Performance of Automated Machine Learning for Diabetic Retinopathy Image Classification from Multi-field Handheld Retinal Images.

PURPOSE: To create and validate code-free automated deep learning models (AutoML) for diabetic retinopathy (DR) classification from handheld retinal images. DESIGN: Prospective development and validation of AutoML models for DR image classification. PARTICIPANTS: A total of 17 829 deidentified retinal images from 3566 eyes with diabetes, acquired using handheld retinal cameras in a community-based DR screening program. METHODS: AutoML models were generated based on previously acquired 5-field (macula-centered, disc-centered, superior, inferior, and temporal macula) handheld retinal images. Each individual image was labeled using the International DR and diabetic macular edema (DME) Classification Scale by 4 certified graders at a centralized reading center under oversight by a senior retina specialist. Images for model development were split 8-1-1 for training, optimization, and testing to detect referable DR ([refDR], defined as moderate nonproliferative DR or worse or any level of DME). Internal validation was performed using a published image set from the same patient population (N = 450 images from 225 eyes). External validation was performed using a publicly available retinal imaging data set from the Asia Pacific Tele-Ophthalmology Society (N = 3662 images). MAIN OUTCOME MEASURES: Area under the precision-recall curve (AUPRC), sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), accuracy, and F1 scores. RESULTS: Referable DR was present in 17.3%, 39.1%, and 48.0% of the training set, internal validation, and external validation sets, respectively. The model's AUPRC was 0.995 with a precision and recall of 97% using a score threshold of 0.5. Internal validation showed that SN, SP, PPV, NPV, accuracy, and F1 scores were 0.96 (95% confidence interval [CI], 0.884-0.99), 0.98 (95% CI, 0.937-0.995), 0.96 (95% CI, 0.884-0.99), 0.98 (95% CI, 0.937-0.995), 0.97, and 0.96, respectively. External validation showed that SN, SP, PPV, NPV, accuracy, and F1 scores were 0.94 (95% CI, 0.929-0.951), 0.97 (95% CI, 0.957-0.974), 0.96 (95% CI, 0.952-0.971), 0.95 (95% CI, 0.935-0.956), 0.97, and 0.96, respectively. CONCLUSIONS: This study demonstrates the accuracy and feasibility of code-free AutoML models for identifying refDR developed using handheld retinal imaging in a community-based screening program. Potentially, the use of AutoML may increase access to machine learning models that may be adapted for specific programs that are guided by the clinical need to rapidly address disparities in health care delivery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Targeted next-generation sequencing identifies a subset of idiopathic hypereosinophilic syndrome with features similar to chronic eosinophilic leukemia, not otherwise specified.

The distinction between chronic eosinophilic leukemia, not otherwise specified and idiopathic hypereosinophilic syndrome largely relies on clonality assessment. Prior to the advent of next-generation sequencing, clonality was usually determined by cytogenetic analysis. We applied targeted next-generation sequencing panels designed for myeloid neoplasms to bone marrow specimens from a cohort of idiopathic hypereosinophilic syndrome patients (n=51), and assessed the significance of mutations in conjunction with clinicopathological features. The findings were further compared with those of 17 chronic eosinophilic leukemia, not otherwise specified patients defined by their abnormal cytogenetics and/or increased blasts. Mutations were detected in 14/51 idiopathic hypereosinophilic syndrome patients (idiopathic hypereosinophilic syndrome/next-generation sequencing-positive) (28%), involving single gene in 7 and ≥2 in 7 patients. The more frequently mutated genes included ASXL1 (43%), TET2 (36%), EZH2 (29%), SETBP1 (22%), CBL (14%), and NOTCH1 (14%). Idiopathic hypereosinophilic syndrome/next-generation sequencing-positive patients showed a number of clinical features and bone marrow findings resembling chronic eosinophilic leukemia, not otherwise specified. Chronic eosinophilic leukemia, not otherwise specified patients showed a disease-specific survival of 14.4 months, markedly inferior to idiopathic hypereosinophilic syndrome/next-generation sequencing-negative (P<0.001), but not significantly different from idiopathic hypereosinophilic syndrome/next-generation sequencing-positive (P=0.117). These data suggest that targeted next-generation sequencing helps to establish clonality in a subset of patients with hypereosinophilia that would otherwise be classified as idiopathic hypereosinophilic syndrome. In conjunction with other diagnostic features, mutation data can be used to establish a diagnosis of chronic eosinophilic leukemia, not otherwise specified in patients presenting with hypereosinophilia.

Evaluation of the pain in varicose vein surgery under tumescent local anaesthesia using sodium bicarbonate as excipient without any intravenous sedation.

OBJECTIVE: In order to simplify varicose vein surgery, we studied the possibility of tumescent local anaesthesia (TLA) using sodium bicarbonate 1.4% as excipient without any intravenous sedation. METHODS: For three months, 215 patients were included in two centres for ambulatory varicose vein surgery performed without any intravenous sedation. Clinical results and pain were evaluated according to the type and duration of surgery. RESULTS: Mean perioperative pain was evaluated at 2.7 on a visual scale (0-10). In 91% of the cases, surgery was deemed to be slightly painful. Preoperative pain was not linked to the technical means of surgery but to the psychological and organizational environment of the centre. CONCLUSIONS: In many of the cases, varicose vein surgery could be performed under TLA without any intravenous sedation. Ambulatory varicose vein surgery without any intravenous sedation could be highly cost-effective.

Classification of saphenous refluxes: implications for treatment.

OBJECTIVE: To determine the possible correlations of patient age, symptoms and signs with findings of Doppler duplex examination in limbs with varicose veins. METHODS: A total of 2275 ultrasound examinations were done on 2275 limbs of 1751 patients (421 men and 1330 women). Ages ranged from 21 to 94 years (mean 50). Symptoms of aching, heaviness, burning pain (venous neuropathy) were recorded, and signs of ankle hyperpigmentation, scars of healed ulcers and presence of open venous ulcers were noted. RESULTS: Presence of symptoms was associated with advancing patient age (50.7 vs. 48.8 years). Varicose veins without great saphenous reflux correlated with younger age (43 vs. 53.5 years). Presence of saphenofemoral junctional incompetence correlated with an older age (54.7 vs. 49.8 years), and reflux to the ankle (Hach stage IV) also correlated with older age (mean 63.7 years). A younger age was associated with less advanced signs (C0-C2: 49.1 vs. C4-C6: 60.1 years). Saphenous vein reflux without clinical varices was associated with more advanced signs (C4-C6: 21.3%). CONCLUSIONS: Ageing is associated with advancing clinical symptoms, signs and increasing multifocal reflux in limbs with venous insufficiency. These facts support the concept of early treatment of venous insufficiency before predictable deterioration occurs.

[Tobacco smoking among medical students of the University of Milano, Italy]. / Indagine conoscitiva sull'abitudine al fumo tra gli studenti di medicina e chirurgia dell'Università degli studi di Milano.

In order to evaluate smoking habits among the future medical class an anonymous questionnaire about tobacco smoking was submitted to 822 students of the University of Milano in six academic years, from 1998/99 to 2003/04. A total of 184 students (22.4%) were smoker 463 (56.3%) had never smoked and 161 (19.6%) had previously smoked. More than half of these last had quit smoking during the university years. Smoking habits resulted influenced by the habits in the family (parents and brothers) and among the friends. Anti-smoking campaigns among medical students are needed taking into account their future role in health promotion and in prevention of tobacco smoking and its consequences.

Antroduodenal motor effects of intravenous erythromycin in children with abnormalities of gastrointestinal motility.

BACKGROUND: The macrolide antibiotic erythromycin (EM) affects gastrointestinal motor activity by acting as agonist of motilin receptors located on the smooth muscle cells of the gastroduodenal tract. We studied the effect of intravenous EM on fasting antroduodenal motility in controls and children with gastrointestinal dysmotility. METHODS: EM lactobionate (rate, 3.0 mg/kg/h) was infused intravenously while antroduodenal manometry was recorded in 10 controls, in 7 patients with functional dyspepsia and in 6 patients with gut pseudo-obstruction. The mean (SD) age (years) was 5.7 (1.4), 6.5 (2.4), and 6.7 (3.2), respectively. Manometry was performed by means of a four- or six-lumen catheter introduced through the nose and perfused with a low compliance pneumohydraulic system. Five controls received EM and five received saline. RESULTS: EM, infused 5 minutes after passage of an activity front (AF), induced in controls a premature antroduodenal AF occurring 15.4 +/- 3.2 minutes after starting infusion; no motor changes were seen after saline; duration and propagation velocity of EM-induced AFs did not differ from spontaneous AFs. In patients with functional dyspepsia EM induced various patterns such as premature antroduodenal AFs, antral phase III-like pattern with short duodenal bursts or prolonged phasic antral waves and no duodenal activity. In patients with neurogenic pseudo-obstruction rare or absent antral activity with incoordinated or absent duodenal activity was induced; no contractions were elicited in two patients with myogenic pseudo-obstruction. CONCLUSIONS: It is confirmed that EM, given at subtherapeutic doses, is a powerful prokinetic agent that can have clinical applications in patients with gastrointestinal dysmotility; however, the effect of the drug seems to be influenced by the nature of the underlying disorder.

Simultaneous prolonged recordings of proximal and distal intraesophageal pH in children with gastroesophageal reflux disease and respiratory symptoms.

OBJECTIVES: To characterize both proximal and distal esophageal acid exposure in children with gastroesophageal reflux-related respiratory disease and to investigate the usefulness of dual-channel intraesophageal pH monitoring in these patients. METHODS: Continuous simultaneous recording of distal and proximal esophageal pH was performed in 40 patients with gastroesophageal reflux disease and respiratory symptoms (wheezing, nocturnal cough, obstructive bronchitis) (age range 3-168 months) (group A), in 20 patients with reflux disease alone (age range 7-156 months) (group B), and in 14 controls (age range 5-108 months) (group C). RESULTS: (expressed as median +/- SD) 1) The two groups of patients did not differ with regard to distal and proximal esophageal acid exposure (percentage of reflux) during both the total recording period [distal, A: 9.2 +/- 4, B: 10.7 +/- 7 (NS), C: 1.9 +/- 1.0; and proximal, A: 4.8 +/- 3.3, B: 4.0 +/- 3.3 (NS), C: 1.0 +/- 0.7] and during nighttime [distal, A: 8.0 +/- 6.2, B: 10.4 +/- 6.1 (NS), C: 0.9 +/- 0.65; and proximal, A: 3.72 +/- 3, B: 3.6 +/- 3.0 (NS), C: 0.75 +/- 0.45]. 2) The two groups did not differ with regard to the ratio between proximal and distal esophageal acid exposure during both total and nocturnal periods of analysis. 3) No significant correlation was found between distal and proximal esophageal acid exposure during total and nocturnal recording periods. 4) In patients with reflux-related respiratory disease, the respiratory symptomatic index was significantly higher during distal esophageal acid exposure alone (47.0 +/- 28.6%) than during simultaneous reflux at the two esophageal levels (26.9 +/- 27%) (p < 0.05). Furthermore, reflux episodes associated with respiratory symptoms reached lower pH values than those in patients without symptoms at the two recording sites. CONCLUSIONS: Gastroesophageal reflux into the proximal esophagus does not discriminate between patients with reflux disease alone and those with reflux disease complicated by respiratory symptoms. Symptoms of asthma in reflux patients appear to be elicited more by a reflex mechanism than by aspiration of gastric refluxate into the airways. Intraesophageal acidification seems to be involved in eliciting respiratory symptoms related to reflux disease, and prolonged intraesophageal two-level pH measurement does not seem to be useful in the approach to patients with reflux disease associated with respiratory symptoms.

Phase II study of mitoxantrone, leucovorin, and infusional fluorouracil for treatment of metastatic breast cancer.

A new combination of mitoxantrone, folinic acid (leucovorin), and infusional fluorouracil (5-FU) was administered to 57 previously treated patients with metastatic breast cancer to evaluate the response rate, response duration, and toxicity of this regimen. Fifty-three patients who received 313 courses of therapy were assessable for response and toxicity. Median age was 48 years (range, 33 to 80 years), and the patients had received an average of 1.5 chemotherapy regimens before this study. Of 53 assessable patients, 24 (45%, or 42% of all entered patients) experienced partial responses (PRs) with a median duration of 6 months (range, 2 to 13 months). Nine (69%) of 13 assessable patients without prior doxorubicin treatment responded, compared with 15 (38%) of 40 with prior doxorubicin (P less than .05). Toxicity was generally mild with dose reductions necessitated more often by mucositis and/or diarrhea than by myelosuppression. One patient with prior high-dose doxorubicin treatment developed congestive heart failure. The combination of mitoxantrone, leucovorin, and infusional 5-FU is an active and well-tolerated regimen for metastatic breast cancer and deserves further evaluation in patients without prior doxorubicin therapy.

Central-peripheral transitional zone of the spinal accessory nerve in the rat.

The spinal accessory nerve rootlets emerge from the lateral aspect of the upper five segments of the cervical spinal cord underlying the nerve trunk. They cross the lateral funiculus of the cord with a slight rostral inclination. Here some pursue a relatively straight course while others have a dorsal convexity. The transitional zones may be classified into three distinct types, related to their orientation as they traverse the glia limitans to emerge as free rootlets. The fibres in Type 1 rootlets bend sharply rostrally on reaching the glia limitans. Type 2 rootlets turn ventrally to run in the glia limitans in the transverse plane of the cord before emerging. Type 3 rootlets are found only at C1. Their fibres initially turn caudally in the glia limitans and then loop rostrally. The morphology of the central-peripheral transitional zones of the spinal accessory rootlets closely resembles that of cervical ventral rootlets, and is therefore correlated with the motor function of these rootlets rather than with their intermediate location between the ventral and dorsal cervical rootlets.