Monday, July 4, 2022

Kindlin-2 loss in condylar chondrocytes causes spontaneous osteoarthritic lesions in the temporomandibular joint in mice

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Perioperative Antibiotic Stewardship in the Organ Transplant Setting

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Abstract

Background

Solid organ transplant (SOT) recipients can benefit from traditional antimicrobial stewardship (AMS) activities directed to improve judicious perioperative prescribing and management, but evidence is lacking. The aim of this expert opinion review is to provide an update on the current landscape of application of AMS practices for optimization of perioperative prophylaxis (PP).

Methods

We reviewed the available literature on early post-operative infectious complications in SOT and PP management, on modified perioperative approaches in case of infection or colonization in recipients and donors and on AMS in transplantation PP.

Results

SOT recipients are at high risk for early post-operative infectious complications due to the complexity of surgical procedures, severity of end stage organ disease, net state of immunosuppression in the post-transplant period and to the high risk for multidrug resistant organism. Moreover, SOT may be exposed to preservation fluid infections and expected or unexpected donor-derived infections. We summarize main factors to take into account when prescribing transplant PP.

Conclusion

Creating personalized PP to avoid unwanted consequences of antimicrobials while improving outcomes is an emerging and critical aspect in SOT setting. Further studies are needed to offer best PP tailored to SOT type and to evaluate interventions efficacy and safety.

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Impact of Narrowing Perioperative Antibiotic Prophylaxis for Left Ventricular Assist Device Implantation

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Abstract

Background

Although infections are a significant potential complication among patients undergoing left ventricular assist device (LVAD) implantation, standardized surgical infection prophylaxis (SIP) regimens are not well defined. At Montefiore Medical Center, a 4-drug SIP regimen containing fluconazole, ciprofloxacin, rifampin, and vancomycin was previously utilized. In January 2020, the antimicrobial stewardship program implemented a 2-drug SIP regimen of vancomycin and cefazolin to limit exposure to broad-spectrum antibiotics. This study evaluated LVAD-associated infection rates prior to and following the SIP revision.

Methods

A retrospective review of patients who underwent LVAD implantation from 1/2018-4/2021 was performed. Infections were classified using the International Society for Heart and Lung Transplantation definitions. Infection rates at 2 weeks, 30 days, and 90-days post-implantation in the 4-drug SIP regimen (1/2018-12/2019) and the 2-drug SIP regimen (1/2020-4/2021) were compared.

Results

A total of 71 patients were included. The number of patients with LVAD-associated infections (including surgical site infections) was not significantly different in either SIP group at 2 weeks (9% vs 4%, p = 0.64), 30 days (9% vs 11%, p = 0.99), or 90 days (19% vs 14%, p = 0.75). There was no statistically significant difference in 30 or 90-day mortality. LVAD-associated gram-negative (7% vs 7%; p>0.99) and fungal (5% vs 0%; p = 0.51) infections were uncommon. The most common organism isolated was Staphylococcus aureus and the most common type of infection was pneumonia in both SIP groups.

Conclusion

No significant difference in LVAD-associated infections or infection-related mortality was observed with de-escalation of perioperative antibiotics. Additional studies with larger sample sizes are needed to endorse the findings of this study.

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Does Esophagectomy Provide a Survival Advantage to Patients Aged 80 Years or Older? Analyzing 5066 Patients in the National Database of Hospital-based Cancer Registries in Japan

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imageObjective: To determine whether esophagectomy provides a survival advantage in octogenarians with resectable thoracic esophageal cancer. Summary Background Data: Elderly patients with thoracic esophageal cancer do not always receive the full standard treatment; however, advanced age alone should not preclude the use of effective treatment that could meaningfully improve survival. Methods: We retrieved the 2008 to 2011 data from the National Database of Hospital-based Cancer Registries from the National Cancer Centerin Japan, divided the patients into a ≥75 group (75–79 years; n = 2935) and a ≥80 group (80 years or older; n = 2131), and then compared the patient backgrounds and survival curves. A multivariable Cox proportional hazards regression model was developed to compare the effects of esophagectomy and chemoradiotherapy in the 2 groups. Results: A significantly greater percentage of patients were treated with esoph-agectomy in the ≥75 group (34.6%) than the ≥80 group (18.4%). Among patients who received esophagectomy, the 3-year survival rate was 51.1% in the ≥ 75 group and 39.0% in the ≥80 group (P
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Fastigial nuclei surgical damage and focal midbrain disruption implicate PAG survival circuits in cerebellar mutism syndrome

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Abstract
Background
Pediatric postoperative cerebellar mutism syndrome (CMS) is a rare but well-known complication of medulloblastoma (Mb) resection with devastating effects on expressive language, mobility, cognition, and emotional regulation that diminishes quality of life for many Mb survivors. The specific anatomical and neuronal basis of CMS remains obscure. We address this issue by identifying patterns of surgical damage and secondary axonal degeneration in Mb survivors with CMS.
Methods
Children with Mb deemed high-risk for CMS based on intraventricular location of the tumor had T1 images analyzed for location(s) of surgical damage using a specially developed algorithm. We used three complementary methods of spatial analysis to identify surgical damage linked to CMS diagnosis. Magnetization transfer ratio (MTR) images were analyzed for evidence of demyelination in anatomic regions downstream of the cerebellum, indicating neuronal dysfunction.
Results
Spatial analyses highlighted damage to the fastigial nuclei and their associated cerebellar cortices as the strongest predictors of CMS. CMS-related MTR decrease was greatest in the ventral periaqueductal grey area (PAG) and highly consistent in the left red nucleus.
Conclusion
Our evidence points to disruption of output from the fastigial nuclei as a likely causal trigger for CMS. We propose that core CMS symptoms result from a disruption in the triggering of survival behaviors regulated by the PAG, including the gating of vocalization and volitional movement. The fastigial nuclei provide the densest output to the PAG from the cerebellum, thus sparing these structures may provide a greater likelihood of CMS prevention.
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