Twists and Turns: A Chiropractic Roller Coaster Experience Unraveling the Intricacies of Bilateral Vertebral Artery Dissection.

The primary insult in vertebral artery dissections (VADs) involves a tear in the vertebral artery intima, resulting in potential thrombus formation and an elevated risk of cerebrovascular events, such as stroke. Despite its relatively low overall incidence rate, VADs contribute to a significant proportion of ischemic strokes within the younger population. VAD has been associated with various risk factors including but not limited to neck trauma from chiropractic manipulation and significant neck movements. Our patient initially presented with a worsening occipital headache but was discharged due to the absence of any red-flag symptoms. However, the patient shortly returned to the ED upon worsening symptoms, and despite the lack of apparent neurological deficits, the patient's history of cervical spine manipulation and exposure to neck trauma risk activities (roller coaster riding) increased suspicion for VAD. This case highlights the importance of considering VAD as a differential diagnosis in young patients presenting with unexplained headaches and neck pain following events that exert stress on the vertebral arteries, such as roller coaster rides and chiropractic neck manipulation. When managed properly, the long-term prognosis of VAD is generally favorable; however, the risk of recurrent dissection and stroke still remains. Thus, this case further emphasizes the need for timely intervention and the role of dual anti-platelet therapy (DAPT) in the management of VAD to prevent further complications such as stroke.

Using Initial Biopsies and Vertical Sections to Improve Trainees' Confidence in Performing Mohs Surgery.

BACKGROUND: Tissue preservation and tumor clearance are hallmarks of Mohs micrographic surgery, but no standardized method currently exists to guide trainees on how to balance the two. OBJECTIVE: The authors provided residents and fellows with additional histologic information to enhance their surgical decision-making without changing the standard methodology of Mohs surgery. METHODS AND MATERIALS: Trainees were provided initial biopsy slides (IS) and frozen vertical sections (VS) of the first Mohs layer. All Mohs layers were excised in standard fashion, and vertically oriented sections were taken from the layer without disturbing the surgical margins to obtain VS. Surveys were used to assess trainees' confidence in performing Mohs surgery with and without these tools. RESULTS: Trainees reported increased confidence in performing Mohs surgery when they reviewed IS before surgery and viewed VS of the first layer. CONCLUSION: Reviewing IS and VS improved trainees' confidence in performing Mohs surgery. This additional histological information was obtained while maintaining the usual steps of Mohs surgery. Objective information obtained from IS and VS may explain why trainees' confidence increased using this technique. Both IS and VS can be valuable teaching tools that may enhance trainees' ability to perform Mohs surgery.

Different COVID-19 treatments' impact on hospital length of stay.

IMPORTANCE: COVID-19 has adversely affected global healthcare infrastructure since 2019. Currently, there are no large-scale published reports on the efficacy of combination therapy of dexamethasone, remdesivir, and tocilizumab on COVID-19 patients. OBJECTIVES: Is the combination therapy of dexamethasone, remdesivir, and tocilizumab superior to other treatments on hospitalized COVID-19 patients? DESIGN: This is a retrospective, comparative effectiveness study. SETTING: Single-center study PARTICIPANTS/INTERVENTIONS: We analyzed different inpatient COVID-19 treatment options available in the United States and their impact on hospital length of stay (LOS) and mortality. Hospitalized COVID-19 were categorized as "mild," "moderate" and "severe'' based on the highest level of oxygen required; room air, nasal cannula, or high flow/PAP/intubation, respectively. Patients were treated in accordance with the availability of medications and the latest treatment guidelines. MAIN OUTCOMES: The endpoints of the study are hospital discharges and death during hospitalization. RESULTS: 1233 COVID-19 patients were admitted from 2020 to 2021. No treatment combinations showed a statistically significant decrease in hospital LOS in mild COVID-19 patients (p = 0.186). In moderate patients, the combination of remdesivir and dexamethasone slightly decreased LOS by 1 day (p = 0.007). In severe patients, the three-drug combination of remdesivir, dexamethasone, and tocilizumab decreased LOS by 8 days (p = 0.0034) when compared to nonviable treatments, such as hydroxychloroquine and convalescent plasma transfusion. However, it did not show any statistically significant benefit when compared to two-drug regimens (dexamethasone plus remdesivir) in severe COVID-19 (p = 0.116). No treatment arm appeared to show a statistically significant decrease in mortality for severe COVID-19 patients. CONCLUSIONS: Our findings suggest that three-drug combination may decrease LOS in severe COVID-19 patients when compared to two-drug therapy. However, the trend was not supported by statistical analysis. Remdesivir may not be clinically beneficial for mild hospitalized COVID-19 patients; considering its cost, one could reserve it for moderate and severe patients. Triple drug therapies, while potentially reducing LOS for severe patients, do not affect overall mortality. Additional patient data may increase statistical power and solidify these findings.

Significance of Basal Cell Carcinomas Exhibiting Intravascular Invasion.

ABSTRACT: Intravascular invasion of tumor cells can be associated with metastasis in many cancers. Basal cell carcinomas (BCCs), however, rarely metastasize; therefore, the clinical impact of intravascularly invasive BCC (IVBCC) is currently unclear. Because of these facts and the rarity of IVBCC, questions have arisen on whether IVBCC truly exists. We present 4 cases of IVBCC: one case with obvious tumor islands within immunolabeled blood vessels in the context of advanced disease and 3 cases found incidentally during Mohs micrographic surgery. We discuss the difficulty in studying IVBCC, the idea that it could be due to artifact, and the lack of direct clinical-pathological correlation. Given these challenges, we propose diagnostic criteria for IVBCC to decrease ambiguity for pathological diagnosis. Such criteria may facilitate further studies on the clinical significance of IVBCC.

Ceftriaxone Resistance in Campylobacter Gastroenteritis.

Annually, millions of people worldwide are exposed to Campylobacter, a species of bacteria that commonly causes gastroenteritis and in cases of immunocompromised individuals, can also lead to life-threatening complications. After stool cultures are obtained, the usual treatment for infectious diarrhea involves metronidazole and quinolones such as ciprofloxacin or levofloxacin. Quinolones are a family of broad-spectrum antibiotics known to be effective against various gram-negative infections that also include Campylobacter jejuni (C. jejuni). However, due to adverse side effects and bacterial resistance risks that may exist with medication use, they are no longer used as a first line. Our patient, initially treated with ceftriaxone for symptoms resembling bacterial meningitis, pneumonia, and infectious diarrhea, showed minimal to no improvement. Subsequent cerebral spinal fluid (CSF) ruled out meningitis while stool studies confirmed C. jejuni as the causative agent. A switch to levofloxacin resulted in a noticeable improvement in the patient's condition. This case emphasizes the importance of considering changes in antibiotic regimen from ceftriaxone to quinolones when faced with persistent infectious diarrhea, due to the high prevalence of ceftriaxone resistance in C. jejuni infections.

MOC-31 Antibody Immunolabeling During Mohs Surgery.

BACKGROUND: Ber-EP4 is an antibody that labels basal cell carcinoma (BCC) by targeting epithelial cell adhesion molecule (Ep-CAM). MOC-31, a monoclonal mouse antibody, also targets Ep-CAM and is currently used to differentiate several extracutaneous epithelial tumors. However, the utility of MOC-31 has not been fully described in cutaneous tumors and in Mohs micrographic surgery (MMS). OBJECTIVE: To evaluate MOC-31 labeling in BCC and other cutaneous tumors and to compare immunolabeling intensity of MOC-31 and Ber-EP4 in BCCs. MATERIALS AND METHODS: Nineteen permanently fixed and 29 frozen BCC specimens and 23 other cutaneous tumors were labeled with MOC-31; labeling intensity of tumors, epidermis, and adnexal structures were recorded. In a separate study, a blinded dermatopathologist compared labeling intensities of 8 BCC specimens, each labeled with MOC-31 and Ber-EP4.4. RESULTS: MOC-31 labeled all BCCs. Eccrine coils and follicular bulbs did label variably, although this did not detract utility of MOC-31. Five of thirteen cutaneous squamous cell carcinomas and one of two Merkel cell carcinomas demonstrated MOC-31 positivity. MOC-31 and Ber-EP4 labeled BCCs similarly. CONCLUSION: MOC-31, an antibody directed against Ep-CAM, is sensitive for BCCs in frozen specimens encountered in MMS and permanently fixed specimen. In addition, MOC-31 demonstrated comparable immunolabeling characteristics with Ber-EP4 for BCCs.

Peritumoral matrilin-2 staining may be useful in distinguishing basal cell carcinoma from folliculocentric basaloid proliferation.

BACKGROUND: Folliculocentric basaloid proliferation (FBP) is a benign and reactive proliferation which can histopathologically mimic basal cell carcinomas (BCCs). The incidental presence of FBP during the excision of a BCC can occasionally lead to excessive tissue removal. One distinguishing feature of BCCs is that they invade the stroma, whereas FBPs generally do not. METHODS: Matrilin-2 is an extracellular matrix protein associated with tumor invasion, and we compared the expression of matrilin-2 in peritumoral cells of BCC and FBP. RESULTS: We found increased matrilin-2 expression within the peritumoral stroma of 41 of 42 BCCs (97.7%), with strong expression in all (100%) cases of infiltrative subtypes and in 21 of 25 (84%) nodular subtypes of BCC. We found no expression of peritumoral matrilin-2 in any of the seven cases of FBP. CONCLUSION: Our results suggest that immunolabeling with the matrilin-2 antibody may help distinguish BCCs from FBPs.

Topical timolol may improve overall scar cosmesis in acute surgical wounds.

Acute wounds created by dermatologists following the removal of nonmelanoma skin cancers are closed either by primary or secondary intention, and the best cosmetic outcome is preferentially desired. One parameter that determines the overall cosmesis of the healed wound is its vascularity. Vascular tone results from a complex interplay of a variety of chemokines in the body and their interaction with receptors located on endothelial cell surfaces. In this study, our aim was to determine if topical timolol could improve the overall cosmesis of acute surgical wounds. We determined that patients who treated their acute surgical wounds with topical timolol had improved cosmesis compared to control.

Histological Mohs Maps Improve the Accuracy of Dermatology Residents' Interpretations of Mohs Slides: A Pilot Study.

BACKGROUND: Effective Mohs surgery depends on accurate histopathological identification and mapping of tumor burden to ensure complete removal of tumor. OBJECTIVE: The purpose of this study is to evaluate whether using a photograph of the histopathological slide as the Mohs map improves mapping accuracy. MATERIALS AND METHODS: Single-blinded pilot study. Five dermatology residents at one academic institution mapped 11 cases of basal cell carcinoma using both traditional hand-drawn maps and color photographic maps. Residents' marked maps were assessed for global diagnostic accuracy, sensitivity, and specificity compared with the Mohs map verified by the attending surgeon on the day of surgery. RESULTS: Diagnostic accuracy, sensitivity, and specificity were higher using the photographic Mohs maps compared with using the traditional hand-drawn maps (58.2% vs 29.1%, 84.5% vs 76.4%, and 87.1% vs 70.8%, respectively). These results were statistically significant for accuracy and specificity, but not for sensitivity. CONCLUSION: Using histopathological photographs as the Mohs map significantly improved accuracy and specificity within a small group of residents with limited Mohs experience. More research is warranted to evaluate whether using histopathological photographs improves accuracy of Mohs mapping for experienced Mohs surgeons in a real-world setting, and whether this translates to improved clinical outcomes.

Patient Satisfaction After Mohs Surgery is not Dependent on Seeing Post-Mohs Defect Prior to Repair.

BACKGROUND: Optimizing patient satisfaction and scar outcomes is important for the practicing Mohs surgeon. OBJECTIVE: To evaluate whether showing or not showing patients their post-Mohs defect prior to repair influences scar satisfaction. MATERIALS AND METHODS: Fifty patients with a nonmelanoma skin cancer on their head or neck requiring Mohs micrographic surgery were randomized to either see or not see their post-Mohs defect in the mirror prior to repair. Patients evaluated their scar at Week 1 and Week 4 using the patient scar assessment questionnaire. RESULTS: There was no statistically significant difference in the primary (scar satisfaction) or secondary outcomes (wound care compliance and complication rates) between the two groups. CONCLUSION: There is no difference in patient scar satisfaction whether patients see or do not see their post-Mohs defect prior to repair.

Drug-associated skin lesions in a patient with myelofibrosis receiving ruxolitinib.

Ruxolitinib, a small molecule JAK-1/2 inhibitor, was approved by the U.S. Food and Drug Administration (FDA) in November 2011, as the first therapeutic for the treatment of intermediate and high-risk myelofibrosis. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of the most well-studied intracellular signaling networks. Recent advances in our understanding of the complexities of signal activation and regulation of gene expression has provided opportunities for targeted therapeutic interventions. Although numerous inhibitors of the JAK/STAT pathway are currently being evaluated in clinical trials, ruxolitinib represents the first FDA approved in-class JAK inhibitor. We report a drug eruption associated with ruxolitinib.

Matrilin-2 is proteolytically cleaved by ADAMTS-4 and ADAMTS-5.

Matrilin-2 is a widely distributed, oligomeric extracellular matrix protein that forms a filamentous network by binding to a variety of different extracellular matrix proteins. We found matrilin-2 proteolytic products in transfected cell lines in vitro and in mouse tissues in vivo. Two putative cleavage sites were identified in the unique domain of matrilin-2; the first site was located between D851 and L852 in the middle of the domain and the second, at the boundary with the coiled-coil domain at the C-terminus. Deletion of the entire unique domain eliminated the proteolysis of matrilin-2. While the first cleavage site was present in all matrilin-2 oligomers, the second cleavage site became apparent only in the matrilin-2 hetero-oligomers with matrilin-1 or matrilin-3. Analysis using a variety of extracellular protease inhibitors suggested that this proteolytic activity was derived from a member or several members  of the ADAMTS family. Recombinant human ADAMTS-4 (aggrecanase-1) and ADAMTS-5 (aggrecanase-2), but not ADAMTS-1, cleaved recombinant matrilin-2, thereby yielding matrilin-2 proteolytic peptides at the predicted sizes. These results suggest that ADAMTS-4 and ADAMTS-5 may destabilize the filamentous network in the extracellular matrix by cleaving matrilin-2 in both homo-oligomers and hetero-oligomers.

Bone marrow cell mobilization by the systemic use of granulocyte colony-stimulating factor (GCSF) improves wound bed preparation.

Innovative approaches are needed to accelerate the healing of human chronic wounds not responding to conventional therapies. An evolving and promising treatment is the use of stem cells. Our group has previously described the use of expanded (in vitro) autologous stem cells aspirated from human bone marrow and applied topically in a fibrin spray to human acute and chronic wounds. More recently, we have sought ways to mobilize stem cells directly from the bone marrow, without in vitro expansion. In this report, we show that systemic injections of granulocyte colony-stimulating factor (GCSF) can mobilize stem cells from bone marrow into the peripheral blood and then to the wound site. Our objectives were to optimize parameters for this method by using mouse models and proof of principle in a human chronic wound situation. Mice were injected for 5 days with 2 different formulations of GCSF and compared to control saline. To monitor stem cell mobilization, flow cytometric measurements of Sca-1 and c-Kit and colony-forming cell assays were performed. Full-thickness tail wounds in mice were created and monitored for healing, and polyvinyl alcohol sponges were implanted dorsally to assess collagen accumulation. To determine bone marrow stem cell homing to the wound site, chimeric mice transplanted with Green Fluorescent Protein bone marrow cells were scanned by live imaging. Additionally, as proof of principle, we tested the systemic GCSF approach in a patient with a nonhealing venous ulcer. Our findings lay the ground work and indicate that the systemic administration of GCSF is effective in mobilizing bone marrow stem cells into the peripheral blood and to the wound site. These findings are associated with an increased accumulation of collagen and promising results in terms of wound bed preparation and healing.

Diagnostic utility of cytokeratin 17 immunostaining in morpheaform basal cell carcinoma and for facilitating the detection of tumor cells at the surgical margins.

BACKGROUND: The morpheaform subtype of basal cell carcinoma (BCC) often presents a diagnostic histological challenge, and its true margin may be difficult to determine with accuracy. This tumor may also be difficult to distinguish from other adnexal neoplasms having a benign clinical course. Previous work has shown that cytokeratin 17 (CK17 or K17) expression is high in BCC. OBJECTIVE: To confirm the expression of K17 across the subtypes of superficial, nodular and morpheaform BCC variants and to compare K17 expression in each of these subtypes of BCC with that in two other adnexal neoplasms. METHODS: Tissue specimens from each tumor category were randomly collected, immunolabeled, and scored for K17 expression according to intensity and extent of immunostaining. RESULTS: Our results indicate that K17 is a useful marker in the identification and outlining of BCC. Moreover, in morpheaform BCC, K17 immunostaining clearly detected individual tumor cells well away from the dermal tumor strands that otherwise seemed nonmalignant according to hematoxylin and eosin staining alone. In addition, the expression of K17 in morpheaform BCC is capable (100% of specimens; p < .001) of distinguishing this tumor from desmoplastic trichoepithelioma. CONCLUSION: We propose that K17 immunostaining could improve the diagnostic and surgical management of these tumors.

Diabetic foot ulcer calluses show histological similarities to HPV infection without evidence of HPV involvement by nested PCR.

A number of studies have reported an association between callus formation and the development of foot ulcers in diabetic patients. However, it has been noted that calluses may continue to form in spite of bed rest and, presumably, excellent patient compliance with offloading. Additionally, the authors have noted that, histologically, calluses in the diabetic foot often resemble lesions induced by human papillomavirus (HPV). As diabetes is associated with immune depression, the authors hypothesized that HPV may play at least a partial role in the pathogenesis of calluses in diabetic patients. The objective of the reported study was to determine whether calluses around diabetic neuropathic foot ulcers are associated with HPV infection. The authors carried out biopsies on 11 independent calluses from 6 patients with diabetic foot ulcers and analyzed each sample by histology and by nested polymerase chain reaction (PCR), screening for the presence of DNA from HPV-1, -2, -3, -4, -6, -10, -11, -16, -18, -27, -28, -29, -31, -41, -50, -57, -60, -63, -65, and -77. The callus biopsy specimens showed histological evidence of koilocytes, papillary hyperplasia, hypergranulosis, and hyperkeratosis, a picture very similar to HPV cutaneous infection. However, nested PCR using positive and negative controls did not show detectable levels of HPV DNA. The authors therefore conclude that HPV infection is unlikely to play a significant role in diabetic foot callus pathogenesis, in spite of histological findings similar to those seen with verruca vulgaris.

3-(Arylthiomethyl)isoxazole-4,5-dicarboxamides: chemoselective nucleophilic chemistry and insecticidal activity.

A collection of 91 3-(arylthiomethyl)isoxazole-4,5-dicarboxamides was prepared starting from dimethyl 3-(chloromethyl)isoxazole-4,5-dicarboxylate. The thioether moieties in these compounds were subsequently oxidized to give the corresponding 3-(arylsulfonylmethyl)isoxazole-4,5-dicarboxamides. By carefully controlling stoichiometry and reaction conditions, the C4 and C5 carbomethoxy groups could be differentially derivatized to carboxamides. A total of 182 trisubstituted isoxazoles are reported and deposited in the National Institutes of Health Molecular Repository; an 80 compound subset was evaluated for insecticidal activity.

The utility of the DNA microarray scanner to simplify the immunofluorescence evaluation of autoimmune bullous diseases.

A DNA microarray scanner was used as a digital fluorescence microscope to simplify the diagnosis of autoimmune bullous diseases. Frozen sections of skin biopsies were taken from 3 patients with bullous pemphigoid and 1 patient each with lichen planus pemphigoides, linear immunoglobulin (Ig) A disease, and dermatitis herpetiformis. After incubation with cyanine-labeled antibodies, the tissues were scanned at 5-mum resolution using an instrument originally designed to study gene expression. The microarray scanner's large field of view, unlike that of fluorescence microscopy, allowed a view of the entire specimen, considerably easing the orientation of tissue. All images were diagnostic and included a linear pattern along the basement membrane zone (BMZ) using anti-IgG and anti-C3 in all cases of bullous pemphigoid, a linear pattern of IgG along the BMZ in lichen planus pemphigoides, and a linear pattern of IgA along the BMZ in linear IgA dermatosis. IgA deposition along dermal papillary tips was seen in dermatitis herpetiformis, but a granular pattern was indiscernible at the 5-mum resolution. The advantages of the microarray scanner over standard fluorescence microscopy include speed, technical ease, large field of view, potential for visualizing multiple antibodies simultaneously in a tissue, and convenience of digital image archiving.

Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds.

The nonhematopoietic component of bone marrow includes multipotent mesenchymal stem cells (MSC) capable of differentiating into fat, bone, muscle, cartilage, and endothelium. In this report, we describe the cell culture and characterization, delivery system, and successful use of topically applied autologous MSC to accelerate the healing of human and experimental murine wounds. A single bone marrow aspirate of 35-50 mL was obtained from patients with acute wounds (n = 5) from skin cancer surgery and from patients with chronic, long-standing, nonhealing lower extremity wounds (n = 8). Cells were grown in vitro under conditions favoring the propagation of MSC, and flow cytometry and immunostaining showed a profile (CD29+, CD44+, CD105+, CD166+, CD34-, CD45-) highly consistent with published reports of human MSC. Functional induction studies confirmed that the MSC could differentiate into bone, cartilage, and adipose tissue. The cultured autologous MSC were applied up to four times to the wounds using a fibrin polymer spray system with a double-barreled syringe. Both fibrinogen (containing the MSC) and thrombin were diluted to optimally deliver a polymerized gel that immediately adhered to the wound, without run-off, and yet allowing the MSC to remain viable and migrate from the gel. Sequential adjacent sections from biopsy specimens of the wound bed after MSC application showed elongated spindle cells, similar to their in vitro counterparts, which immunostained for MSC markers. Generation of new elastic fibers was evident by both special stains and antibodies to human elastin. The application of cultured cells was safe, without treatment-related adverse events. A strong direct correlation was found between the number of cells applied (greater than 1 x 10(6) cells per cm2 of wound area) and the subsequent decrease in chronic wound size (p = 0.0058). Topical application of autologous MSC also stimulated closure of full-thickness wounds in diabetic mice (db/db). Tracking of green fluorescent protein (GFP)+ MSC in mouse wounds showed GFP+ blood vessels, suggesting that the applied cells may persist as well as act to stimulate the wound repair process. These findings indicate that autologous bone marrow-derived MSC can be safely and effectively delivered to wounds using a fibrin spray system.

Immunophenotype of conjunctival melanomas: comparisons with uveal and cutaneous melanomas.

OBJECTIVE: To characterize the immunophenotypic expression pattern of conjunctival melanomas, with the use of standard melanoma markers as well as microphthalmia transcription factor and p75 neurotrophin receptor. DESIGN: Eleven conjunctival melanomas, including 1 caruncular melanoma, were immunolabeled with a panel of antibodies that included S100, tyrosinase, melan-A, HMB-45 and HMB-50 combination, microphthalmia transcription factor, and p75 neurotrophin receptor. The results were tabulated on the basis of intensity and pervasiveness of labeling and compared with a previous study of uveal melanomas. RESULTS: Immunolabeling with S100 was at significantly higher levels in conjunctival melanomas than in uveal melanomas. Tyrosinase, HMB-45 and HMB-50 combination, melan-A, and microphthalmia transcription factor were expressed at high levels in conjunctival melanomas, whereas p75 neurotrophin receptor was not expressed. CONCLUSIONS: Melanomas of the conjunctiva, including the caruncle, expressed S100, tyrosinase, melan-A, HMB-45 and HMB-50 combination, and microphthalmia transcription factor at high levels, suggesting that these are good markers for this melanoma subtype. Expression of S100 was significantly higher in conjunctival melanomas than in uveal melanomas. The immunophenotypic pattern of conjunctival melanomas is most similar to the epithelioid subtype of cutaneous melanomas.