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Pathophysiology, Clinical Presentation, and Treatment of Psoriasis : A Review

• 1 Keck School of Medicine, Department of Dermatology, University of Southern California Los Angeles
• 2 Department of Medicine, Imperial College London, London, United Kingdom

Importance   Approximately 125 million people worldwide have psoriasis. Patients with psoriasis experience substantial morbidity and increased rates of inflammatory arthritis, cardiometabolic diseases, and mental health disorders.

Observations   Plaque psoriasis is the most common variant of psoriasis. The most rapid advancements addressing plaque psoriasis have been in its pathogenesis, genetics, comorbidities, and biologic treatments. Plaque psoriasis is associated with a number of comorbidities including psoriatic arthritis, cardiometabolic diseases, and depression. For patients with mild psoriasis, topical agents remain the mainstay of treatment, and they include topical corticosteroids, vitamin D analogues, calcineurin inhibitors, and keratolytics. The American Academy of Dermatology-National Psoriasis Foundation guidelines recommend biologics as an option for first-line treatment of moderate to severe plaque psoriasis because of their efficacy in treating it and acceptable safety profiles. Specifically, inhibitors to tumor necrosis factor α (TNF-α) include etanercept, adalimumab, certolizumab, and infliximab. Other biologics inhibit cytokines such as the p40 subunit of the cytokines IL-12 and IL-23 (ustekinumab), IL-17 (secukinumab, ixekizumab, bimekizumab, and brodalumab), and the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab, and mirikizumab). Biologics that inhibit TNF-α, p40IL-12/23, and IL-17 are also approved for the treatment of psoriatic arthritis. Oral treatments include traditional agents such as methotrexate, acitretin, cyclosporine, and the advanced small molecule apremilast, which is a phosphodiesterase 4 inhibitor. The most commonly prescribed light therapy used to treat plaque psoriasis is narrowband UV-B phototherapy.

Conclusions and Relevance   Psoriasis is an inflammatory skin disease that is associated with multiple comorbidities and substantially diminishes patients’ quality of life. Topical therapies remain the cornerstone for treating mild psoriasis. Therapeutic advancements for moderate to severe plaque psoriasis include biologics that inhibit TNF-α, p40IL-12/23, IL-17, and p19IL-23, as well as an oral phosphodiesterase 4 inhibitor.

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Armstrong AW , Read C. Pathophysiology, Clinical Presentation, and Treatment of Psoriasis : A Review . JAMA. 2020;323(19):1945–1960. doi:10.1001/jama.2020.4006

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• Published: 13 November 2020

Clinical presentations, laboratory and radiological findings, and treatments for 11,028 COVID-19 patients: a systematic review and meta-analysis

• Carlos K. H. Wong 1 , 2   na1 ,
• Janet Y. H. Wong 3   na1 ,
• Eric H. M. Tang 1 ,
• C. H. Au 1 &
• Abraham K. C. Wai 4  

Scientific Reports volume  10 , Article number:  19765 ( 2020 ) Cite this article

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This systematic review and meta-analysis investigated the comorbidities, symptoms, clinical characteristics and treatment of COVID-19 patients. Epidemiological studies published in 2020 (from January–March) on the clinical presentation, laboratory findings and treatments of COVID-19 patients were identified from PubMed/MEDLINE and Embase databases. Studies published in English by 27th March, 2020 with original data were included. Primary outcomes included comorbidities of COVID-19 patients, their symptoms presented on hospital admission, laboratory results, radiological outcomes, and pharmacological and in-patient treatments. 76 studies were included in this meta-analysis, accounting for a total of 11,028 COVID-19 patients in multiple countries. A random-effects model was used to aggregate estimates across eligible studies and produce meta-analytic estimates. The most common comorbidities were hypertension (18.1%, 95% CI 15.4–20.8%). The most frequently identified symptoms were fever (72.4%, 95% CI 67.2–77.7%) and cough (55.5%, 95% CI 50.7–60.3%). For pharmacological treatment, 63.9% (95% CI 52.5–75.3%), 62.4% (95% CI 47.9–76.8%) and 29.7% (95% CI 21.8–37.6%) of patients were given antibiotics, antiviral, and corticosteroid, respectively. Notably, 62.6% (95% CI 39.9–85.4%) and 20.2% (95% CI 14.6–25.9%) of in-patients received oxygen therapy and non-invasive mechanical ventilation, respectively. This meta-analysis informed healthcare providers about the timely status of characteristics and treatments of COVID-19 patients across different countries.

PROSPERO Registration Number: CRD42020176589

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Introduction.

Following the possible patient zero of coronavirus infection identified in early December 2019 1 , the Coronavirus Disease 2019 (COVID-19) has been recognized as a pandemic in mid-March 2020 2 , after the increasing global attention to the exponential growth of confirmed cases 3 . As on 29th March, 2020, around 690 thousand persons were confirmed infected, affecting 199 countries and territories around the world, in addition to 2 international conveyances: the Diamond Princess cruise ship harbored in Yokohama, Japan, and the Holland America's MS Zaandam cruise ship. Overall, more than 32 thousand died and about 146 thousand have recovered 4 .

A novel bat-origin virus, 2019 novel coronavirus, was identified by means of deep sequencing analysis. SARS-CoV-2 was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%) 5 , both of which were respectively responsible for two zoonotic human coronavirus epidemics in the early twenty-first century. Following a few initial human infections 6 , the disease could easily be transmitted to a substantial number of individuals with increased social gathering 7 and population mobility during holidays in December and January 8 . An early report has described its high infectivity 9 even before the infected becomes symptomatic 10 . These natural and social factors have potentially influenced the general progression and trajectory of the COVID-19 epidemiology.

By the end of March 2020, there have been approximately 3000 reports about COVID-19 11 . The number of COVID-19-related reports keeps growing everyday, yet it is still far from a clear picture on the spectrum of clinical conditions, transmissibility and mortality, alongside the limitation of medical reports associated with reporting in real time the evolution of an emerging pathogen in its early phase. Previous reports covered mostly the COVID-19 patients in China. With the spread of the virus to other continents, there is an imminent need to review the current knowledge on the clinical features and outcomes of the early patients, so that further research and measures on epidemic control could be developed in this epoch of the pandemic.

Search strategy and selection criteria

The systematic review was conducted according to the protocol registered in the PROSPERO database (CRD42020176589). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline throughout this review, data were identified by searches of MEDLINE, Embase and references from relevant articles using the search terms "COVID", “SARS-CoV-2”, and “novel coronavirus” (Supplementary material 1 ). Articles published in English up to 27th March, 2020 were included. National containment measures have been implemented at many countries, irrespective of lockdown, curfew, or stay-at-home orders, since the mid of March 2020 12 , except for China where imposed Hubei province lockdown at 23th January 2020, Studies with original data including original articles, short and brief communication, letters, correspondences were included. Editorials, viewpoints, infographics, commentaries, reviews, or studies without original data were excluded. Studies were also excluded if they were animal studies, modelling studies, or did not measure symptoms presentation, laboratory findings, treatment and therapeutics during hospitalization.

After the removal of duplicate records, two reviewers (CW and CHA) independently screened the eligibility criteria of study titles, abstracts and full-texts, and reference lists of the studies retrieved by the literature search. Disagreements regarding the procedures of database search, study selection and eligibility were resolved by discussion. The second and the last authors (JW and AW) verified the eligibility of included studies.

Outcomes definitions

Signs and symptoms were defined as the presentation of fever, cough, sore throat, headache, dyspnea, muscle pain, diarrhea, rhinorrhea, anosmia, and ageusia at the hospital admission 13 .

Laboratory findings included a complete blood count (white blood count, neutrophil, lymphocyte, platelet count), procalcitonin, prothrombin time, urea, and serum biochemical measurements (including electrolytes, renal-function and liver-function values, creatine kinase, lactate dehydrogenase, C-reactive protein, Erythrocyte sedimentation rate), and treatment measures (i.e. antiviral therapy, antibiotics, corticosteroid therapy, mechanical ventilation, intubation, respiratory support, and renal replacement therapy). Radiological outcomes included bilateral involvement identified and pneumonia identified by chest radiograph.

Comorbidities of patients evaluated in this study were hypertension, diabetes, chronic obstructive pulmonary disease (COPD), cardiovascular disease, chronic kidney disease, liver disease and cancer.

In-patient treatment included intensive care unit admission, oxygen therapy, non-invasive ventilation, mechanical ventilation, Extracorporeal membrane oxygenation (ECMO), renal replacement therapy, and pharmacological treatment. Use of antiviral and interferon drugs (Lopinavir/ritonavir, Ribavirin, Umifenovir, Interferon-alpha, or Interferon-beta), antibiotic drugs, corticosteroid, and inotropes (Nor-adrenaline, Adrenaline, Vasopressin, Phenylephrine, Dopamine, or Dobutamine) were considered.

Data analysis

Three authors (CW, EHMT and CHA) extracted data using a standardized spreadsheet to record the article type, country of origin, surname of first author, year of publications, sample size, demographics, comorbidities, symptoms, laboratory and radiology results, pharmacological and non-pharmacological treatments.

We aggregated estimates across 90 eligible studies to produce meta-analytic estimates using a random-effects model. For dichotomous outcomes, we estimated the proportion and its respective 95% confidence interval. For laboratory parameters as continuous outcomes, we estimated the mean and standard deviation from the median and interquartile range if the mean and standard deviation were not available from the study 14 , and calculated the mean and its respective 95% confidence intervals. Random-effect models on DerSimonian and Laird method were adopted due to the significant heterogeneity, checked by the I 2 statistics and the p values. I 2 statistic of < 25%, 25–75% and ≥ 75% is considered as low, moderate, high likelihood of heterogeneity. Pooled estimates were calculated and presented by using forest plots. Publication bias was estimated by Egger’s regression test. Funnel plots of outcomes were also presented to assess publication bias.

All statistical analyses were conducted using the STATA Version 13.0 (Statacorp, College Station, TX). The random effects model was generated by the Stata packages ‘Metaprop’ for proportions 15 and ‘Metan’ for continuous variables 16 .

The selection and screen process are presented in Fig.  1 . A total of 241 studies were found by our searching strategy (71 in PubMed and 170 in Embase). 46 records were excluded due to duplication. After screening the abstracts and titles, 100 English studies were with original data and included in full-text screening. By further excluding 10 studies with not reporting symptoms presentation, laboratory findings, treatment and therapeutics, 90 studies 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 and 76 studies with more than one COVID-19 case 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 34 , 35 , 36 , 37 , 38 , 39 , 42 , 43 , 44 , 45 , 49 , 50 , 51 , 53 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 67 , 69 , 70 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 98 , 100 , 101 , 102 , 103 , 104 , 105 were included in the current systematic review and meta-analysis respectively. 73.3% 66 studies were conducted in China. Newcastle–Ottawa Quality Assessment Scale has been used to assess study quality of each included cohort study 107 . 30% (27/90) of included studies had satisfactory or good quality. The summary of the included study is shown in Table 1 .

PRISMA flowchart reporting identification, searching and selection processes.

Of those 90 eligible studies, 11,028 COVID-19 patients were identified and included in the systematic review. More than half of patients (6336, 57.5%) were from mainland China. The pooled mean age was 45.8 (95% CI 38.6–52.5) years and 49.3% (pooled 95% CI 45.6–53.0%) of them were male.

For specific comorbidity status, the most prevalent comorbidity was hypertension (18.1%, 95% CI 15.4–20.8%), followed by cardiovascular disease (11.8%, 95% CI 9.4–14.2%) and diabetes (10.4%, 95% CI 8.7–12.1%). The pooled prevalence (95% CI) of COPD, chronic kidney disease, liver disease and cancer were 2.0% (1.3–2.7%), 5.2% (1.7–8.8%), 2.5% (1.7–3.4%) and 2.1% (1.3–2.8%) respectively. Moderate to substantial heterogeneity between reviewed studies were found, with I 2 statistics ranging from 39.4 to 95.9% ( p values between < 0.001–0.041), except for liver disease (I 2 statistics: 1.7%, p  = 0.433). Detailed results for comorbidity status are displayed in Fig.  2 .

Random-effects meta-analytic estimates for comorbidities. ( A ) Diabetes mellitus, ( B ) Hypertension, ( C ) Cardiovascular disease, ( D ) Chronic obstructive pulmonary disease, ( E ) Chronic kidney disease, ( F ) Cancer.

Regarding the symptoms presented at hospital admission, the most frequent symptoms were fever (pooled prevalence: 72.4%, 95% CI 67.2–77.7%) and cough (pooled prevalence: 55.5%, 95% CI 50.7–60.3%). Sore throat (pooled prevalence: 16.2%, 95% CI 12.7–19.7%), dyspnoea (pooled prevalence: 18.8%, 95% CI 14.7–22.8%) and muscle pain (pooled prevalence: 22.1%, 95% CI 18.6–25.5%) were also common symptoms found in COVID-19 patients, but headache (pooled prevalence: 10.5%, 95% CI 8.7–12.4%), diarrhoea (pooled prevalence: 7.9%, 95% CI 6.3–9.6%), rhinorrhoea (pooled prevalence: 9.2%, 95% CI 5.6–12.8%) were less common. However, none of the included papers reported prevalence of anosmia and ageusia. The I 2 statistics varied from 68.5 to 97.1% (all p values < 0.001), indicating a high heterogeneity exists across studies. Figure  3 shows the pooled proportion of symptoms of patients presented at hospital.

Random-effects meta-analytic estimates for presenting symptoms. ( A ) Fever, ( B ) Cough, ( C ) Dyspnoea, ( D ) Sore throat, ( E ) Muscle pain, ( F ) Headache.

For laboratory parameters, white blood cell (pooled mean: 5.31 × 10 9 /L, 95% CI 5.03–5.58 × 10 9 /L), neutrophil (pooled mean: 3.60 × 10 9 /L, 95% CI 3.31–3.89 × 10 9 /L), lymphocyte (pooled mean: 1.11 × 10 9 /L, 95% CI 1.04–1.17 × 10 9 /L), platelet count (pooled mean: 179.5 U/L, 95% CI 172.6–186.3 U/L), aspartate aminotransferase (pooled mean: 30.3 U/L, 95% CI 27.9–32.7 U/L), alanine aminotransferase (pooled mean: 27.0 U/L, 95% CI 24.4–29.6 U/L) and C-reactive protein (CRP) (pooled mean: 22.0 mg/L, 95% CI 18.3–25.8 mg/L) and D-dimer (0.93 mg/L, 95% CI 0.68–1.18 mg/L) were the common laboratory test taken for COVID-19 patients. Above results and other clinical factors are depicted in Fig.  4 . Same with the comorbidity status and symptoms, high likelihood of heterogeneity was detected by I 2 statistics for a majority of clinical parameters.

Random-effects meta-analytic estimates for laboratory parameters. ( A ) White blood cell, ( B ) Lymphocyte, ( C ) Neutrophil, ( D ) C-creative protein, ( E ) D-dimer, ( F ) Lactate dehydrogenase.

Figure  5 presents the distribution of the pharmacological treatments received for COVID-19 patients. 10.6% of patients admitted to intensive care units (pooled 95% CI 8.1–13.2%). For drug treatment, 63.9% (pooled 95% CI 52.5–75.3%), 62.4% (pooled 95% CI 47.9–76.8%) and 29.7% (pooled 95% CI 21.8–37.6%) patients used antibiotics, antiviral, and corticosteroid, respectively. 41.3% (pooled 95% CI 14.3–68.3%) and 50.7% (pooled 95% CI 9.2–92.3%) reported using Lopinavir/Ritonavir and interferon-alpha as antiviral drug treatment, respectively. Among 14 studies reporting proportion of corticosteroid used, 7 studies (50%) specified the formulation of corticosteroid as systemic corticosteroid. The remaining one specified the use of methylprednisolone. No reviewed studies reported the proportion of patients receiving Ribavirin, Interferon-beta, or inotropes.

Random-effects meta-analytic estimates for pharmacological treatments and intensive unit care at hospital. ( A ) Antiviral or interferon drugs, ( B ) Lopinavir/Ritonavir, ( C ) Interferon alpha (IFN-α), ( D ) Antibiotic drugs, ( E ) Corticosteroid, ( F ) Admission to Intensive care unit.

The prevalence of radiological outcomes and non-pharmacological treatments were presented in Fig.  6 . Radiology findings detected chest X-ray abnormalities, with 74.4% (95% CI 67.6–81.1%) of patients with bilateral involvement and 74.9% (95% CI 68.0–81.8%) of patients with viral pneumonia. 62.6% (pooled 95% CI 39.9–85.4%), 20.2% (pooled 95% CI 14.6–25.9%), 15.3% (pooled 95% CI 11.0–19.7%), 1.1% (pooled 95% CI 0.4–1.8%) and 4.7% (pooled 95% CI 2.1–7.4%) took oxygen therapy, non-invasive ventilation, mechanical ventilation, ECMO and dialysis respectively.

Random-effects meta-analytic estimates for radiological findings and non-pharmacological treatments at hospital. ( A ) Bilateral involvement, ( B ) Pneumonia, ( C ) Oxygen therapy, ( D ) Non-invasive ventilation, ( E ) Extracorporeal membrane oxygenation (ECMO), ( F ) Dialysis.

The funnel plots and results Egger’s test of comorbidity status, symptoms presented, laboratory test and treatment were presented in eFigure 1 – S5 in the Supplement. 63% (19/30) of the funnel plots (eFigure 1 – S5 ) showed significance in the Egger’s test for asymmetry, suggesting the possibility of publication bias or small-study effects caused by clinical heterogeneity.

This meta-analysis reveals the condition of global medical community responding to COVID-19 in the early phase. During the past 4 months, a new major epidemic focus of COVID-19, some without traceable origin, has been identified. Following its first identification in Wuhan, China, the virus has been rapidly spreading to Europe, North America, Asia, and the Middle East, in addition to African and Latin American countries. Three months since Wuhan CDC admitted that there was a cluster of unknown pneumonia cases related to Huanan Seafood Market and a new coronavirus was identified as the cause of the pneumonia 108 , as on 1 April, 2020, there have been 858,371 persons confirmed infected with COVID-19, affecting 202 countries and territories around the world. Although this rapid review is limited by the domination of reports from patients in China, and the patient population is of relative male dominance reflecting the gender imbalance of the Chinese population 109 , it provides essential information.

In this review, the pooled mean age was 45.8 years. Similar to the MERS-CoV pandemic 110 , middle-aged adults were the at-risk group for COVID-19 infections in the initial phase, which was different from the H1N1 influenza pandemic where children and adolescents were more frequently affected 111 . Biological differences may affect the clinical presentations of infections; however, in this review, studies examining the asymptomatic COVID-19 infections or reporting any previous infections were not included. It is suggested that another systematic review should be conducted to compare the age-specific incidence rates between the pre-pandemic and post-pandemic periods, so as to understand the pattern and spread of the disease, and tailor specific strategies in infection control.

Both sexes exhibited clinical presentations similar in symptomatology and frequency to those noted in other severe acute respiratory infections, namely influenza A H1N1 112 and SARS 113 , 114 . These generally included fever, new onset or exacerbation of cough, breathing difficulty, sore throat and muscle pain. Among critically ill patients usually presented with dyspnoea and chest tightness 22 , 29 , 39 , 72 , 141 (4.6%) of them with persistent or progressive hypoxia resulted in the requirement of intubation and mechanical ventilation 115 , while 194 (6.4%) of them required non-invasive ventilation, yielding a total of 11% of patients requiring ventilatory support, which was similar to SARS 116 .

The major comorbidities identified in this review included hypertension, cardiovascular diseases and diabetes mellitus. Meanwhile, the percentages of patients with chronic renal diseases and cancer were relatively low. These chronic conditions influencing the severity of COVID-19 had also been noted to have similar effects in other respiratory illnesses such as SARS, MERS-CoV and influenza 117 , 118 . Higher mortality had been observed among older patients and those with comorbidities.

Early diagnosis of COVID-19 was based on recognition of epidemiological linkages; the presence of typical clinical, laboratory, and radiographic features; and the exclusion of other respiratory pathogens. The case definition had initially been narrow, but was gradually broadened to allow for the detection of more cases, as milder cases and those without epidemiological links to Wuhan or other known cases had been identified 119 , 120 . Laboratory investigations among COVID-19 patients did not reveal specific characteristics—lymphopenia and elevated inflammatory markers such as CRP are some of the most common haematological and biochemical abnormalities, which had also been noticed in SARS 121 . None of these features were specific to COVID-19. Therefore, diagnosis should be confirmed by SARS-CoV–2 specific microbiological and serological studies, although initial management will continue to be based on a clinical and epidemiological assessment of the likelihood of a COVID-19 infection.

Radiology imaging often plays an important role in evaluating patients with acute respiratory distress; however, in this review, radiological findings of SARS-CoV-2 pneumonia were non-specific. Despite chest radiograph usually revealed bilateral involvement and Computed Tomography usually showed bilateral multiple ground-glass opacities or consolidation, there were also patients with normal chest radiograph, implying that chest radiograph might not have high specificity to rule out pneumonia in COVID-19.

Limited clinical data were available for asymptomatic COVID-19 infected persons. Nevertheless, asymptomatic infection could be unknowingly contagious 122 . From some of the official figures, 6.4% of 150 non-travel-related COVID-19 infections in Singapore 123 , 39.9% of cases from the Diamond Princess cruise ship in Japan 124 , and up to 78% of cases in China as extracted on April 1st, 2020, were found to be asymptomatic 122 . 76% (68/90) studies based on hospital setting which provided care and disease management to symptomatic patients had limited number of asymptomatic cases of COVID-19 infection. This review calls for further studies about clinical data of asymptomatic cases. Asymptomatic infection intensifies the challenges of isolation measures. More global reports are crucially needed to give a better picture of the spectrum of presentations among all COVID-19 infected persons. Also, public health policies including social and physical distancing, monitoring and surveillance, as well as contact tracing, are necessary to reduce the spread of COVID-19.

Concerning potential treatment regime, 62.4% of patients received antivirals or interferons (including oseltamivir, lopinavir-ritonavir, interferon alfa), while 63.9% received antibiotics (such as moxifloxacin, and ceftriaxone). In this review, around one-third of patients were given steroid, suggestive as an adjunct to IFN, or sepsis management. Interferon and antiviral agents such as ribavirin, and lopinavir-ritonavir were used during SARS, and the initial uncontrolled reports then noted resolution of fever and improvement in oxygenation and radiographic appearance 113 , 125 , 126 , without further evidence on its effectiveness. At the time of manuscript preparation, there has been no clear evidence guiding the use of antivirals 127 . Further research is needed to inform clinicians of the appropriate use of antivirals for specific groups of infected patients.

Limitations of this meta-analysis should be considered. First, a high statistical heterogeneity was found, which could be related to the highly varied sample sizes (9 to 4226 patients) and study designs. Second, variations of follow-up period may miss the event leading to heterogeneity. In fact, some patients were still hospitalized in the included studies. Third, since only a few studies had compared the comorbidities of severe and non-severe patients, sensitivity analysis and subgroup analysis were not conducted. Fourthly, the frequency and severity of signs and symptoms reported in included studies, primarily based on hospitalized COVID-19 patients were over-estimated. Moreover, different cutoffs for abnormal laboratory findings were applied across countries, and counties within the same countries. Lastly, this meta-analysis reviewed only a limited number of reports written in English, with a predominant patient population from China. This review is expected to inform clinicians of the epidemiology of COVID-19 at this early stage. A recent report estimated the number of confirmed cases in China could reach as high as 232,000 (95% CI 161,000, 359,000) with the case definition adopted in 5th Edition. In this connection, further evidence on the epidemiology is in imminent need.

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These authors contributed equally: Carlos K. H. Wong and Janet Y. H. Wong.

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Department of Family Medicine and Primary Care, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

Carlos K. H. Wong, Eric H. M. Tang & C. H. Au

Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

Carlos K. H. Wong

School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China

Janet Y. H. Wong

Emergency Medicine Unit, Li Ka Shing, Faculty of Medicine, The University of Hong Kong, Hong Kong, China

Abraham K. C. Wai

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C.W., J.W. and A.W. contributed equally to all aspects of study design, conduct, data interpretation, and the writing of the manuscript. C.W., E.T. and C.H.A. contributed to eligibility screening, data extraction from eligible studies, and data analysis and interpretation.

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Wong, C.K.H., Wong, J.Y., Tang, E.H.M. et al. Clinical presentations, laboratory and radiological findings, and treatments for 11,028 COVID-19 patients: a systematic review and meta-analysis. Sci Rep 10 , 19765 (2020). https://doi.org/10.1038/s41598-020-74988-9

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DOI : https://doi.org/10.1038/s41598-020-74988-9

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How to present clinical cases

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Presenting a patient is an essential skill that is rarely taught

Clinical presenting is the language that doctors use to communicate with each other every day of their working lives. Effective communication between doctors is crucial, considering the collaborative nature of medicine. As a medical student and later as a doctor you will be expected to present cases to peers and senior colleagues. This may be in the setting of handovers, referring a patient to another specialty, or requesting an opinion on a patient.

A well delivered case presentation will facilitate patient care, act a stimulus for timely intervention, and help identify individual and group learning needs. 1 Case presentations are also used as a tool for assessing clinical competencies at undergraduate and postgraduate level.

Medical students are taught how to take histories, examine, and communicate effectively with patients. However, we are expected to learn how to present effectively by observation, trial, and error.

Principles of presentation

Remember that the purpose of the case presentation is to convey your diagnostic reasoning to the listener. By the end of your presentation the examiner should have a clear view of the patient’s condition. Your presentation should include all the facts required to formulate a management plan.

There are no hard and fast rules for a perfect presentation, rather the content of each presentation should be determined by the case, the context, and the audience. For example, presenting a newly admitted patient with complex social issues on a medical ward round will be very different from presenting a patient with a perforated duodenal ulcer who is in need of an emergency laparotomy.

Whether you’re presenting on a busy ward round or during an objective structured clinical examination (OSCE), it is important that you are concise yet get across all the important points. Start by introducing patients with identifiers such as age, sex, and occupation, and move on to the complaint that they presented with or the reason that they are in hospital. The presenting complaint is an important signpost and should always be clearly stated at the start of the presentation.

Presenting a history

After you’ve introduced the patient and stated the presenting complaint, you can proceed in a chronological approach—for example, “Mr X came in yesterday with worsening shortness of breath, which he first noticed four days ago.” Alternatively you can discuss each of the problems, starting with the most pertinent and then going through each symptom in turn. This method is especially useful in patients who have several important comorbidities.

The rest of the history can then be presented in the standard format of presenting complaint, history of presenting complaint, medical history, drug history, family history, and social history. Strictly speaking there is no right or wrong place to insert any piece of information. However, in some instances it may be more appropriate to present some information as part of the history of presenting complaints rather than sticking rigidly to the standard format. For example, in a patient who presents with haemoptysis, a mention of relevant risk factors such as smoking or contacts with tuberculosis guides the listener down a specific diagnostic pathway.

Apart from deciding at what point to present particular pieces of information, it is also important to know what is relevant and should be included, and what is not. Although there is some variation in what your seniors might view as important features of the history, there are some aspects which are universally agreed to be essential. These include identifying the chief complaint, accurately describing the patient’s symptoms, a logical sequence of events, and an assessment of the most important problems. In addition, senior medical students will be expected to devise a management plan. 1

The detail in the family and social history should be adapted to the situation. So, having 12 cats is irrelevant in a patient who presents with acute appendicitis but can be relevant in a patient who presents with an acute asthma attack. Discerning the irrelevant from the relevant is not always easy, but it comes with experience. 2 In the meantime, learning about the diseases and their associated features can help to guide you in the things you need to ask about in your history. Indeed, it is impossible to present a good clinical history if you haven’t taken a good history from the patient.

Presenting examination findings

When presenting examination findings remember that the aim is to paint a clear picture of the patient’s clinical status. Help the listener to decide firstly whether the patient is acutely unwell by describing basics such as whether the patient is comfortable at rest, respiratory rate, pulse, and blood pressure. Is the patient pyrexial? Is the patient in pain? Is the patient alert and orientated? These descriptions allow the listener to quickly form a mental picture of the patient’s clinical status. After giving an overall picture of the patient you can move on to present specific findings about the systems in question. It is important to include particular negative findings because they can influence the patient’s management. For example, in a patient with heart failure it is helpful to state whether the patient has a raised jugular venous pressure, or if someone has a large thyroid swelling it is useful to comment on whether the trachea is displaced. Initially, students may find it difficult to know which details are relevant to the case presentation; however, this skill becomes honed with increasing knowledge and clinical experience.

Presenting in an exam

Although the same principles as presenting in other situations also apply in an exam setting, the exam situation differs in the sense that its purpose is for you to show your clinical competence to the examiner.

It’s all about making a good impression. Walk into the room confidently and with a smile. After taking the history or examining the patient, turn to the examiner and look at him or her before starting to present your findings. Avoid looking back at the patient while presenting. A good way to avoid appearing fiddly is to hold your stethoscope behind your back. You can then wring to your heart’s content without the examiner sensing your imminent nervous breakdown.

Start with an opening statement as you would in any other situation, before moving on to the main body of the presentation. When presenting the main body of your history or examination make sure that you show the examiner how your findings are linked to each other and how they come together to support your conclusion.

Finally, a good summary is just as important as a good introduction. Always end your presentation with two or three sentences that summarise the patient’s main problem. It can go something like this: “In summary, this is Mrs X, a lifelong smoker with a strong family history of cardiovascular disease, who has intermittent episodes of chest pain suggestive of stable angina.”

Improving your skills

The RIME model (reporter, interpreter, manager, and educator) gives the natural progression of the clinical skills of a medical student. 3 Early on in clinical practice students are simply reporters of information. As the student progresses and is able to link together symptoms, signs, and investigation results to come up with a differential diagnosis, he or she becomes an interpreter of information. With further development of clinical skills and increasing knowledge students are actively able to suggest management plans. Finally, managers progress to become educators. The development from reporter to manager is reflected in the student’s case presentations.

The key to improving presentation skills is to practise, practise, and then practise some more. So seize every opportunity to present to your colleagues and seniors, and reflect on the feedback you receive. 4 Additionally, by observing colleagues and doctors you can see how to and how not to present.

Remember the purpose of the presentation

Be flexible; the context should dictate the content of the presentation

Always include a presenting complaint

Present your findings in a way that shows understanding

Have a system

Use appropriate terminology

Additional tips for exams

Start with a clear introductory statement and close with a brief summary

After your summary suggest a working diagnosis and a management plan

Practise, practise, practise, and get feedback

Present with confidence, and don’t be put off by an examiner’s poker face

Be honest; do not make up signs to fit in with your diagnosis

Originally published as: Student BMJ 2010;18:c1539

Competing interests: None declared.

Provenance and peer review: Not commissioned; externally peer reviewed.

See “Medical ward rounds” ( Student BMJ 2009;17:98-9, http://archive.student.bmj.com/issues/09/03/life/98.php ).

• ↵ Green EH, Durning SJ, DeCherrie L, Fagan MJ, Sharpe B, Hershman W. Expectations for oral case presentations for clinical clerks: Opinions of internal medicine clerkship directors. J Gen Intern Med 2009 ; 24 : 370 -3. OpenUrl CrossRef PubMed Web of Science
• ↵ Lingard LA, Haber RJ. What do we mean by “relevance”? A clinical and rhetorical definition with implications for teaching and learning the case-presentation format. Acad Med 1999 ; 74 : S124 -7. OpenUrl CrossRef PubMed Web of Science
• ↵ Pangaro L. A new vocabulary and other innovations for improving descriptive in-training evaluations. Acad Med 1999 ; 74 : 1203 -7. OpenUrl CrossRef PubMed Web of Science
• ↵ Haber RJ, Lingard LA. Learning oral presentation skills: a rhetorical analysis with pedagogical and professional implications. J Gen Intern Med 2001 ; 16 : 308 -14. OpenUrl CrossRef PubMed Web of Science

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INTERATRIAL BLOCK AS A FIRST CLINICAL PRESENTATION OF ATRIAL CARDIOMYOPATHY RELATED TO A NOVEL LMNA VARIANT: A CASE REPORT

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M Iavarone, S Covino, R Pettillo, V Russo, INTERATRIAL BLOCK AS A FIRST CLINICAL PRESENTATION OF ATRIAL CARDIOMYOPATHY RELATED TO A NOVEL LMNA VARIANT: A CASE REPORT, European Heart Journal Supplements , Volume 26, Issue Supplement_2, April 2024, Page ii190, https://doi.org/10.1093/eurheartjsupp/suae036.457

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Delayed Presentation of IRAK4 Deficiency

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Picard C, von Bernuth H, Ghandil P, Chrabieh M, Levy O, Arkwright PD, et al. Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Med (Baltim). 2010;89(6):403–25.

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Garcia-Garcia A, Perez de Diego R, Flores C, Rinchai D, Sole-Violan J, Deya-Martinez A et al. Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia. J Exp Med. 2023;220(5).

McKelvie B, Top K, McCusker C, Letenyi D, Issekutz TB, Issekutz AC. Fatal pneumococcal meningitis in a 7-year-old girl with interleukin-1 receptor activated kinase deficiency (IRAK-4) despite prophylactic antibiotic and IgG responses to Streptococcus pneumoniae vaccines. J Clin Immunol. 2014;34(3):267–71.

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Verma N, Tadros S, Bahal S, Lowe DM, Burns SO. Case of fatal meningitis in an adult patient with IRAK4 Deficiency. J Clin Immunol. 2023;43(6):1137–8.

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Acknowledgements

We are grateful to this patient and the staff that has contributed to his care. MAS is supported by the Gail Slap Pediatric Fellowship Award.

This work was supported by funding by the Gail Slap Pediatric Fellowship Award to MAS.

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Allergy-Immunology Division, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

Maria A. Sacta & Juhee Lee

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MAS wrote the main manuscript text and prepared figures. JL edited the main manuscript and figures. All authors contributed to the conception and preparation of this manuscript. All authors read and approved the final manuscript.

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Sacta, M.A., Lee, J. Delayed Presentation of IRAK4 Deficiency. J Clin Immunol 44 , 122 (2024). https://doi.org/10.1007/s10875-024-01729-2

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Predicting visual acuity for open-globe injuries using machine learning

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Introduction Open-globe injuries (OGI) are severe ocular injuries with the potential for poor clinical outcomes. Outcomes such as visual acuity (VA) remain challenging to predict accurately on a patient-by-patient basis. We tested the hypothesis that machine learning (ML) could accurately predict visual acuity outcomes in the setting of an OGI. Methods Clinical data for patients suffering OGIs treated at Massachusetts Eye and Ear between 2012 and 2022 were collected and manually validated to ensure accuracy and completeness. The following were selected as input variables to the ML model: age, sex, race, ethnicity, mechanism of injury, zone of injury, presenting VA (logMAR), afferent pupillary defect, intraocular foreign body, lensectomy, and time from presentation to operating room. The data were split into 80% training and 20% hold-out testing. The following ML regression models were evaluated with tenfold cross validation: random forest, adaptive boosting, gradient boosting, extra trees, and linear regression. Performance was measured with mean absolute error (MAE) and mean squared error (MSE). Relative importance of input variables was evaluated for the best performing model. Results A total of 903 patients were reviewed and included in analysis. Random forest regression showed the best performance from 10-fold cross validation of all models assessed. Subsequent evaluation of the random forest model on the testing holdout showed an MAE and MSE of 0.58 logMAR and 0.62 logMAR, respectively, with an optimal hyperparameter of 500 decision trees. Relative feature importance revealed age, time to the operating room, and presenting VA as most predictive for final VA. Conclusions Our results suggest that ML may be a useful tool for predicting VA for patients suffering OGI based on presenting clinical features and patient demographics. Random forest model showed the best performed of all ML models. Future work should work to prospectively validate ML VA predictions through multi-institutional collaboration.

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Robot-assisted thoracoscopic resection of a posterior mediastinal tumor with immunoglobulin G4-related disease: a case report

• Taihei Takeuchi 1 ,
• Hiromitsu Takizawa 1 ,
• Yoshimi Bando 2 ,
• Akio Hosokawa 1 ,
• Hiroyuki Sumitomo 1 ,
• Naoki Miyamoto 1 ,
• Shinichi Sakamoto 1 ,
• Atsushi Morishita 1 ,
• Naoya Kawakita 1 &
• Hiroaki Toba 1  

Journal of Cardiothoracic Surgery volume  19 , Article number:  291 ( 2024 ) Cite this article

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Immunoglobulin (Ig)G4-related disease affects nearly every organ, and its clinical course varies depending on the involved organ; however, its occurrence in the mediastinum is rarely reported.

Case presentation

A 58-year-old woman presented with a posterior mediastinal tumor along the thoracic spine on imaging. Based on her elevated serum IgG4 level of 349.7 mg/dL, IgG4-related disease was suspected. Since the tumor was growing and malignancy could not be excluded, surgical resection was performed for definitive diagnosis. Robot-assisted thoracoscopic surgery was performed via the left semipronation and right thoracic approaches. The irregularly-shaped tumor was located on the level of the seventh to ninth thoracic vertebra, along the sympathetic nerve. A malignancy was not excluded based on the appearance of the tumor. The tumor had poor mobility. The sympathetic nerves, intercostal arteries, and veins were also excised. In this case, the articulated forceps, used during the robotic surgery, were useful in achieving complete tumor resection along the vertebral body. The pathological examination revealed IgG4-positive plasma infiltration, which fulfilled the criteria for IgG4-related diseases. The postoperative course was uneventful, and the patient underwent follow-up on an outpatient basis without additional medications.

The clinical presentation of IgG4-related disease varies, based on the involved organs. This case was rare because the mediastinum was involved, and it emphasized the effectiveness of surgical resection.

Peer Review reports

Immunoglobulin G4-related disease (IgG4-RD) is a systemic autoimmune disorder characterized by enlarged, massive, and thickened lesions, a high serum IgG4 concentration, marked lymphocytic and IgG4-positive plasma infiltration, and tissue fibrosis [ 1 ]. It affects nearly every organ, with varying clinical course depending on the involved organ; however, few reports exist on its occurrence in the mediastinum. In rare cases, particularly when the mediastinum is involved, IgG4-RD diagnosis can be difficult. Furthermore, standardized diagnostic and treatment modalities have not yet been established. A surgical biopsy is therefore essential for a definitive diagnosis, especially for growing lesions and for excluding the possibility of malignancy. This study reports a case of robot-assisted thoracoscopic surgery (RATS) for a posterior mediastinal tumor in a patient with IgG4-RD.

A 58-year-old woman was referred to our hospital for a detailed examination of a posterior mediastinal tumor. She had been receiving treatment for hypertension and type 2 diabetes mellitus. She underwent surgery for sialadenitis at 40 years of age and developed a pancreatic nodule at 45 years of age; she was being followed up with magnetic resonance imaging (MRI). The patient reported no new subjective symptoms. The MRI, however, revealed a posterior mediastinal tumor along the thoracic vertebral bodies 3 years ago. Over the next 3 years, the tumor size increased by 1 cm. Because the patient had a history of salivary gland inflammation and autoimmune pancreatitis, IgG4-related disease was suspected. Her serum IgG4 concentration was measured preoperatively and was found to be elevated at 349.7 mg/dL. Contrast-enhanced computed tomography showed a smooth tumor, measuring 55 mm, along the right side of the seventh to ninth thoracic vertebrae, with no invasion into the surrounding tissues (Fig.  1 ). Therefore, an IgG4-related disease affecting the posterior mediastinum was suspected. The tumor grew over time, and a histological diagnosis was required to exclude malignancy. However, performing a needle biopsy was deemed difficult due to the tumor’s location. Thus, complete surgical excision of the tumor was performed.

Thoracic contrast-enhanced computed tomography. Thoracic contrast-enhanced computed tomography reveals a mass, measuring 23 × 13 × 55 mm, on the right side of the seventh to ninth thoracic vertebrae. The area indicated by the yellow arrows shows the mass

RATS was performed via the right thoracic approach with the patient in a left semi-prone position. During the procedure, carbon dioxide gas was insufflated into the thoracic cavity through a trocar at a pressure of 8 mmHg. Then, 8-mm trocars were inserted into the third, fifth, and eighth intercostal spaces (ICS) through the anterior axillary line for the da Vinci surgical system. A 12-mm trocar was inserted for the assistant at the eighth ICS through the middle axillary line. The irregularly-shaped tumor was located at the level of the seventh to ninth thoracic vertebrae along the sympathetic nerve. It was elastic, hard, and firmly attached to the chest wall. The parietal pleura around the tumor was opened for mobilization. The sympathetic nerve, three intercostal veins, and two intercostal arteries were excised, and the tumor was removed using the joint motion of the robot arm (Figs.  2 and 3 ). The total duration of the surgery was 139 min. Histological examination revealed infiltration of lymphocytes and plasma cells with collagenous fibers. In the immunohistochemical analysis, a proportion of IgG4-positive cells/IgG-positive cells exceeding 60% was observed. Additionally, the IgG4-positive cell count significantly surpassed the 10/high power field, meeting the diagnostic criteria for IgG4-RD (Fig.  4 ).

Tumor resection. Complete tumor resection was achieved by robot-assisted thoracic surgery

Macroscopic examination. Macroscopic examination reveals elastic, red tumor with thickened soft tissue at the center of the sympathetic nerve

Hematoxylin-eosin and immunohistochemical staining of specimen. ( a ) Hematoxylin-eosin staining of the specimen at (×40). ( b ) Immunoglobulin G immunohistochemical staining (×400). ( c ) Immunoglobulin G4 immunohistochemical staining (×400)

The postoperative course was uneventful, and the patient was discharged on the third postoperative day. The patient underwent follow-up on an outpatient basis without additional medications since there were no signs of residual disease. The patient has been recurrence-free for six months following surgery and has not complained of symptoms related to the sympathectomy.

When lesions associated with IgG4-RD manifest across multiple organs, systemic steroid therapy is the treatment of choice [ 1 ]. However, when the lesions are confined to a single resectable organ, as in this case, the optimal treatment intervention is debatable. After confirming a IgG4-RD diagnosis, physicians may consider follow-up observation in asymptomatic cases and pharmaceutical intervention upon detection of lesion enlargement. However, there are notable disadvantages to both this approach and the administration of steroids. One, there is a lack of consensus regarding the side effects and duration of steroid therapy. Two, surgery may become more difficult to perform if lesion enlargement occurs during the follow-up period; however, despite the risk of flare-ups associated with systemic disease in the long term [ 2 ], the ability to follow up without resorting to steroid treatment is considered greatly advantageous for surgical resection.

Four cases of IgG4-RD occurring exclusively in the posterior mediastinum have been reported in previous literature (Table  1 ). In all cases, percutaneous biopsy was difficult, and in two cases, resection was performed as the intraoperative rapid pathological examination did not rule out malignancy [ 3 , 4 ]. Likewise, in two cases, biopsy was performed only for diagnostic purposes [ 5 , 6 ]. Clinical features of paravertebral lesions encompass challenges in performing percutaneous biopsy and a lack of subjective symptoms. Furthermore, it is difficult to distinguish them from lymphoma or other malignant diseases using biopsy alone. If there is a tendency toward enlargement, resection for diagnostic purposes is desirable. Consequently, if resection is necessary, paravertebral lesions require dissection tangential to the chest wall plane. The usefulness of robotic surgery for this purpose has been previously reported [ 7 ]. In this case, the tumor was relatively hard and widely tangential to the chest wall, and the application of an articulated forceps, a feature of robotic surgery, proved instrumental in achieving complete resection of the tumor.

Data availability

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Abbreviations

Glucocorticoids

Intercostal spaces

Immunoglobulin

• Immunoglobulin G4-related disease

Magnetic resonance imaging

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Acknowledgements

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Department of Thoracic, Endocrine Surgery, and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima City, Tokushima, 770-8503, Japan

Taihei Takeuchi, Hiromitsu Takizawa, Akio Hosokawa, Hiroyuki Sumitomo, Naoki Miyamoto, Shinichi Sakamoto, Atsushi Morishita, Naoya Kawakita & Hiroaki Toba

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TT wrote this paper. HT performed the surgery. HS and NM joined the operation. AH and SS was involved in the acquisition of data and preparation of the figures. YB conducted the pathological studies and contributed to make the diagnosis. AM, NK and HT conceived the study, critically revised the whole manuscript, in addition to proofreading. All authors read and approved the final manuscript.

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Correspondence to Taihei Takeuchi .

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Takeuchi, T., Takizawa, H., Bando, Y. et al. Robot-assisted thoracoscopic resection of a posterior mediastinal tumor with immunoglobulin G4-related disease: a case report. J Cardiothorac Surg 19 , 291 (2024). https://doi.org/10.1186/s13019-024-02655-5

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DOI : https://doi.org/10.1186/s13019-024-02655-5

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