Immune checkpoint inhibitors in advanced nasopharyngeal carcinoma: Beyond an era of chemoradiation?

Now is an exciting era of development in immunotherapy checkpoint inhibitors and their effect on the treatment of NPC. While the general prognosis of R/M disease is poor, immunotherapy offers some promise in a malignancy associated with EBV and characterized by a peritumoural immune infiltrate. Our study aims to review past and on-going clinical trials of monoclonal antibody therapies against the checkpoint inhibitors (e.g. PD1 and CTLA-4), in R/M NPC. All randomized and nonrandomized controlled trials involving immune checkpoint inhibitor interventions for treatment of NPC were included in the study. We utilized a validated “risk of bias” tool to assess study quality. Four separate Phase I–II trials report the potential of PD1 inhibitor treatment for patients with NPC. Within the observed groups, camrelizumab combined with chemotherapy achieved an objective response in 91% of patients as first-line treatment for metastatic NPC (PFS 68% at 1-year) but this was associated with a high rate of grade >3 adverse events (87%; CTCAE version 4.03). The remaining three studies focused on recurrent NPC disease in patients who had received at least one line of prior chemotherapy. Within this group, camrelizumab monotherapy achieved an objective response in 34% of patients (PFS 27% at 1-year; range across all three studies 20.5–34%). No NPC trial has yet reported on specific outcomes for non-PD1 checkpoint inhibitors but 11 on-going studies include alternative targets (e.g. PD-L1/CTLA-4) as combination or monotherapy treatments. In considering checkpoint immunotherapies for NPC, initial results show promise for anti-PD1 interventions. Further phase I–III trials are in progress to clarify clinical outcomes, fully determine safety profiles, and optimize drug combinations and administration schedules.     

What do I do? Developing a competency inventory for postgraduate (residency) program directors

Background: Few new Residency Program Directors (PD) are formally trained for the demands and responsibilities of the leadership aspect of their role. Currently, there are no comprehensive frameworks that describe specific leadership competencies that can inform PD self-reflection or faculty development.

Methods: The authors developed a Postgraduate Program Director Competency Inventory (PPDCI) in order to frame the performance of PDs for a multisource feedback (MSF) program. The development of the PPDCI occurred in five phases which involved: development of an initial inventory, implementation of a key informant survey of national opinion leaders, execution of a validity survey with postgraduate education leaders and committee members and implementation of a further refined inventory with 17 PD and 147 raters as part of a pilot MSF program.

Outcomes: Five distinct domains of leadership competence were identified which included: Communication and relationship management, leadership, professionalism and self-management, environmental engagement, and management skills and knowledge. The content validity of the PPDCI was endorsed by 85% of the key informants. The validity survey indicated strong endorsement of the PPDCI domains and recognition of its utility for both orientation of new PD as well as a frame for self-assessment. The pilot MSF program yielded a further refined and reduced inventory of 26 items of competence as well as recommendations for its utility.

Conclusions: Use of this leadership inventory has the potential to ensure effective leadership of postgraduate programs.     

Outcome of isolated posterior cruciate ligament reconstruction at mean 6.3-year follow up: a consecutive case series

Objectives: There is a paucity of reporting on surgical outcomes of isolated posterior cruciate ligament reconstruction (PCLR). We hypothesize that isolated PCL injuries failing nonoperative treatment achieve good outcomes and are able to return to sport following PCLR.

Methods: A retrospective analysis was performed to identify patients with isolated PCL injuries that underwent reconstruction between 2001 and 2014. Patients with multi-ligamentous injury or another concomitant knee pathology were excluded. Medical records were reviewed for demographic, clinical and operative data. Patients were contacted for administration of a telephone-based questionnaire which included the International Knee Documentation Committee (IKDC) Subjective Knee Evaluation form, Lysholm-Tegner scales, Marx activity scale (MAS), return to sport status, and patient satisfaction instruments.

Results: A total of 15 isolated PCL reconstructions in 14 patients with a mean age of 27.5 years (range 17–43) met the study inclusion criteria; mean follow up was 6.3 years (range 1.4–15.2). Pre-operatively, the primary complaint was knee instability in all patients; on physical examination, lack of a firm end point during posterior drawer testing was found in 93% (14/15) of the knees. In total, 12 of 15 knees underwent transtibial, single-bundle PCLR and three of 15 underwent tibial inlay, double bundle PCLR. Graft types included: quadriceps autograft (7/15), Achilles allograft (6/15), and hamstring autograft (2/15). There were no graft failures in our patient cohort. At most recent follow up the mean scores respectively on the IKDC form, Lysholm-Tegner scales and MAS were (standard deviation): 77.3 (16.5), 83.1 (17.9), 6.13 (2.6), and 7.1 (6.0). All fourteen patients were athletes prior to their injury and 79% (11/14) returned to sport and overall patient satisfaction was 9.2/10.

Conclusions: Isolated PCLR provides good outcomes at mean medium-term follow up with restoration of function, high rate of return to sport and overall patient satisfaction.     

Love and Justice in the Family

The Patient in the Family: An Ethics of Medicine and Families. By Hilde Lindemann Nelson and James Lindemann Nelson.     

Improved rat liver preservation by hypothermic continuous machine perfusion using polysol, a new, enriched preservation solution.

For experimental machine perfusion (MP) of the liver, the modified University of Wisconsin solution (UW-G) is most often used. In our search for an enriched MP preservation solution, Polysol was developed. Polysol is enriched with various amino acids, vitamins, and other nutrients for the liver metabolism. The aim of this study was to compare Polysol with UW-G for MP preservation of the liver. Rat livers were preserved during 24 hours with hypothermic MP using UW-G (n = 5) or Polysol (n = 5). Hepatocellular damage (aspartate aminotransferase [AST], alanine aminotransferase [ALT], lactate dehydrogenase [LDH], alpha-glutathione-S-transferase [alpha-GST]) and bile production were measured during 60 minutes of reperfusion (37 degrees C) with Krebs-Henseleit buffer. Control livers were reperfused after 24 hours of cold storage in UW (n = 5). MP using UW-G or Polysol showed less liver damage when compared with controls. Livers machine perfused with Polysol showed less enzyme release when compared to UW-G. Bile production was higher after MP using either UW-G or Polysol compared with controls. In conclusion, machine perfusion using Polysol results in better quality liver preservation than cold storage with UW and machine perfusion using UW-G.     

Early Results of the Mau Osteotomy for Correction of Moderate to Severe Hallux Valgus: A Review of 24 Cases

In our retrospective study, we report the objective results of the Mau osteotomy in the treatment of hallux valgus. We reviewed the results of 24 cases of moderate to severe hallux valgus deformities corrected with the Mau osteotomy of the first metatarsal combined with a distal soft-tissue procedure. Follow-up was possible in 24 cases. Preoperatively the mean hallux valgus and first intermetatarsal angles were 31.3 degrees and 16.6 degrees respectively, and were corrected postoperatively to an average of 13.00 degrees+/-7.15 degrees and 9.80 degrees+/-2.43 degrees respectively (P< .001). In the sagittal plane, the first metatarsal was shortened by an average of 2.00 mm. Two (8.3%) cases had dorsal elevation of the osteotomy fragment. Complications included 3 recurrences of the deformity, 1 frank nonunion, 8 dorsal cortical nonunions, 5 cases of undercorrection, and 1 case of broken hardware that was present in the nonunion that went on to revision. There were no superficial or deep infections, and no cases of transfer metatarsalgia were noted. In this series, the use of an oblique first metatarsal osteotomy with a dorsal shelf resulted in reliable and powerful correction of the first intermetatarsal angle in patients with moderate to severe hallux valgus. Particular attention should be paid to severe IM angles and the possibility of undercorrections. Despite ambulation postoperatively, the Mau osteotomy minimized dorsal malunion and the incidence of transfer metatarsalgia. LEVEL OF CLINICAL EVIDENCE: 4.     

Reliability and validity of neuropsychological screening and assessment strategies in MS

Journal of Neurology - Neuropsychological impairment is common in MS but routine evaluation is cumbersome. Many proposed avenues to more cost effective evaluation of cognition in MS have appeared...