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There are four conditions caused by Kaposi sarcoma herpesvirus (KSHV): Kaposi sarcoma, KSHV-associated multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and KSHV inflammatory cytokine syndrome (KICS). These KSHV-associated disorders (KADs) often occur in people with HIV and can lead to multiorgan dysfunction requiring admission to the ICU. However, little is known about patient outcomes in this setting.A retrospective study of patients with KADs admitted to the ICU between 2010 and 2021 was conducted, examining KAD admission diagnoses, HIV characteristics, selected cytokine profiles, and ICU interventions. Primary outcomes were 60-day and median overall survival from ICU admission to death from any cause.Forty-seven patients (all but one with HIV coinfection) were included. At ICU admission, 44 patients (94%) were on antiretroviral therapy with a median CD4 + count of 88 cells/μl and HIV viral load of 23 copies/ml. The most common presentation was respiratory failure alone (19%) or with hypotension (17%). Twenty-two (47%) patients had presumed KICS (with or without Kaposi sarcoma) at admission and an additional KAD was diagnosed in 36% of these patients. IL-6 levels did not vary across KAD subtype. Twenty (43%) patients received KAD-directed therapy in the ICU. Sixty-day survival was 70% and median overall survival was 9 months.The majority of patients with HIV and KADs admitted to the ICU had well controlled HIV. Additional KAD were diagnosed during ICU admission in a proportion of patients who presented with presumed KICS. Critical illness did not preclude a subset of patients from receiving KAD-directed therapy in the ICU.

Purpose:Kaposi sarcoma (KS) is caused by Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). KS, which develops most frequently among people with HIV, is generally treated with chemotherapy, but these drugs have acute and cumulative toxicities. We previously described initial results of a trial of pomalidomide, an oral immunomodulatory derivative of thalidomide, in patients with KS. Here, we present results on the full cohort and survival outcomes.Patients and Methods:Participants with KS with or without HIV were treated with pomalidomide 5 mg once daily for 21 days per 28-day cycle with aspirin 81 mg daily for thromboprophylaxis. Participants with HIV received antiretroviral therapy. Response was defined by modified version of the AIDS Clinical Trial Group KS criteria. We evaluated tumor responses (including participants who had a second course), adverse events, progression-free survival (PFS), and long-term outcomes.Results:Twenty-eight participants were enrolled. Eighteen (64%) were HIV positive and 21 (75%) had advanced (T1) disease. The overall response rate was 71%: 95% confidence interval (CI) 51%–87%. Twelve of 18 HIV-positive (67%; 95% CI, 41–87%) and 8 of 10 HIV-negative participants (80%; 95% CI, 44%–97%) had a response. Two of 4 participants who received a second course of pomalidomide had a partial response. The median PFS was 10.2 months (95% CI: 7.6–15.7 months). Grade 3 neutropenia was noted among 50% of participants. In the follow-up period, 3 participants with HIV had other KSHV-associated diseases.Conclusions:Pomalidomide is a safe and active chemotherapy-sparing agent for the treatment of KS among individuals with or without HIV.

Supplementary Table from Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection

Supplementary Figure from Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection

Background Scant PK data are available with CZA-ATM in combination. Occurrence of ALT/AST elevations are common with ATM, and it is unknown if it is exacerbated by use of CZA-ATM. This analysis of COMBINE sought to describe the popPK of CZA-ATM and to assess the association between ATM exposures and ALT/AST elevations. Methods COMBINE was a Phase I study of 48 healthy subjects aged 18-45 years (NCT03978091). Subjects were enrolled into 1 of 6 Cohorts (Table 1). Drug(s) were administered for 7 D and intensive plasma and urine PK sampling was performed. PopPK models were developed for ceftazidime (CAZ), avibactam (AVI), and ATM. Empirical Bayesian estimates from the ATM PopPK model were used to simulate ATM day 1 (D1) exposures. Associations between D1 ATM exposures and highest observed ALT/AST were assessed with curvilinear regression (CR) and generalized linear models (GLM). Results Of enrolled 48 subjects, 35% had ALT/AST elevations; 94% occurred in ATM/CZA-ATM Cohorts. Two severe study product related ALT/AST AEs were observed with in the continuous infusion (CI) ATM Cohort. All subjects with ALT/ATS elevations were asymptomatic with no other signs of liver injury. In the ATM PopPK model, CZA-ATM administration reduced ATM non-renal clearance (CLNR) by 1 L/hr (16% of total CL) (Table 2). Administration of CAZ-ATM had a negligible effect on total CAZ CL in the CAZ PopPK model and CZA-ATM was not a covariate in final AVI PopPK model. In the CR, no ATM exposure-ALT/AST associations were identified in overall analyses. Associations (R2=0.18-0.22, p< 0.05) between D1 AUC and ALT/AST were observed in CR analyses restricted to the intermittent infusion (II) ATM Cohorts (Figure 1). In GLM, D1 AUC was significantly associated with ALT/AST in the ATM II Cohort analyses. Administration of CZA-ATM was not associated with ALT/AST in the GLM analyses. Figure 1 Conclusion Administration of CZA-ATM was found to reduce ATM CL, resulting in higher daily ATM AUCs, but did not exacerbate AST/ALT elevations relative to ATM alone. The observed association between ATM AUC and ALT/AST elevations in subjects who received II ATM suggest the risks vs benefits of using II of ATM 8 g/daily vs 6 g/daily with CZA should be considered. Use of CI ATM should be used with caution given the 2 severe ALT/ASTs in the CI ATM Cohort. Disclosures Thomas Lodise, Jr., Pharm.D., PhD, BioFire Diagnostics: Grant/Research Support|cidara: Advisor/Consultant|cidara: Honoraria|Entasis: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Paratek: Advisor/Consultant|Shionogi: Advisor/Consultant|Spero: Advisor/Consultant|Venatrox: Advisor/Consultant J Nicholas O'Donnell, Pharm.D., Merck & Co, Inc: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support Stephen Balevic, MD, Purdue Pharma: Grant/Research Support|UCB: Advisor/Consultant Jeffrey Guptill, MD, argenx: Stocks/Bonds Vance G. Fowler, Jr, MD, MHS, Affinergy: Grant/Research Support|Affinergy: Honoraria|Affinium: Honoraria|Amphliphi Biosciences: Honoraria|ArcBio: Stocks/Bonds|Basilea: Grant/Research Support|Basilea: Honoraria|Bayer: Honoraria|C3J: Honoraria|Cerexa/Forest/Actavis/Allergan: Grant/Research Support|Contrafect: Grant/Research Support|Contrafect: Honoraria|Cubist/Merck: Grant/Research Support|Debiopharm: Grant/Research Support|Deep Blue: Grant/Research Support|Destiny: Honoraria|Genentech: Grant/Research Support|Genentech: Honoraria|Integrated Biotherapeutics: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|Karius: Grant/Research Support|Medicines Co.: Honoraria|MedImmune: Grant/Research Support|MedImmune: Honoraria|NIH: Grant/Research Support|Novartis: Grant/Research Support|Novartis: Honoraria|Pfizer: Grant/Research Support|Regeneron: Grant/Research Support|Regeneron: Honoraria|Sepsis diagnostics: Sepsis diagnostics patent pending|UpToDate: Royalties|Valanbio: Stocks/Bonds henry chambers, MD, Merck: DSMB member|Merck: Stocks/Bonds|Moderna: Stocks/Bonds.

The integrase strand transfer inhibitor (INSTI) dolutegravir is commonly used in combination antiretroviral therapy regimens and retains strong potency even with primary resistance mutations to some other INSTIs. Acquisition of accessory mutations to primary mutations results in significant increases in dolutegravir resistance. Previously, we reported that addition of the secondary mutation T97A can result in rapid treatment failure in individuals with INSTI mutations at positions 140 and 148. Here, we conducted a detailed case study of one of these individuals and find that T97A-containing HIV emerged from a large replicating population from only a few (≤4) viral lineages. When combined with primary INSTI resistance mutations, T97A provides a strong selective advantage; the finding that T97A-containing variants spread by replication and recombination, and persisted for months after discontinuing dolutegravir, has important implications as dolutegravir is rolled out worldwide.

Thyroglossal duct remnants and branchial arch anomalies are the most common congenital neck masses. These anomalies typically present in childhood or early adulthood as cysts, sinuses or cartilaginous remnants, but may rarely present in late adulthood. Although both thyroglossal duct remnants and branchial cysts may be encountered individually, these anomalies are rarely encountered together in the same individual. We report the third such case of co-existing branchial cyst and thyroglossal cyst occurring in the same individual with review of embryological development of thyroglossal duct cysts and second branchial arch anomalies.

A single, subanesthetic dose of (R,S)-ketamine (ketamine) exerts rapid and robust antidepressant effects. Several groups previously reported that (2S,6S;2R,6R)-hydroxynorketamine (HNK) had antidepressant effects in rodents, and that (2R,6R)-HNK increased cortical electroencephalographic gamma power. This exploratory study examined the relationship between ketamine metabolites, clinical response, psychotomimetic symptoms, and gamma power changes in 34 individuals (ages 18-65) with treatment-resistant depression (TRD) who received a single ketamine infusion (0.5 mg/kg) over 40 min. Plasma concentrations of ketamine, norketamine, and HNKs were measured at 40, 80, 120, and 230 min and at 1, 2, and 3 days post-infusion. Linear mixed models evaluated ketamine metabolites as mediators of antidepressant and psychotomimetic effects and their relationship to resting-state whole-brain magnetoencephalography (MEG) gamma power 6-9 h post-infusion. Three salient findings emerged. First, ketamine concentration positively predicted distal antidepressant response at Day 11 post-infusion, and an inverse relationship was observed between (2S,6S;2R,6R)-HNK concentration and antidepressant response at 3 and 7 days post-infusion. Norketamine concentration was not associated with antidepressant response. Second, ketamine, norketamine, and (2S,6S;2R,6R)-HNK concentrations at 40 min were positively associated with contemporaneous psychotomimetic symptoms; post-hoc analysis revealed that ketamine was the predominant contributor. Third, increased (2S,6S;2R,6R)-HNK maximum observed concentration (C

Conventional knee and cranial implant systems have been in use for many years for patients suffering from arthritis and skull fractures. These implants are commercially available in standard sizes. However, the increasing number of failure occurrences and the demand to increase the longevity of implants has directed towards the need for patient-specific implant designs. This work combines clinical imaging, computer-aided design, analyses, and manufacturing to develop patient-specific knee and cranial implant that can accommodate the variations in size and shape among individuals. Patient-specific stacked image data based on Computed Tomography (CT) is used to build the surface 3D models using commercial medical image processing software. This 3D files represented in STL format are converted to IGES format and transferred into CAD environment to model and design the implants. The modeled implants are then subjected to structural, fatigue and impact analyses using finite element method based on Co-Cr and titanium alloy as the implant material. The results revealed that the designed knee implant could last about 108 cycles which could be translated to more than 50 years for an average built person. The designed cranial implant can withstand high impact loads up to deceleration of five times acceleration due to gravity. Finally, the developed knee and cranial implant prototypes are fabricated using Fused Model Deposition (FDM) based additive manufacturing method for the design approval of a competent medical practitioner.

OBJECTIVE: To report a case of ethmoid sinus capillary hemangioma and to discuss its management and treatment options with special mention on the clinical presentation , radiographic features and surgical options. METHOD: case report and review of literature . CONCLUSION: This case of a capillary hemangioma occu rring in the ethmoid sinus is a rare entity as capillary hemangiomas are usually seen arising from the septum. Transnasal endoscopic excision of the mass was done without embolization