective was to evaluate overall survival and prognostic factors affecting overall survival. The projected 5-year overall and disease-free survival rates were 40.7% and 35.6%, respectively. The assessment of prognostic factors revealed that lower disease (lower anatomical subsites), bone invasion, and lymph nodal spread significantly affected survival. Patients with disease in an upper anatomical location without bone and nodal involvement can achieve fairly good survival (projected 5-year overall survival of 64.2%) when compared to the other subsets of patients. We propose a re-evaluation of the current staging system based on the prognostic features, so that all patients are not considered under a single stage, since their survival differs significantly.

Cutaneous cryptococcal infection: Initial manifestation of acquired T-cell immunodeficiency due to malignant thymoma.

Background and Purpose: Cryptococcosis is a known opportunistic infection. Thymomas are known to cause immune dysregulation. We describe an atypical case of cutaneous cryptococcosis in a patient with acquired T cell immunodeficiency that has been found to be secondary to a type B3 thymoma with progression to carcinoma. Case report: A 63-year-old male presented with a chronic skin lesion confirmed as Cryptococcus neoformans on biopsy and an incidental mediastinal mass found during infectious work-up for the notable cluster of differentiation 4 (CD4)+ lymphopenia. This led to the diagnosis of a type B3 thymoma requiring resection. The cryptococcal lesion was treated successfully with azole therapy. Conclusion: C. neoformans is an opportunistic infection rarely associated with isolated T cell immunodeficiency due to thymomas. A multidisciplinary approach and understanding of the pathogenicity of cryptococcus and the immunological effect of thymic dysfunction are paramount to diagnosis and treatment.

Is it possible to store spotted wolffish (Anarhichas minor) sperm by refrigeration?

Spotted wolffish Anarhichas minor reproduction in captivity is dependent on in vitro fertilization. However, it is often challenging to acquire sufficient fresh sperm to fertilize the eggs that are obtained. In this study, we evaluate the possibility to store spotted wolffish sperm by refrigeration. Spotted wolffish sperm has the particularity that is already motile on stripping, and currently it is not possible to immobilize and reactivate. Thus, sperm refrigeration protocols should focus in extending this motility period that usually lasts up to 2 days. In a first experiment, we evaluated the possibility that the motility period of the sperm was limited by contamination with urine. The urea concentration in the sperm obtained both by stripping (17.10 ± 1.98 mg/dL) and directly from the testis (12.59 ± 2.37 mg/dL) was similar (p > 0.05), which indicate that the sperm collection method used avoid contamination with urine. Afterwards, we tested the possibility that the sperm motility period was limited by energy stores. The ATP concentration (initial value 5.65 ± 0.86 nmol/109 cells) remained stable (p = 0.099) during 30 h after sperm collection, and similar values (p = 0.329) were recorded at end of sperm storage in both diluted (3.88 ± 1.35 nmol/109 cells) and undiluted samples (4.76 ± 1.08 nmol/109). This indicates that the low intracellular ATP consumption, derived from the slow sperm motility, can probably be compensated rapidly enough by mitochondrial synthesis of ATP in the spotted wolffish sperm. In both experiments, diluted sperm kept higher percentage of motile cells during the storage time.

Longitudinal health utilities, symptoms and toxicities in patients with ALK-rearranged lung cancer treated with tyrosine kinase inhibitors: a prospective real-world assessment.

Background: Tyrosine kinase inhibitors (tkis) have dramatically improved the survival of patients with ALK-rearranged (ALK+) non-small-cell lung cancer (nsclc). Clinical trial data can generally compare drugs in a pair-wise fashion. Real-world collection of health utility data, symptoms, and toxicities allows for the direct comparison between multiple tki therapies in the population with ALK+ nsclc. Methods: In a prospective cohort study, outpatients with ALK+ recruited between 2014 and 2018, treated with a variety of tkis, were assessed every 3 months for clinico-demographic, patient-reported symptom and toxicity data and EQ-5D-derived health utility scores (hus). Results: In 499 longitudinal encounters of 76 patients with ALK+ nsclc, each tki had stable longitudinal hus when disease was controlled, even after months to years: the mean overall hus for each tki ranged from 0.805 to 0.858, and longitudinally from 0.774 to 0.912, with higher values associated with second- or third-generation tkis of alectinib, brigatinib, and lorlatinib. Disease progression was associated with a mean hus decrease of 0.065 (95% confidence interval: 0.02 to 0.11). Health utility scores were inversely correlated to multiple symptoms or toxicities: rho values ranged from -0.094 to -0.557. Fewer symptoms and toxicities were associated with the second- and third-generation tkis compared with crizotinib. In multivariable analysis, only stable disease state and baseline Eastern Cooperative Oncology Group performance status were associated with improved hus. Conclusions: There was no significant decrease in hus when patients with ALK+ disease were treated longitudinally with each tki, as long as patients were clinically stable. Alectinib, brigatinib, and lorlatinib had the best toxicity profiles and exhibited high mean hus longitudinally in the real-world setting.

Evaluating S100B as a serum biomarker for central neurosarcoidosis.

BACKGROUND: S100B is a calcium-binding protein found primarily in glial cells. In the setting of neuronal injury and disruption of the blood brain barrier, S100B can leak into the cerebrospinal fluid and systemic circulation. OBJECTIVES: To determine if serum S100B distinguishes patients with central neurosarcoidosis (NS) from patients with extra-neurologic sarcoidosis (ENS) and healthy controls, and if S100B levels correlate with MRI measures of disease burden. METHODS: Patients were enrolled from the Cleveland Clinic Sarcoidosis Center. Patients with traumatic brain injury, central nervous system (CNS) infections, CNS malignancy, neurodegenerative disorders, schizophrenia, bipolar disorder, or melanoma were excluded. S100B levels were compared between patients with NS, ENS, and healthy controls, and between NS patients with varying degrees of post-contrast enhancement on MRI. RESULTS: Median (interquartile range) S100B levels were 101 pg/mL (92, 136) for 11 NS patients, 89 pg/mL (73, 107) for 11 ENS patients, and 60 pg/mL (39, 74) for 26 healthy controls. There was a significant difference between NS and control groups (p = 0.01). The difference between NS and ENS groups did not rise to the level of statistical significance (p = 0.178). S100B levels were significantly different between NS patients with varying degrees of enhancement on MRI (p = 0.04). CONCLUSIONS: S100B deserves additional study as a biomarker for CNS injury in NS. It may be useful as a longitudinal measure of disease activity.

Amyloidosis secondary to chronic pulmonary aspergillosis: Case report and a systematic review of literature.

Secondary amyloidosis results from the deposition of abnormally folded proteins in body organs due to chronic inflammatory disorders. Kidneys are the most commonly affected organ and manifest as nephrotic syndrome with or without renal failure. Chronic pulmonary aspergillosis (CPA) is a chronic infection of lung parenchyma affecting those with an underlying structural lung disease. Herein, we present a case of CPA where the initial manifestation was that of nephrotic syndrome due to renal amyloidosis. We also perform a systematic review for studies describing secondary amyloidosis due to CPA.

The Role of Extracorporeal Septoplasty in Severely Deviated Nasal Septum.

Extracorporeal septoplasty is a valuable tool in the armamentarium of the nasal surgeon for the reconstruction of the severely deviated septum. Extracorporeal septoplasty offers the surgeon the opportunity to correct the septum under direct visualization, shape the nasal vault and address the nasal dorsum with the ultimate goal of providing both form and function for the patient with a complex septal deviation. The study was conducted with the aim to measure the outcomes of extracorporeal septoplasty in severely deviated nasal septum, relief of symptoms (nasal obstruction), surgical complications, if any, revision, if any with objective to evaluate the functional outcome and aesthetic aspects of extracorporeal septoplasty. This was a prospective observational study of 35 patients with severe deviated nasal septum with or without external deformity of nose attending the ENT OPD between Jan 2015 and Jan 2016 at Sri Aurobindo Medical College and Post Graduate Institute, Indore (M.P.). In this study, 17 patients (48.57%) shows excellent improvement on VAS scale, out of which 13 patients shows excellent improvement and 4 patients shows good improvement on photographic assessment. 11 patients (31.43%) show good improvement on VAS as well as photographic assessment and 7 patients (20%) show moderate improvement on VAS scale and fair improvement on photographic assessment. Extracorporeal septal reconstruction is an important surgical option for the correction of the markedly deviated nasal septum. Fixation of the straightened and replanted septum at the nasal spine and dorsal septum border with the upper lateral cartilages is essential. Spreader grafts for stabilization of the internal nasal valve and dorsal onlay grafts to prevent dorsal irregularity are strongly encouraged.

Radiation Dose and Image Quality in Pediatric Neck CT.

BACKGROUND AND PURPOSE: Optimization of pediatric neck CT protocols is of critical importance in order to maintain good diagnostic image quality while reducing the radiation burden. Our aim was to evaluate the image quality of pediatric neck CT studies before and after the implementation of a low radiation dose protocol. MATERIALS AND METHODS: We retrospectively reviewed 179 pediatric neck CT studies, 75 before and 104 after the implementation of low-dose protocols, performed in children 0-16 years of age. The 2 cohorts were divided into 3 age groups, 0-4, 5-9, and 10-16 years. The signal-to-noise ratio was calculated using the axial image through the true vocal folds. Three neuroradiologists assessed the image quality of the same CT scan using a 5-point scoring system. We compared the CT dose index volume, dose-length product, image-quality ratings, and SNR of studies conducted at baseline and with low-dose protocols. RESULTS: Image-quality ratings were lower in the low-dose than in the baseline cohort in children 10-16 years of age, but not in children 0-4 and 5-9 years of age. The SNR was lower in the low-dose cohort than in the baseline cohort in children 0-4 and 10-16 years of age, but not in children 5-9 years of age. Despite the decrease in image-quality scores in older children, 97% of the studies (73/75) in the baseline cohort and 96% of studies (100/104) in the low-dose cohort were considered of sufficient image quality. CONCLUSIONS: Images acquired with the low-dose CT protocols were deemed to be of sufficient quality for making a clinical diagnosis. Our initial results suggest that there may be an opportunity for further radiation dose reduction without compromising diagnostic image quality using iterative reconstruction algorithms.

Effectiveness of a multidisciplinary patient care bundle for reducing surgical-site infections.

BACKGROUND: Surgical-site infection (SSI) is associated with significant healthcare costs. To reduce the high rate of SSI among patients undergoing colorectal surgery at a cancer centre, a comprehensive care bundle was implemented and its efficacy tested. METHODS: A pragmatic study involving three phases (baseline, implementation and sustainability) was conducted on patients treated consecutively between 2013 and 2016. The intervention included 13 components related to: bowel preparation; oral and intravenous antibiotic selection and administration; skin preparation, disinfection and hygiene; maintenance of normothermia during surgery; and use of clean instruments for closure. SSI risk was evaluated by means of a preoperative calculator, and effectiveness was assessed using interrupted time-series regression. RESULTS: In a population with a mean BMI of 30 kg/m2 , diabetes mellitus in 17·5 per cent, and smoking history in 49·3 per cent, SSI rates declined from 11·0 to 4·1 per cent following implementation of the intervention bundle (P = 0·001). The greatest reductions in SSI rates occurred in patients at intermediate or high risk of SSI: from 10·3 to 4·7 per cent (P = 0·006) and from 19 to 2 per cent (P < 0·001) respectively. Wound care modifications were very different in the implementation phase (43·2 versus 24·9 per cent baseline), including use of an overlying surface vacuum dressing (17·2 from 1·4 per cent baseline) or leaving wounds partially open (13·2 from 6·7 per cent baseline). As a result, the biggest difference was in wound-related rather than organ-space SSI. The median length of hospital stay decreased from 7 (i.q.r. 5-10) to 6 (5-9) days (P = 0·002). The greatest reduction in hospital stay was seen in patients at high risk of SSI: from 8 to 6 days (P < 0·001). SSI rates remained low (4·5 per cent) in the sustainability phase. CONCLUSION: Meaningful reductions in SSI can be achieved by implementing a multidisciplinary care bundle at a hospital-wide level.

Health utility scores from EQ-5D and health-related quality of life in patients with esophageal cancer: a real-world cross-sectional study.

Esophageal cancer and its treatment can cause serious morbidity/toxicity. These effects on health-related quality of life (HRQOL) can be measured using disease-specific scales such as FACT-E, generic scales such as EQ-5D-3L, or through symptoms. In a two-year cross-sectional study, we compared HRQOL across esophageal cancer patients treated in an ambulatory clinic and across multiple disease states, among patients with all stages of esophageal cancer. Consenting patients completed FACT-E, EQ-5D, a visual analog scale, and patient reported (PR)-ECOG. Symptom complexes were constructed from FACT-E domains. Responses were categorized by disease state: pre-, during, and post-treatment, surveillance, progression, and palliative chemotherapy. Spearman correlation and multivariable linear regression characterized these associations. In total, 199 patients completed 317 questionnaires. Mean FACT-E and subscale scores dropped from baseline through treatment and recovered during post-treatment surveillance (P < 0.001); EQ-5D health utility scores (HUS) displayed a similar pattern but with smaller differences (P = 0.07), and with evidence of ceiling effect. Among patients with stage II/III esophageal cancer, mean EQ-5D HUS varied across disease states (P < 0.001), along with FACT-E and subscales (P < 0.001). Among patients with advanced disease, there was no significant difference between baseline and on-treatment total scores, but improved esophageal cancer-specific scales were noted (P = 0.003). Strong correlation was observed between EQ-5D and FACT-E (R = 0.73), along with physical and functional subscales. In addition, the association between FACT-E and EQ-5D HUS was maintained in a multivariable model (P < 0.001). We interpret these results to suggest that in a real-world clinic setting, FACT-E, EQ-5D HUS, and symptoms were strongly correlated. Most HRQOL and symptom parameters suggested that patients had worse HRQOL and symptoms during curative therapy, but recovered well afterwards. In contrast, palliative chemotherapy had a neutral to positive impact on HRQOL/symptoms when compared to their baseline pre-treatment state.

Multidisciplinary team approach in the oral rehabilitation of patients with cleidocranial dysplasia to achieve a functional aesthetic outcome.

Cleidocranial dysplasia is a hereditary congenital disorder that results in delayed ossification of midline structures, and is caused by mutations in the RunX2 (runt-related transcription factor 2) gene located on the short arm of chromosome 6. Successful treatment depends on multidisciplinary assessment and a comprehensive staged treatment plan. We present a case series of 12 patients who were managed with a specifically tailored combination of surgery, orthodontics, and prosthodontics to provide a functional dentition and restore their smile and facial contour. Successful dental rehabilitation can be challenging in this group because patients often have multiple dental anomalies and a reduced quantity and density of alveolar bone. Rehabilitation with early intervention and a carefully planned multidisciplinary approach has been successful in the long term.

Incidental Detection of Hepatocellular Carcinoma on 68Ga-Labeled Prostate-Specific Membrane Antigen PET/CT.

A 66-year-old man with history of prostate carcinoma underwent Ga-labeled prostate-specific membrane antigen PET/CT for surveillance of rising prostate-specific antigen. Intense tracer uptake was noted in segments 2, 7, and 8 of the liver. The lesions were not FDG avid on F-FDG PET/CT. Further characterization with magnetic resonance cholangiopancreatography with Gd-EOB (Primovist) contrast revealed ill-defined arterially enhancing lesions with central washout in the venous phase. CT-guided core biopsy was performed, and histopathology confirmed well-differentiated hepatocellular carcinoma.