Clinical Impact of Prospective Whole Genome Sequencing in Sarcoma Patients

With more than 70 different histological sarcoma subtypes, accurate classification can be challenging. Although characteristic genetic events can largely facilitate pathological assessment, large-scale molecular profiling generally is not part of regular diagnostic workflows for sarcoma patients. We hypothesized that whole genome sequencing (WGS) optimizes clinical care of sarcoma patients by detection of diagnostic and actionable genomic characteristics, and of underlying hereditary conditions. WGS of tumor and germline DNA was incorporated in the diagnostic work-up of 83 patients with a (presumed) sarcomas in a tertiary referral center. Clinical follow-up data were collected prospectively to assess impact of WGS on clinical decision making. In 12/83 patients (14%), the genomic profile led to revision of cancer diagnosis, with change of treatment plan in eight. All twelve patients had undergone multiple tissue retrieval procedures and immunohistopathological assessments by regional and expert pathologists prior to WGS analysis. Actionable biomarkers with therapeutic potential were identified for 30/83 patients. Pathogenic germline variants were present in seven patients. In conclusion, unbiased genomic characterization with WGS identifies genomic biomarkers with direct clinical implications for sarcoma patients. Given the diagnostic complexity and high unmet need for new treatment opportunities in sarcoma patients, WGS can be an important extension of the diagnostic arsenal of pathologists.

Frequency reallocation based on cochlear place frequencies in cochlear implants: a pilot study

Purpose The aim of this study is to evaluate speech perception outcomes after a frequency reallocation performed through the creation of an anatomically based map obtained with Otoplan®, a tablet-based software that allows the cochlear duct length to be calculated starting from CT images. Methods Ten postlingually deafened patients who underwent cochlear implantation with MED-EL company devices from 2015 to 2019 in the Tertiary referral center University Hospital of Verona have been included in a retrospective study. The postoperative CT scans were evaluated with Otoplan®; the position of the intracochlear electrodes was obtained, an anatomical mapping was carried out and then it was submitted to the patients. All patients underwent pure tonal and speech audiometry before and after the reallocation and the audiological results were processed considering the Speech Recognition Threshold (SRT), the Speech Awareness Threshold (SAT) and the Pure Tone Average (PTA). The differences in the PTA, SAT and SRT values before and after the reallocation were determined. The results were statistically processed using the software Stata with a significance value of α < 0.05. Results The mean values of SRT (61.25 dB versus 51.25 dB) and SAT (49 dB versus 41 dB) were significantly lower (p: 0.02 and p: 0.04, respectively) after the reallocation. No significant difference was found between PTA values (41.5 dB versus 39.25 dB; p: 0.18). Conclusions Our preliminary results demonstrate better speech discrimination and rapid adaptation in implanted postlingually deaf patients after anatomic mapping and subsequent frequency reallocation.

A prediction model for recurrence after translabyrinthine surgery for vestibular schwannoma: toward personalized postoperative surveillance

Purpose The aim of this study is to compute and validate a statistical predictive model for the risk of recurrence, defined as regrowth of tumor necessitating salvage treatment, after translabyrinthine removal of vestibular schwannomas to individualize postoperative surveillance. Methods The multivariable predictive model for risk of recurrence was based on retrospectively collected patient data between 1995 and 2017 at a tertiary referral center. To assess for internal validity of the prediction model tenfold cross-validation was performed. A ‘low’ calculated risk of recurrence in this study was set at < 1%, based on clinical criteria and expert opinion. Results A total of 596 patients with 33 recurrences (5.5%) were included for analysis. The final prediction model consisted of the predictors ‘age at time of surgery’, ‘preoperative tumor growth’ and ‘first postoperative MRI outcome’. The area under the receiver operating curve of the prediction model was 89%, with a C-index of 0.686 (95% CI 0.614–0.796) after cross-validation. The predicted probability for risk of recurrence was low (< 1%) in 373 patients (63%). The earliest recurrence in these low-risk patients was detected at 46 months after surgery. Conclusion This study presents a well-performing prediction model for the risk of recurrence after translabyrinthine surgery for vestibular schwannoma. The prediction model can be used to tailor the postoperative surveillance to the estimated risk of recurrence of individual patients. It seems that especially in patients with an estimated low risk of recurrence, the interval between the first and second postoperative MRI can be safely prolonged.

Vitamin D Deficiency and Outcomes After Ankle Fusion: A Short Report

Background: Vitamin D deficiency has been postulated as a cause for impaired bone healing and remodeling. The purpose of this study was to assess the potential association between low vitamin D levels and reoperation for nonunion following ankle fusion surgery. Methods: All adult patients (aged ≥18 years) who underwent ankle fusion procedures at a tertiary referral center from January 2010 to January 2019 with available vitamin D levels within 12 months preoperatively were retrospectively reviewed (n = 47). Patients were categorized as vitamin D deficient (<30 ng/mL) vs normal (31-80 ng/mL). The primary outcome was the incidence of reoperation secondary to nonunion. Secondary outcomes included incidence of reoperation not related to nonunion and the need for repeat reoperation. Results: The average level in the vitamin D–deficient group (n = 17; 36.2%) was 16.9 vs 46.4 ng/mL in the normal group (n = 30; 63.8%). All recorded reoperations for nonunion occurred exclusively in the vitamin D–deficient cohort (4/17 [23.5%]; P = .013). There were similar reoperation rates for causes other than nonunion (2/17 [11.8%] vs 4/30 [13.3%]; P > .99) and repeat reoperation rates (3/17 [17.6%] vs 1/30 [3.3%]; P = .128) among vitamin D–deficient vs normal patients. Conclusion: Vitamin D deficiency may be associated with an increased risk of reoperation for nonunion after ankle fusion.

Approval rates for corneal donation and the origin of donor tissue for transplantation at a university-based tertiary referral center with corneal subspecialization hosting a LIONS Eye Bank

Background With the increasing demand for corneas, eye banks must optimize the tissue donation, collection, and selection process. This retrospective monocentric study analyzed the approval rates for corneal donation and the origin of and reasons for discarding donor corneas from 2010 to 2019. Methods Data included the number of deceased, approval or rejection by the family for corneal donation and contraindications. Corneal grafts were included from all deceased persons who were full-body and multi-organ donors at the Saarland University Medical Center (UKS) and from external institutions. Additional analyzed parameters included endothelial cell count (ECC), blood sample serology for infections, and conjunctival swab testing . Results A total of 1748 corneoscleral buttons were harvested from 10,265 deceased persons (17% with no contraindication) at the UKS between 2010 and 2019, with a consent rate of 23.3%. The number of keratoplasties increased from 136 in 2010 (15% of the deceased, total = 925) to 251 in 2019 (21%, total = 1214). Both the general and department-specific data showed similar percentages for corneal donation over the years, with intensive care and palliative units recently providing the most corneas. The increase in the number of corneas processed by the cornea bank over the years (368 in 2010 compared with 857 in 2019) was linked both to a better internal supply in 2010 (262, 71.2% of the total) compared with 2019 (519, 60.6%) and to an external supply by reinforcement of cooperation with external hospitals, including Luxembourg in 2010 (106, 28.8% of the total) compared with 2019 (338, 39.4%). A total of 195 of 377 corneas (52%) were discarded in 2009 compared with 260 out of 715 (36%) in 2019. The main reasons for discarding were low ECC (36% of discarded corneas in 2009; 11% in 2019), positive conjunctival swab (11% in 2009; 13% in 2019), and blood sample serology (6% in 2009 and in 2019). Conclusion Despite an increasing number of donors, the demand for corneas is still rising. Improved cooperation with internal departments and with external clinics has led to an increasing number of explanted corneas. The main reason for discarding corneas was low ECC, followed by a positive conjunctival swab for fungal or bacterial contamination and serology. Increased donation rates and continued improvements in collection and selection processes are necessary to cover the high demand for corneas.

Oxygen care and treatment of retinopathy of prematurity in ocular and neurological prognosis

This retrospective cohort study aimed to investigate the effects of neonatal oxygen care and retinopathy of prematurity (ROP) treatment on ROP-related ocular and neurological prognoses. We included premature infants treated for ROP at a tertiary referral center between January 2006 and December 2019. Demographic and clinical data were collected from electronic medical records. Odds ratios (ORs) of oxygen care- and ROP treatment-related factors were calculated for ocular and neurological comorbidities 3 years after ROP treatment, after adjusting for potential confounders. ROP requiring treatment was detected in 171 eyes (88 infants). Laser treatment for ROP (OR = 4.73, 95% confidence interval [CI] 1.64–13.63) and duration of invasive ventilation (OR = 1.02, 95% CI 1.00–1.03) were associated with an increase in ocular comorbidities, along with a history of neonatal seizure (OR = 28.29, 95% CI 5.80–137.95) and chorioamnionitis (OR = 32.13, 95% CI 5.47–188.74). No oxygen care- or ROP treatment-related factors showed significant odds for neurological comorbidities. Shorter duration of invasive oxygen supply during neonatal care (less than 49 days) and anti-vascular endothelial growth factor injection as the primary treatment for ROP are less likely to cause ocular comorbidities. No association was identified between ROP treatment modalities and the risk of neurological comorbidities.

Operating room efficiency in a low resource setting: a pilot study from a large tertiary referral center in Ethiopia

Background The operating room (OR) is one of the most expensive areas of a hospital, requiring large capital and recurring investments, and necessitating efficient throughput to reduce costs per patient encounter. On top of increasing costs, inefficient utilization of operating rooms results in prolonged waiting lists, high rate of cancellation, frustration of OR personnel as well as increased anxiety that negatively impacts the health of patients. This problem is magnified in developing countries, where there is a high unmet surgical need. However, no system currently exists to assess operating room utilization in Ethiopia. Methodology A prospective study was conducted over a period of 3 months (May 1 to July 31, 2019) in a tertiary hospital. Surgical case start time, end time, room turnover time, cancellations and reason for cancellation were observed to evaluate the efficiency of eight operating rooms. Results A total of 933 elective procedures were observed during the study period. Of these, 246 were cancelled, yielding a cancellation rate of 35.8%. The most common reasons for cancellation were related to lack of OR time and patient preparation (8.7% and 7.7% respectively). Shortage of facilities (instrument, blood, ICU bed) were causes of cancelation in 7.7%. Start time was delayed in 93.4% (mean 8:56 am ± 52 min) of cases. Last case completion time was early in 47.9% and delayed in 20.6% (mean 2:54 pm ± 156 min). Turnover time was prolonged in 34.5% (mean 25 min ± 49 min). Total operating room utilization ranged from 10.5% to 174%. Operating rooms were underutilized in 42.7% while overutilization was found in 14.6%. Conclusion We found a high cancellation rate, most attributable to late start times leading to delays for the remainder of cases, and lack of preoperative patient preparation. In a setting with a high unmet burden of surgical disease, OR efficiency must be maximized with improved patient evaluation workflows, adequate OR staffing and commitment to punctual start times. We recommend future quality improvement projects focusing on these areas to increase OR efficiency.

Incidence, prevalence, and outcome of moderate to severe neurotrophic keratopathy in a German tertiary referral center from 2013 to 2017

Background Neurotrophic keratopathy (NK) is an orphan disease, with an estimated prevalence of 1–5/10,000. No data regarding the incidence exists. The primary aim was to evaluate incidence and prevalence of NK at a tertiary referral center in Germany, and the secondary aim was to analyze demographic parameters, etiology, and clinical features and therapeutic outcomes. Methods and material All patients treated for NK with serum eye drops (SED), amnionic membrane transplantation (AMT), or penetrating keratoplasty (PK) in 2013–2017 were identified. Age, sex, etiology of NK, visual acuity, disease stage, treatment, and visual acuity were analyzed. Incidence and prevalence of NK in our hospital and the overall population of the city were calculated. Results In 63 eyes of 60 patients (56.7% male; 68 ± 16 years), the most common underlying diseases were herpetic infections (23.8%), neurological causes (19%), and diabetes mellitus (14.3%). The annual incidence of NK in our tertiary referral center ranges between 5/10,000 and 3/10,000, the prevalence between 9/10,00 and 22/10,000. In all patients treated with corneal ulcers, the prevalence was up to 27% (2706/10,000). The incidence in the overall population is estimated at 0.1–0.3/10,000, the prevalence at 0.2–0.5/10,000 to 0.5/10,000. Conclusion Based on our assessment, the prevalence of NK in the overall population is lower than estimated before. However, in patients with corneal ulcers, the percentage of NK is comparably high. The disease may still be underdiagnosed due to the variety of underlying disorders and unknown comorbidities. Thus, in cases of therapy-refractive superficial keratopathy or ulcerations, NK should be considered more frequently.