Recent advances in strategies for immunotherapy of human papillomavirus-induced lesions

Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for "proof of concept" studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in preclinical models for HPV-induced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed.     

What is the predictive value of intraoperative somatosensory evoked potential monitoring for postoperative neurological deficit in cervical spine surgery?—a meta-analysis

BACKGROUND CONTEXTCervical decompression and fusion surgery remains a mainstay of treatment for a variety of cervical pathologies. Potential intraoperative injury to the spinal cord and nerve roots poses nontrivial risk for consequent postoperative neurologic deficits. Although neuromonitoring with intraoperative somatosensory evoked potentials (SSEPs) is often used in cervical spine surgery, its therapeutic value remains controversial.PURPOSEThe purpose of the present study was to evaluate whether significant SSEP changes can predict postoperative neurologic complications in cervical spine surgery. A subgroup analysis was performed to compare the predictive power of SSEP changes in both anterior and posterior approaches.STUDY DESIGNThe present study was a meta-analysis of the literature from PubMed, Web of Science, and Embase to identify prospective/retrospective studies with outcomes of patients who underwent cervical spine surgeries with intraoperative SSEP monitoring.PATIENT SAMPLEThe total cohort consisted of 7,747 patients who underwent cervical spine surgery with intraoperative SSEP monitoring.METHODSInclusion criteria for study selection were as follows: (1) prospective or retrospective cohort studies, (2) studies conducted in patients undergoing elective cervical spine surgery not due to aneurysm, tumor, or trauma with intraoperative SSEP monitoring, (3) studies that reported postoperative neurologic outcomes, (4) studies conducted with a sample size ≥20 patients, (5) studies with only adult patients ≥18 years of age, (6) studies published in English, (7) studies inclusive of an abstract.OUTCOME MEASURESThe sensitivity, specificity, diagnostic odds ratio (DOR), and likelihood ratios of overall SSEP changes, reversible SSEP changes, irreversible SSEP changes, and SSEP loss for predicting postoperative neurological deficit were calculated.RESULTSThe total rate of postoperative neurological deficits was 2.50% (194/7,747) and the total rate of SSEP changes was 7.36% (570/7,747). The incidence of postoperative neurological deficit in patients with intraoperative SSEP changes was 16.49% (94/570) while only 1.39% (100/7,177) in patients without. All significant intraoperative SSEP changes had a sensitivity of 46.0% and specificity of 96.7% with a DOR of 27.32. Reversible and irreversible SSEP changes had sensitivities of 17.7% and 37.1% and specificities of 97.5% and 99.5%, respectively. The DORs for reversible and irreversible SSEP changes were 9.01 and 167.90, respectively. SSEP loss had a DOR of 51.39, sensitivity of 17.3% and specificity 99.6%. In anterior procedures, SSEP changes had a DOR of 9.60, sensitivity of 34.2%, and specificity of 94.7%. In posterior procedures, SSEP changes had a DOR of 13.27, sensitivity of 42.6%, and specificity of 94.0%.CONCLUSIONSSSEP monitoring is highly specific but weakly sensitive for postoperative neurological deficit following cervical spine surgery. The analysis found that patients with new postoperative neurological deficits were nearly 27 times more likely to have had significant intraoperative SSEP change. Loss of SSEP signals and irreversible SSEP changes seem to indicate a much higher risk of injury than reversible SSEP changes.     

Comparison of mortality and medical complications between older and younger malignant melanoma inpatients

Previous studies have identified older age as a negative prognostic factor in malignant melanoma patients. To compare comorbidities, medical complications, and inpatient mortality between younger and older malignant melanoma inpatients. All adult patient encounters with a diagnosis of cutaneous malignant melanoma were identified using the 2003 to 2012 National Inpatient Sample database. Concurrent comorbidities and inpatient medical complications were queried. Comparisons were made between older and younger adults, defined as ≥65 years and 18 to 64 years, respectively. In total, 8153 patient encounters were identified in the database (51.6% older and 48.4% younger). Older adults had a higher prevalence of numerous comorbidities, including chronic pulmonary disease, chronic renal failure, congestive heart failure, diabetes mellitus, hypertension, hypothyroidism, peripheral vascular disease, and pulmonary circulation disorder (P < .001). In contrast, younger adults were more likely to have obesity (P < .001) and coagulopathy (P = .005). On multivariable analysis of medical complications, older adult inpatients were more likely to experience urinary tract infection (OR = 1.54, P = .021), but less likely to experience acute respiratory failure (OR = 0.46, P = .012) and venous thromboembolism (OR = 0.44, P = .026). Notably, inpatient mortality did not significantly differ. Older adult inpatients with malignant melanoma have different comorbidities than younger patients and have a larger overall comorbidity burden. Surprisingly, however, the odds of most inpatient medical complications and mortality were found to be similar in younger vs older patients.     

Recurrent menstrual toxic shock syndrome despite discontinuation of tampon use: Is menstrual toxic shock syndrome really caused by tampons?

Menstrual toxic shock syndrome (MTSS) is a rare and potentially life‐threatening illness. We present a case of recurrent MTSS initially associated with tampon use that continued to recur when tampons were discontinued, which was successfully treated with rifampicin and clindamycin.     

Cervical cancer prevention: Human papillomavirus testing as primary screening

Low- and middle-income countries carry a high burden of preventable cervical cancer cases and deaths. Because human papillomavirus DNA-based testing is increasingly becoming the preferred method of screening for cervical cancer prevention, this commentary discusses next steps and key considerations for its expansion.     

A vesicular variant of pseudoverrucous papules and nodules in the genital area of an incontinent 4‐year‐old

Irritant contact dermatitis is a common cause of chronic vulvitis in patients wearing diapers and incontinence garments. In most cases the diagnosis is obvious; however, atypical presentations may mimic more serious dermatoses. We present a 4‐year‐old girl who presented at birth with cloacal atresia corrected surgically and resulting in chronic incontinence requiring full‐time diapers. She presented with crops of herpetiform vesicles and bullae on a base that ranged from normal skin to severe erythema and oedema. A histological examination revealed a well‐demarcated lesion showing a thickened epidermis with hyperkeratosis and parakeratosis, acanthosis and an abrupt transition to pallor of the upper half. Focal full thickness epidermis necrosis and small areas of spongiosis, acantholysis and apoptotic keratinocytes were seen. Immunofluorescence was negative. The lesions improved with the treatment of secondary infection and minimal topical therapy with an emollient only. This case represents an unusual vesicular variant of pseudoverrucous papules and nodules, which has been reported only once previously.     

South Asian women's coping strategies in the face of domestic violence in the United States

We conducted in-depth telephone interviews with a convenience sample of 20 South Asian women experiencing domestic violence in the United States. Utilizing the emotion-focused and problem-focused coping framework, the researchers analyzed the narratives of abused South Asian women. Emotion-focused coping strategies include (a) spirituality and/or religion and (b) the role of children. Problem-focused coping strategies include (c) informal and formal support and (d) strategies of resisting, pacifying, safety planning. Implications for practice and future research in the United States and internationally are discussed.     

Pseudomyxoma Peritonei: Inflammatory Responses in the Peritoneal Microenvironment

Background

Pseudomyxoma peritonei (PMP), a peritoneal mucinous neoplasm of appendiceal origin, is associated with inflammation and fibrosis, which is central to its biology. The significance of the microenvironment in PMP has not been well characterized.

Methods

Immunoassays were used to measure cytokines and C-reactive protein (CRP). Forty-two cytokines were initially measured in 23 PMP ascites and 10 PMP peritoneal washings. On the basis of these results, matching serum and ascites samples were analyzed for ten relevant cytokines (n = 32) and CRP (n = 28). Immunohistochemistry was performed on formalin-fixed tissue sections. Statistical analysis was by Wilcoxon signed rank test, Mann–Whitney U-test, and bivariate analysis.

Results

Serum CRP was elevated in PMP and correlated to CRP level in ascites. Interleukin (IL)-6, IL-8 (CXCL8), interferon gamma-induced protein 10 (IP-10), (CXCL10), monocyte chemotactic protein (MCP)-1 (CCL2), and macrophage inflammatory protein (MIP)-1α (CCL3) levels were grossly elevated in ascites but did not correlate with serum levels. Cytokines normally associated with infection or tissue injury (e.g., IL-1, IL-2, interferon gamma) were not elevated. Immunohistochemistry localized IL-6 to stroma, IP-10, and MCP-1 to tumor cells and IL-8 to adipose tissue. There were complex interactions among cytokines. IL-6, in particular, had many significant correlations in ascites. Serum IL-8, MIP-1β, and CRP were higher in PMP compared to controls.

Conclusions

The pattern of cytokines in PMP is distinct from infection- or injury-associated inflammation. The results support peritoneal synthesis for cytokines. CRP, IL-8, and MIP-1β are potential serum markers for PMP. IL-6 appears to play a central role in PMP biology. This study provides new details about PMP tumor biology and identifies possible therapeutic targets.