Recognizing Minimal Cutaneous Involvement or Systemic Symptoms in Monkeypox.

This case report describes 2 umbilicated and ulcerated, skin-colored papules on the genitals, as well as a honey-colored crusted papule on the face.

Rituximab therapy in patients with bullous pemphigoid: A retrospective study of 20 patients.

BACKGROUND: Bullous pemphigoid (BP) is the most common autoimmune blistering disease requiring treatment with immunosuppressive medications; however, finding a therapy that has a sustained durable response and an acceptable side effect profile has been challenging. OBJECTIVE: Our study aimed to evaluate the clinical outcomes of patients with BP treated with rituximab therapy at a single academic center. METHODS: A retrospective chart review was performed on 20 patients who received at least 1 dose of rituximab therapy, either as initial therapy for severe BP or as therapy for recalcitrant disease after having failed conventional immunotherapies. RESULTS: Within our cohort, 75% of patients (n = 15) achieved remission an average of 169 days following rituximab therapy. There were no rituximab-related deaths and significantly fewer adverse events following rituximab therapy. LIMITATIONS: This study was limited by its retrospective nature, focus on a single academic center, and small sample size. CONCLUSION: Use of rituximab therapy demonstrated high rates of remission, steroid-sparing activity, and an acceptable safety profile in our cohort of patients with severe BP or disease refractory to conventional therapies.

A Good Case of Recurrent Pneumonia.

Bordetella bronchiseptica infection is a common cause of pneumonia in animals but rarely causes disease in humans. Additionally, coinfection with Pneumocystis jirovecii is very uncommon and is occasionally seen in patients with acquired immunodeficiency syndrome (AIDS). We report a case of a 61-year-old HIV-negative man, who presented with hypoxic respiratory failure 2 days after completion of systemic intravenous antibiotic treatment for B bronchiseptica. His past medical history was significant for a benign thymoma. The patient was found to be coinfected with B bronchiseptica and P jirovecii. Laboratory results showed panhypogammaglobulinemia and low absolute B- and CD4 T-cells. Therefore, the patient was diagnosed with Good's syndrome. However, despite treatment with intravenous antibiotics and intravenous immunoglobulin, the patient continued to deteriorate and expired. This patient demonstrates the importance of recognizing this rare immunodeficiency early in order to improve morbidity and mortality. Furthermore, this case highlights the importance of early immunoglobulin screening in the presence of asymptomatic thymoma.

Does enoxaparin interfere with HMGB1 signaling after TBI? A potential mechanism for reduced cerebral edema and neurologic recovery.

BACKGROUND: Enoxaparin (ENX) has been shown to reduce cerebral edema and improve neurologic recovery after traumatic brain injury (TBI), through blunting of cerebral leukocyte (LEU) recruitment. High mobility group box 1 (HMGB1) protein may induce inflammation through LEU activation. We hypothesized that ENX after TBI reduces LEU-mediated edema through blockade of HMGB1 signaling. METHODS: Twenty-three CD1 mice underwent severe TBI by controlled cortical impact and were randomized to one of four groups receiving either monoclonal antibody against HMGB1 (MAb) or isotype (Iso) and either ENX (1 mg/kg) or normal saline (NS): NS + Iso (n = 5), NS + MAb (n = 6), ENX + Iso (n = 6), ENX + MAb (n = 6). ENX or NS was administered 2, 8, 14, 23 and 32 hours after TBI. MAb or Iso (25 µg) was administered 2 hours after TBI. At 48 hours, cerebral intravital microscopy served to visualize live LEU interacting with endothelium and microvascular fluorescein isothiocyanate-albumin leakage. The Neurological Severity Score (NSS) graded neurologic recovery; wet-to-dry ratios determined cerebral/lung edema. Analysis of variance with Bonferroni correction was used for statistical analyses. RESULTS: ENX and MAb similarly reduced in vivo pial LEU rolling without demonstrating additive effect. In vivo albumin leakage was greatest in vehicle-treated animals but decreased by 25% with either MAb or ENX but by 50% when both were combined. Controlled cortical impact-induced cerebral wet-to-dry ratios were reduced by MAb or ENX without additive effect. Postinjury lung water was reduced by ENX but not by MAb. Neurologic recovery at 24 hours and 48 hours was similarly improved with ENX, MAb, or both treatments combined. CONCLUSION: Mirroring ENX, HMGB1 signaling blockade reduces LEU recruitment, cerebrovascular permeability, and cerebral edema following TBI. ENX further reduced lung edema indicating a multifaceted effect beyond HMGB1 blockade. Further study is needed to determine how ENX may play a role in blunting HMGB1 signaling in brain injury patients.

Enoxaparin ameliorates post-traumatic brain injury edema and neurologic recovery, reducing cerebral leukocyte endothelial interactions and vessel permeability in vivo.

BACKGROUND: Traumatic brain injury (TBI) confers a high risk of venous thrombosis, but early prevention with heparinoids is often withheld, fearing cerebral hematoma expansion. Yet, studies have shown heparinoids not only to be safe but also to limit brain edema and contusion size after TBI. Human TBI data also suggest faster radiologic and clinical neurologic recovery with earlier heparinoid administration. We hypothesized that enoxaparin (ENX) after TBI blunts in vivo leukocyte (LEU) mobilization to injured brain and cerebral edema, while improving neurologic recovery without increasing the size of the cerebral hemorrhagic contusion. METHODS: CD1 male mice underwent either TBI by controlled cortical impact (CCI, 1-mm depth, 6 m/s) or sham craniotomy. ENX (1 mg/kg) or vehicle (VEH, 0.9% saline, 1 mL/kg) was administered at 2, 8, 14, 23, and 32 hours after TBI. At 48 hours, intravital microscopy was used to visualize live LEUs interacting with endothelium and microvascular leakage of fluorescein isothiocyanate-albumin. Neurologic function (Neurological Severity Score, NSS), activated clotting time, hemorrhagic contusion size, as well as brain and lung wet-to-dry ratios were evaluated post mortem. Analysis of variance with Bonferroni correction was used for statistical comparisons between groups. RESULTS: Compared with VEH, ENX significantly reduced in vivo LEU rolling on endothelium (72.7 ± 28.3 LEU/100 µm/min vs. 30.6 ± 18.3 LEU/100 µm/min, p = 0.02) and cerebrovascular albumin leakage (34.5% ± 8.1% vs. 23.8% ± 5.5%, p = 0.047). CCI significantly increased ipsilateral cerebral hemisphere edema, but ENX treatment reduced post-CCI edema to near control levels (81.5% ± 1.5% vs. 77.6% ± 0.6%, p < 0.01). Compared with VEH, ENX reduced body weight loss at 24 hours (8.7% ± 1.2% vs. 5.8% ± 1.1%, p < 0.01) and improved NSS at 24 hours (14.5 ± 0.5 vs. 16.2 ± 0.4, p < 0.01) and 48 hours (15.1 ± 0.4 vs. 16.7 ± 0.5, p < 0.01) after injury. There were no significant differences in activated clotting time, hemorrhagic contusion size, and lung water content between the groups. CONCLUSION: ENX reduces LEU recruitment to injured brain, diminishing visible microvascular permeability and edema. ENX may also accelerate neurologic recovery without increasing cerebral contusion size. Further study in humans is necessary to determine safety, appropriate dosage, and timing of ENX administration early after TBI.

In vivo leukocyte-mediated brain microcirculatory inflammation: a comparison of osmotherapies and progesterone in severe traumatic brain injury.

BACKGROUND: Mannitol, hypertonic saline, and progesterone may blunt leukocyte recruitment after traumatic brain injury (TBI). We hypothesized that progesterone reduces pericontusional recruitment of leukocytes to a greater extent than either osmotherapy a day after TBI. METHODS: CD1 mice underwent controlled cortical impact and were treated with osmotherapy (mannitol and hypertonic saline) or progesterone. Thirty-two hours after TBI, live pial microscopy was used to evaluate leukocyte-endothelial interactions and immunohistochemistry was used for the detection of pericontusional tissue polymorphonuclear neutrophils. Neurologic recovery was assessed before sacrifice. RESULTS: Mannitol resulted in the lowest in vivo leukocyte recruitment compared with progesterone (795 ± 282 vs 1,636 ± 434 LEU/100 µm/minutes, P < .05). Mannitol also displayed lower tissue accumulation of leukocytes as compared with progesterone (5.7 ± 1.7 vs 15.2 ± .1 LEU/mm(2), P = .03). However, progesterone resulted in better neurologic recovery than either osmotherapy. CONCLUSIONS: Leukocyte recruitment to injured brain is lowest with mannitol administration. How different agents alter progression of secondary brain injury will require further evaluation in humans.

Neuroprotective effects of progesterone in traumatic brain injury: blunted in vivo neutrophil activation at the blood-brain barrier.

BACKGROUND: Progesterone (PRO) may confer a survival advantage in traumatic brain injury (TBI) by reducing cerebral edema. We hypothesized that PRO reduces edema by blocking polymorphonuclear (PMN) interactions with endothelium (EC) in the blood-brain barrier (BBB). METHODS: CD1 mice received repeated PRO (16 mg/kg intraperitoneally) or vehicle (cyclodextrin) for 36 hours after TBI. Sham animals underwent craniotomy without TBI. The modified Neurological Severity Score graded neurologic recovery. A second craniotomy allowed in vivo observation of pial EC/PMN interactions and vascular macromolecule leakage. Wet/dry ratios assessed cerebral edema. RESULTS: Compared with the vehicle, PRO reduced subjective cerebral swelling (2.9 ± .1 vs 1.2 ± .1, P < .001), PMN rolling (95 ± 1.8 vs 57 ± 2.0 cells/100 µm/min, P < .001), total EC/PMN adhesion (2.0 ± .4 vs .8 ± .1 PMN/100 µm, P < .01), and vascular permeability (51.8% ± 4.9% vs 27.1% ± 4.6%, P < .01). TBI groups had similar a Neurological Severity Score and cerebral wet/dry ratios (P > .05). CONCLUSIONS: PRO reduces live pericontusional EC/PMN and BBB macromolecular leakage after TBI. Direct PRO effects on the microcirculation warrant further investigation.

Similar effects of hypertonic saline and mannitol on the inflammation of the blood-brain barrier microcirculation after brain injury in a mouse model.

BACKGROUND: There has been substantial debate regarding the efficacy of hypertonic saline (HTS) versus mannitol (MTL) in treating moderate and severe traumatic brain injury (TBI). HTS blunts polymorphonuclear neutrophil (PMN) and endothelial cell (EC) activation and reduces tissue edema after resuscitated shock in systemic microvascular beds. MTL also modulates PMN activation markers. It remains unknown if either of these osmotherapies exert similar anti-inflammatory effects along the blood-brain barrier (BBB). We hypothesized that HTS, as compared with MTL, would more greatly reduce PMN-EC interactions, thereby reducing BBB permeability and tissue edema after simulated TBI. METHODS: CD1 male mice (25-30 g) underwent craniotomy and window placement for observation of in vivo PMN-EC interactions in pial venules using intravital video microscopy. TBI was simulated through local suffusion of the brain surface with interleukin 1ß (100 ng/0.1 mL). Animals were randomized to receive a single, equiosmolar, intravenous dose of 20% MTL or 5% HTS after injury. Live microcirculatory footage was obtained every 15 minutes for 2 hours, after which fluorescent-labeled albumin was administered to assess microvascular permeability. PMN rolling and adhesion and macromolecular leakage were analyzed offline by a blinded observer and postmortem brain and lung edema assessed by wet-to-dry ratios. Student's t test and Mann-Whitney U test determined significance (p ≤ 0.05). RESULTS: Neither osmotherapy resulted in significant differences in PMN rolling or adhesion; however, both trended higher in HTS. Similarly, vessel permeability did not differ between groups but also trended higher with HTS. In contrast, brain and lung edema was greater in MTL than HTS as compared with controls (p = 0.05). CONCLUSION: MTL and HTS have indistinguishable effects on PMN-EC interactions in the brain after simulated TBI. Additional studies are needed to determine if either osmotherapy has more subtle effects on BBB PMN-EC interactions after injury exerting a potential clinical advantage.

The impact of anxiety on conversion from mild cognitive impairment to Alzheimer's disease.

OBJECTIVE: To compare state and trait anxiety in mild cognitive impairment (MCI) patients and matched control subjects, and to assess the impact of these variables in predicting conversion to Alzheimer's disease. METHODS: One hundred and forty-eight patients with MCI, broadly defined, were assessed and followed systematically. Baseline predictors for follow-up conversion to AD (entire sample: 39/148 converted to Alzheimer's disease (AD)) included the Spielberger State-Trait Anxiety Inventory (STAI). RESULTS: At baseline evaluation, MCI patients had higher levels of state and trait anxiety than controls, with no differences between future AD converters (n = 39) and non-converters. In age-stratified Cox proportional hazards model analyses, STAI State was not a significant predictor of conversion to AD (STAI State < or =30 vs. > 30 risk ratio, 1.68; 95% CI, 0.75, 3.77; p = 0.21), but higher Trait scores indicated a lower risk of conversion when STAI State, education, the Folstein Mini-Mental State Examination and HAM-D (depression score) were also included in the model (STAI Trait < or =30 vs. > 30 risk ratio, 0.36; 95% CI, 0.16, 0.82; p = 0.015). CONCLUSIONS: In contrast to two other recent studies that showed anxiety predicted cognitive decline or conversion to AD, in this clinic-based sample, state anxiety was not a significant predictor. However, higher Trait anxiety predicted a lower risk of future conversion to AD. Further research with systematic long-term follow-up in larger samples is needed to clarify the role of state and trait anxiety in predicting MCI conversion to AD.

An open trial of aripiprazole augmentation for SSRI non-remitters with late-life depression.

OBJECTIVE: To evaluate the efficacy and tolerability of aripiprazole augmentation in elderly depressed patients who did not reach remission after treatment with an SSRI. METHOD: Outpatients 50 years and older with major depressive disorder not remitting after adequate treatment with an SSRI were eligible for the study. In the 6-week long augmentation phase, antidepressants were continued without change and aripiprazole was titrated if needed to a maximum dose of 15 mg per day. Patients were evaluated at the study endpoint on an intent to treat basis, and the primary outcome measure was remission of depression as measured by Hamilton Rating Scale for Depression (HRSD)

Surgical management of obese patients with eating disorders: a survey of current practice.

BACKGROUND: This study examined the current practice of bariatric surgeons and their colleagues regarding patients with binge eating disorder (BED) and night eating syndrome (NES) who present for Roux-en-Y gastric bypass (RYGBP) for obesity. METHOD: We conducted a 9-item internet survey of American Society for Bariatric Surgery (ASBS) members. For each item, the numbers of respondents endorsing each possible response, including "Other" and "Unknown or not applicable," were tabulated, and percentages of the total sample of respondents were calculated. RESULTS: Most respondents' screening process included mental health (82.0%) and nutritional (78.0%) evaluations. Most inquired about binge eating (88.0%) and other eating disturbances (83.3%), while fewer respondents (52.7%) screened for night eating. Management of patients with eating disorders varied widely. For patients with binge eating, 20.0% of respondents proceeded with surgery, 2.7% recommended against surgery, and 27.3% postponed surgery, with the remainder (50.0%) reporting that their management varied. For night eating and other eating disturbances, responses were similarly diverse. Respondents who postponed surgery reported a wide range of estimates of how often patients with eating disorders follow through with treatment for their eating problem and return for surgery: 16% (always/almost always), 36% (usually), 24% (sometimes), 12% (occasionally), and 12% (never/almost never). CONCLUSION: Although bariatric surgeons commonly screen for eating disorders such as BED, there are limited empirical data and no consensus regarding the optimal management of these patients.