Myalgic Encephalomyelitis/Chronic Fatigue Syndrome After SARS-CoV-2 Infection.

Importance: Chronic symptoms reported following an infection with SARS-CoV-2, such as cognitive problems, overlap with symptoms included in the definition of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Objective: To evaluate the prevalence of ME/CFS-like illness subsequent to acute SARS-CoV-2 infection, changes in ME/CFS symptoms through 12 months of follow-up, and the association of ME/CFS symptoms with SARS-CoV-2 test results at the acute infection-like index illness. Design, Setting, and Participants: This prospective, multisite, longitudinal cohort study (Innovative Support for Patients with SARS-CoV-2 Infections Registry [INSPIRE]) enrolled participants from December 11, 2020, to August 29, 2022. Participants were adults aged 18 to 64 years with acute symptoms suggestive of SARS-CoV-2 infection who received a US Food and Drug Administration-approved SARS-CoV-2 test at the time of illness and did not die or withdraw from the study by 3 months. Follow-up surveys were collected through February 28, 2023. Exposure: COVID-19 status (positive vs negative) at enrollment. Main Outcome and Measures: The main outcome was the weighted proportion of participants with ME/CFS-like illness based on the 2015 Institute of Medicine clinical case definition using self-reported symptoms. Results: A total of 4378 participants were included in the study. Most were female (3226 [68.1%]). Mean (SD) age was 37.8 (11.8) years. The survey completion rates ranged from 38.7% (3613 of 4738 participants) to 76.3% (1835 of 4738) and decreased over time. The weighted proportion of participants identified with ME/CFS-like illness did not change significantly at 3 through 12 months of follow-up and was similar in the COVID-19-positive (range, 2.8%-3.7%) and COVID-19-negative (range, 3.1%-4.5%) groups. Adjusted analyses revealed no significant difference in the odds of ME/CFS-like illness at any time point between COVID-19-positive and COVID-19-negative individuals (marginal odds ratio range, 0.84 [95% CI, 0.42-1.67] to 1.18 [95% CI, 0.55-2.51]). Conclusions and Relevance: In this prospective cohort study, there was no evidence that the proportion of participants with ME/CFS-like illness differed between those infected with SARS-CoV-2 vs those without SARS-CoV-2 infection up to 12 months after infection. A 3% to 4% prevalence of ME/CFS-like illness after an acute infection-like index illness would impose a high societal burden given the millions of persons infected with SARS-CoV-2.

Transmembrane protein 53 craniotubular dysplasia (OMIM # 619727): The skeletal disease and consequent blindness of this new disorder.

Craniotubular dysplasia, Ikegawa type (OMIM #619727) denotes the autosomal recessive skeletal disease identified in 2021 featuring blindness acquired in childhood. Five young members of four Indian families harbored a homozygous indel within TMEM53 (OMIM *619722), the gene that encodes transmembrane protein 53 (TMEM53). When intact, TMEM53 spans the nuclear envelope of osteoprogenitor cells, dampens BMP-SMAD signaling, and thereby slows bone formation. Consequently, defective TMEM53 accelerates osteogenesis. Herein, an American boy is compound heterozygous for a novel deletion and a novel missense mutation within TMEM53. His vision and sensorineural hearing became impaired. Radiographic survey revealed diploic thickening of his skull, broad calvarial and facial bones, skeletal modeling errors, vertebral body flattening, wide ribs, and osteopenia of expanded bones. DXA areal bone density (gm/cm2) Z-scores were low. His optic, auditory, and spinal canals were narrow. Mineral metabolism was intact. Serum alkaline phosphatase and osteocalcin levels were normal yet CTX was high. Iliac crest histomorphometry documented accelerated bone formation. His acute vision loss briefly improved following prednisone administration, optic canal decompression, and optic nerve sheath fenestration, but then progressed despite further surgeries and zoledronate treatment aimed to suppress bone turnover. Next generation sequencing of genes associated with elevated skeletal mass, including from high bone turnover, did not suggest an etiology. Whole genome sequencing then revealed within TMEM53: i) a paternally transmitted 54-base deletion, which included the mRNA splice acceptor site for exon 2 as well as 31 bases of exonic sequence (c. 62-23_92del), and ii) a maternally transmitted missense variant (c.650C > T, p.Ser217Leu: NM_024587.4/NP_078863.2) which is extremely rare in gnomAD (frequency = 0.000036), replaces Ser217 highly conserved across species, and is scored as damaging by SIFT and Mutation Taster. We call this new osteopathy TMEM53 craniotubular dysplasia.

Assessment of arterial supply to the stomach after bariatric surgery using multidetector CT arteriography.

PURPOSE: To describe residual arterial supply to the stomach after bariatric surgery via a systematic arterial-phase CT assessment approach that can aid in diagnosis and treatment of postoperative complications and facilitate planning for future procedures. METHODS: Arterial-phase CT of 46 patients who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at 3 academic institutions were retrospectively reviewed to assess patency of left gastric artery (LGA), right gastric artery (RGA), gastroepiploic artery (GEA), and left inferior phrenic artery (LIPA) and presence of gastric perforators. RESULTS: In 25 RYGB and 21 SG patients, mean diameters were LGA 2.2 ± 0.4 mm, RGA 1.6 ± 0.5 mm, and GEA 1.7 ± 0.4 mm. On RYGB scans, all LGAs, RGAs, and 24/25 (96%) of GEAs were identified. Excellent to good patency was seen in 20/25 (80%) LGAs, 21/25 (84%) RGAs, and 23/24 (96%) GEAs. On SG scans, all LGAs, 18/21 (86%) of RGAs, and 20/21 (95%) GEAs were identified. Excellent to good patency was seen in 17/21 (81%) LGAs, 15/18 (83%) RGAs, and 20/20 (100%) GEAs. In terms of gastric perforators, LGA supply was seen on 23/25 (92%) of RYGB and 17/17 (100%) of SG scans. RGA supply was seen on 13/21 (62%) RYGB and 9/18 (50%) SG scans. GEA supply was seen on 19/23 (83%) RYGB scans. No gastric supply via GEA was seen on SG scans. CONCLUSION: In this study, arterial supply to the stomach through the LGA was consistently identified in all RYGB and SG cases, indicating an uncomplicated surgical approach with regard to preserving the LGA. Dedicated CT angiography protocol or catheter-directed angiography is recommended for accurate and comprehensive assessment of the gastric blood supply, particularly before surgical re-intervention.

Racial and Ethnic Disparities among Participants in Hepatocellular Carcinoma Clinical Studies Evaluating Transarterial Therapies.

PURPOSE: To evaluate the racial and ethnic representation of transarterial therapy for hepatocellular carcinoma (HCC) clinical trials in the United States. MATERIALS AND METHODS: The ClinicalTrials.gov database was examined to identify all completed studies with transarterial therapies for the management of HCC in the United States and extract information about the observed number of participants for each racial and ethnic group (based on the Office of Management and Budget definitions). The expected number of participants was calculated by multiplying the total number of participants in a trial with the U.S.-population HCC-based proportion for each group. The effects of the study phase, funding source, number of centers involved in the study, and the location of the participating center on racial and ethnic distribution were explored. RESULTS: Seventy-nine relevant studies were identified, of which 27 (34.2%) and 18 (22.8%) reported ethnic and race characteristics, respectively. Most study participants were White (81%, 1,591/1,964) by ethnicity and not Hispanic or Latino (93%, 937/1,008) by race. In terms of the observed-to-expected ratios by race and ethnicity in all trials, White and not Hispanic or Latino participants were overrepresented with a ratio of 1.22 (1.10-1.37) and 1.33 (1.26-1.41), respectively, and all other racial and ethnic groups were underrepresented. The enrollment of African Americans and Asian Americans varied by the study phase, and a higher enrollment of African Americans was noted in the National Institutes of Health-funded and multicenter studies (P < .05). CONCLUSIONS: This cross-sectional study demonstrates that in HCC transarterial therapy clinical trials, racial and ethnic minorities were underrepresented and the majority of the studies identified failed to report this demographic information.

Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): A longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection.

BACKGROUND: Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection. METHODS: INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses. RESULTS: Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. CONCLUSIONS: This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection.

Coalescing expansile skeletal disease: Delineation of an extraordinary osteopathy involving the IFITM5 mutation of osteogenesis imperfecta type V.

In 2003, we briefly reported the remarkable osteopathy of a 12-year-old boy who at age two months began fracturing his limbs with subsequent hyperplastic callus formation and expansion and fusion of appendicular bones. By age ten years he had coalesced his lumbosacral spine, pelvis, femurs, and leg and foot bones as a single structure. Computed tomography of expanded bone revealed a thin cortical shell, diminished irregular trabeculae, and cystic areas. Histopathology featured foci of woven bone, densely packed osteocytes, cartilage, fibrovascular tissue, and massive fat deposition in the marrow space lacking hematogenous precursor cells. Bone turnover markers indicated accelerated remodeling and the few radiographically assessable appendicular bones improved during brief adherence to alendronate therapy. Following puberty, serum multiplex biomarker profiling confirmed accelerated bone turnover. At age 23 years, macrospecimens from leg amputation revealed ossification along capsular tissue together with hyaline cartilage degeneration. Concurrently, the life-long course of this same disorder was delineated in an unrelated woman until her death at age 51 years. Both patients demonstrated the radiographic hallmarks and harbored the heterozygous point mutation (c.-14C>T) in the 5'-UTR of IFITM5 associated with osteogenesis imperfecta type V (OI-V). Herein, we detail the clinical, radiological, histopathological, biochemical, and molecular findings and discuss the etiology and pathogenesis of this extraordinary osteopathy that we call coalescing expansile skeletal disease.

Iron replacement ameliorates hypophosphatemia in autosomal dominant hypophosphatemic rickets: A review of the role of iron.

Autosomal dominant hypophosphatemic rickets (ADHR) is remarkable among the hypophosphatemic rickets syndromes for its variable age of presentation and periods of quiescence during which serum phosphate and fibroblast growth factor 23 (FGF 23) levels are normal without therapy. In contrast, hypophosphatemia in X-linked hypophosphatemic rickets (XLH) manifests soon after birth and requires lifelong therapy. This suggests that there are environmental factors which can alter FGF 23 activity in ADHR but not in XLH. We present an adult with ADHR in whom resolution of hypophosphatemia was achieved by correcting iron deficiency without the need for phosphate supplementation. Serial iron and FGF 23 levels revealed an inverse relationship (r=-0.79, p<0.04). All patients with ADHR who present with hypophosphatemia and worsening symptoms should be screened for iron deficiency. If iron deficiency is detected, therapy with a combination of calcitriol and iron supplementation should be considered without phosphate supplementation.

Impact of doffing errors on healthcare worker self-contamination when caring for patients on contact precautions.

OBJECTIVE: We assessed the impact of personal protective equipment (PPE) doffing errors on healthcare worker (HCW) contamination with multidrug-resistant organisms (MDROs). DESIGN: Prospective, observational study. SETTING: The study was conducted at 4 adult ICUs at 1 tertiary-care teaching hospital. PARTICIPANTS: HCWs who cared for patients on contact precautions for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci, or multidrug-resistant gram-negative bacilli were enrolled. Samples were collected from standardized areas of patient body, garb sites, and high-touch environmental surfaces in patient rooms. HCW hands, gloves, PPE, and equipment were sampled before and after patient interaction. Research personnel observed PPE doffing and coded errors based on CDC guidelines. RESULTS: We enrolled 125 HCWs; most were nurses (66.4%) or physicians (19.2%). During the study, 95 patients were on contact precautions for MRSA. Among 5,093 cultured sites (HCW, patient, environment), 652 (14.7%) yielded the target MDRO. Moreover, 45 HCWs (36%) were contaminated with the target MDRO after patient interactions, including 4 (3.2%) on hands and 38 (30.4%) on PPE. Overall, 49 HCWs (39.2%) made multiple doffing errors and were more likely to have contaminated clothes following a patient interaction (risk ratio [RR], 4.69; P = .04). All 4 HCWs with hand contamination made doffing errors. The risk of hand contamination was higher when gloves were removed before gowns during PPE doffing (RR, 11.76; P = .025). CONCLUSION: When caring for patients on CP for MDROs, HCWs appear to have differential risk for hand contamination based on their method of doffing PPE. An intervention as simple as reinforcing the preferred order of doffing may reduce HCW contamination with MDROs.

Effectiveness of Probiotic for Primary Prevention of Clostridium difficile Infection: A Single-Center Before-and-After Quality Improvement Intervention at a Tertiary-Care Medical Center.

OBJECTIVETo evaluate probiotics for the primary prevention of Clostridium difficile infection (CDI) among hospital inpatients.DESIGNA before-and-after quality improvement intervention comparing 12-month baseline and intervention periods.SETTINGA 694-bed teaching hospital.INTERVENTIONWe administered a multispecies probiotic comprising L. acidophilus (CL1285), L. casei (LBC80R), and L. rhamnosus (CLR2) to eligible antibiotic recipients within 12 hours of initial antibiotic receipt through 5 days after final dose. We excluded (1) all patients on neonatal, pediatric and oncology wards; (2) all individuals receiving perioperative prophylactic antibiotic recipients; (3) all those restricted from oral intake; and (4) those with pancreatitis, leukopenia, or posttransplant. We defined CDI by symptoms plus C. difficile toxin detection by polymerase chain reaction. Our primary outcome was hospital-onset CDI incidence on eligible hospital units, analyzed using segmented regression.RESULTSThe study included 251 CDI episodes among 360,016 patient days during the baseline and intervention periods, and the incidence rate was 7.0 per 10,000 patient days. The incidence rate was similar during baseline and intervention periods (6.9 vs 7.0 per 10,000 patient days; P=.95). However, compared to the first 6 months of the intervention, we detected a significant decrease in CDI during the final 6 months (incidence rate ratio, 0.6; 95% confidence interval, 0.4-0.9; P=.009). Testing intensity remained stable between the baseline and intervention periods: 19% versus 20% of stools tested were C. difficile positive by PCR, respectively. From medical record reviews, only 26% of eligible patients received a probiotic per the protocol.CONCLUSIONSDespite poor adherence to the protocol, there was a reduction in the incidence of CDI during the intervention, which was delayed ~6 months after introducing probiotic for primary prevention.Infect Control Hosp Epidemiol 2018;765-770.

Automated red blood cell exchange in preparation for filgrastim mobilization of autologous peripheral blood hematopoietic progenitor cells in a patient with sickle cell anemia.

Increasing survival of patients with sickle cell anemia (SCA) well into adulthood results in a rising likelihood of developing hematological malignancy. High-dose chemotherapy with autologous hematopoietic progenitor cell (HPC) rescue is standard of care for several hematological malignancies, but the risk of severe or life-threatening vaso-occlusive phenomena during filgrastim mobilization of HPC for collection poses a potential barrier to this approach. We report the use of automated red cell exchange in preparation for filgrastim mobilization in a patient with homozygous SCA. Red cell exchange was repeated just prior to high-dose chemotherapy to mitigate the need for red cell transfusion during bone marrow reconstitution. The patient experienced no vaso-occlusive phenomena throughout the entire episode of care and did not become iron overloaded. This approach should be considered for all patients with homozygous or compound heterozygous sickle cell disease who are candidates for auto-HPC rescue therapy.

Therapeutic apheresis using a mononuclear cell program to lower the microfilaria burden of a 23-year-old African woman with loiasis.

Apheresis has been used to lower the parasite burden of patients with Loa loa infection, but there are no reports regarding how to do this using modern, continuous flow equipment with a currently available program. A 23-year-old female refugee from Cameroon with known Loa loa infection presented to our Emergency Department with acute mental status changes and a picture of encephalitis. Lumbar puncture revealed Loa loa in her cerebrospinal fluid. Her midday blood microfilaria count was 15,000/mL. Because treatment with diethylcarbamazine was under consideration, we were asked to lower her parasite burden using apheresis. One single 2-total blood volume apheresis using the mononuclear cell program (without hydroxyethyl starch) on a COBE® Spectra Apheresis System decreased the microfilarial load from 15,000/mL to 10,666/mL, a 29% reduction. J. Clin. Apheresis 32:200-202, 2017. © 2016 Wiley Periodicals, Inc.

Multidrug- and Carbapenem-Resistant Pseudomonas aeruginosa in Children, United States, 1999-2012.

BACKGROUND: Pseudomonas aeruginosa is a common cause of healthcare-associated infection. Multidrug-resistant (MDR) (>3 classes) and carbapenem-resistant (CR) P aeruginosa are significant threats globally. We used a large reference-laboratory database to study the epidemiology of P aeruginosa in children in the United States. METHODS: Antimicrobial susceptibility data from the Surveillance Network were used to phenotypically identify MDR and CR P aeruginosa isolates in children aged 1 to 17 years between January 1999 and July 2012. Logistic regression analysis was used to calculate trends in the prevalence of MDR and CR P aeruginosa. Isolates from infants (<1 year old) and patients with cystic fibrosis were excluded. RESULTS: Among the isolates tested, the crude proportion of MDR P aeruginosa increased from 15.4% in 1999 to 26% in 2012, and the proportion of CR P aeruginosa increased from 9.4% in 1999 to 20% in 2012. The proportion of both MDR and CR P aeruginosa increased each year by 4% (odds ratio [OR], 1.04 [95% confidence interval (CI), 1.03-1.04] and 1.04 [95% CI, 1.04-1.05], respectively). In multivariable analysis, both MDR and CR P aeruginosa were more common in the intensive care setting, among children aged 13 to 17 years, in respiratory specimens, and in the West North Central region. In addition, resistance to other antibiotic classes (aminoglycosides, fluoroquinolones, cephalosporins, and piperacillin-tazobactam) often used to treat P aeruginosa increased. CONCLUSIONS: Rates of MDR and CR P aeruginosa infection in children are rising nationally. Aggressive prevention strategies, including instituting antimicrobial stewardship programs in pediatric settings, are essential for combating antimicrobial resistance.

Therapeutic plasma exchange performed in tandem with hemodialysis without supplemental calcium in the apheresis circuit.

Therapeutic plasma exchange (TPE) and hemopoietic progenitor cell (HPC) collection are apheresis procedures that can safely be performed in tandem with hemodialysis. Despite the return of citrate-anticoagulated blood to the patient during HPC collection, it is not necessary to administer supplemental calcium during these procedures because the ionized calcium concentration is restored as the returning blood passes through the dialyzer. It is not known whether this applies to TPE, in which a mixture of blood and pharmaceutical albumin, an avid binder of plasma ionized calcium, is returned to the patient through the dialyzer. We report on three dialysis-dependent patients who required TPE and underwent tandem treatments without supplemental calcium in the apheresis circuit. Overall, ionized calcium fell 4-12% (P = 0.0.024) and patients reported no symptoms of hypocalcemic toxicity. Tandem hemodialysis/TPE can be performed without supplemental calcium in the apheresis circuit. J. Clin. Apheresis 32:154-157, 2017. © 2016 Wiley Periodicals, Inc.

Skeletal inflammation and attenuation of Wnt signaling, Wnt ligand expression, and bone formation in atherosclerotic ApoE-null mice.

ApoE-null (ApoE-KO) mice fed a high-fat diet (HFD) develop atherosclerosis, due in part to activation of vascular inflammation by oxidized low-density lipoprotein. Since bone loss also occurs in these mice, we used them to investigate the impact of oxidized lipids on bone homeostasis and to search for underlying pathogenic pathways. Four-month-old female ApoE-KO mice fed a HFD for three months exhibited increased levels of oxidized lipids in bone, as well as decreased femoral and vertebral trabecular and cortical bone mass, compared with ApoE-KO mice on normal diet. Despite HFD-induced increase in expression of Alox15, a lipoxygenase that oxidizes LDL and promotes atherogenesis, global deletion of this gene failed to ameliorate the skeletal impact of HFD. Osteoblast number and function were dramatically reduced in trabecular and cortical bone of HFD-fed mice, whereas osteoclast number was modestly reduced only in trabecular bone, indicating that an imbalance in favor of osteoclasts was responsible for HFD-induced bone loss. These changes were associated with decreased osteoblast progenitors and increased monocyte/macrophages in the bone marrow as well as increased expression of IL-1ß, IL-6, and TNF. HFD also attenuated Wnt signaling as evidenced by reduced expression of Wnt target genes, and it decreased expression of pro-osteoblastogenic Wnt ligands. These results suggest that oxidized lipids decrease bone mass by increasing anti-osteoblastogenic inflammatory cytokines and decreasing pro-osteoblastogenic Wnt ligands.

Therapeutic leukocytapheresis for improvement in respiratory function in a woman with hyperleukocytosis and mantle cell lymphoma with a circulating small lymphocyte phenotype.

Mantle cell lymphoma is an aggressive malignant B-cell disorder that often presents with a leukemic picture. Circulating lymphoma cell morphology may vary from small round mature-appearing lymphocytes resembling the lymphocytes of chronic lymphocytic leukemia to large prolymphocytoid or blastoid cells. Rare reports of hyperleukocytosis with leukostasis, treated with leukocytapheresis, are described in patients with prolymphocytoid or blastoid morphology. We report an 88 year old woman with mantle cell lymphoma, hyperleukocytosis (WBC > 400 × 10(3) /µL) with severe respiratory compromise but without interstitial or alveolar infiltrates on radiograph or computerized tomography of the chest. She was afebrile and had no central nervous system signs. Circulating lymphoma cell morphology was predominantly of the small lymphocyte type. A two-whole-blood-volume leukocytapheresis reduced her WBC from 465 to 221 × 10(3) /µL in 150 min. Her respiratory rate decreased from 28/min to 18/min and her arterial oxygen saturation (SpO2 ) rose from 91% to 97% on 6 L/min of oxygen by nasal cannula. Severe breathlessness before the procedure abated completely by the end of the procedure. Respiratory compromise may occur in mantle cell lymphoma with hyperleukocytosis with a mature lymphoma cell phenotype, even without a clear picture of leukostasis. Although the ultimate survival of the patient depends on treatment with chemotherapy, leukocytapheresis for alleviation of symptoms may be warranted and should be considered. Respiratory status and response to leukocytapheresis should be documented with physiological measurements. J. Clin. Apheresis 31:398-402, 2016. © 2015 Wiley Periodicals, Inc.

Physiological measurements corroborate symptomatic improvement after therapeutic leukapheresis in a pregnant woman with chronic myelogenous leukemia.

Therapeutic leukapheresis can control the white blood cell count (WBC) of pregnant women with chronic myelogenous leukemia (CML) who have hyperleukocytosis without leukostasis. The medical justification for this treatment has not been objectively documented. We report a 27-year-old woman, diagnosed with CML at 10-week gestation, who developed severe dyspnea on exertion. A workup that included chest CT and echocardiography with a bubble study detected no cardiopulmonary pathology to explain her symptoms, and thus she was referred for leukapheresis. Prior to her first leukapheresis, which lowered her WBC from 154 × 10(3) /µL to 133 × 10(3) /µL, her oxygen saturation (SpO2 ) on room air decreased from 98 to 93% during 100 feet of slow ambulation and she was dyspneic. Just after the leukapheresis, her dyspnea on exertion was much improved and her SpO2 remained at 98% with repeat ambulation. Spirometry and lung volume studies obtained before and after her first leukapheresis demonstrated 32 and 31% improvements in forced vital capacity and forced expiratory volume in 1 s respectively, a 25% increase in functional residual capacity, and a 142% improvement in expiratory reserve volume. Residual volume decreased by almost 20%. Three times in a week, leukapheresis was continued until her WBC was controlled with interferon α-2b approximately 4 weeks later. Her dyspnea had completely resolved. She gave birth by elective caesarean section to a healthy boy at 32 weeks. Corroboration of symptom relief by leukapheresis with physiological data may justify such treatment in pregnant patients with CML. J. Clin. Apheresis 31:393-397, 2016. © 2015 Wiley Periodicals, Inc.

The Effects of Androgens on Murine Cortical Bone Do Not Require AR or ERα Signaling in Osteoblasts and Osteoclasts.

In men, androgens are critical for the acquisition and maintenance of bone mass in both the cortical and cancellous bone compartment. Male mice with targeted deletion of the androgen receptor (AR) in mature osteoblasts or osteocytes have lower cancellous bone mass, but no cortical bone phenotype. We have investigated the possibility that the effects of androgens on the cortical compartment result from AR signaling in osteoprogenitors or cells of the osteoclast lineage; or via estrogen receptor alpha (ERα) signaling in either or both of these two cell types upon conversion of testosterone to estradiol. To this end, we generated mice with targeted deletion of an AR or an ERα allele in the mesenchymal (AR(f/y);Prx1-Cre or ERα(f/f);Osx1-Cre) or myeloid cell lineage (AR(f/y);LysM-Cre or ERα(f/f);LysM-Cre) and their descendants. Male AR(f/y);Prx1-Cre mice exhibited decreased bone volume and trabecular number, and increased osteoclast number in the cancellous compartment. Moreover, they did not undergo the loss of cancellous bone volume and trabecular number caused by orchidectomy (ORX) in their littermate controls. In contrast, AR(f/y);LysM-Cre, ERα(f/f);Osx1-Cre, or ERα(f/f);LysM-Cre mice had no cancellous bone phenotype at baseline and lost the same amount of cancellous bone as their controls following ORX. Most unexpectedly, adult males of all four models had no discernible cortical bone phenotype at baseline, and lost the same amount of cortical bone as their littermate controls after ORX. Recapitulation of the effects of ORX by AR deletion only in the AR(f/y);Prx1-Cre mice indicates that the effects of androgens on cancellous bone result from AR signaling in osteoblasts-not on osteoclasts or via aromatization. The effects of androgens on cortical bone mass, on the other hand, do not require AR or ERα signaling in any cell type across the osteoblast or osteoclast differentiation lineage. Therefore, androgens must exert their effects indirectly by actions on some other cell type(s) or tissue(s).

Automated red blood cell exchange for acute drug removal in a patient with sirolimus toxicity.

Sirolimus is an immunosuppressant used to prevent graft versus host disease in allogeneic hematopoietic stem cell transplant recipients. It has a large volume of distribution (12 ± 7.5 l/kg) and within the intravascular space ∼95% of it is bound to red blood cells. Because of potential toxic effects at high trough levels, therapeutic drug monitoring is recommended for sirolimus. We present a case of severe hepatic dysfunction due to Hepatitis B and sirolimus toxicity, in a 51-year-old male stem cell transplant recipient. An automated red cell exchange decreased his blood sirolimus level from 22.6 to 10.3 ng/ml (55% reduction) and improved his liver enzymes. Re-equilibration of sirolimus from other compartments to the blood necessitated a series of four red cell exchanges, after which the sirolimus level was 4.7 ng/ml. Although the patient ultimately succumbed to multiorgan failure, red cell exchange may be considered for acute removal of sirolimus in selected patients.

From Albania to Zambia: travel back to country of origin as a goal of care for terminally ill patients.

BACKGROUND: With unprecedented levels of international migration, physicians in the United States may care for terminally ill patients who have strong connections to their country of origin and such patients may desire to return in the final stages of life. OBJECTIVE: In this study, we analyzed how often terminally ill patients cited travel to country of origin as a goal of care, how often travel occurred, and factors associated with successful travel. DESIGN: A retrospective chart review from January 1, 2005 through May 1, 2007. SETTING/SUBJECTS: All foreign-born patients seen by a palliative care consultation service, including inpatient and outpatient consultations, in an urban safety-net health system in the United States. MEASUREMENTS: We determined whether patients expressed a desire to travel to their country of origin and the factors, including demographics and functional status associated with travel. RESULTS: Of 336 foreign-born patients, 129 (38%) expressed a desire to travel to their country of origin; 60 (47%) successfully returned to 24 unique countries. Countries to which the largest number of patients returned were Mexico (n=14), Poland (n=11), and the Philippines (n=7). Although patients with the best functional status were most likely to travel successfully, 16 (31%) who wanted to travel despite having the worst functional status (Eastern Cooperative Oncology Group [ECOG] score indicating confinement to bed or chair) traveled successfully. There were no deaths en route or flight diversions due to medical crisis; all trips were made on regularly scheduled commercial airline flights. CONCLUSIONS: A substantial proportion of patients in our cohort expressed a desire to return to their country of origin. We facilitated successful travel for nearly half of these patients. Our findings identify the need to include travel back to country of origin in the framework of planning care for terminally ill patients.