The field of vascularized composite allografts (VCAs) has undergone significant advancement in recent decades, and VCAs are increasingly common and accepted in the clinical setting, bringing hope of functional recovery to patients with debilitating injuries. A major obstacle facing the widespread application of VCAs is the side effect profile associated with the current immunosuppressive regimen, which can cause a wide array of complications such as infection, malignancy, and even death. Significant concerns remain regarding whether the treatment outweighs the risk. The potential solution to this dilemma would be achieving VCA tolerance, which would allow recipients to receive allografts without significant immunosuppression and its sequelae. Promising tolerance protocols are being studied in kidney transplantation; four major trials have attempted to withdraw immunosuppressive treatment with various successes. The common theme in all four trials is the use of radiation treatment and donor cell transplantation. The knowledge gained from these trials can provide valuable insight into the development of a VCA tolerance protocol. Despite similarities, VCAs present additional barriers compared to kidney allografts regarding tolerance induction. VCA donors are likely to be deceased, which limits the time for significant pre-conditioning. VCA donors are also more likely to be human leukocyte antigen–mismatched, which means that tolerance must be induced across major immunological barriers. This review also explores adjunct therapies studied in large animal models that could be the missing element in establishing a safe and stable tolerance induction method.

Formation of the periodontium begins following onset of tooth-root formation in a coordinated manner after birth. Dental follicle progenitor cells are thought to form the cementum, alveolar bone and Sharpey's fibers of the periodontal ligament (PDL). However, little is known about the regulatory morphogens that control differentiation and function of these progenitor cells, as well as the progenitor cells involved in crown and root formation. We investigated the role of bone morphogenetic protein-2 (Bmp2) in these processes by the conditional removal of the Bmp2 gene using the Sp7-Cre-EGFP mouse model. Sp7-Cre-EGFP first becomes active at E18 in the first molar, with robust Cre activity at postnatal day 0 (P0), followed by Cre activity in the second molar, which occurs after P0. There is robust Cre activity in the periodontium and third molars by 2 weeks of age. When the Bmp2 gene is removed from Sp7(+) (Osterix(+)) cells, major defects are noted in root, cellular cementum and periodontium formation. First, there are major cell autonomous defects in root-odontoblast terminal differentiation. Second, there are major alterations in formation of the PDLs and cellular cementum, correlated with decreased nuclear factor IC (Nfic), periostin and α-SMA(+) cells. Third, there is a failure to produce vascular endothelial growth factor A (VEGF-A) in the periodontium and the pulp leading to decreased formation of the microvascular and associated candidate stem cells in the Bmp2-cKO(Sp7-Cre-EGFP). Fourth, ameloblast function and enamel formation are indirectly altered in the Bmp2-cKO(Sp7-Cre-EGFP). These data demonstrate that the Bmp2 gene has complex roles in postnatal tooth development and periodontium formation.
Actins ; analysis ; Activating Transcription Factor 2 ; genetics ; Age Factors ; Ameloblasts ; pathology ; Amelogenesis ; genetics ; Animals ; Bone Morphogenetic Protein 2 ; genetics ; Cell Adhesion Molecules ; analysis ; Cell Differentiation ; genetics ; Cementogenesis ; genetics ; Dental Cementum ; pathology ; Dental Pulp ; blood supply ; Fluorescent Dyes ; Green Fluorescent Proteins ; Male ; Mice ; Mice, Knockout ; Microvessels ; pathology ; Molar ; growth & development ; Molar, Third ; growth & development ; NFI Transcription Factors ; analysis ; Odontoblasts ; pathology ; Odontogenesis ; genetics ; Periodontal Ligament ; growth & development ; Sp7 Transcription Factor ; Stem Cells ; physiology ; Tooth Root ; growth & development ; Transcription Factors ; genetics ; Vascular Endothelial Growth Factor A ; analysis ; Zinc Fingers ; genetics

The Anterior Inferior Cerebellar Artery-Posterior Inferior Cerebellar Artery (AICA-PICA) common trunk is a rare variant of cerebral posterior circulation in which a single vessel originating from either the basilar or vertebral arteries supplies both cerebellum and brainstem territories. We present the first case of an unruptured right AICA-PICA aneurysm treated with flow diversion using a Shield-enhanced pipeline endovascular device (PED, VANTAGE Embolization Device with Shield Technology, Medtronic, Canada). We expand on this anatomic variant and review the relevant literature.A 39-year-old man presented to our treatment center with vertigo and right hypoacusis. The initial head CT/CTA was negative, but a 4-month follow-up MRI revealed a 9 mm fusiform dissecting aneurysm of the right AICA. The patient underwent a repeat head CTA and cerebral angiogram, which demonstrated the presence of an aneurysm on the proximal portion of an AICA-PICA anatomical variant. This was treated with an endovascular approach that included flow diversion via a PED equipped with Shield Technology. The patient’s post-procedure period was uneventful, and he was discharged home after two days with an intact neurological status. The patient is still asymptomatic after a 7-month follow-up, with MR angiogram evidence of stable aneurysm obliteration and no ischemic lesions.Aneurysms of the AICA-PICA common trunk variants have a high morbidity risk due to the importance and extent of the territory vascularized by a single vessel. Endovascular treatment with flow diversion proved to be both safe and effective in obliterating unruptured cases.

Medical complications in peripartum patients are uncommon. Often, these patients are transferred to tertiary care centers, but their conditions and outcomes are not well understood. Our study examined peripartum patients transferred to an intensive care unit (ICU) at an academic quaternary center. Methods: We reviewed charts of adult, non-trauma, interhospital transfer (IHT) peripartum patients sent to an academic quaternary ICU between January 2017 and December 2021. We conducted a descriptive analysis and used multivariable ordinal regression to examine associations of demographic and clinical factors with ICU length of stay (LOS) and hospital length of stay (HLOS). Results: Of 1,794 IHT peripartum patients, 60 (3.2%) were directly transferred to an ICU. The average was 32 years, with a median Sequential Organ Failure Assessment (SOFA) score of 3 (1–4.25) and Acute Physiology and Chronic Health Evaluation (APACHE) II score of 8 (7–12). Respiratory failure was most common (32%), followed by postpartum hemorrhage (15%) and sepsis (14%). Intubation was required for 24 (41%), and 4 (7%) needed extracorporeal membrane oxygenation. Only 1 (1.7%) died, while 45 (76.3%) were discharged. Median ICU LOS and HLOS were 5 days (212) and 8 days (5–17). High SOFA score was linked to longer HLOS, as was APACHE II. Conclusions: Transfers of critically ill peripartum patients between hospitals were rare but involved severe medical conditions. Despite this, their outcomes were generally positive. Larger studies are needed to confirm our findings.

Medical complications in peripartum patients are uncommon. Often, these patients are transferred to tertiary care centers, but their conditions and outcomes are not well understood. Our study examined peripartum patients transferred to an intensive care unit (ICU) at an academic quaternary center. Methods: We reviewed charts of adult, non-trauma, interhospital transfer (IHT) peripartum patients sent to an academic quaternary ICU between January 2017 and December 2021. We conducted a descriptive analysis and used multivariable ordinal regression to examine associations of demographic and clinical factors with ICU length of stay (LOS) and hospital length of stay (HLOS). Results: Of 1,794 IHT peripartum patients, 60 (3.2%) were directly transferred to an ICU. The average was 32 years, with a median Sequential Organ Failure Assessment (SOFA) score of 3 (1–4.25) and Acute Physiology and Chronic Health Evaluation (APACHE) II score of 8 (7–12). Respiratory failure was most common (32%), followed by postpartum hemorrhage (15%) and sepsis (14%). Intubation was required for 24 (41%), and 4 (7%) needed extracorporeal membrane oxygenation. Only 1 (1.7%) died, while 45 (76.3%) were discharged. Median ICU LOS and HLOS were 5 days (212) and 8 days (5–17). High SOFA score was linked to longer HLOS, as was APACHE II. Conclusions: Transfers of critically ill peripartum patients between hospitals were rare but involved severe medical conditions. Despite this, their outcomes were generally positive. Larger studies are needed to confirm our findings.

Medical complications in peripartum patients are uncommon. Often, these patients are transferred to tertiary care centers, but their conditions and outcomes are not well understood. Our study examined peripartum patients transferred to an intensive care unit (ICU) at an academic quaternary center. Methods: We reviewed charts of adult, non-trauma, interhospital transfer (IHT) peripartum patients sent to an academic quaternary ICU between January 2017 and December 2021. We conducted a descriptive analysis and used multivariable ordinal regression to examine associations of demographic and clinical factors with ICU length of stay (LOS) and hospital length of stay (HLOS). Results: Of 1,794 IHT peripartum patients, 60 (3.2%) were directly transferred to an ICU. The average was 32 years, with a median Sequential Organ Failure Assessment (SOFA) score of 3 (1–4.25) and Acute Physiology and Chronic Health Evaluation (APACHE) II score of 8 (7–12). Respiratory failure was most common (32%), followed by postpartum hemorrhage (15%) and sepsis (14%). Intubation was required for 24 (41%), and 4 (7%) needed extracorporeal membrane oxygenation. Only 1 (1.7%) died, while 45 (76.3%) were discharged. Median ICU LOS and HLOS were 5 days (212) and 8 days (5–17). High SOFA score was linked to longer HLOS, as was APACHE II. Conclusions: Transfers of critically ill peripartum patients between hospitals were rare but involved severe medical conditions. Despite this, their outcomes were generally positive. Larger studies are needed to confirm our findings.

Medical complications in peripartum patients are uncommon. Often, these patients are transferred to tertiary care centers, but their conditions and outcomes are not well understood. Our study examined peripartum patients transferred to an intensive care unit (ICU) at an academic quaternary center. Methods: We reviewed charts of adult, non-trauma, interhospital transfer (IHT) peripartum patients sent to an academic quaternary ICU between January 2017 and December 2021. We conducted a descriptive analysis and used multivariable ordinal regression to examine associations of demographic and clinical factors with ICU length of stay (LOS) and hospital length of stay (HLOS). Results: Of 1,794 IHT peripartum patients, 60 (3.2%) were directly transferred to an ICU. The average was 32 years, with a median Sequential Organ Failure Assessment (SOFA) score of 3 (1–4.25) and Acute Physiology and Chronic Health Evaluation (APACHE) II score of 8 (7–12). Respiratory failure was most common (32%), followed by postpartum hemorrhage (15%) and sepsis (14%). Intubation was required for 24 (41%), and 4 (7%) needed extracorporeal membrane oxygenation. Only 1 (1.7%) died, while 45 (76.3%) were discharged. Median ICU LOS and HLOS were 5 days (212) and 8 days (5–17). High SOFA score was linked to longer HLOS, as was APACHE II. Conclusions: Transfers of critically ill peripartum patients between hospitals were rare but involved severe medical conditions. Despite this, their outcomes were generally positive. Larger studies are needed to confirm our findings.

Objective: Stroke is the second-leading cause of death globally. Intracranial atherosclerotic stenosis (ICAS) represents 10-15% of ischemic strokes in Western countries and up to 47% in Asian countries. Patients with ICAS have an especially high risk of stroke recurrence. The aim of this meta-analysis is to reassess recurrent stroke, transient ischemic attack (TIA), and other outcomes with stenting versus best medical management for symptomatic ICAS. Methods: The search protocol was developed a priori according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The OVID Medline, Embase, Web of Science, and Cochrane Library databases were searched from inception to August 14th, 2022. Results: This Meta-analysis Included Four Randomized Controlled Trials (Rcts), With A Total Number Of 991 Patients. The Mean Age Of Participants Was 57 Years. The Total Number Of Intracranial Stenting Patients Was 495, And The Number Of Medical Treatment Patients Was 496. The Included Studies Were Published Between 2011 And 2022. Two Studies Were Conducted In The Usa, And The Other Two In China. All Included Studies Compared Intracranial Stenting To Medical Treatment For Icas. Conclusions In patients with ischemic stroke due to symptomatic severe intracranial atherosclerosis, the rate of 30-day ischemic stroke, 30-day intracerebral hemorrhage, one-year stroke in territory or mortality favored the medical treatment alone without intracranial stenting. The risk of same-territory stroke at last follow-up, disabling stroke at last follow-up, and mortality did not significantly favor either group. Intracranial stenting for atherosclerosis did not result in significant benefit over medical treatment.

Aged ; Cholecystectomy, Laparoscopic ; methods ; Cholelithiasis ; complications ; diagnosis ; surgery ; Clinical Laboratory Techniques ; Coronavirus Infections ; complications ; diagnosis ; Elective Surgical Procedures ; methods ; Follow-Up Studies ; Humans ; Infection Control ; methods ; Male ; Pandemics ; Patient Safety ; Pneumonia, Viral ; complications ; diagnosis ; Postoperative Care ; methods ; Risk Assessment ; Singapore ; Treatment Outcome

INTRODUCTION: Pregnant women are reported to be at increased risk of severe coronavirus disease 2019 (COVID-19) due to underlying immunosuppression during pregnancy. However, the clinical course of COVID-19 in pregnancy and risk of vertical and horizontal transmission remain relatively unknown. We aim to describe and evaluate outcomes in pregnant women with COVID-19 in Singapore. METHODS: Prospective observational study of 16 pregnant patients admitted for COVID-19 to 4 tertiary hospitals in Singapore. Outcomes included severe disease, pregnancy loss, and vertical and horizontal transmission. RESULTS: Of the 16 patients, 37.5%, 43.8% and 18.7% were infected in the first, second and third trimesters, respectively. Two gravidas aged ≥35 years (12.5%) developed severe pneumonia; one patient (body mass index 32.9kg/m2) required transfer to intensive care. The median duration of acute infection was 19 days; one patient remained reverse transcription polymerase chain reaction (RT-PCR) positive >11 weeks from diagnosis. There were no maternal mortalities. Five pregnancies produced term live-births while 2 spontaneous miscarriages occurred at 11 and 23 weeks. RT-PCR of breast milk and maternal and neonatal samples taken at birth were negative; placenta and cord histology showed non-specific inflammation; and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific immunoglobulins were elevated in paired maternal and umbilical cord blood (n=5). CONCLUSION The majority of COVID-19 infected pregnant women had mild disease and only 2 women with risk factors (obesity, older age) had severe infection; this represents a slightly higher incidence than observed in age-matched non-pregnant women. Among the women who delivered, there was no definitive evidence of mother-to-child transmission via breast milk or placenta.
Abortion, Spontaneous/epidemiology* ; Adult ; COVID-19/transmission* ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; Cohort Studies ; Disease Transmission, Infectious/statistics & numerical data* ; Female ; Fetal Blood/immunology* ; Humans ; Infectious Disease Transmission, Vertical/statistics & numerical data* ; Live Birth/epidemiology* ; Maternal Age ; Milk, Human/virology* ; Obesity, Maternal/epidemiology* ; Placenta/pathology* ; Pregnancy ; Pregnancy Complications, Infectious/physiopathology* ; Pregnancy Outcome/epidemiology* ; Pregnancy Trimester, First ; Pregnancy Trimester, Second ; Prospective Studies ; RNA, Viral/analysis* ; Risk Factors ; SARS-CoV-2 ; Severity of Illness Index ; Singapore/epidemiology* ; Umbilical Cord/pathology* ; Young Adult