Supporting servicemembers and veterans during their transition to civilian life using certified sponsors: A three-arm randomized controlled trial.

Transitioning servicemembers and veterans (TSMVs) face difficulties throughout their reintegration to civilian life, including challenges with employment, poor social connection, and elevated risk for suicide. To meet the needs of this high-risk population, national initiatives have leveraged community-based interventions. Authors conducted a three-arm randomized controlled trial (n = 200) to evaluate two community-based interventions. The first, Team Red, White, and Blue (RWB), connects TSMVs to their community through physical/social activities. The second, Expiration Term of Service Sponsorship Program (ETS-SP) provides one-on-one certified sponsors to TSMVs who provide support during the reintegration process. TSMVs were assessed at baseline, 3, 6, and 12 months. The primary hypothesis was not supported as reintegration difficulties and social support were not significantly different for participants randomly assigned to the two community-based interventions (Arm-2/RWB and Arm-3/RWB + ETS-SP), when the data from the separate arms were collapsed and combined, compared to the waitlist. The results did support the secondary hypothesis as Arm-3/RWB + ETS-SP had less reintegration difficulties over 12 months and initially had more social support compared to Arm-2/RWB, which suggest that augmenting interventions with sponsors outperforms participation in community-based interventions alone. Overall, the results show some limitations of the studied community-based interventions, as implemented and researched within this study. The authors identified factors that may have contributed to the null findings for the primary hypothesis, which can be addressed in future studies, such as addressing the unique needs of TSMVs, enrolling TSMVs into interventions prior to military discharge, measuring and improving participation levels, and providing stepped-care interventions based on risk levels. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Exploring the trajectory and correlates of social isolation for veterans across a 6-month period during COVID-19.

Social isolation is a relevant problem for veterans who are at risk for disengaging from others as a function of transition stress from military life to civilian life, and given high rates of exposure to trauma and psychological distress. Few researchers have examined social isolation in veterans over time, particularly during COVID-19 that led to significant barriers and restrictions on social interactions. The purpose of this longitudinal study was to assess veterans' experience of social isolation and its mental health and social functioning correlates during a 6-month period of the COVID-19 pandemic. Participants were 188 United States veterans of the Iraq and Afghanistan wars. A total of four assessments were administered: one every two months for a total duration of six months. The average number of completed assessments across all participants was 3.70 (SD = 0.75) with 159 participants (84.13%) completing all four timepoints. Surveys included measures of global mental health and social functioning as indicated by perceived emotional support, quality of marriage, and couple satisfaction. Multilevel modeling was used to assess 1) growth models to determine whether social isolation changed over time and the trajectory of that change (i.e., linear or quadratic); and 2) whether social isolation was related to both concurrent and prospective indicators of mental health and social functioning. All analyses included person mean centered and grand mean centered isolation to assess for within-and between-person effects. Veterans reported a quadratic trajectory in social isolation that decreased slightly and stabilized over time. Findings indicate that higher social isolation, at both the within- and between-person level, was negatively associated with concurrent emotional support, mental health, quality of marriage, and couple satisfaction. However, all prospective effects were nonsignificant at the within-person level. Results suggest although isolation may decrease over time, veterans report worse mental health and social functioning during times when they report higher levels of social isolation compared to themselves and others. Future work is needed to determine if interventions can be applied during those times to prevent or target those negative associations.

Partnered implementation of the veteran sponsorship initiative: protocol for a randomized hybrid type 2 effectiveness-implementation trial.

BACKGROUND: The USA is undergoing a suicide epidemic for its youngest Veterans (18-to-34-years-old) as their suicide rate has almost doubled since 2001. Veterans are at the highest risk during their first-year post-discharge, thus creating a "deadly gap." In response, the nation has developed strategies that emphasize a preventive, universal, and public health approach and embrace the value of community interventions. The three-step theory of suicide suggests that community interventions that reduce reintegration difficulties and promote connectedness for Veterans as they transition to civilian life have the greatest likelihood of reducing suicide. Recent research shows that the effectiveness of community interventions can be enhanced when augmented by volunteer and certified sponsors (1-on-1) who actively engage with Veterans, as part of the Veteran Sponsorship Initiative (VSI). METHOD/DESIGN: The purpose of this randomized hybrid type 2 effectiveness-implementation trial is to evaluate the implementation of the VSI in six cities in Texas in collaboration with the US Departments of Defense, Labor and Veterans Affairs, Texas government, and local stakeholders. Texas is an optimal location for this large-scale implementation as it has the second largest population of these young Veterans and is home to the largest US military installation, Fort Hood. The first aim is to determine the effectiveness of the VSI, as evidenced by measures of reintegration difficulties, health/psychological distress, VA healthcare utilization, connectedness, and suicidal risk. The second aim is to determine the feasibility and potential utility of a stakeholder-engaged plan for implementing the VSI in Texas with the intent of future expansion in more states. The evaluators will use a stepped wedge design with a sequential roll-out to participating cities over time. Participants (n=630) will be enrolled on military installations six months prior to discharge. Implementation efforts will draw upon a bundled implementation strategy that includes strategies such as ongoing training, implementation facilitation, and audit and feedback. Formative and summative evaluations will be guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework and will include interviews with participants and periodic reflections with key stakeholders to longitudinally identify barriers and facilitators to implementation. DISCUSSION: This evaluation will have important implications for the national implementation of community interventions that address the epidemic of Veteran suicide. Aligned with the Evidence Act, it is the first large-scale implementation of an evidence-based practice that conducts a thorough assessment of TSMVs during the "deadly gap." TRIAL REGISTRATION: ClinicalTrials.gov ID number: NCT05224440 . Registered on 04 February 2022.

Development and Validation of the State Moral Elevation Scale: Assessing State-Level Elevation Across Nonclinical and Clinical Samples.

Research on moral elevation has steadily increased and identified several psychosocial benefits that bear relevance to both the general population and people with psychological distress. However, elevation measurement is inconsistent, and few state-level measures have been created and critically evaluated to date. To address this gap, the State Moral Elevation Scale (SMES) was developed and tested using an online sample (N = 930) including subsamples of general participants (nonclinical) and those who screened positive for mental health symptoms (clinical). Factor analysis indicated a single factor structure with nine items that demonstrated excellent reliability. Multigroup confirmatory factor analysis indicated good fit statistics and strict measurement invariance across clinical and nonclinical subsamples. Lastly, correlational analyses with related constructs provided evidence of construct validity for both subsamples. Thus, the SMES is a psychometrically valid and reliable assessment tool for state-level elevation which can be used in both general and clinical populations. Supplementary Information: The online version contains supplementary material available at 10.1007/s10902-022-00533-2.

Resilience predicts posttraumatic cognitions after a trauma reminder task and subsequent positive emotion induction among veterans with PTSD.

[Correction Notice: An Erratum for this article was reported in Vol 14(S1) of Psychological Trauma: Theory, Research, Practice, and Policy (see record 2022-45004-002). In the article (https://doi.org/10.1037/tra0001143), the Supplemental materials link was missing from the title page. All versions of this article have been corrected.] Objective: Posttraumatic stress disorder (PTSD) is a common problem for veterans. Resilience, the tendency to bounce back from difficult circumstances, is negatively associated with posttraumatic cognitions (PTCs) among individuals with a history of trauma, and it may be important to understand responses to trauma reminders. METHOD: Using a quasi-experimental design, we examined the association between trait resilience and state PTCs in veterans with PTSD (n = 47, Mage = 48.60, 91.8% male) at two points: following a written trauma narrative exposure (Time 1 [T1]), and following a subsequent positive distraction task (i.e., brief, positive video; Time 2 [T2]). RESULTS: After controlling for PTSD symptom severity and combat exposure, resilience was negatively associated with PTCs at T1 (ΔR2 = .19) and T2 (ΔR2 = .13). However, resilience was a poor predictor of change in PTCs from T1 to T2. We also examined the relationship between resilience and subtypes of PTCs: resilience was associated with negative views of the self (T1, ΔR2 = .24) but not negative views of the world or self-blame (T1, ΔR2s ≤ .07); these results were consistent at T2. CONCLUSIONS: Thus, resilience may attenuate negative trauma-related cognitions after trauma recall; however, this study was not designed to test causal pathways. Future research could examine whether resilience-building exercises reduce negative PTCs after trauma reminders among veterans. Additional research is needed to generalize to other trauma-exposed populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Predicting healthcare-seeking behavior based on stated readiness to act: development and validation of a prediction model.

A starting point of many digital health interventions informed by the Stages of Change Model of behavior change is assessing a person's readiness to change. In this paper, we use the concept of readiness to develop and validate a prediction model of health-seeking behavior in the context of family planning. We conducted a secondary analysis of routinely collected, anonymized health data submitted by 4,088 female users of a free health chatbot in Kenya. We developed a prediction model of (future) self-reported action by randomly splitting the data into training and test data sets (80/20, stratified by the outcome). We further split the training data into 10 folds for cross-validating the hyperparameter tuning step in model selection. We fit nine different classification models and selected the model that maximized the area under the receiver operator curve. We then fit the selected model to the full training dataset and evaluated the performance of this model on the holdout test data. The model predicted who will visit a family planning provider in the future with high precision (0.93) and moderate recall (0.75). Using the Stages of Change framework, we concluded that 29% of women were in the "Preparation" stage, 21% were in the "Contemplation" stage, and 50% were in the "Pre-Contemplation" stage. We demonstrated that it is possible to accurately predict future healthcare-seeking behavior based on information learned during the initial encounter. Models like this may help intervention developers to tailor strategies and content in real-time.

Influence of cochlear parameters on the current practice in cochlear implantation : Development of a concept for personalized medicine.

Since the introduction of cochlear implants into clinical routine, the interest in measuring cochlear parameters, particularly the cochlear duct length (CDL) has increased, since these can have an influence on the correct selection of the electrode. On the one hand, coverage of an optimal frequency band is relevant for a good audiological result, and on the other hand, cochlear trauma due to too deep insertion or displacement of the electrode must be avoided. Cochlear implants stimulate the spiral ganglion cells (SGC). The number of SGC and particularly their distribution can also have an influence on the function of a cochlear implant. In addition, the frequency assignment of each electrode contact can play a decisive role in the postoperative success, since the frequency distribution of the human cochlea with varying CDL shows substantial interindividual differences. The aim of this work is to provide an overview of the methods used to determine the cochlear parameters as well as of relevant studies on the CDL, the number and distribution of SGZ, and the frequency assignment of electrode contacts. Based on this, a concept for individualized cochlear implantation will be presented. In summary, this work should help to promote individualized medicine in the field of cochlear implants in the future, in order to overcome current limitations and optimize audiological outcomes.

[Influence of cochlear parameters on the current practice in cochlear implantation : Development of a concept for personalized medicine. German version]. / Einfluss cochleärer Parameter auf die aktuelle Cochleaimplantatversorgung : Entwicklung eines Konzepts für die personalisierte Medizin.

Since the introduction of cochlear implants into clinical routine, the interest in measuring cochlear parameters, particularly the cochlear duct length (CDL) has increased, since these can have an influence on the correct selection of the electrode. On the one hand, coverage of an optimal frequency band is relevant for a good audiological result, and on the other hand, cochlear trauma due to too deep insertion or displacement of the electrode must be avoided. Cochlear implants stimulate the spiral ganglion cells (SGC). The number of SGC and particularly their distribution can also have an influence on the function of a cochlear implant. In addition, the frequency assignment of each electrode contact can play a decisive role in the postoperative success, since the frequency distribution of the human cochlea with varying CDL shows substantial interindividual differences. The aim of this work is to provide an overview of the methods used to determine the cochlear parameters as well as of relevant studies on the CDL, the number and distribution of SGZ, and the frequency assignment of electrode contacts. Based on this, a concept for individualized cochlear implantation will be presented. In summary, this work should help to promote individualized medicine in the field of cochlear implants in the future, in order to overcome current limitations and optimize audiological outcomes.

Cognitive Restructuring vs. Defusion: Impact on craving, healthy and unhealthy food intake.

Coping with food cravings is crucial for weight management. Individuals tend to use avoidance strategies to resist food cravings and prevent overeating, but such strategies may not result in the benefits sought. This study compared the effects of two cognitive techniques (Restructuring vs. Defusion) for dealing with food cravings in terms of their impact on healthy vs. unhealthy eating behavior (i.e., consumption of chocolate and/or carrots following the intervention). Sixty-five participants (Mage = 19.65 years) received either a 30-minute face-to-face instruction on cognitive restructuring (CR) or cognitive defusion (CD) along with 15 min of practice, or 45 min of obesity education and discussion (control). To examine craving and eating choices following the intervention, participants received bags of chocolate and carrots and were asked to carry these with them at all times over the next week, exchanging the bags every 2 days. Participants in the CD group ate fewer chocolates (M = 11.74) compared to CR (M = 17.06) and Control groups (M = 29.18) during the experimental week. The groups did not differ in number of carrot pieces eaten, though the CD group ate more carrots than chocolates. CD resulted in fewer self-reported cravings compared to CR and CO groups. At a final taste test, both CD and CR groups ate significantly fewer chocolates compared to the CO group. CD appears to be an effective technique in managing food craving and to present some advantages over CR.

SOCIAL ENGAGEMENT EARLY IN THE U.S. COVID-19 CRISIS: EXPLORING SOCIAL SUPPORT AND PROSOCIAL BEHAVIOR BETWEEN THOSE WITH AND WITHOUT DEPRESSION OR ANXIETY IN AN ONLINE SAMPLE.

INTRODUCTION: Social distancing and sheltering-in-place mitigate the physical health risks of the novel coronavirus (COVID-19); however, there are concerns about the impact on mental health and social engagement. METHODS: We used data from a U.S.-based online survey (March 2020) to examine patterns of social support and prosocial behavior, explore differences between people with and without depression or anxiety, and explore correlates of social engagement in both groups, including symptom severity in the clinical group. RESULTS: The clinical group reported greater social engagement. In both groups, social engagement was positively associated with COVID-19-related worry and trait moral elevation; mindfulness was positively associated with all outcomes for the clinical group only. Social interaction frequency had little influence on outcomes. Depressive symptom severity was positively associated with all outcomes, whereas anxiety was negatively associated with prosocial behavior. DISCUSSION: These findings highlight how social engagement was experienced early in the U.S. COVID-19 crisis.

The association of hypotension during non-cardiac surgery, before and after skin incision, with postoperative acute kidney injury: a retrospective cohort analysis.

Intra-operative hypotension is associated with acute postoperative kidney injury. It is unclear how much hypotension occurs before skin incision compared with after, or whether hypotension in these two periods is similarly associated with postoperative kidney injury. We analysed the association of mean arterial pressure < 65 mmHg with postoperative kidney injury in 42,825 patients who were anaesthetised for elective non-cardiac surgery. Intra-operative hypotension occurred in 30,423 (71%) patients: 22,569 (53%) patients before skin incision; and 24,102 (56%) patients after incision. Anaesthetised patients who were hypotensive had mean arterial pressures < 65 mmHg for a median (IQR [range]) of 5.5 (0.0-14.7 [0.0-60.0]) min.h-1 before skin incision, compared with 1.7 [0.3-5.1 [0.0-57.5]) min.h-1 after incision: a median (IQR [range]) of 36% (0%-84% [0%-100%]) of hypotensive readings were before incision. We diagnosed postoperative kidney injury in 2328 (5%) patients. The odds ratio (95%CI) for acute kidney injury was 1.05 (1.02-1.07) for each doubling of the duration of hypotension, p < 0.001. Postoperative kidney injury was associated with the product of hypotension duration and severity, that is, area under the curve, before skin incision and after, odds ratio (95%CI): 1.02 (1.01-1.04), p = 0.004; and 1.02 (1.00-1.04), p = 0.016, respectively. A substantial fraction of all hypotension happened before surgical incision and was thus completely due to anaesthetic management. We recommend that anaesthetists should avoid mean arterial pressure < 65 mmHg during surgery, especially after induction, assuming that its association with postoperative kidney injury is, at least in part, causal.

Effect of aspirin in vascular surgery in patients from a randomized clinical trial (POISE-2).

BACKGROUND: In the POISE-2 (PeriOperative ISchemic Evaluation 2) trial, perioperative aspirin did not reduce cardiovascular events, but increased major bleeding. There remains uncertainty regarding the effect of perioperative aspirin in patients undergoing vascular surgery. The aim of this substudy was to determine whether there is a subgroup effect of initiating or continuing aspirin in patients undergoing vascular surgery. METHODS: POISE-2 was a blinded, randomized trial of patients having non-cardiac surgery. Patients were assigned to perioperative aspirin or placebo. The primary outcome was a composite of death or myocardial infarction at 30 days. Secondary outcomes included: vascular occlusive complications (a composite of amputation and peripheral arterial thrombosis) and major or life-threatening bleeding. RESULTS: Of 10 010 patients in POISE-2, 603 underwent vascular surgery, 319 in the continuation and 284 in the initiation stratum. Some 272 patients had vascular surgery for occlusive disease and 265 had aneurysm surgery. The primary outcome occurred in 13·7 per cent of patients having aneurysm repair allocated to aspirin and 9·0 per cent who had placebo (hazard ratio (HR) 1·48, 95 per cent c.i. 0·71 to 3·09). Among patients who had surgery for occlusive vascular disease, 15·8 per cent allocated to aspirin and 13·6 per cent on placebo had the primary outcome (HR 1·16, 0·62 to 2·17). There was no interaction with the primary outcome for type of surgery (P = 0·294) or aspirin stratum (P = 0·623). There was no interaction for vascular occlusive complications (P = 0·413) or bleeding (P = 0·900) for vascular compared with non-vascular surgery. CONCLUSION: This study suggests that the overall POISE-2 results apply to vascular surgery. Perioperative withdrawal of chronic aspirin therapy did not increase cardiovascular or vascular occlusive complications. Registration number: NCT01082874 ( http://www.clinicaltrials.gov).

Systematic review and consensus definitions for standardised endpoints in perioperative medicine: postoperative cancer outcomes.

BACKGROUND: The Standardising Endpoints for Perioperative Medicine group was established to derive an appropriate set of endpoints for use in clinical trials related to anaesthesia and perioperative medicine. Anaesthetic or analgesic technique during cancer surgery with curative intent may influence the risk of recurrence or metastasis. However, given the current equipoise in the existing literature, prospective, randomised, controlled trials are necessary to test this hypothesis. As such, a cancer subgroup was formed to derive endpoints related to research in onco-anaesthesia based on a current evidence base, international consensus and expert guidance. METHODS: We undertook a systematic review to identify measures of oncological outcome used in the oncological, surgical, and wider literature. A multiround Delphi consensus process that included up to 89 clinician-researchers was then used to refine a recommended list of endpoints. RESULTS: We identified 90 studies in a literature search, which were the basis for a preliminary list of nine outcome measures and their definitions. A further two were added during the Delphi process. Response rates for Delphi rounds one, two, and three were 88% (n=9), 82% (n=73), and 100% (n=10), respectively. A final list of 10 defined endpoints was refined and developed, of which six secured approval by ≥70% of the group: cancer health related quality of life, days alive and out of hospital at 90 days, time to tumour progression, disease-free survival, cancer-specific survival, and overall survival (and 5-yr overall survival). CONCLUSION: Standardised endpoints in clinical outcomes studies will support benchmarking and pooling (meta-analysis) of trials. It is therefore recommended that one or more of these consensus-derived endpoints should be considered for inclusion in clinical trials evaluating a causal effect of anaesthesia-analgesia technique on oncological outcomes.

Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: patient comfort.

BACKGROUND: Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures. RESULTS: We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: pain intensity (at rest and during movement) at 24 h postoperatively, nausea and vomiting (0-6 h, 6-24 h, and overall), one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to mobilisation, and sleep quality. CONCLUSIONS: As standardised outcomes will support benchmarking and pooling (meta-analysis) of trials, one or more of these recommended endpoints should be considered for inclusion in clinical trials assessing patient comfort and pain after surgery.

Supplemental oxygen and surgical-site infections: an alternating intervention controlled trial.

BACKGROUND: The main defence against bacterial infection is oxidative killing by neutrophils, which requires molecular oxygen in wounded tissues. High inspired-oxygen fractions increase tissue oxygenation. But, whether improving tissue oxygenation actually reduces surgical-site infection (SSI) remains controversial. We therefore tested the primary hypothesis that supplemental oxygen (80% vs 30%) reduces the risk of a 30-day composite of deep tissue or organ-space SSI, healing-related wound complications, and mortality. METHODS: In an isolated suite of operating rooms, the inspired-oxygen concentration was alternated between 30% and 80% at 2-week intervals for 39 months. The analysis was restricted to patients who had major intestinal surgery lasting at least 2 h. Qualifying operations (5749) were analysed, including 2843 (49%) colorectal resections, 1866 (32%) lower gastrointestinal therapeutic procedures, 373 (6%) small-bowel resections, and 667 (13%) other colorectal procedures. RESULTS: The 80% and 30% oxygen groups were well balanced on all of the demographic, baseline, and procedural variables. The oxygen intervention had no effect on the composite primary outcome or any of its components. The overall observed incidence of the composite outcome was 10.8% (314/2896) in the 80% oxygen group and 11.0% (314/2853) in the 30% group. The estimated relative risk was 0.99 (95% CI: 0.85, 1.14) for 80% vs 30%, P=0.85. CONCLUSIONS: Supplemental oxygen does not prevent major infection and healing-related complications after major intestinal surgery. CLINICAL TRIAL REGISTRATION: NCT01777568.

Reviewing the current evidence supporting early B-cells as the cellular origin of Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a highly malignant skin cancer characterized by early metastases and poor survival. Although MCC is a rare malignancy, its incidence is rapidly increasing in the U.S. and Europe. The discovery of the Merkel cell polyomavirus (MCPyV) has enormously impacted our understanding of its etiopathogenesis and biology. MCCs are characterized by trilinear differentiation, comprising the expression of neuroendocrine, epithelial and B-lymphoid lineage markers. To date, it is generally accepted that the initial assumption of MCC originating from Merkel cells (MCs) is unlikely. This is owed to their post-mitotic character, absence of MCPyV in MCs and discrepant protein expression pattern in comparison to MCC. Evidence from mouse models suggests that epidermal/dermal stem cells might be of cellular origin in MCC. The recently formulated hypothesis of MCC originating from early B-cells is based on morphology, the consistent expression of early B-cell lineage markers and the finding of clonal immunoglobulin chain rearrangement in MCC cells. In this review we elaborate on the cellular ancestry of MCC, the identification of which could pave the way for novel and more effective therapeutic regimens.

Incorporation studies of clickable ceramides in Jurkat cell plasma membranes.

The incorporation properties of ceramide analogues for click chemistry in Jurkat T cells were investigated. The analogues varied in the acyl chain length and the position of the functional group for click chemistry. Fluorescence microscopy studies including anisotropy and quenching experiments showed significant differences in the accessibility of the functional group indicating different incorporation properties into the plasma membrane.

[Merkel cell carcinoma: cutaneous manifestation of a highly malignant pre-/pro-B cell neoplasia? : Novel concept about the cellular origin of Merkel cell carcinoma]. / Merkelzellkarzinom: kutane Manifestation einer hochmalignen Prä-/pro-B-Zell-Neoplasie? : Neues Konzept zum zellulären Ursprung des Merkelzellkarzinoms.

Merkel cell carcinoma (MCC) is a relatively rare but highly malignant non-melanoma skin cancer of the elderly and immunosuppressed patients. The discovery of the Merkel cell polyomavirus (MCPyV) in 2008 significantly impacted the understanding of the etiopathogenesis of MCC. MCPyV is clonally integrated into the MCC genome and approximately 80% of MCC are MCPyV-positive. Recent results of clinical trials using blockade of the PD-1 immune modulatory pathway are promising for the future treatment of MCC. Despite this major progress of the past few years, the cellular origin of MCC still remains obscure. Based on histomorphology, gene expression profiling, and molecular analyses, we have recently hypothesized that MCC originates from pre­/pro-B cells. Here we review putative cells of MCC, including Merkel cells, (epi­)dermal stem cells, and pro­/pre-B cells. In the present work, the focus is on the concept of pre­/pro-B cells as the cellular origin of MCC, which might also impact the understanding of other human small cell malignancies of unknown cellular origin, such as small cell carcinomas of the lung and other anatomical locations. In addition, this concept might pave the way for novel treatment options, especially for advanced MCC.