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Background: Due to the risk of cerebral vascular injury, children and adolescents with high-risk sickle cell disease (SCD) experience neurocognitive decline over time. Haploidentical stem cell transplantation (HISCT) from human leukocyte antigen-matched sibling donors may slow or stop progression of neurocognitive changes. Objectives: The study is to determine if HISCT can ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression, determine which specific areas of neurocognitive functioning are particularly vulnerable to SCD, and determine if there are age-related differences in neurocognitive functioning over time. Methods: We performed neurocognitive and neuroimaging in SCD recipients following HISCT. Children and adolescents with high-risk SCD who received parental HISCT utilizing CD34+ enrichment and mononuclear cell (T-cell) addback following myeloimmunoablative conditioning received cognitive evaluations and neuroimaging at three time points: pre-transplant, 1 and 2 years post-transplant. Results: Nineteen participants (13.1 ± 1.2 years [3.3-20.0]) received HISCT. At 2 years post-transplant, neuroimaging and cognitive function were stable. Regarding age-related differences pre-transplantation, older children (≥13 years) had already experienced significant decreases in language functioning (p < 0.023), verbal intelligence quotient (p < 0.05), non-verbal intelligence quotient (p < 0.006), and processing speed (p < 0.05), but normalized post-HISCT in all categories. Conclusion: Thus, HISCT has the potential to ameliorate SCD-associated neurocognitive changes and prevent neurocognitive progression. Further studies are required to determine if neurocognitive performance remains stable beyond 2 years post-HISCT.Clinical trial registration: The study was conducted under an investigator IND (14359) (MSC) and registered at clinicaltrials.gov (NCT01461837).
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Cytomegalovirus (CMV) reactivation is a major cause of morbidity and nonrelapse mortality (NRM) in pediatric allogeneic stem cell transplantation (alloSCT) recipients. Approximately 80% of CMV seropositive alloHCT recipients will experience CMV reactivation without prophylaxis. The impacts of ganciclovir prophylaxis and subsequent CMV viremia on 1-year survival and 1-year NRM are unknown. The primary objective of this study was to determine the effect of CMV viremia on the probability of 1-year survival and 1-year NRM in pediatric alloSCT recipients receiving 100 days of ganciclovir prophylaxis. The secondary objective was to determine the effect of other risk factors on 1-year survival and 1-year NRM. All patients age 0 to 26 years who underwent alloSCT between June 2011 and May 2020 and received ganciclovir prophylaxis for 100 days at Westchester Medical Center, an academic medical center, were analyzed. Ganciclovir was administered to at-risk alloSCT recipients (donor and or recipient CMV+ serostatus) as 5 mg/kg every 12 hours from the first day of conditioning through day -1 (recipient CMV+ only) followed by 6 mg/kg every 24 hours on Monday through Friday beginning on the day of an absolute neutrophil count >750/mm3 and continuing through day +100. National Cancer Institute Common Terminology Criteria for Adverse Events 5.0 criteria were used to grade toxicity. NRM was analyzed using competing survival analysis with relapse death as a competing event. The log-rank and Gray tests were performed to compare the 1-year survival probabilities and NRM cumulative incidence between patients who experienced CMV viremia post-alloSCT and those who did not. Univariate Cox regression analysis was performed for the following risk factors: CMV viremia, donor source, sex, malignant disease, disease risk index, conditioning intensity, receipt of rabbit antithymocyte globulin (rATG)/alemtuzumab, graft-versus-host disease (GVHD) prophylaxis, CMV donor/recipient serostatus, grade II-IV acute GVHD, and grade 3/4 neutropenia necessitating discontinuation of ganciclovir, treating the last 3 factors as time-dependent covariates. Those with P values < .2 were included in the multivariate Cox regression analysis. Eighty-four alloSCT recipients (41 males, 43 females; median age, 10.8 years [range, .4 to 24.4 years]) were analyzed. Multivariate analysis showed significantly lower 1-year survival and significantly higher 1-year NRM in patients who developed CMV viremia compared to those who did not (P = .0036). No other risk factors were significantly associated with 1-year survival or 1-year NRM. One-year survival was significantly decreased and 1-year NRM was significantly increased in pediatric alloSCT recipients who developed CMV viremia following ganciclovir prophylaxis. No other risk factors were found to be associated with 1-year survival or 1-year NRM. Alternative CMV prophylaxis regimens that reduce CMV viremia should be investigated in pediatric alloSCT recipients at risk for CMV infection.
Subject(s)
Cytomegalovirus Infections , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Male , Female , Humans , Child , Infant, Newborn , Ganciclovir/therapeutic use , Cytomegalovirus/physiology , Viremia/prevention & control , Viremia/drug therapy , Viremia/etiology , Transplantation, Homologous/adverse effects , Cytomegalovirus Infections/prevention & control , Risk Factors , Hematopoietic Stem Cell Transplantation/adverse effects , Graft vs Host Disease/prevention & controlABSTRACT
Objectives: The risk factors for anastomotic leak (AL) after resection and primary anastomosis for traumatic bucket handle injury (BHI) have not been previously defined. This multicenter study was conducted to address this knowledge gap. Methods: This is a multicenter retrospective study on small intestine and colonic BHIs from blunt trauma between 2010 and 2021. Baseline patient characteristics, risk factors, presence of shock and transfusion, operative details, and clinical outcomes were compared using R. Results: Data on 395 subjects were submitted by 12 trauma centers, of whom 33 (8.1%) patients developed AL. Baseline details were similar, except for a higher proportion of patients in the AL group who had medical comorbidities such as diabetes, hypertension, and obesity (60.6% vs. 37.3%, p=0.015). AL had higher rates of surgical site infections (13.4% vs. 5.3%, p=0.004) and organ space infections (65.2% vs. 11.7%, p<0.001), along with higher readmission and reoperation rates (48.4% vs. 9.1%, p<0.001, and 39.4% vs. 11.6%, p<0.001, respectively). There was no difference in intensive care unit length of stay or mortality (p>0.05). More patients with AL were discharged with an ostomy (69.7% vs. 7.3%, p<0.001), and the mean duration until ostomy reversal was 5.85±3 months (range 2-12.4 months). The risk of AL significantly increased when the initial operation was a damage control procedure, after adjusting for age, sex, injury severity, presence of one or more comorbidities, shock, transfusion of >6 units of packed red blood cells, and site of injury (adjusted RR=2.32 (1.13, 5.17)), none of which were independent risk factors in themselves. Conclusion: Damage control surgery performed as the initial operation appears to double the risk of AL after intestinal BHI, even after controlling for other markers of injury severity. Level of evidence: III.
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BACKGROUND: Primary aim was to assess the relative risk (RR) of anastomotic leak (AL) in intestinal bucket-handle (BH) compared to non-BH injury. METHODS: Multi-center study comparing AL in BH from blunt trauma 2010-2021 compared to non-BH intestinal injuries. RR was calculated for small bowel and colonic injury using R. RESULTS: AL occurred in 20/385 (5.2%) of BH vs. 4/225 (1.8%) of non-BH small intestine injury. AL was diagnosed 11.6 ± 5.6 days from index operation in small intestine BH and 9.7 ± 4.3 days in colonic BH. Adjusted RR for AL was 2.32 [0.77-6.95] for small intestinal and 4.83 [1.47-15.89] for colonic injuries. AL increased infections, ventilator days, ICU & total length of stay, reoperation, and readmission rates, although mortality was unchanged. CONCLUSION: BH carries a significantly higher risk of AL, particularly in the colon, than other blunt intestinal injuries.
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Abdominal Injuries , Wounds, Nonpenetrating , Humans , Anastomotic Leak/epidemiology , Anastomotic Leak/etiology , Retrospective Studies , Colon/surgery , Colon/injuries , Intestines/injuries , Wounds, Nonpenetrating/surgery , Abdominal Injuries/surgery , Anastomosis, SurgicalABSTRACT
Altered body composition in preterm infants is associated with risks to cognitive development, but the effect specific to prefrontal cortex (PFC) development is unknown. We were interested in the impact of fat mass (FM) and fat free mass (FFM) gains out to 4 months corrected gestational age (CGA) on PFC development, as indexed by working memory and temperament. This is a prospective observational pilot study recruiting 100 preterm (<33 weeks gestation), appropriate for gestational age, and very low birth weight infants, of which 49 infants met inclusion criteria. Body composition was measured using air displacement plethysmography at hospital discharge and 4 months CGA. Questionnaire based temperament assessments were completed at 12 and 24 months CGA and a working memory assessment was completed at 24 months CGA. Associations between developmental tests and body composition obtained at term and 4 months were analyzed. Increased FM at discharge was associated with increased fear and decreased soothability at 12 months. Increased FM at 4 months was associated with increased activity level, increased distress from limitations at 12 months and decreased attentional shifting, decreased frustration, and decreased inhibitory control at 24 months. Increased FFM at 4 months was associated with increased activity level at 12 months and increased impulsivity and decreased low intensity pleasure at 24 months. In this exploratory pilot study, increased FM out to 4 months and increased FFM after discharge are associated with negative markers of infant temperament. Infant temperament may be sensitive to body composition status at least to 4 months CGA.
Subject(s)
Infant, Premature , Memory, Short-Term , Infant , Infant, Newborn , Humans , Pilot Projects , Temperament , Body CompositionABSTRACT
Incidental appendectomy (IA) is sometimes performed in patients undergoing abdominal operations to prevent subsequent development of appendicitis. Patients who undergo laparotomy for major abdominal trauma are at high risk of developing dense adhesions, increasing the risk of future operations. Therefore, there is a potential benefit to IA for patients undergoing trauma laparotomy. We performed a retrospective review of patients who underwent IA during laparotomy for abdominal trauma at a Level 1 trauma center between January 2010, and June 2020. Twenty-three patients underwent IA; they tended to be young (33.7 ± 18.9 years) and male (87%) with 12 penetrating and 11 blunt injuries. Regarding indications, 13 had no documented intra-operative abnormalities of the appendix, 6 patients had a fecalith, and 3 had trauma to the appendix. One patient's appendix was adhered to the peritoneum and one patient had unusual anatomic location. Only one patient developed an appendiceal stump leak after IA.
Subject(s)
Abdominal Injuries , Appendicitis , Appendix , Humans , Male , Appendectomy , Laparotomy , Appendix/surgery , Appendicitis/complications , Appendicitis/surgery , Abdominal Injuries/complications , Abdominal Injuries/surgery , Retrospective StudiesSubject(s)
Hematopoietic Stem Cell Transplantation , Lymphoma, Non-Hodgkin , Humans , Child , Young Adult , Adolescent , Transplantation, Autologous , Hematopoietic Stem Cell Transplantation/adverse effects , Neoplasm Recurrence, Local , Lymphoma, Non-Hodgkin/therapy , Immunotherapy/adverse effects , Transplantation Conditioning , Stem Cell TransplantationABSTRACT
Introduction: We previously reported the initial results of a phase II multicenter transplant trial using haploidentical parental donors for children and aolescents with high-risk sickle cell disease achieving excellent survival with exceptionally low rates of graft-versus-host disease and resolution of sickle cell disease symptoms. To investigate human leukocyte antigen (HLA) sensitization, graft characteristics, donor chimerism, and immune reconstitution in these recipients. Methods: CD34 cells were enriched using the CliniMACS® system with a target dose of 10 x 106 CD34+ cells/kg with a peripheral blood mononuclear cell (PBMNC) addback dose of 2x105 CD3/kg in the final product. Pre-transplant HLA antibodies were characterized. Donor chimerism was monitored 1-24 months post-transplant. Comprehensive assessment of immune reconstitution included lymphocyte subsets, plasma cytokines, complement levels, anti-viral T-cell responses, activation markers, and cytokine production. Infections were monitored. Results: HLA antibodies were detected in 7 of 11 (64%) evaluable patients but rarely were against donor antigens. Myeloid engraftment was rapid (100%) at a median of 9 days. At 30 days, donor chimerism was 93-99% and natural killer cell levels were restored. By 60 days, CD19 B cells were normal. CD8 and CD4 T-cells levels were normal by 279 and 365 days, respectively. Activated CD4 and CD8 T-cells were elevated at 100-365 days post-transplant while naïve cells remained below baseline. Tregs were elevated at 100-270 days post-transplant, returning to baseline levels at one year. At one year, C3 and C4 levels were above baseline and CH50 levels were near baseline. At one year, cytokine levels were not significantly different from baseline. Discussion: These results suggest that haploidentical transplantation with CD34-enriched cells and peripheral blood mononuclear cell addback results in rapid engraftment, sustained donor chimerism and broad-based immune reconstitution.
Subject(s)
Anemia, Sickle Cell , Hematopoietic Stem Cell Transplantation , Immune Reconstitution , Child , Humans , Transplantation, Haploidentical , Hematopoietic Stem Cell Transplantation/methods , Leukocytes, Mononuclear , Chimerism , Anemia, Sickle Cell/therapy , CytokinesABSTRACT
Retrospective studies indicate that the parenteral provision of calories, proteins, and lipids in the first week of life is associated with improved later neurodevelopment. We aimed to determine whether infants randomized to an enhanced parenteral nutrition protocol had improved developmental outcomes at 4, 12, or 24 months corrected age (CA). In total, 90 preterm infants (<32 weeks gestational age and <1500 g) were randomized to receive enhanced parenteral nutrition (PN) or standard PN during the first week of life. The enhanced group received a higher glucose infusion rate and intralipids. Neurodevelopmental outcomes included pattern-reversal visually evoked potentials (VEP) at 4 months CA (n = 33) and the Bayley Scales of Infant Development (BSID) at 12 (n = 46) and 24 (n = 29) months CA. P100 latency was longer in the intervention group, indicating slower processing speed (145 vs. 178 ms, p = 0.01). This association did not hold in multivariable analysis adjusting for potentially confounding variables. BSID scores were not associated with enhanced PN. Higher enteral energy and protein intake regardless of randomization group were associated with faster processing speed at 4 months CA (p ≤ 0.02 for both). Enhanced early PN was not associated with improved neurodevelopment; however, first-week enteral caloric and protein intake were associated with improved speed of processing.
Subject(s)
Infant, Premature , Parenteral Nutrition , Child , Glucose , Humans , Infant , Infant, Newborn , Lipids , Parenteral Nutrition/methods , Retrospective StudiesABSTRACT
Objectives: Multiple temporary abdominal closure (TAC) techniques are currently used to manage the open abdomen (OA) in severely injured trauma patients, with variability in efficacy and cost. We evaluated the clinical outcomes of two commonly used TAC methods: ABTHERA Negative Pressure Therapy System and whipstitch suture closure (WC). Methods: We conducted a retrospective review of patients who had blunt or penetrating trauma from 2015 to 2021 with OA managed using either ABTHERA, WC, or both. Primary outcomes included overall and intensive care unit length of stay, ventilator days, number of laparotomies, time to definitive fascial closure, and complications (bleeding, evisceration, wound dehiscence, and reoperation). Univariate and multivariate analyses were used to compare baseline characteristics, outcomes, and complications. Potential mediators of the relationship between the type of TAC and outcomes were explored using mediation analyses. Results: A total of 112 TAC were analyzed; 86 patients had a single type of TAC placement (either WC or ABTHERA), whereas 26 had both types. A majority of patients had blunt trauma in both WC (77%) and ABTHERA (76%) cohorts. There were no differences in baseline characteristics, including injury severity (27.5±12.4 and 27.5±12.0 for ABTHERA and WC, respectively). There was no statistically significant difference among individual complications and overall complications (OR=0.622 (0.274 to 1.412)). No differences were found between the outcomes, and any apparent differences seen were mediated by factors such as a higher number of laparotomies. Conclusion: WC is a low-cost option for TAC in trauma, with similar clinical outcomes and complications to ABTHERA. Level of evidence: Level III therapeutic/care management study.
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Background: Frequency, microbiology, and outcomes of necrotizing soft tissue infections (NSTIs) could vary across the United States because of differences in locoregional and environmental factors. We synthesized the literature from across the regions of the United States on NSTIs in a systematic review/meta-analysis. Methods: PubMed, ProQuest, Scopus, and Web of Science databases were systematically searched and screened. DerSimonian-Laird random-effects meta-analyses were performed using 'meta' package in R to determine pooled prevalences. Meta-regression analyses examined moderator effects of risk factors. Results: Twenty-seven studies (2,242 total patients) were included. Pooled prevalences of polymicrobial and monomicrobial infections were 52.2% and 39.9%, respectively. The prevalence of monomicrobial NSTIs increased over the last two decades (p = 0.018), whereas polymicrobial infections declined (p = 0.003). Meta-regression analysis showed that most polymicrobial NSTIs were Fournier gangrene (p < 0.001), whereas monomicrobial NSTIs mostly affected extremities (p < 0.001). Staphylococcus aureus was the most common organism isolated (predominantly in the South), followed by Bacteroides spp. (predominately in the East) and Streptococcus pyogenes. Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 11.9% of NSTIs, mainly in the South. The overall mortality rate was 17.8% and declined over last two decades (p < 0.001), with the lowest rate reported in the last decade at 13% without any regional differences. Conclusions: Advancement in the management of NSTIs may have contributed to the observed decline in NSTI-related mortality in the United States. However, the proportion of monomicrobial NSTIs seems to be increasing, possibly because of increased comorbidities affecting extremities. Causative organisms varied by region. Multi-center observational studies are warranted to confirm our observations.
Subject(s)
Coinfection , Fasciitis, Necrotizing , Fournier Gangrene , Methicillin-Resistant Staphylococcus aureus , Soft Tissue Infections , Coinfection/epidemiology , Coinfection/microbiology , Fasciitis, Necrotizing/epidemiology , Humans , Male , Retrospective Studies , Soft Tissue Infections/microbiology , Streptococcus pyogenesABSTRACT
STUDY OBJECTIVES: To examine current evidence of the relationship between sleep and pain from the neonatal period through adolescence. This review serves as a critical review of the literature and of the needs for future research on pediatric sleep and pain. METHODS: The PubMed online database was queried from January 1, 1960, to March 1, 2020, producing 149 articles applicable to pain and sleep in the pediatric population. Of those, 97 articles were cited in this review with the key articles including over 3800 participants. RESULTS: The pediatric literature supports the relationship between poor sleep (both sleep efficiency and nighttime awakenings) and subsequent risk for pain, especially among children with chronic disease. The reverse effect of pain on sleep is not yet well delineated. The key moderating factors explored in the literature are pharmacologic and nonpharmacologic therapies, psychologic health, and the etiology of pain. There is evidence that both altered sleep and pain early in life impact neurodevelopment, as seen by changes in sleep structure in clinical studies and alterations in brain development in animal models. CONCLUSIONS: The complicated relationship between sleep and pain is critically important during pediatric development when alterations to a normal sleep structure can have a lifelong impact. It is becoming clear that sleep deprivation and poor sleep quality exacerbate pain. Further research is needed into the complex alterations of sleep in chronic pain conditions as well as treatments to improve sleep in pediatric care. CITATION: Morris EE, Howell MJ, Pickup E, Iber C, Wang SG. Pediatric sleep and pain: etiologies, consequences, and clinical considerations. J Clin Sleep Med. 2022;18(9):2281-2289.
Subject(s)
Chronic Pain , Sleep Initiation and Maintenance Disorders , Animals , Child , Chronic Pain/etiology , Chronic Pain/psychology , Chronic Pain/therapy , Humans , Pain Measurement , SleepABSTRACT
Allogeneic stem cell transplantation (AlloSCT) represents the only curative therapy for sickle cell disease (SCD). However, limited availability of matched related donors and suboptimal outcomes following AlloSCT with unrelated donors has led to investigation of alternative donors. Among children with high-risk SCD, we evaluated health-related quality of life (HRQoL) impact in the two years following familial haploidentical SCT. HRQoL was collected from parent and child raters, using the Child Health Ratings Inventories Generic measure and haploidentical SCT-specific module. Repeated measures models were fit to assess HRQoL changes over time and by rater. Nineteen children (mean age 12.9 yrs [standard deviation, 5.3]; 63% male) and their parents were included. There were no differences in the 2-yr trajectories of child physical or emotional functioning (EF) by rater. Child physical functioning and EF scores were significantly lower at day +45 than baseline, but scores recovered by day +180. There was significant improvement in EF (p = 0.03) at 2 yrs vs baseline. A similar pattern of scores over time was seen for parent ratings of child's global HRQoL. Despite treatment intensity in the initial months following AlloSCT, patient scores recovered or exceeded baseline scores at two years. This trial is registered at clinicaltrials.gov (NCT01461837).
Subject(s)
Anemia, Sickle Cell , Hematopoietic Stem Cell Transplantation , Anemia, Sickle Cell/therapy , Child , Female , Humans , Male , Parents/psychology , Quality of Life/psychology , Stem Cell TransplantationABSTRACT
OBJECTIVE: Neonatal opioid withdrawal syndrome (NOWS) describes infants' withdrawal signs and symptoms after birth due to an interruption of prenatal opioid exposure. Many infants with NOWS are also exposed to nonopioids, however. This study was to determine hospital outcomes of infants exposed to opioids alone or coexposed with nonopioid substances (polysubstance). STUDY DESIGN: We reviewed infants of ≥34 weeks of gestation with prenatal opioid exposure from April 2015 to May 2018. We compared the median lengths of stay (LOS) and treatment (LOT) and the percentages of infants requiring pharmacologic and adjunctive treatment in infants exposed to opioids alone or polysubstance. We used Wilcoxon's test for continuous outcomes or Chi-squared test for categorical outcomes to determine statistical significance. We used multivariable regression model to calculate each drug category's estimates of adjusted mean ratios for LOS and LOT plus estimates of adjusted odds ratios for pharmacologic/adjunctive treatments. RESULTS: Of the 175 infants, 33 (19%) infants had opioid exposure alone. Opioid exposure included short- and/or long-acting opioids. A total of 142 (81%) had polysubstance exposure with 47% of mothers using nicotine products. We saw similar hospital outcomes between infants exposed to opioids alone or polysubstance; however, a higher percentage of infants with both short- and long-acting opioid exposure required pharmacologic treatment compared with either opioid alone. Focusing on individual drug categories, we detected differential hospital outcomes in which short-acting opioids decreased LOT, whereas long-acting opioids increased LOS, LOT, and need for pharmacologic and adjunctive treatment. Coexposure of opioids with stimulants decreased LOT and reduced need for adjunctive treatment. Coexposures with antidepressants increased LOT, while with antiepilepetics increased LOS. CONCLUSION: Because infants with NOWS often have coexposures to other nonopioid substances, appreciating the associated risks of individual or combination of drugs in modulating hospital outcomes may help counsel families on their infants' expected hospital course. KEY POINTS: · Hospital outcomes were similar between infants exposed to opioids alone or polysubstance including opioids.. · Infants with short- and long-acting opioids required pharmacologic treatment more often than either opioid alone.. · Differential hospital outcomes exist for various co-exposures of opioids with nonopioids..
Subject(s)
Analgesics, Non-Narcotic , Neonatal Abstinence Syndrome , Opioid-Related Disorders , Analgesics, Non-Narcotic/therapeutic use , Analgesics, Opioid/adverse effects , Female , Humans , Infant , Infant, Newborn , Length of Stay , Mothers , Neonatal Abstinence Syndrome/diagnosis , Neonatal Abstinence Syndrome/drug therapy , Neonatal Abstinence Syndrome/epidemiology , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/epidemiology , Pregnancy , Tertiary Care CentersABSTRACT
OBJECTIVES: To investigate the association between pre-pregnancy subclinical insulin resistance and cardiovascular dysfunction in healthy nulliparous women, and with hypertension in subsequent pregnancy. STUDY DESIGN: Secondary analysis of a single center prospective observational study conducted November 2011-June 2014. Healthy nulliparous women underwent detailed cardiovascular and metabolic assessment. Insulin resistance was determined by homeostasis model assessment (HOMA-IR). Associations of HOMA-IR with metabolic and cardiovascular measurements were assessed with Spearman correlations. Charts were reviewed in women who conceived singleton pregnancies. MAIN OUTCOME MEASURES: Metabolic measurements included serum glucose, insulin, creatinine, CRP, and lipids. HOMA-IR was calculated using fasting serum insulin and glucose. Indices of cardiovascular stiffness were determined from pulse wave velocity and response to volume challenge. Pregnancy outcomes included delivery mode and gestational age, birthweight, and hypertension. RESULTS: HOMA-IR was positively associated with BMI (r = 0.462, p < 0.001), body fat percentile (r = 0.463, p < 0.001), CRP (r = 0.364, p = 0.003), and negatively associated with serum HDL (r = -0.38, p = 0.002) and creatinine (r = -0.242, p = 0.049). HOMA-IR was positively associated with blood pressure (r = 0.347, p = 0.004), resting heart rate (r = 0.433, p = <0.001), response to volume challenge (r = 0.325, p < 0.01). Increased HOMA-IR was associated with a faster cardiac ejection time in response to volume challenge (r = -0.415, p < 0.001), which is a marker of decreased cardiac compliance to volume increase, or cardiac stiffness. CONCLUSION: HOMA-IR is associated with pre-pregnancy cardiac stiffness. Cholesterol was not associated with cardiovascular dysfunction. A non-significant trend was observed between HOMA-IR and hypertension in subsequent pregnancy.
Subject(s)
Insulin Resistance , Pre-Eclampsia/epidemiology , Adult , Biomarkers/blood , Cardiometabolic Risk Factors , Female , Humans , Pregnancy , Prospective StudiesABSTRACT
BACKGROUND: Frequency, microbiology, and outcomes of necrotizing soft tissue infections vary based on locoregional and environmental factors; however, there has been no global survey of these patterns. We performed a systematic review/meta-analysis on published reports of necrotizing soft tissue infections from across the globe. METHODS: Peer-reviewed empirical studies examining rates of polymicrobial and monomicrobial necrotizing soft tissue infections with microbial isolation and overall mortality rate were extracted along with geographic location using PubMed, Scopus, ProQuest, and Web of Science. Random-effects meta-analyses and sensitivity analyses were performed, adjusting for publication bias. Meta-regression analyses examined moderator effects of risk factors. RESULTS: One hundred and five studies (8,718 total patients) were included. Pooled prevalence of polymicrobial and monomicrobial infections were 53% and 37.9%, respectively. Truncal necrotizing soft tissue infections were commonly polymicrobial (P < .001), whereas monomicrobial infections prevailed in extremities (P = .008). Global prevalence of monomicrobial necrotizing soft tissue infections was observed to increase by 1.1% annually (P = .003). Staphylococcus aureus was the most common organism globally and in North America, Asia, the Middle East, and Africa, followed by Streptococcus pyogenes and Escherichia coli. Methicillin-resistant S. aureus accounted for 16% of necrotizing soft tissue infections globally. Overall mortality was 23.1%, observed to decline globally over the last decade (P = .020). No regional differences were noted for mortality. CONCLUSION: Although polymicrobial infections remain predominant worldwide, the incidence of monomicrobial infections is increasing. The observed decline in necrotizing soft tissue infection-related mortality is encouraging and may reflect advances in management, despite major variations in available healthcare resources globally.
Subject(s)
Coinfection/epidemiology , Escherichia coli Infections/epidemiology , Soft Tissue Infections/epidemiology , Staphylococcal Infections/epidemiology , Streptococcal Infections/epidemiology , Coinfection/diagnosis , Coinfection/microbiology , Coinfection/therapy , Escherichia coli/isolation & purification , Escherichia coli Infections/diagnosis , Escherichia coli Infections/microbiology , Escherichia coli Infections/therapy , Global Burden of Disease/trends , Humans , Incidence , Mortality/trends , Necrosis/epidemiology , Necrosis/microbiology , Necrosis/therapy , Soft Tissue Infections/diagnosis , Soft Tissue Infections/microbiology , Soft Tissue Infections/therapy , Staphylococcal Infections/diagnosis , Staphylococcal Infections/microbiology , Staphylococcal Infections/therapy , Staphylococcus aureus/isolation & purification , Streptococcal Infections/diagnosis , Streptococcal Infections/microbiology , Streptococcal Infections/therapy , Streptococcus pyogenes/isolation & purification , Treatment OutcomeABSTRACT
Children with sickle cell disease (SCD) are at high-risk of progressive, chronic pulmonary and cardiac dysfunction. In this prospective multicenter Phase II trial of myeloimmunoablative conditioning followed by haploidentical stem cell transplantation in children with high-risk SCD, 19 patients, 2.0-21.0 years of age, were enrolled with one or more of the following: history of (1) overt stroke; (2) silent stroke; (3) elevated transcranial Doppler velocity; (4) multiple vaso-occlusive crises; and/or (5) two or more acute chest syndromes and received haploidentical transplants from 18 parental donors. Cardiac and pulmonary centralized cores were established. Pulmonary function results were expressed as percent of the median of healthy reference cohorts, matched for age, sex, height and race. At 2 years, pulmonary functions including forced expiratory volume (FEV), FEV1/ forced vital capacity (FVC), total lung capacity (TLC), diffusing capacity of lung for carbon monoxide (DLCO) were stable to improved compared to baseline values. Importantly, specific airway conductance was significantly improved at 2 years (p < 0.004). Left ventricular systolic function (fractional shortening) and tricuspid regurgitant velocity were stable at 2 years. These results demonstrate that haploidentical stem cell transplantation can stabilize or improve cardiopulmonary function in patients with SCD.
Subject(s)
Anemia, Sickle Cell , Hematopoietic Stem Cell Transplantation , Anemia, Sickle Cell/therapy , Child , Humans , Lung , Prospective Studies , Vital CapacityABSTRACT
Disseminated herpes simplex virus 2 (HSV-2) infection, is a rare but devastating infection in pregnancy women. We present the case of a 30-year-old gravida 3, para 2-0-0-2, at 26 weeks 2 days gestation who presented with eleven days of vague and indolent symptoms before a diagnosis of disseminated HSV-2 infection with associated hepatitis was made. While the patient clinically improved with empiric acyclovir treatment, possibility of significant harm to the fetus remained, and the patient request elective termination. The authors review the epidemiology, diagnosis, treatment, and prognosis of disseminated HSV-2 infection in pregnancy.
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