Efficacy of Nd:YAG laser therapy for the treatment of verrucae: a literature review.

Verrucae are benign epithelial proliferations, characteristically 1-20 mm in diameter, caused by human papilloma virus (HPV) infection occurring on the skin and mucosa (Photomed Laser Surg 33(6):338-42, 2015; Lasers Med Sci 29(3):1111-6, 2014). Prevalence of verrucae is 5-20% in children and young adults with peak incidence reported during teenage years (Lasers Med Sci 29(3):1111-6, 2014; J Am Acad Dermatol 22(4):547-66, 1990; J Korean Med Sci 24(5):889-93, 2009). Patients often express significant displeasure with quality of life due to this cosmetic insecurity, as well as functional problems and physical discomfort when they occur on palms of hands and soles of feet. Traditional therapeutic options for warts, such as topical salicyclic acid, topical imiquimod, bleomycin injections, cryotherapy, surgical excision, and electrocautery, have proven somewhat effective but often lead to high recurrence rates or scarring (Photomed Laser Surg 33(6):338-42, 2015). Laser therapy offers an alternative solution by employing selective tissue destruction with minimal risks. We performed a broad literature search in PubMed to obtain all available published articles that studied the treatment of verrucae on the skin with 1064-nm neodymium-doped yttrium aluminum garnet laser. This laser is specifically suited for verruca treatment due to its deeply penetrating 1064-nm wavelength and relatively low risk of pigmentation changes in dark skin types (Photomed Laser Surg 33(6):338-42, 2015). Laser therapy is effective in the treatment of verrucae and has enabled clinicians to provide direct, targeted treatment of warts.

The picosecond laser for tattoo removal.

The prevalence of tattoos continues to grow as modern society's stigma towards this form of body art shifts towards greater acceptance. Approximately one third of Americans aged 18-25 and 40 % of Americans aged 26-40 are tattooed. As tattoos continue to rise in popularity, so has the demand for an effective method of tattoo removal such as lasers. The various colors of tattoo inks render them ideal targets for specific lasers using the principle of selective photothermolysis. Traditional laser modalities employed for tattoo removal operate on pulse durations in the nanosecond domain. However, this pulse duration range is still too long to effectively break ink into small enough particles. Picosecond (10-12) lasers have emerged at the forefront of laser tattoo removal due to their shorter pulse lengths, leading to quicker heating of the target chromophores, and consequently, more effective tattoo clearance. Recent studies have cited more effective treatment outcomes using picosecond lasers. Future comparative studies between picosecond lasers of various settings are necessary to determine optimal laser parameters for tattoo clearance.

Prevention of health care-associated infections.

Health care-associated infections cause approximately 75,000 deaths annually, in addition to increasing morbidity and costs. Over the past decade, a downward trend in health care-associated infections has occurred nationwide. Basic prevention measures include administrative support, educating health care personnel, and hand hygiene and isolation precautions. Prevention of central line- or catheter-associated infections begins with avoidance of unnecessary insertion, adherence to aseptic technique when inserting, and device removal when no longer necessary. Specific recommendations for preventing central line-associated bloodstream infections include use of chlorhexidine for skin preparation, as a component of dressings, and for daily bathing of patients in intensive care units. Catheter-associated urinary tract infections are the most common device-related health care-associated infection. Maintaining a closed drainage system below the patient reduces the risk of infection. To prevent ventilator-associated pneumonia, which is associated with high mortality, mechanically ventilated patients should be placed in the semirecumbent position and receive antiseptic oral care. Prevention of surgical site infections includes hair removal using clippers, glucose control, and preoperative antibiotic prophylaxis. Reducing transmission of Clostridium difficile and multidrug-resistant organisms in the hospital setting begins with hand hygiene and contact precautions. Institutional efforts to reduce unnecessary antibiotic prescribing are also strongly recommended. Reducing rates of methicillin-resistant Staphylococcus aureus infection can be achieved through active surveillance cultures and decolonization therapy with mupirocin.

SHEA position statement on pandemic preparedness for policymakers: building a strong and resilient healthcare workforce.

Throughout the COVID-19 pandemic, many areas in the United States experienced healthcare personnel (HCP) shortages tied to a variety of factors. Infection prevention programs, in particular, faced increasing workload demands with little opportunity to delegate tasks to others without specific infectious diseases or infection control expertise. Shortages of clinicians providing inpatient care to critically ill patients during the early phase of the pandemic were multifactorial, largely attributed to increasing demands on hospitals to provide care to patients hospitalized with COVID-19 and furloughs.1 HCP shortages and challenges during later surges, including the Omicron variant-associated surges, were largely attributed to HCP infections and associated work restrictions during isolation periods and the need to care for family members, particularly children, with COVID-19. Additionally, the detrimental physical and mental health impact of COVID-19 on HCP has led to attrition, which further exacerbates shortages.2 Demands increased in post-acute and long-term care (PALTC) settings, which already faced critical staffing challenges difficulty with recruitment, and high rates of turnover. Although individual healthcare organizations and state and federal governments have taken actions to mitigate recurring shortages, additional work and innovation are needed to develop longer-term solutions to improve healthcare workforce resiliency. The critical role of those with specialized training in infection prevention, including healthcare epidemiologists, was well-demonstrated in pandemic preparedness and response. The COVID-19 pandemic underscored the need to support growth in these fields.3 This commentary outlines the need to develop the US healthcare workforce in preparation for future pandemics.

SHEA position statement on pandemic preparedness for policymakers: introduction and overview.

Throughout history, pandemics and their aftereffects have spurred society to make substantial improvements in healthcare. After the Black Death in 14th century Europe, changes were made to elevate standards of care and nutrition that resulted in improved life expectancy.1 The 1918 influenza pandemic spurred a movement that emphasized public health surveillance and detection of future outbreaks and eventually led to the creation of the World Health Organization Global Influenza Surveillance Network.2 In the present, the COVID-19 pandemic exposed many of the pre-existing problems within the US healthcare system, which included (1) a lack of capacity to manage a large influx of contagious patients while simultaneously maintaining routine and emergency care to non-COVID patients; (2) a "just in time" supply network that led to shortages and competition among hospitals, nursing homes, and other care sites for essential supplies; and (3) longstanding inequities in the distribution of healthcare and the healthcare workforce. The decades-long shift from domestic manufacturing to a reliance on global supply chains has compounded ongoing gaps in preparedness for supplies such as personal protective equipment and ventilators. Inequities in racial and socioeconomic outcomes highlighted during the pandemic have accelerated the call to focus on diversity, equity, and inclusion (DEI) within our communities. The pandemic accelerated cooperation between government entities and the healthcare system, resulting in swift implementation of mitigation measures, new therapies and vaccinations at unprecedented speeds, despite our fragmented healthcare delivery system and political divisions. Still, widespread misinformation or disinformation and political divisions contributed to eroded trust in the public health system and prevented an even uptake of mitigation measures, vaccines and therapeutics, impeding our ability to contain the spread of the virus in this country.3 Ultimately, the lessons of COVID-19 illustrate the need to better prepare for the next pandemic. Rising microbial resistance, emerging and re-emerging pathogens, increased globalization, an aging population, and climate change are all factors that increase the likelihood of another pandemic.4.

Society for Healthcare Epidemiology of America position statement on pandemic preparedness for policymakers: mitigating supply shortages.

The COVID-19 has had major direct (e.g., deaths) and indirect (e.g., social inequities) effects in the United States. While the public health response to the epidemic featured some important successes (e.g., universal masking ,and rapid development and approval of vaccines and therapeutics), there were systemic failures (e.g., inadequate public health infrastructure) that overshadowed these successes. Key deficiency in the U.S. response were shortages of personal protective equipment (PPE) and supply chain deficiencies. Recommendations are provided for mitigating supply shortages and supply chain failures in healthcare settings in future pandemics. Some key recommendations for preventing shortages of essential components of infection control and prevention include increasing the stockpile of PPE in the U.S. National Strategic Stockpile, increased transparency of the Stockpile, invoking the Defense Production Act at an early stage, and rapid review and authorization by FDA/EPA/OSHA of non-U.S. approved products. Recommendations are also provided for mitigating shortages of diagnostic testing, medications and medical equipment.

SHEA position statement on pandemic preparedness for policymakers: pandemic data collection, maintenance, and release.

The Society for Healthcare Epidemiology in America (SHEA) strongly supports modernization of data collection processes and the creation of publicly available data repositories that include a wide variety of data elements and mechanisms for securely storing both cleaned and uncleaned data sets that can be curated as clinical and research needs arise. These elements can be used for clinical research and quality monitoring and to evaluate the impacts of different policies on different outcomes. Achieving these goals will require dedicated, sustained and long-term funding to support data science teams and the creation of central data repositories that include data sets that can be "linked" via a variety of different mechanisms and also data sets that include institutional and state and local policies and procedures. A team-based approach to data science is strongly encouraged and supported to achieve the goal of a sustainable, adaptable national shared data resource.

COVID-19 Outcomes in Stage IV Cancer Patients Receiving Immune Checkpoint Inhibitors.

Cancer patients are a vulnerable population in the current coronavirus disease 2019 (COVID-19) outbreak. The impact of immune checkpoint inhibitors (ICIs) on the outcomes of COVID-19 infection in cancer patients remains largely unclear. We retrospectively investigated all solid cancer patients who received at least one cycle of ICIs at a single institution between August 2020 and August 2021. All stage IV solid cancer patients who were on or ceased ICI treatment when diagnosed with COVID-19 were eligible. All COVID-19 infections were confirmed by RT-PCR. Risk factors for hospitalization, severe symptoms, and death were analyzed. A total of 56 patients were included in our study. Twenty (35.7%) patients require hospitalization, 12 (21.4%) developed severe symptoms, and 10 (17.9%) died from COVID-19 infection. ICI treatment was interrupted in 37 patients (66.1%), 24 of whom (64.9%) had treatment resumed. Eight (80%) COVID-19-related death occurred in unvaccinated individuals. Reinfection occurred in seven patients (12.5%), and three of them died from their second COVID-19 infection. Factors associated with hospitalization were high Charlson comorbidity score (OR 1.56, 95% CI 1.10-2.23, p = 0.01) and lymphocyte ≤ 1500 mm3 (OR 10.05, 95% CI 2.03-49.85, p = 0.005). Age, chemoimmunotherapy, and ICI treatment duration were not associated with increased risk of hospitalization, severe symptoms, or COVID-19-related mortality. ICI therapy does not impose an increased risk for severe COVID-19 infection in stage IV cancer patients. Vaccination should be encouraged among this population. Clinicians should be cognizant of a potential worse outcome in COVID-19-reinfected patients.

ICU outcomes and survival in patients with severe COVID-19 in the largest health care system in central Florida.

BACKGROUND: Observational studies have consistently described poor clinical outcomes and increased ICU mortality in patients with severe coronavirus disease 2019 (COVID-19) who require mechanical ventilation (MV). Our study describes the clinical characteristics and outcomes of patients with severe COVID-19 admitted to ICU in the largest health care system in the state of Florida, United States. METHODS: Retrospective cohort study of patients admitted to ICU due to severe COVID-19 in AdventHealth health system in Orlando, Florida from March 11th until May 18th, 2020. Patients were characterized based on demographics, baseline comorbidities, severity of illness, medical management including experimental therapies, laboratory markers and ventilator parameters. Major clinical outcomes analyzed at the end of the study period were: hospital and ICU length of stay, MV-related mortality and overall hospital mortality of ICU patients. RESULTS: Out of total of 1283 patients with COVID-19, 131 (10.2%) met criteria for ICU admission (median age: 61 years [interquartile range (IQR), 49.5-71.5]; 35.1% female). Common comorbidities were hypertension (84; 64.1%), and diabetes (54; 41.2%). Of the 131 ICU patients, 109 (83.2%) required MV and 9 (6.9%) received ECMO. Lower positive end expiratory pressure (PEEP) were observed in survivors [9.2 (7.7-10.4)] vs non-survivors [10 (9.1-12.9] p = 0.004]. Compared to non-survivors, survivors had a longer MV length of stay (LOS) [14 (IQR 8-22) vs 8.5 (IQR 5-10.8) p< 0.001], Hospital LOS [21 (IQR 13-31) vs 10 (7-1) p< 0.001] and ICU LOS [14 (IQR 7-24) vs 9.5 (IQR 6-11), p < 0.001]. The overall hospital mortality and MV-related mortality were 19.8% and 23.8% respectively. After exclusion of hospitalized patients, the hospital and MV-related mortality rates were 21.6% and 26.5% respectively. CONCLUSIONS: Our study demonstrates an important improvement in mortality of patients with severe COVID-19 who required ICU admission and MV in comparison to previous observational reports and emphasizes the importance of standard of care measures in the management of COVID-19.

Clinical presentation of nipah virus infection in Bangladesh.

BACKGROUND: In Bangladesh, 4 outbreaks of Nipah virus infection were identified during the period 2001-2004. METHODS: We characterized the clinical features of Nipah virus-infected individuals affected by these outbreaks. We classified patients as having confirmed cases of Nipah virus infection if they had antibodies reactive with Nipah virus antigen. Patients were considered to have probable cases of Nipah virus infection if they had symptoms consistent with Nipah virus infection during the same time and in the same community as patients with confirmed cases. RESULTS: We identified 92 patients with Nipah virus infection, 67 (73%) of whom died. Although all age groups were affected, 2 outbreaks principally affected young persons (median age, 12 years); 62% of the affected persons were male. Fever, altered mental status, headache, cough, respiratory difficulty, vomiting, and convulsions were the most common signs and symptoms; clinical and radiographic features of acute respiratory distress syndrome of Nipah illness were identified during the fourth outbreak. Among those who died, death occurred a median of 6 days (range, 2-36 days) after the onset of illness. Patients who died were more likely than survivors to have a temperature >37.8 degrees C, altered mental status, difficulty breathing, and abnormal plantar reflexes. Among patients with Nipah virus infection who had well-defined exposure to another patient infected with Nipah virus, the median incubation period was 9 days (range, 6-11 days). CONCLUSIONS: Nipah virus infection produced rapidly progressive severe illness affecting the central nervous and respiratory systems. Clinical characteristics of Nipah virus infection in Bangladesh, including a severe respiratory component, appear distinct from clinical characteristics reported during earlier outbreaks in other countries.

Nitric Oxide Production by Myeloid-Derived Suppressor Cells Plays a Role in Impairing Fc Receptor-Mediated Natural Killer Cell Function.

Purpose: mAbs are used to treat solid and hematologic malignancies and work in part through Fc receptors (FcRs) on natural killer cells (NK). However, FcR-mediated functions of NK cells from patients with cancer are significantly impaired. Identifying the mechanisms of this dysfunction and impaired response to mAb therapy could lead to combination therapies and enhance mAb therapy.Experimental Design: Cocultures of autologous NK cells and MDSC from patients with cancer were used to study the effect of myeloid-derived suppressor cells (MDSCs) on NK-cell FcR-mediated functions including antibody-dependent cellular cytotoxicity, cytokine production, and signal transduction in vitro Mouse breast cancer models were utilized to study the effect of MDSCs on antibody therapy in vivo and test the efficacy of combination therapies including a mAb and an MDSC-targeting agent.Results: MDSCs from patients with cancer were found to significantly inhibit NK-cell FcR-mediated functions including antibody-dependent cellular cytotoxicity, cytokine production, and signal transduction in a contact-independent manner. In addition, adoptive transfer of MDSCs abolished the efficacy of mAb therapy in a mouse model of pancreatic cancer. Inhibition of iNOS restored NK-cell functions and signal transduction. Finally, nonspecific elimination of MDSCs or inhibition of iNOS in vivo significantly improved the efficacy of mAb therapy in a mouse model of breast cancer.Conclusions: MDSCs antagonize NK-cell FcR-mediated function and signal transduction leading to impaired response to mAb therapy in part through nitric oxide production. Thus, elimination of MDSCs or inhibition of nitric oxide production offers a strategy to improve mAb therapy. Clin Cancer Res; 24(8); 1891-904. ©2018 AACR.

Monocular diplopia-associated migraine-like headache induced by nicotine withdrawal.

We describe an extremely rare case of migraine-associated monocular diplopia developed in a 23-year-old man after sudden cessation of smoking. The physical examination and brain MRI scan were unremarkable. The symptoms resolved after starting nicotine patch. We reviewed the literature and discussed the diagnosis and possible mechanism of this phenomenon.

Safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in hepatitis C virus/human immunodeficiency virus co-infected patients.

AIM: To evaluate the safety and efficacy of ledipasvir/sofosbuvir on hepatitis C eradication in patients with hepatitis C virus (HCV)/human immunodeficiency virus (HIV) co-infection in an urban HIV clinic. METHODS: A retrospective cohort study of 40 subjects co-infected with HIV-1 and HCV treated with the fixed-dose combination of ledipasvir and sofosbuvir for 12 wk from 2014 to 2016. All patients included were receiving antiretroviral therapy (ART) with HIV RNA values of 100 copies/mL or fewer regardless of baseline HCV RNA level. The primary end point was a sustained virologic response of HCV at 12 wk (SVR12) after the end of therapy. RESULTS: Of the 40 patients enrolled, 55% were black, 22.5% had been previously treated for HCV, and 25% had cirrhosis. The patients were on a wide range of ART. Overall, 39 patients (97.5%) had a SVR 12 after the end of therapy, including rates of 97.1% in patients with HCV genotype 1a and 100% in those with HCV genotype 1b. One patient with HCV genotype 3a was included and achieved SVR12. Rates of SVR12 were similar regardless of previous treatment or the presence of compensated cirrhosis. Only 1 patient experienced relapse at week 12 following treatment and deep sequencing didn't reveal any resistance associated mutation in the NS5A or NS5B region. Interestingly, 7 (17.5%) patients who were adherent to ART experienced HIV viral breakthrough which resolved after continuing the same ART regimen. Two (5%) patients experienced HIV-1 virologic rebound due to noncompliance with HIV therapy, which resolved after resuming the same ART regimen. No severe adverse events were observed and no patient discontinued treatment because of adverse events. The most common adverse events included headache (12.5%), fatigue (10%), and diarrhea (2.5%). CONCLUSION: This retrospective study demonstrated the high rates of SVR12 of ledipasvir/sofosbuvir on HCV eradication in patients co-infected with HCV and HIV, regardless of HCV baseline levels, HCV treatment history or cirrhosis condition. The oral combination of ledipasvir/sofosbuvir represents a safe and well tolerated HCV treatment option that does not require modification for many of the common HIV ART. Occasional HIV virologic rebound occurred but later resolved without the need to change ART.

Vascular Features of Nail Psoriasis Using Dynamic Optical Coherence Tomography.

BACKGROUND: Nail psoriasis is a painful and disfiguring nail disease that often leads to invasive biopsies. Dermoscopy of the hyponychium can be useful in the diagnosis showing twisted coiled vessels. Structural features of nail psoriasis have been described with optical coherence tomography (OCT). OBJECTIVES: To investigate vascular features of nail psoriasis using dynamic OCT. METHODS: This was an observational, prospective, controlled study in which psoriasis patients with psoriatic nail changes and healthy control patients underwent OCT imaging of the distal nail plate and proximal nail fold. Vertical and horizontal OCT images were analyzed to describe structural and vascular features and to quantify blood flow at depth. RESULTS: Sixteen psoriatic nails and 16 control nails were included. Psoriatic nails had significantly increased blood flow in the proximal nail fold at depths of 0.72 mm (p = 0.035) and 0.76 mm (p = 0.027). Nail thickness was significantly greater in psoriatic nails compared to control nails (p = 0.0016). Compared to control nails, psoriatic nails had dilated, disorganized blood vessels superficially in the proximal nail fold. LIMITATIONS: The main limitation of our study is the relatively small sample size. CONCLUSIONS: OCT can identify structural and vascular features specific to nail psoriasis.

Effects of a predictive preventive model for prevention of Clostridium difficile infection in patients in intensive care units.

BACKGROUND: Health care-acquired Clostridium difficile infection (HACDI) is associated with adverse outcomes at both the organization and patient level. Factors that increase risk for development of HACDI have been identified. Objectives of this study were to develop a predictive screening tool to identify patients at risk for HACDI and implement a bundle of mitigation interventions. METHODS: A predictive screening tool was developed based on risk factors identified in the literature and validated by retrospective analysis of all HACDI cases occurring in critically ill patients during 2013. The tool was used to screen all patients admitted to an intensive care unit. Evidence-based interventions (bundle) were implemented for patients identified as being at high risk for HACDI. Effectiveness of the model was measured by reduction of HACDI rate during the intervention period compared with the preintervention period. RESULTS: During the 12-month intervention period 217 high-risk patients were identified as infected with Clostridium difficile. Sixty-two of these met exclusion criteria, resulting in a study population of 157 patients. During the preintervention phase, 10 cases of HACDI occurred (overall incidence rate, 14.7). During the 12-month study period, 2 cases of HACDI were identified (incidence rate, 3.12). The reduction was statistically significant. CONCLUSION: A strategy for identifying patients at increased risk and implementation of multidisciplinary risk-mitigation strategies is effective in reducing incidence of HACDI.

Targeting myeloid-derived suppressor cells using a novel adenosine monophosphate-activated protein kinase (AMPK) activator.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of early myeloid cells that accumulate in the blood and tumors of patients with cancer. MDSC play a critical role during tumor evasion and promote immune suppression through variety of mechanisms, such as the generation of reactive oxygen and nitrogen species (ROS and RNS) and cytokines. AMPactivated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that regulates energy homeostasis and metabolic stress. However, the role of AMPK in the regulation of MDSC function remains largely unexplored. This study was designed to investigate whether treatment of MDSC with OSU-53, a PPAR-inactive derivative that stimulates AMPK kinase, can modulate MDSC function. Our results demonstrate that OSU-53 treatment increases the phosphorylation of AMPK, significantly reduces nitric oxide production, inhibits MDSC migration, and reduces the levels of IL-6 in murine MDSC cell line (MSC2 cells). OSU53 treatment mitigated the immune suppressive functions of murine MDSC, promoting T-cell proliferation. Although OSU-53 had a modest effect on tumor growth in mice inoculated with EMT-6 cells, importantly, administration of OSU53 significantly (p < 0.05) reduced the levels of MDSC in the spleens and tumors. Furthermore, mouse MDSC from EMT-6 tumor-bearing mice and human MDSC isolated from melanoma patients treated with OSU-53 showed a significant reduction in the expression of immune suppressive genes iNOS and arginase. In summary, these results demonstrate a novel role of AMPK in the regulation of MDSC functions and provide a rationale of combining OSU-53 with immune checkpoint inhibitors to augment their response in cancer patients.

Myeloid-Derived Suppressor Cells Express Bruton's Tyrosine Kinase and Can Be Depleted in Tumor-Bearing Hosts by Ibrutinib Treatment.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that expand in tumor-bearing hosts in response to soluble factors produced by tumor and stromal cells. MDSC expansion has been linked to loss of immune effector cell function and reduced efficacy of immune-based cancer therapies, highlighting the MDSC population as an attractive therapeutic target. Ibrutinib, an irreversible inhibitor of Bruton's tyrosine kinase (BTK) and IL2-inducible T-cell kinase (ITK), is in clinical use for the treatment of B-cell malignancies. Here, we report that BTK is expressed by murine and human MDSCs, and that ibrutinib is able to inhibit BTK phosphorylation in these cells. Treatment of MDSCs with ibrutinib significantly impaired nitric oxide production and cell migration. In addition, ibrutinib inhibited in vitro generation of human MDSCs and reduced mRNA expression of indolamine 2,3-dioxygenase, an immunosuppressive factor. Treatment of mice bearing EMT6 mammary tumors with ibrutinib resulted in reduced frequency of MDSCs in both the spleen and tumor. Ibrutinib treatment also resulted in a significant reduction of MDSCs in wild-type mice bearing B16F10 melanoma tumors, but not in X-linked immunodeficiency mice (XID) harboring a BTK mutation, suggesting that BTK inhibition plays an important role in the observed reduction of MDSCs in vivo Finally, ibrutinib significantly enhanced the efficacy of anti-PD-L1 (CD274) therapy in a murine breast cancer model. Together, these results demonstrate that ibrutinib modulates MDSC function and generation, revealing a potential strategy for enhancing immune-based therapies in solid malignancies. Cancer Res; 76(8); 2125-36. ©2016 AACR.