Evaluation of the Safety Profile of Direct-Acting Antivirals on Patients with Hepatitis C Virus: A Pharmacovigilance Study.

BACKGROUND: Hepatitis C virus (HCV) is the primary contributor to chronic hepatic diseases. A rapid change in the situation took place with the advent of oral direct-acting antivirals (DAAs). However, a comprehensive review of the adverse event (AE) profile of the DAAs is lacking. This cross-sectional study aimed to analyze the reported Adverse Drug Reactions (ADRs) with DAA treatment using data from VigiBase, the WHO Individual Case Safety Report (ICSR) database. METHODS: All ICSRs reported to VigiBase with sofosbuvir (SOF), daclatasvir (DCV), sofosbuvir /ledipasvir (SOF/LDV) and ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in Egypt were extracted. Descriptive analysis was performed to summarize patients' and reactions' characteristics. Information components (ICs) and proportional reporting ratios (PRRs) for all reported ADRs were calculated to identify signals of disproportionate reporting. Logistic regression analysis was performed to identify the DAAs association with serious events of concern while adjusting for age, gender, pre-existing cirrhosis, and ribavirin use. RESULTS: Out of 2925 reports, 1131 (38.6%) were serious. The most commonly reported reactions; anaemia (21.3%), HCV relapse (14.5%) and headache (14%). For the disproportionality signals; HCV relapse was reported with SOF/DCV (IC 3.65, 95% CrI 3.47-3.79) and SOF/RBV (IC 3.69, 95% CrI 3.37-3.92), while anaemia (IC 2.85, 95% CrI 2.26-3.27) and renal impairment (IC 2.12, 95% CrI 0.7-3.03) were reported with OBV/PTV/r. CONCLUSION: The highest severity index and seriousness were reported with SOF/RBV regimen. A significant association was found for OBV/PTV/r with renal impairment and anaemia although being the superior regimen in terms of efficacy. The study findings call for further population-based studies for clinical validation.

Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy.

Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.

Hepatoprotective and renoprotective effects of silymarin against salinomycin-induced toxicity in adult rabbits.

Background and Aim: Salinomycin sodium, a licensed coccidiostat in rabbits, is used for fattening at a dose of 20-25 mg/kg. Salinomycin toxicity may arise from many risk factors (e.g., overdosage or use in non-target animal species). Silymarin extracted from milk thistle has antioxidant, anti-inflammatory, and antiviral properties. This study aimed to investigate the adverse impacts of oral administration of salinomycin for 28 consecutive days and how to reduce its risks and side effects by administering silymarin. Materials and Methods: Eighty-four male New Zealand White bucks (1.750-2.000 kg) were randomly divided into seven groups (12 each). Group one was the control. Groups two and three were administered salinomycin orally (doses of 20 and 40 mg/kg ration). Group four was administered salinomycin (20 mg/kg ration) and silymarin (6.5 mg/kg body weight [BW]). Group five received salinomycin (40 mg/kg ration) and silymarin (13 mg/kg BW). Groups six and seven were administered silymarin at doses of 6.5 and 13 mg/kg BW. Rabbits were euthanized and slaughtered on day 29 using the Halal method. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, urea, total proteins, albumin, total cholesterol, and high- and low-density lipoprotein (HDL and LDL) were analyzed in serum. Glutathione (GSH), superoxide dismutase (SOD), catalase, and malondialdehyde (MDA) were estimated in the liver. A histopathological investigation was performed on the liver and kidney. Results: The MDA activity, AST, ALT, total protein, albumin, total cholesterol, triglyceride, LDL, urea, and creatinine values were significantly elevated in groups two and three. The GSH, catalase, SOD, and HDL were significantly lower in these groups than in the control group. There were moderate pathologic changes in the liver and kidney of the third group. However, the results of the fourth and fifth groups improved more than those of the second and third groups. The results of the sixth and seventh groups were nearly the same as those of the control group. Conclusion: Salinomycin toxicity was caused by oxidative damage because of reactive oxygen species formation. Silymarin (6.5 or 13 mg/kg BW) tends to prevent and treat accidental toxicity. However, the high dose of silymarin (13 mg/kg BW) had more renal and hepatoprotective capacities.

Study on the application of the Internet + nursing service in family rehabilitation of common bone and joint diseases in the elderly.

OBJECTIVE: To explore the feasibility of the Internet + nursing service mode in family rehabilitation of elderly patients with osteoarthritic diseases. PATIENTS AND METHODS: The control group (n=50) received routine rehabilitation treatment procedures and discharge guidance. For the observation group (n=50), extended nursing rehabilitation service was conducted through the Internet + nursing service platform based on the routine treatment in the control group. RESULTS: (1) The compliance with follow-up of the patients in the observation group was significantly higher than that in the control group; (2) The total satisfaction of patients in the observation group was significantly higher than that in the control group; (3) The VAS (1 month: 4.36±1.15 vs. 5.86±1.61, p<0.05; 3 months 4.36±1.15 vs. 5.86±1.61, p<0.05), SAS (1 month: 37.21±14.16 vs. 49.31±13.45, p<0.05; 3 months 26.73±8.25 vs. 40.33±9.50, p<0.05), SDS (1 month: 32.36±10.15 vs. 46.32±12.61, p<0.05; 3 months 27.11±8.08 vs. 40.62±11.40, p<0.05) and PSQI (1 month: 13.64 ± 1.13 vs. 16.31 ± 3.45, p<0.05; 3 months 11.54 ± 1.87 vs. 15.74 ± 1.36, p<0.05) scores in the observational group were significantly lower than that in control group at one month and three months after discharge. The ADL (1 month: 86.86 ± 4.13 vs. 74.33 ± 3.44, p<0.05; 3 months 90.34 ± 7.87 vs. 78.52 ± 6.36, p<0.05) scores in the observational group were significantly higher than that in control group at one month and three months after discharge. CONCLUSIONS: The extended rehabilitation nursing management for family rehabilitation of elderly patients with osteoarthritic diseases through the Internet + nursing service is a family rehabilitation model suitable for elderly patients with osteoarthritic diseases in China and has positive significance in developing a diversified medical nursing model.

Comparison of whole breast dosimetry techniques - From 3DCRT to VMAT and the impact on heart and surrounding tissues.

INTRODUCTION: Various techniques for whole breast radiation therapy (WBRT) have been reported to increase dose to contralateral tissues. Heart dose is of critical importance as there is no apparent dose threshold below which there is no risk. The aim of this study was to compare planning techniques for WBRT that achieves the best target dosimetry and lowest organ at risk (OAR) dose. METHODS: Thirty early-stage whole breast patient datasets, 15 each left- and right-sided cases, were retrospectively selected. Five techniques were generated for each data set: three-dimensional conformal radiation therapy (3DCRT), hybrid intensity modulated radiation therapy (HYI), hybrid volumetric modulated arc therapy (VMAT) - (HYV), reduced arc VMAT - bowtie (BT), and BT flattening filter free (FFF) - (BTFFF). Plan goals and OARs were evaluated and compared between techniques. RESULTS: BT had the highest median conformity index (CI) values (0.82, IQR: 0.80-0.85 left and 0.83, IQR 0.80-0.86 right). BT recorded lower mean heart doses (median value 1.19Gy, IQR: 0.90-1.55), and BTFFF recorded lower heart V2.5 Gy , V5 Gy ; median 3.96% (IQR: 2.90-6.80) and 0.90% (IQR: 0.50-1.50) respectively for left-sided patients. There was a statistically significant difference in all ipsilateral lung measures, (p < 0.001) with BTFFF producing significantly lower doses across all measures: mean, V5 Gy , V10 Gy and V20 Gy . CONCLUSION: Overall BT and BTFFF techniques produced lower OAR doses and equivalent PTV coverage for WBRT. BT and BTFFF techniques increased contralateral lung and breast doses; however, these were within prescribed tolerances and comparable to results published in the literature.

Identifying breast cancer patients who gain the most dosimetric benefit from deep inspiration breath hold radiotherapy.

INTRODUCTION: Deep inspiration breath hold (DIBH) has been proven to reduce cardiac dose for women receiving left breast and chest wall radiation therapy. However, it utilises extra departmental resources and patient exertion. The aim of this exploratory study was to investigate if any factors existed that could identify breast cancer patients who may benefit most from DIBH, to facilitate appropriate utilisation of departmental resources. METHODS: Left-sided breast cancer patients aged 18-70 years, and right-sided breast cancer patients with internal mammary nodes included, were recruited. DIBH and free breathing (FB) plans were created for all patients. Patient demographic and clinical history were recorded. Variables including lung threshold value, lung volume, patient separation, maximum heart in field, volume of planning target volume (PTV), heart dose, ipsilateral lung dose were compared between plans. RESULTS: Plans for 31 patients were analysed. No correlations were found between lung threshold value or patient separation and cardiac dose. Moderate to strong correlations were found with BMI, PTV volume and lung volume change however no definitive thresholds were determined. A significant difference was found in the maximum heart in field between DIBH and FB (P < 0.001) with those patients with greater than 0.7 cm heart in the field on the FB scan demonstrating greater reductions in mean heart dose. CONCLUSION: Maximum heart in the field of greater than 0.7 cm in FB could be a potential factor to identify patients who may benefit most from DIBH. This factor warrants investigation in a larger patient cohort to test its validity.

Radiation therapy for augmenting the efficacy of immunotherapy in advanced non-small cell lung cancer: a case-controlled study.

This study investigated the effects of previous radiation therapy on outcomes from nivolumab in advanced NSCLC, and found that previous radiation therapy resulted in significantly higher survival in patients treated with nivolumab for advanced NSCLC http://bit.ly/3btOFSL.

Preoperative cisplatin, fluorouracil, and docetaxel with or without radiotherapy after poor early response to cisplatin and fluorouracil for resectable oesophageal adenocarcinoma (AGITG DOCTOR): results from a multicentre, randomised controlled phase II trial.

BACKGROUND: Patients with oesophageal/gastro-oesophageal junction adenocarcinoma (EAC) not showing early metabolic response (EMR) to chemotherapy have poorer survival and histological response rates <5%. We investigated whether tailoring neoadjuvant therapy can improve outcomes in these patients. PATIENTS AND METHODS: Patients with resectable EAC were enrolled and randomised into two single-arm, multicentre phase II trials. After induction cisplatin and 5-fluorouracil (CF), all were assessed by day 15 positron emission tomography (PET). Patients with an EMR [maximum standardised uptake values (SUVmax) ≥35% reduction from baseline to day 15 PET] received a second CF cycle then oesophagectomy. Non-responders were randomised 1 : 1 to two cycles of CF and docetaxel (DCF, n = 31) or DCF + 45 Gy radiotherapy (DCFRT, n = 35) then oesophagectomy. The primary end point was major histological response (<10% residual tumour) in the oesophagectomy specimen; secondary end points were overall survival (OS), progression-free survival (PFS), and locoregional recurrence (LR). RESULTS: Of 124 patients recruited, major histological response was achieved in 3/45 (7%) with EMR, 6/30 (20%) DCF, and 22/35 (63%) DCFRT patients. Grade 3/4 toxicities occurred in 12/45 (27%) EMR (CF), 13/31 (42%) DCF, and 25/35 (71%) DCFRT patients. No treatment-related deaths occurred. LR by 3 years was seen in 5/45 (11%) EMR, 10/31 (32%) DCF, and 4/35 (11%) DCFRT patients. PFS [95% confidence interval (CI)] at 36 months was 47% (31% to 61%) for EMR, 29% (15% to 45%) for DCF, and 46% (29% to 61%) for DCFRT patients. OS (95% CI) at 60 months was 53% (37% to 67%) for EMR, 31% (16% to 48%) for DCF, and 46% (29% to 61%) for DCFRT patients. CONCLUSIONS: EMR is associated with favourable OS, PFS, and low LR. For non-responders, the addition of docetaxel augmented histological response rates, but OS, PFS, and LR remained inferior compared with responders. DCFRT improved histological response and PFS/LR outcomes, matching the EMR group. Early PET/CT has the potential to tailor therapy for patients not showing an early response to chemotherapy. TRIAL REGISTRATION: ACTRN12609000665235.

Stereotactic ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): a phase 3, open-label, randomised controlled trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is widely used to treat inoperable stage 1 non-small-cell lung cancer (NSCLC), despite the absence of prospective evidence that this type of treatment improves local control or prolongs overall survival compared with standard radiotherapy. We aimed to compare the two treatment techniques. METHODS: We did this multicentre, phase 3, randomised, controlled trial in 11 hospitals in Australia and three hospitals in New Zealand. Patients were eligible if they were aged 18 years or older, had biopsy-confirmed stage 1 (T1-T2aN0M0) NSCLC diagnosed on the basis of 18F-fluorodeoxyglucose PET, and were medically inoperable or had refused surgery. Patients had to have an Eastern Cooperative Oncology Group performance status of 0 or 1, and the tumour had to be peripherally located. Patients were randomly assigned after stratification for T stage and operability in a 2:1 ratio to SABR (54 Gy in three 18 Gy fractions, or 48 Gy in four 12 Gy fractions if the tumour was <2 cm from the chest wall) or standard radiotherapy (66 Gy in 33 daily 2 Gy fractions or 50 Gy in 20 daily 2·5 Gy fractions, depending on institutional preference) using minimisation, so no sequence was pre-generated. Clinicians, patients, and data managers had no previous knowledge of the treatment group to which patients would be assigned; however, the treatment assignment was subsequently open label (because of the nature of the interventions). The primary endpoint was time to local treatment failure (assessed according to Response Evaluation Criteria in Solid Tumors version 1.0), with the hypothesis that SABR would result in superior local control compared with standard radiotherapy. All efficacy analyses were based on the intention-to-treat analysis. Safety analyses were done on a per-protocol basis, according to treatment that the patients actually received. The trial is registered with ClinicalTrials.gov (NCT01014130) and the Australia and New Zealand Clinical Trials Registry (ACTRN12610000479000). The trial is closed to new participants. FINDINGS: Between Dec 31, 2009, and June 22, 2015, 101 eligible patients were enrolled and randomly assigned to receive SABR (n=66) or standard radiotherapy (n=35). Five (7·6%) patients in the SABR group and two (6·5%) in the standard radiotherapy group did not receive treatment, and a further four in each group withdrew before study end. As of data cutoff (July 31, 2017), median follow-up for local treatment failure was 2·1 years (IQR 1·2-3·6) for patients randomly assigned to standard radiotherapy and 2·6 years (IQR 1·6-3·6) for patients assigned to SABR. 20 (20%) of 101 patients had progressed locally: nine (14%) of 66 patients in the SABR group and 11 (31%) of 35 patients in the standard radiotherapy group, and freedom from local treatment failure was improved in the SABR group compared with the standard radiotherapy group (hazard ratio 0·32, 95% CI 0·13-0·77, p=0·0077). Median time to local treatment failure was not reached in either group. In patients treated with SABR, there was one grade 4 adverse event (dyspnoea) and seven grade 3 adverse events (two cough, one hypoxia, one lung infection, one weight loss, one dyspnoea, and one fatigue) related to treatment compared with two grade 3 events (chest pain) in the standard treatment group. INTERPRETATION: In patients with inoperable peripherally located stage 1 NSCLC, compared with standard radiotherapy, SABR resulted in superior local control of the primary disease without an increase in major toxicity. The findings of this trial suggest that SABR should be the treatment of choice for this patient group. FUNDING: The Radiation and Optometry Section of the Australian Government Department of Health with the assistance of Cancer Australia, and the Cancer Society of New Zealand and the Cancer Research Trust New Zealand (formerly Genesis Oncology Trust).

Anterior cervical incision-sparing thyroidectomy: Comparing retroauricular and transoral approaches.

OBJECTIVES: The robotic retroauricular approach and transoral endoscopic thyroidectomy vestibular approach (TOETVA) have been employed to avoid anterior neck scarring in thyroidectomy with good success. However, outcomes have yet to be compared between techniques. We compare our initial clinical experience with these approaches for thyroid lobectomy at our institution. METHODS: A review of initial consecutive patients who underwent robotic facelift thyroidectomy (RFT) (August 2011-August 2016) at our institution was conducted. This was compared with the same number of initial consecutive patients who underwent TOETVA (September 2016-September 2017) at our institution. Demographics, operative time, pathology, complications, and learning curve were compared between cohorts. Learning curve was defined based on the slope of linear regression models of operative time versus case number. RESULTS: There were 20 patients in each cohort. There was no statistically significant difference in demographic data between cohorts. One hundred percent of RFT cases versus 95% TOETVA cases (P = .999) were completed without conversion to standard open technique with median operative times of 201 (124-293) minutes versus 188 (89-343) minutes with RFT and TOETVA, respectively (P = .36). There was no incidence of permanent recurrent laryngeal nerve injury in either cohort. The slopes of the regression models were 0.29 versus -8.32 (P = .005) for RFT and TOETVA, respectively. CONCLUSION: RFT and TOETVA are safe and feasible options for patients motivated to avoid an anterior neck scar. However, the quicker learning curve without the need for a costly robotic system may make TOETVA the preferred technique for institutions wishing to perform anterior cervical incision-sparing thyroidectomy. LEVEL OF EVIDENCE: 4.

Patterns of Failure Following Dose-escalated Chemoradiotherapy for Fluorodeoxyglucose Positron Emission Tomography Staged Squamous Cell Carcinoma of the Oesophagus.

AIMS: To analyse outcomes and patterns of failure following dose-escalated definitive chemoradiotherapy (CRT) for oesophageal squamous cell carcinoma using fluorodeoxyglucose positron emission tomography for staging and treatment planning. MATERIALS AND METHODS: A retrospective review of patients with oesophageal squamous cell carcinoma receiving definitive CRT to a dose of ≥56 Gy was conducted. Patient and tumour characteristics, treatment received and first sites of relapse were analysed. RESULTS: Between 2003 and 2014, 72 patients were treated with CRT to a median dose of 60 Gy (range 56-66 Gy). The median age was 63 years; most (61%) were stage III/IVa. The median follow-up was 57 months. Three year in-field control, relapse-free survival and overall survival was 64% (95% confidence interval 50-75%), 38% (95% confidence interval 27-50%) and 42% (95% confidence interval 30-53%), respectively. Of the 41 failures prior to death or at last follow-up date, isolated locoregional relapse occurred in 16 patients (22%) with isolated in-field recurrence in 11 patients (15%). Distant failure as first site of relapse was present in 25 patients (35%). No in-field failures occurred in the 11 patients with cT1-2, N0-1 tumours. The median survival for cT4 tumours was 8 months, with five of eight patients developing local progression within the first 6 months. CONCLUSIONS: Dose-escalated radiotherapy was associated with promising rates of in-field local control, with the exception of cT4 tumours. Distant failure remains a significant competing risk. Our data supports the need for current trials re-examining the role of dose escalation in the modern era.

The incidence of vocal fold motion impairment after primary thyroid and parathyroid surgery for a single high-volume academic surgeon determined by pre- and immediate post-operative fiberoptic laryngoscopy.

BACKGROUND: Vocal fold motion impairment (VFMI) is a well-recognized complication of thyroid and parathyroid surgery. Preoperative counseling requires a thorough understanding of the incidence, risk factors, and value of early diagnosis of postoperative VFMI. Our objective is to describe the incidence of and risk factors for VFMI for a single high-volume academic surgeon, and to assess the utility of immediate postoperative fiberoptic laryngoscopy (FOL) in early diagnosis of VFMI. METHODS: Retrospective cohort study of patients undergoing primary thyroid and parathyroid procedures by a single high-volume surgeon at an academic tertiary care center. All patients underwent preoperative and immediate postoperative FOL. The primary outcome was incidence of VFMI, either temporary (<1 year) or permanent (1 year or more). The unit of analysis was number of recurrent laryngeal nerves (RLN) at risk. Risk factors for VFMI were analyzed using logistic regression, reporting unadjusted and adjusted odds ratios (OR and aOR) and 95% confidence intervals (CI). RESULTS: The study population comprised 1547 patients undergoing 1580 procedures for a total of 2527 nerves at risk, excluding the 27 nerves found to have motion impairment on preoperative FOL. Sixty-seven new incidents of VFMI were identified on postoperative FOL, with an additional six new incidents detected after voice complaints prompted FOL upon follow-up. Thus, the incidence of postoperative VFMI was 2.9% of RLNs at risk (73 of 2527). The sensitivity and negative predictive value of immediate postoperative FOL were 92% and 99.8% respectively. Permanent VFMI occurred in 9 cases (0.4%), 3 of which were from intentional RLN transection for malignancy. Odds of VFMI were significantly lower after parathyroidectomy (aOR = 0.1, 95%CI = 0.01-0.8 compared with hemithryoidectomy) and higher with central neck dissection (aOR = 2.4, 95CI = 1.0-5.9). Among cases of malignancy, odds of VFMI increased significantly with increasing T-stage (adjusted ptrend<0.001). CONCLUSION: VFMI is rare and usually temporary after primary thyroid and parathyroid procedures, with increased risk associated with larger primary malignancies and the inclusion of central neck dissection. Immediate postoperative FOL is useful for early detection of VFMI that may allow for clear definition of temporary and permanent immobility rehabilitation especially if there is evidence to support early intervention.

Early outcomes in transoral vestibular thyroidectomy: Robotic versus endoscopic techniques.

BACKGROUND: The transoral thyroidectomy vestibular approach has been utilized via both robotic (TORTVA) and endoscopic (TOETVA) techniques to perform thyroidectomy. However, there have been no studies evaluating outcomes between these approaches. Here we describe our outcomes for thyroid lobectomy with TORTVA and TOETVA. METHODS: All cases of transoral vestibular approach thyroid lobectomy at Johns Hopkins Hospital were reviewed. Primary outcomes and demographic data were then compared between TORTVA and TOETVA. RESULTS: Twenty-seven cases were identified, 7 using the robotic approach and 20 using the endoscopic approach. The procedural success rate for the robotic and endoscopic cohorts was 5 of 7 (71%) and 19 of 20 (95%), respectively (P = .15). There were no persistent nerve injuries, mental, or recurrent in either cohort. Median operative time for TOETVA was 188 minutes versus 322 minutes for TORTVA (P = .001). CONCLUSION: Thyroid lobectomy can be safely performed via both techniques, although performed more quickly endoscopically, which is likely due in part to differences in the learning curves.

Postoperative IPTH compared with IPTH gradient as predictors of post-thyroidectomy hypocalcemia.

OBJECTIVES/HYPOTHESIS: Predicting patients' risk for hypocalcemia after thyroidectomy may allow for same-day discharge. This study was designed to compare postoperative intact parathyroid hormone (IPTH) alone with percentage change in IPTH (IPTH gradient) in predicting post-thyroidectomy hypocalcemia. STUDY DESIGN: Retrospective cohort study. METHODS: Patients undergoing total thyroidectomy by the senior author from May 2015 to May 2016 were included. Serum IPTH was measured preoperatively and 1 hour postoperatively, and IPTH gradient was calculated. Postoperative hypocalcemia was mild (≥8.0, <8.4) or severe (<8.0 and/or hypocalcemic symptoms). Postoperative IPTH and IPTH gradient were compared with hypocalcemia using logistic regression. Receiver operating characteristic analysis of IPTH measures as predictors of hypocalcemia was performed, and the area under the curve (AUC) was calculated. RESULTS: Overall, 119 patients were included. Forty-seven percent of the patients developed postoperative hypocalcemia, including 26 (22%) with mild and 30 (25%) with severe hypocalcemia. Thirteen patients had hypocalcemic symptoms. Median IPTH gradient and postoperative IPTH each differed significantly by category of hypocalcemia (P < .001). Higher IPTH gradient was significantly associated with odds of severe and symptomatic hypocalcemia (adjusted odds ratio [aOR]: 1.21, 95% confidence interval [CI]: 1.06-1.39 and aOR: 1.34, 95% CI: 1.05-1.71 per 10% increase), whereas lower postoperative IPTH was not (aOR: 1.27, 95% CI: 0.95-1.68 and aOR: 1.44, 95% CI: 0.90-2.31 per 10 pg/mL decrease). The AUC for predicting severe hypocalcemia was nonsignificantly higher for IPTH gradient than postoperative IPTH (AUC = 0.77 vs. 0.69, P = .10). The AUC for predicting symptomatic hypocalcemia was significantly higher for IPTH gradient (AUC = 0.75 vs. 0.72, P = .03). CONCLUSIONS: Our results suggest that the IPTH gradient may be more useful than postoperative IPTH alone in predicting risk of post-thyroidectomy hypocalcemia. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:769-774, 2018.

Online and call center referral for endocrine surgical pathology within institutions.

OBJECTIVES/HYPOTHESIS: We hypothesized that self-referred patients to academic centers will be equally distributed between general surgery and otolaryngology departments that perform thyroid surgery. We sought to quantify disparities in the assignment of these self-referred patients who may reach an institution through call centers or online pathways. STUDY DESIGN: Cross-sectional survey. METHODS: Key words "thyroid surgery" and "thyroid cancer" were used along with the name of the Accreditation Council for Graduate Medical Education-listed otolaryngology program in both Google and Bing search engines. The top three search results for departments were reviewed, and a tally was given to general surgery (GS), otolaryngology-head and neck surgery (OLHNS), or neither. A multidisciplinary center with both GS and OLHNS was recorded as "equitable." Telephone calls were tallied if they were directed to GS or OLHNS. RESULTS: Out of 400 program tallies, 117 (29.25%) patients were directed to GS and 50 (12.5%) were directed to OLHNS. An additional 181 (45.25%) were directed to neither group ("neither") (P < .05). Fifty-two (13%) of the patients were referred to multidisciplinary groups ("equitable"). A telephone call survey had 62 patients (62%) assigned to a general surgeon, as opposed to 38 (38%) for OLHNS (P < .05). Five institutions offered a multidisciplinary group when searching with Bing, and 11 were found by searching with Google. CONCLUSIONS: There is not an equal distribution of self-referred patients with thyroid surgical pathology. It may be important to increase the online presence of OLHNS surgeons who perform thyroid surgery at academic medical institutions. Multidisciplinary centers focused on thyroid and parathyroid surgical disease represents one model of assigning self-referred patients. LEVEL OF EVIDENCE: NA Laryngoscope, 1977-1981, 2018.

Preoperative information for thyroid surgery.

The preoperative information necessary to communicate to the patient to obtain informed consent in thyroid surgery is not detailed in length in the current medical literature. Advances in technology and the advent of remote access approaches in thyroid surgery have increased the need for a detailed communication of risks, benefits and alternatives to achieve an informed consent. In this review article, we outline the indications for thyroid surgery, risks of thyroid surgery, different approaches to thyroidectomy, and possible consequences of using advanced technology using intraoperative nerve monitoring (IONM) as an example. A truly detailed informed consent in the modern age of thyroid surgery is crucial. This article not only details the risks, benefits and alternatives of thyroid surgery, but also incorporates new practices, guidelines and technologies to allow patients to achieve a comprehensive preoperative understanding of treatment recommendations.

Transoral thyroidectomy and parathyroidectomy - A North American series of robotic and endoscopic transoral approaches to the central neck.

OBJECTIVE: Most thyroid surgery in North America is completed via a cervical incision, which leaves a permanent scar. Approaches without cutaneous incisions offer aesthetic advantages. This series represents the largest series of transoral vestibular approaches to the central neck in North America, and the first published reports of robotic transoral vestibular thyroidectomy for thyroid carcinoma. MATERIALS AND METHODS: Data was prospectively collected for patients that underwent transoral vestibular approach thyroidectomy and/or parathyroidectomy between April 2016 and February 2017. RESULTS: Fifteen patients underwent the procedure for removal of the thyroid (n=12), parathyroid (n=2) or both thyroid and parathyroid glands (n=1). The first case was converted to an open procedure. Fourteen were completed through these remote access incisions, including patients with a body mass index as high as 44. There were no permanent complications. The postoperative median Dermatology Life Quality Index score was 3, which indicates a small effect on quality of life. CONCLUSION: The transoral vestibular approach to the central neck is a promising technique for patients who desire to optimize aesthetics.

Transoral robotic thyroidectomy: a preclinical feasibility study using the da Vinci Xi platform.

Transoral thyroid surgery allows the surgeon to conceal incisions within the oral cavity without significantly increasing the amount of required dissection. TORT provides an ideal scarless, midline access to the thyroid gland and bilateral central neck compartments. This approach, however, presents multiple technical challenges. Herein, we present our experience using the latest generation robotic surgical system to accomplish transoral robotic thyroidectomy (TORT). In two human cadavers, the da Vinci Xi surgical system (Intuitive Surgical, Sunnyvale, CA, USA) was used to complete TORT. Total thyroidectomy and bilateral central neck dissection was successfully completed in both cadavers. The da Vinci Xi platform offered several technologic advantages over previous robotic generations including overhead docking, narrower arms, and improved range of motion allowing for improved execution of previously described TORT techniques.

Minimally invasive and remote-access thyroid surgery in the era of the 2015 American Thyroid Association guidelines.

Thyroid surgery has evolved throughout the years from being one of the most dangerous surgeries to becoming one of the safest surgical procedures performed today. Recent technologic innovations have allowed surgeons to remove the thyroid gland from a remote site while avoiding visible neck scars. There are many endoscopic approaches for thyroidectomy. The most common cervical approach is the minimally invasive video-assisted technique developed by Miccoli et al. The robotic transaxillary and axillary breast approaches avoid a neck scar and have been demonstrated to be safe and effective in international populations. Novel approaches under investigation include face-lift robotic thyroidectomy and the transoral approach. This article aims to provide the reader with an overview of the current minimally invasive and alternate-site approaches used and their capability to assist the surgeons in accomplishing remote-access thyroid surgery under the scope of the 2015 American Thyroid Association Guidelines.

Botulinum toxin injections combined with or without sodium hyaluronate in the absence of electromyography for the treatment of infantile esotropia: a pilot study.

OBJECTIVE: To evaluate the feasibility and safety of a revised technique of botulinum toxin type A (BTA) injections for the treatment of infantile esotropia. METHODS: Forty-seven patients with infantile esotropia were randomly divided into two groups. In group A, 23 cases were treated with a bilateral injection of 2.5-3.75 U BTA combined with sodium hyaluronate (SH) to the medial rectus muscle. In group B, 24 cases were treated with a bilateral injection of 2.5-3.75 U BTA solution alone to the medial rectus muscle. Electromyography was not used in the study. All patients received one injection and were evaluated 2 weeks, 3 months, and 6 months following injection. RESULTS: The measured changes between groups A and B included the frequencies of good alignment 6 months after injections (30.4% vs 37.5%), complicated ptosis (2.2% vs 20.8%), and vertical deviation (2.2% vs 2.1%). CONCLUSION: BTA injections combined with or without SH in the absence of electromyography demonstrated effectiveness and feasibility in the treatment of infantile esotropia. A relative decrease in the frequency of complicated ptosis resulted from injections of BTA+SH.