Recurrent glioblastoma multiforme (rGBM) has a grim prognosis, with current therapies offering no survival benefit. Several combination therapies involving anti-VEGF agents have been studied with mixed results. A systematic search was performed using five electronic databases: PubMed, Scopus, ISI, Embase, and the Cochrane Library, without language limitations. The primary outcome of interest was progression-free survival (PFS). Secondary outcomes were overall survival (OS), objective response ratio (ORR), and grade ≥ 3 adverse events. Estimates for PFS and OS were calculated as random effects hazard ratio (HR) with 95% confidence intervals (CIs) using the generic inverse variance method. Estimates for ORR and grade ≥ 3 adverse events were calculated using a random-effects risk ratio (RR) with 95% confidence intervals (CIs) using the Mantel-Haenszel method. Thirteen studies met the inclusion criteria and a total of 1994 patients were included in the analysis. There was no statistically significant improvement in PFS (HR 0.84; 95% CI (0.68, 1.03); I2=81%), OS (HR 0.99; 95% CI (0.88, 1.12); I2=0%), and ORR (RR 1.36; 95% CI (0.96, 1.92); I2=61%) in the combination therapy group when compared to the control group. Significantly higher grade ≥ 3 adverse events (RR 1.30; 95% CI (1.14, 1.48); I2=47%) were seen in the combination therapy when compared to the control group. Our analysis showed that the use of combination therapy with anti-VEGF agents did not offer any benefit in PFS, OS, or ORR. In contrast, it had significantly higher grade 3-5 adverse events. Further studies are needed to identify effective therapies in rGBM that can improve survival.

BackgroundStudies comparing the outcomes of bariatric surgery followed by total knee arthroplasty (TKA) versus TKA alone in obese patients have disparate results. This systematic review and meta-analysis sought to compare TKA with and without prior bariatric surgery in obese patients. MethodsMEDLINE, PubMed, and Embase were searched from inception to April 9, 2023. There were twelve included studies that yielded 2,876,547 patients, of whom 62,818 and 2,813,729 underwent TKA with and without prior bariatric surgery, respectively. Primary outcomes were medical complications (ie, urinary tract infection, pneumonia, renal failure, respiratory failure, venous thromboembolism [VTE], arrhythmia, myocardial infarction, and stroke); surgical complications (ie, wound complications [eg, infection, hematoma, dehiscence, delayed wound healing, and seroma], periprosthetic joint infection, mechanical complications, periprosthetic fracture, knee stiffness, and failed hardware); revision, and mortality. Secondary outcomes were blood transfusion, length of stay (day), and readmission. ResultsThe odds ratios (OR) of 90-day VTE (OR = 0.75 [0.66, 0.85], P < .00001), 90-day stroke (OR = 0.58 [0.41, 0.81], P = .002), and 1-year periprosthetic fracture (OR = 0.74 [0.55, 0.99], P = .04) were lower in those who underwent bariatric surgery before TKA. Although the mean difference in hospital stays (−0.19 days [−0.23, −0.15], P < .00001) was statistically less in those who underwent bariatric surgery before TKA, it was not clinically relevant. The other outcomes were similar between the groups. ConclusionsBariatric surgery before TKA is beneficial in terms of a lower risk of VTE, stroke, and periprosthetic fracture. This analysis suggests surgeons consider discussing bariatric surgery before TKA in obese patients, especially those who are at risk of VTE and stroke.

IntroductionPrior bariatric surgery (PBS) status in obese patients is thought to curtail the risk of cardiovascular events, but its role in change of outcomes of patients with obesity developing new acute cardiac events such as cardiac arrests (CA) remains largely unknown. MethodsHospitalizations among adult patients with obesity and CA were identified retrospectively using the National Inpatient Sample (2015 October-2017 December). Propensity-matched analysis (1:1) was performed for sociodemographic/hospital characteristics to identify two cohorts, with (PBS+) or without (PBS-) status. The primary endpoint was in-hospital mortality, and the secondary endpoint was healthcare resource utilization. ResultsBoth cohorts (n = 1275 each), had patients with comparable age (mean 58 years), with a higher frequency of white (>70 %), females (>60 %), and Medicare enrollees (>40 %). PBS + cohort had lower rates of diabetes (27.8 % vs 36.1 %), hyperlipidemia (33.7 % vs 48.6 %), renal failure (17.3 % vs 22.0 %), chronic pulmonary disease (11.8 % vs 21.2 %) and higher rates of anemias (18.4 % vs 12.2 %), liver disease (5.1 % vs 2.4 %) and alcohol abuse (6.7 % vs 2.4 %) than PBS- cohort (p < 0.05). All-cause mortality (46.3 % vs 45.1 %, p = 0.551) was comparable between the two cohorts. The PBS + cohort was less often transferred routinely (p<0.001) but had a shorter hospital stay (p<0.001) with equivalent hospital charges compared to the PBS- cohort. ConclusionsThe PBS status (regardless of chronology) did not increase survival in CA admissions among patients with obesity. Preventive measures are necessary to manage enduring cardiovascular disease risk factors that may limit the advantages of surgery for patients with obesity and aggravate the worse outcomes of future cardiac events.

BackgroundFunctional gallbladder disorder (FGBD) remains a controversial indication for cholecystectomy. MethodsA prospective cohort study enrolled patients strictly meeting Rome criteria for FGBD, and cholecystectomy was performed. They were assessed pre- and 3 and 6 months postoperatively with surveys of abdominal pain and quality of life (RAPID and SF-12 surveys, respectively). Interim analysis was performed. ResultsAlthough neither ejection fraction nor pain reproduction predicted success after cholecystectomy, the vast majority of enrolled patients had a successful outcome after undergoing cholecystectomy for FGBD: of a planned 100 patients, 46 were enrolled. Of 31 evaluable patients, 26 (83.9 ​%) reported RAPID improvement and 28 (93.3 ​%) SF12 improvement at 3- or 6-month follow-up. ConclusionFGBD, strictly diagnosed, should perhaps no longer be a controversial indication for cholecystectomy, since its success rate for biliary pain in this study was similar to that for symptomatic cholelithiasis. Larger-scale studies or randomized trials may confirm these findings.

Palifermin is a truncated form of human recombinant keratinocyte growth factor (KGF) that binds to the FGF receptor 2b expressed in epithelia including that of the epidermis, oral and GI mucosa, and thymus. In animal models, the cytoprotective and regenerative effects of KGF showed efficacy in controlling acute and chronic graft-versus-host disease (A/C GVHD), but these were not demonstrated in subsequent clinical studies using the FDA-approved dosing schedule for oral mucositis prevention (60 µg/kg/day for 3 consecutive days). The current study aims to investigate alterations in immune cell reconstitution and cytokine expression among patients (n=31) participating in the ongoing prospective open-label phase 1/2 trial NCT02356159. This trial evaluates the incidence of severe CGVHD (primary objective of phase 2) following the addition of a single high dose of palifermin to GVHD prophylaxis with TMS (tacrolimus, methotrexate, sirolimus). Four different dose levels of palifermin (DL1: 180 µg/kg; DL2: 360 µg/kg; DL3: 540 µg/kg; DL4: 720 µg/kg) were tested on day −7 in the phase 1 part of the trial, with the recommended phase 2 dose being 720 µg/kg. All patients received cyclophosphamide (total 4.8 g/m 2) and fludarabine (total 120 mg/m 2) as conditioning on days −6 to −3 followed by infusion of an 8/8 HLA-matched unrelated donor peripheral blood cell graft on day 0. Results of correlative studies were compared with patients of the identical TMS treatment arm of the NCT00520130 study without palifermin (n=31). In the DL4 group, a previous interim analysis revealed no cases of classic (day +100) AGVHD II-IV in 16 patients (P=0.014), whereas the TMS group showed a 22.6% (95% CI: 9.8% to 38.6%) incidence (Schulz et al. Cell Ther Transplant. 2023;29(2):S258). T, B and NK cells were routinely measured by flow cytometry at days +14, +28, +60, +100, +180, +365, +730. The V-PLEX human cytokine 36-plex kit and U-PLEX assays of human BAFF, CXCL9 and IL1RL1/ST2 (all MSD, Rockville, MD) were used to measure cytokine levels in plasma at days −8, 0, +14, +28, +60, +100. The measures at various time points were compared between two treatment groups using multiple Mann-Whitney tests, and the false discovery rate approach was applied with Q=0.05. Comparison between the four DL groups and the TMS group was performed using the Kruskal-Wallis H-test and Dunn's post-hoc test, with a significance threshold set at P&amp;lt;0.05. The statistical analyses were conducted using GraphPad Prism 9. In comparison to patients receiving TMS only, those treated with KGF exhibited reduced NK cell counts at day +28 (Q=0.0155) and increased B cell counts from day +60 (Q&amp;lt;0.01) onwards. However, there were no differences in the absolute numbers of CD3+, CD4+, and CD8+ T cells between patients from both trials. Additionally, no apparent dose-response relationship was observed. KGF-treated patients showed significantly reduced plasma levels of proinflammatory cytokines, including TNF-α at day 0, TNF-β at days 0, +14, +28, IL-12/IL23p40 at days 0 and +14, and CXCL9 at days 0 and +14, compared to patients receiving TMS only. Notably, levels of homeostatic IL-7, previously linked to AGVHD, were significantly lower in KGF-treated patients from day +28 (TMS vs. DL4, P=0.002) to +100. There was a trend towards lower levels of IL-22 at days 0 and +14 (both unadjusted P&amp;lt;0.05, Q&amp;gt;0.05) in KGF-treated patients. Other proinflammatory biomarkers showed increased levels in KGF-treated patients: IL-15 at day 0 (Q=0.0121), BAFF at days +14 and +28 (both Q&amp;lt;0.01), and ST2 at day 0 and day +14 (both Q&amp;lt;0.01). As reported previously by others, patients who developed classic or late onset AGVHD II-IV without prior relapse up to day +180 had higher ST2 levels at day +14 compared to patients without AGVHD II-IV (P=0.03). Here, this association was mainly observed in patients from the TMS and DL1 groups (6/8 tested patients with any AGVHD II-IV). The administration of a single high dose of palifermin (KGF) prior to conditioning treatment resulted in a notably distinct cytokine profile, characterized by a reduction in several GVHD associated pro-inflammatory cytokines, consistent with KGF's proposed cytoprotective effect. Further investigations focusing on GI microbiome and immune cell subsets are needed to elucidate the consequences of cytokine alterations induced by KGF on immune cell reconstitution. This research was supported by the Intramural Research Program of the NIH, NCI, CCR.

Abstract On a recent surgical medical mission caring for Ukrainian pediatric burn and trauma patients in Poland, an assessment of the mental health and well-being of children and their caregivers was completed. Children living in war zones frequently experience significant distress and mental health problems, but little is known about the impact of co-existing related or unrelated burn injuries or physical disabilities. 19 Ukrainian children and their caregivers were interviewed utilizing validated questionnaires Child Behavioral Checklist (CBCL) and Youth Self-Report (YSR) to assess their risk for developing or for the presence of clinically-significant mental health problems. We found a high percentage of children at risk for developing mental health disorders and an unexpectedly high number of children meeting criteria for mental health disorders. As a result of interviewing the caregivers, agreement was seen between the self-assessment in children and the perception of parents about their children’s wellbeing. Further study is needed to better understand the complex interactions between pre-existing burn and traumatic injuries and their impact on the psychosocial wellbeing of children living in war-torn environments.

Whether through minimally invasive or conventional open techniques, thoracic surgery is often reported to be one of the most painful surgical procedures due to the incision of intercostal and respiratory muscles, rib injury or resection, and placement of surgical drains. Some of the more severe complications related to poor analgesia include prolonged intensive care unit stay, mechanical ventilation, pneumonia, and the development of chronic postoperative pain syndromes. Over the past few decades, much progress has been made in recognizing the importance of multimodal analgesic techniques. These may include a variety of regional anesthetic techniques such as epidural anesthesia, fascial plane blocks, and intrapleural catheters, as well as the utilization of opioid and opioid-sparing oral regimens. This article provides an up-to-date review of pain management following thoracic surgery, emphasizing multimodal techniques and enhanced recovery pathways. In our review, we included articles published between 2010 and 2022. PubMed and Google Scholar were researched using the keywords thoracic, cardiac, pain control, thoracic epidural analgesia, fascial plane blocks, multimodal analgesia, and Enhanced Recovery after Surgery in thoracic surgery. Over 100 articles were then reviewed. We excluded articles not in English and articles that were not pertinent to cardiac or thoracic surgery. Eventually, 53 articles were included in the review, composed of clinical trials, case series, and retrospective cohort studies. A variety of pain control methods employed in thoracic and cardiac surgery range from opioids and opioid-sparing medications, such as acetaminophen and gabapentin, to regional techniques, such as fascial plane blocks to epidural anesthesia. Multimodal anesthesia combining regional and opioid-sparing analgesics and their combination in enhanced recovery protocols were shown to provide adequate pain control, decrease opioid consumption and lead to shorter lengths of stay. Postoperative pain control remains one of the biggest challenges in the care of thoracic surgery patients. Analgesic plans must be individualized for each patient. Multimodal analgesia remains the gold standard; however, more studies are still warranted. Finding the optimal combination of opioid and non-opioid pain medication and local anesthetic delivered via suitable regional technique will improve the outcomes and lead to successful patient recovery.

Extragonadal parasitic dermoid cysts are rare. Diagnosis of such extragonadal parasitic teratoma is often done intraoperatively during surgical exploration of abdominal mass.

Burn injury accounts for a large proportion of surgically treatable disease. It is estimated that over 180,000 flame burn deaths occur annually across the globe, with roughly 95% occurring in low- or middle-income countries (LMIC). Within these countries children account for a disproportionately high number of burn injuries. As such, the WHO has identified burn prevention as a topic of interest, with an increased need in low- and middle-income countries. Here we describe the creation and implementation of a burn prevention program in Ukraine. We instituted a five-step burn prevention initiative consisting of; data gathering, program design, implementation, outcome evaluation, program maintenance, and expansion. The burn prevention initiative has been adopted nationally leading to policy change. Active education and an information campaign were used to target pediatric scald injuries and improve first aid care. The authors have successfully implemented a targeted multi-faceted, national, burn prevention program within Ukraine. The described approach may be used as a guide and adapted to create similar prevention programs within other countries or regions. At this time the Russo-Ukrainian War has caused an abrupt hold on our role in the prevention program and left the healthcare system in havoc. Moving forward, our team is prepared to reevaluate the impact of the war on social life and the medical system and aid in redesigning the prevention program when appropriate.