Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

Robotic retroperitoneal partial nephrectomy: a four-arm approach.

INTRODUCTION: Robotic partial nephrectomy is an effective alternative to laparoscopic partial nephrectomy. The 3-arm and 4-arm transperitoneal robotic approaches are well described in the literature. However, a retroperitoneal robotic technique has yet to be fully described. We report our technique and initial experience with robotic retroperitoneal partial nephrectomy with a novel 4-arm approach. MATERIALS AND METHODS: We reviewed our current experience with the robotic retroperitoneal approach. Descriptive statistics on patient characteristics, operative parameters, and oncologic outcomes are reported. RESULTS: A total of 67 robotic-assisted partial nephrectomies were performed by one surgeon between October 2009 and October 2010. The 4-arm retroperitoneal approach was used in 8 patients (12%) with no complications. Median tumor size was 2cm. All were posterior renal tumors, with 5 located in the upper pole. The median operative time, warm ischemia time, estimated blood loss, and length of stay were 202 minutes, 18 minutes, 100cc, and 2 days, respectively. Pathology indicated renal cell carcinoma (RCC) in 7 patients with negative margins. CONCLUSION: The 4-arm robotic approach to retroperitoneal partial nephrectomy is safe, reproducible, and easily used. The fourth arm provides optimal traction on target tissues in key maneuvers and may decrease complications and positive margins secondary to impaired exposure

Treatment of splenic injury during laparoscopic nephrectomy with BioGlue, a surgical adhesive.

Splenic laceration is a recognized complication of both open and laparoscopic renal surgery. Laparoscopic renal surgery continues to become the new standard of care, and this potentially problematic complication may be encountered during mobilization to gain access to the retroperitoneum. We present 2 cases of splenic injury managed with BioGlue, a new surgical adhesive, during one hand-assisted and one pure laparoscopic nephrectomy. Application of the BioGlue adhesive resulted in satisfactory hemostasis for both injuries without the need for further intervention. These preliminary observations suggest that BioGlue may be a useful addition to the urologic armamentarium to achieve hemostasis in laparoscopic surgery

The incidence of fluoroquinolone resistant infections after prostate biopsy--are fluoroquinolones still effective prophylaxis?

PURPOSE: Fluoroquinolones have been shown to decrease infective complications after prostate biopsy. However, fluoroquinolone resistance is emerging. We quantified contemporary rates of infective complications and the incidence of fluoroquinolone resistant infections after prostate biopsy under fluoroquinolone prophylaxis. MATERIALS AND METHODS: We retrospectively evaluated the records of 1,273 patients who underwent prostate biopsy at New York Harbor Veterans Affairs Hospital from January 2004 to December 2006. Patients received levofloxacin or gatifloxacin. Using the Veterans Affairs computerized patient record system we reviewed all patient visits within 1 month after prostate biopsy. Visits were queried for infective symptoms. Positive cultures were evaluated for resistance patterns. The annual and overall incidence of infective complications and fluoroquinolone resistant infections was calculated. RESULTS: Of 1,273 patients 31 (2.4%) presented with infective symptoms after biopsy. The overall incidence of fluoroquinolone resistant infections was 1.2% (15 cases). When stratified by year, there were statistically significant increases in the incidence of infective complications and fluoroquinolone resistance from 2004 to 2006. Of the positive cultures those from 89% of patients yielded Escherichia coli and 90% were fluoroquinolone resistant. Fluoroquinolone resistant E. coli were also resistant to gentamicin in 22% of cases, trimethoprim/sulfamethoxazole in 44%, piperacillin in 72% and ampicillin in 94%. However, 100% sensitivity was demonstrated for amikacin, ceftazidime and ceftriaxone. CONCLUSIONS: Fluoroquinolones are still effective as antibiotic prophylaxis for prostate biopsies but there is an increase in infective complications and fluoroquinolone resistance. When patients present with post-prostate biopsy infective symptoms, almost 50% are associated with fluoroquinolone resistant pathogens. Empirical treatment with ceftriaxone, ceftazidime or amikacin should be initiated until culture specific therapy can be implemented

The Role of Surgeon-Performed Ultrasound in Patients with Possible Cardiac Wounds.

OBJECTIVE: The authors evaluate surgeon-performed ultrasound in determining the need for operation in patients with possible cardiac wounds. BACKGROUND DATA: Ultrasound quickly is becoming part of the surgeon\u27s diagnostic armamentarium; however, its role for the patient with penetrating injury is less well-defined. Although accurate for the detection of hemopericardium, the lack of immediate availability of the cardiologist to perform the test may delay the diagnosis, adversely affecting patient outcome. To be an effective diagnostic test in trauma centers, ultrasound must be immediately available in the resuscitation area and performed and interpreted by surgeons. METHODS: Surgeons performed pericardial ultrasound examinations on patients with penetrating truncal wounds but no immediate indication for operation. The subcostal view detected hemopericardium, and patients with positive examinations underwent immediate operation by the same surgeon. Vital signs, base deficit, time from examination to operation, operative findings, treatment, and outcome were recorded. RESULTS: During 13 months, 247 patients had surgeon-performed ultrasound. There were 236 true-negative and 10 true-positive results, and no false-negative or false-positive results; however, the pericardial region could not be visualized in one patient. Sensitivity, specificity, and accuracy were 100%; mean examination time was 0.8 minute (246 patients). Of the ten true-positive examinations, three were hypotensive. The mean time (8 patients) from ultrasound to operation was 12.1 minutes; all survived. Operative findings (site of cardiac wounds) were: left ventricle (4), right ventricle (3), right atrium (2), right atrium/superior vena cava (1), and right atrium/inferior vena cava (1). CONCLUSIONS: Surgeon-performed ultrasound is a rapid and accurate technique for diagnosing hemopericardium. Delay times from admission to operating room are minimized when the surgeon performs the ultrasound examination

Iliac Vessel Injury: Operative Physiology Related to Outcome.

BACKGROUND: Fifty-three patients treated at a level I trauma center with iliac vessel injury were studied to determine if body temperature and acid-base status in the operating room predicts outcome. METHODS: Records were reviewed for demographics, mechanism of injury, body temperature, acid-base status, operative management, and outcome. Statistical methods included Student\u27s t test, odds ratio determination, and chi-square analysis to determine statistical significance. RESULTS: Fifty-three patients (47 male, 6 female) sustained 92 iliac vascular injuries (36 arterial, 56 venous). Mortality was 34%, with 72% of deaths due to shock within 24 hours. Physiologic parameters differed significantly between survivors and nonsurvivors. Odds ratio identified six conditions; the number present predicted outcome. CONCLUSIONS: (1) There are significant differences between initial and final operating room temperature and acid-base status in survivors versus nonsurvivors with iliac vessel injury. Conditions for odds ratio can be calculated and correlated with outcome. (2) A patient with two or more conditions should be considered for an abbreviated laparotomy to allow for reversal of physiologic failure

First-line Osimertinib for Lung Cancer With Uncommon EGFR Exon 19 Mutations and EGFR Compound Mutations

Introduction: Up to 20% of EGFR-mutated NSCLC cases harbor uncommon EGFR mutations, including atypical exon 19 and compound mutations. Relatively little is known about the efficacy of osimertinib in these cases. Methods: Patients treated with first-line osimertinib for NSCLC with rare EGFR exon 19 (non E746_A750del) or compound mutations were included. Response assessment and time to progression were determined using Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Kaplan-Meier analyses were used to estimate progression-free survival (PFS), time to treatment discontinuation (TTD), and overall survival (OS). Results: Thirty-seven patients with NSCLC harboring an atypical EGFR exon 19 mutation or compound mutation were treated with first-line osimertinib at Johns Hopkins from 2016 to 2021. Overall response rate (ORR) was 76% and median PFS, TTD, and OS were 13 months (95% confidence interval [CI]: 10–15), 22 months (95% CI: 17–32) and 36 months (95% CI, 29–48), respectively. Among atypical exon 19 mutations (n = 25), ORR was 80%, median PFS was 12 months (95% CI: 10–15), median TTD was 19 months (95% CI: 17–38), and median OS was 48 months (95% CI: 25–not reached). Compound mutations (n = 12) had an ORR of 67%, median PFS of 14 months (95% CI: 5–22), median TTD of 26 months (95% CI: 5–36), and median OS of 36 months (95% CI: 20–46). Twelve patients (32%) continued first-line osimertinib after local therapy for oligoprogression. Conclusions: Osimertinib exhibited favorable outcomes for rare EGFR exon 19 and compound mutations. The heterogeneity in outcomes among these groups of tumors with similar mutations underscores the need for continued reporting and further study of outcomes among rare variants to optimize management for each patient