Background: The Ki-67 antigen and the D-type cyclins play a key role in the cell cycle regulation. Objective: The goal of this study was to evaluate an immunohistochemical expression status of Cyclin D1 and Ki-67 in basal cell carcinoma (BCC) of the skin and to find out whether there is a correlation between them. Material and Methods: The study included biopsy specimens from 29 BCCs, which were immunohistochemically stained for Cyclin D1 and Ki-67. The cases were graded on a semiquantitative scale based on the average proportion of immunoreactive cells: 0 (<1%), 1+ (1-10%), 2+ (11-50%) and 3+ (>50%). Results: All BCCs were positive for both proteins. As for Cyclin D1, the grades 1+, 2+ and 3+ were found in 4 cases (13.8%), 18 cases (62.1%) and 7 cases (24.1%). As for Ki-67, the grades 1+, 2+ and 3+ were found in 1 case (3.4%), 18 cases (62.1%) and 10 cases (34.5%). In adjacent epidermis, all cases exhibited a mild degree of Cyclin D1 and Ki-67 immunoreactivity. Comparing both markers, there were 22 BCCs (75.9%) showing the same semiquantitative grade of Ki-67 and Cyclin D1 expression and 7 BCCs (24.1%), in which Ki-67 grade was one degree higher than Cyclin D1 grade. Conclusion: All BCCs expressed Cyclin D1 and Ki-67 that were more pronounced in tumor tissue than in adjacent normal epidermis. This indicates, both markers play a role in the carcinogenesis of cutaneous BCC. The expression of Cyclin D1 appeared to have a positive correlation with Ki-67 expression, suggesting the production of Cyclin D1 protein is directly related to cell proliferation.

Background: Scrub typhus is a zoonotic disease, which is caused by a parasite Orientia tsutsugamushi (O. tsutsugamushi). It is endemic and documented zoonotic disease in the state of Himachal Pradesh as the climatic and geographical conditions are conducive for spread of vector of this disease. The aim of this study is to determine the respiratory manifestations among patients with Scrub typhus. Materials and Methods: This cross-sectional Sero-Epidemiological study was conducted in the department of Paediatrics, Indira Gandhi Medical College and Shimla from 1st June 2017 to 30th Nov 2018. The study participants were newly diagnosed paediatric cases (n-102) of scrub typhus with a positive Scrub Typhus IgM ELISA test. Results: Shortness of breath was present in 45 (44.1%), dry cough 20 (19.6%) and productive cough in 1 (0.9%) patients. On examination tachypnea was present in 30 (29.4%), bilateral crepitations in 24 (23.5%) patients and decreased breath sounds in 10 (9.8%) patients on auscultation. On X-ray chest (PA view), 18 (17.6%) patients had features of ARDS, 10 (9.8%) had features of pleural effusion and 8 (7.8%) patients had features of consolidation. Conclusion: The general physicians should be sensitized regarding respiratory Findings associated with Scrub typhus which are useful diagnostic clue.

Scrub typhus is endemic and documented zoonotic disease in the state of Himachal Pradesh as the climatic and geographical conditions are conducive for spread of vector of this disease. The aim of this study is to determine the Cardio-logical manifestations among patients with Scrub typhus. Materials and Methods: This cross-sectional Sero-Epidemiological study was conducted in the department of Paediatrics, Indira Gandhi Medical College and Shimla from 1st June 2017 to 30th Nov 2018. The study participants were newly diagnosed paediatric cases (n-102) of scrub typhus with a positive Scrub Typhus IgM ELISA test. Results: In the present study tachycardia was present in 96 (94.1%), hypotension in 37 (36.3%) and feature suggestive of congestive heart failure in 1 (0.9%) patient. On ECG, 1st degree heart block in 1 (0.9%) patient, complete heart block in 1 (0.9%) patient, atrial fibrillation and flutter in 1 (0.9%) patient. Other ECG findings like sinus tachycardia and nonspecific T wave changes were present in 24 (23.5%) patients. Echocardiography was done in patients with ECG changes and it revealed minimal pericardial effusion in 2 (1.9%) patients with normal myocardial function and ejection fraction. Conclusion: Early recognition and focused management of cardiac complications may help reducemorbidity and mortality associated with Scrub typhus infection.

Introduction: The use of Central Venous Catheters (CVC) is a common practice among ill pediatric patients with most common complication being catheter-related blood stream infections. Objectives: The primary objective is to study the CVC settings in Rafic Hariri University Hospital (RHUH) including assessment of the types of CVCs used, indications and determining the complications, especially infection. Secondary objectives are to assess the factors predisposing to infections, evaluate care guidelines applied in comparison to the international guidelines and come up with proposal of improvement plan. Subjects and Methods: This is a retrospective study, at RHUH. Charts reviewed of all patients <18 years admitted to the hospital from 1-1-2016 till 31-12-2017 and had CVC insertion. The data collected included the age of patients, CVC type and complications. Data was treated using SPSS version 22. Results: One hundred three pediatric patients were included. CVCs were mainly inserted for prolonged Intravenous (IV) therapy. The most prevalent type of CVC was Umbilical Venous Catheter (UVC). The most common complication was infection 68.75%. The predictors of CVC-related infection were increased age, longer CVC duration and chemotherapy. However, the only indication that persisted as an independent predictor of infection was chemotherapy 16 times higher risk). A statistically significant correlation was set at P-value less than 0.05. Conclusion: CVCs, mainly UVC, are mainly inserted in newborns due to prolonged IV therapy with infection as main complication. Residents, Neonatal Intensive Care Unit (NICU), prolonged insertion, malignancy and older age of the population proved significant effect on increasing risk of catheter related blood stream infections.

With interest we read the article by Pantelis et al. about the neurological, neuropsychiatric, and neurodevelopmental comorbidities in patients infected with SARS-CoV-2 (COVID-19).[1] One of the key messages of the review was that neurological involvement is increasingly recognised [1]. We have the following comments and concerns.

Neurological involvement in SARS-CoV-2 infected patients is more divers than discussed. Neurological involvement may be found in the central nervous system (CNS) and the peripheral nervous system (PNS).[2] CNS-disease so far reported in SARS-CoV-2 infected patients include meningitis/encephalitis, acute hemorrhaghic, necrotising encephalopathy (AHNE), auto-immune encephalitis (AIE), encephalopathy, epilepsy, ischemic stroke, intracerebral bleeding, sinus venous thrombosis, acute disseminated encephalo-myelitis (ADEM), posterior reversible encephalopathy syndrome (PRES). Parkinson’s disease, cerebral hypoxia, delirium, myelitis, cerebral hypoxia, and optic neuritis.[2] 

Involvement of the PNS includes hypogeusia, hypo-osmia, myositis, myalgia, myasthenia gravis, myasthenic syndrome, Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), critical-ill neuropathy, critical-ill myopathy, and rhabdomyolysis. Since some of these conditions may precede the onset of typical clinical manifestations of COVID-19, it is crucial to know about the spectrum of neurological disease associated with SARS-CoV-2. Alertness about the neurological complications in SARS-CoV-2 infected patients may lead to early diagnosis and thus better outcome in general. 

Not discussed in the review was the effect of drugs given for treating COVID-19 on the CNS and PNS. There is increasing evidence that for example creatine-kinase elevation or even rhabdomyolysis in SARS-CoV-2 infected patients may be frequently triggered by drugs such as azithromycin, piperacillin, meropenem, hydroxyl-chloroquine, steroids, acetaminophen, furosemide, colchicine, hydrochlorothiazide, or propofol. Thus, it is crucial in SARS-CoV-2 infected patients that all drugs applied to these patients are carefully considered with regard to potential side effects. It is also crucial to mention that certain drugs should be avoided in the treatment of COVID-19 particularly if patients additionally have neurological complication or underlying neurological disease such as myasthenia or epilepsy. Certain antibiotics, which trigger seizures and drugs leading to exacerbation of myasthenia gravis should be strictly avoided.[3] 

Overall, the interesting review by Pantelis et al. has a number of shortcomings, which should be addressed before drawing final conclusions. The spectrum of CNS or PNS involvement in COVID-19 is much broader than so far described. Not only frequent neurological manifestations but also rare complications should be considered. Drugs with potential neurological side effects on the CNS or PNS should  be  avoided.  Since  neurological disease in COVID-19 may precede the pulmonary compromise, recognising the association may be the clue to early diagnosis.

With interest we read the article by Needham et al. about a retrospective observational study of 69 patients with severe COVID-19 requiring mechanical ventilation during 16-73 days [1]. Eleven of these patients developed mononeuritis multiplex, diagnosed upon the clinical presentation and results of nerve conduction studies. We have the following comments and concerns.

The main shortcoming of the study is that the cause of mononeuritis multiplex was not identified in any patient [1]. Though the authors speculate that the distribution of sensory or motor deficits suggested vasculitis, none of the 11 patients had undergone nerve biopsy. To diagnose vasculitic neuropathy, it is a prerequisite that nerve biopsy is carried out.

There is increasing evidence that SARS-CoV-2 can trigger the development of Guillain-Barre syndrome (GBS) [2]. GBS is particularly difficult to diagnose in intubated, mechanically ventilated, and sedated patients. To exclude GBS as the cause of motor or sensory deficits in the 11 patients it is crucial to investigate the cerebrospinal fluid (CSF) and demonstrate the dissociation cyto-albuminique. However, none of the 11 patients had undergone a spinal tap why GBS was not excluded as cause of neuropathy in any patient. Though nerve conduction studies (NCSs) did not reveal demyelinating features, this does not exclude the presence of the GBS subtypes acute motor axonal neuropathy (AMAN) or acute motor and sensory axonal neuropathy (AMSAN).     

Four of the 11 patients with mononeuritis multiplex had diabetes [1]. We should be told how diabetic neuropathy was excluded in these four cases. Particularly, we should know the HbA1c values and if any of the four patients had symptoms or signs prior to the infection with SARS-CoV-2 suggesting diabetic neuropathy. 

A further shortcoming is that the individual history was not carefully taken.  It is crucial to know if any of the 11 patients had been diagnosed with neuropathy already prior to the acquisition of the viral infection. Particularly, we should know how many were alcoholics, how may had renal insufficiency, vitamin deficiency, a history of malignancy, or a history of chemotherapy prior to the viral infection. 

It is also unreported which drugs the eleven patients were receiving prior to the admission to the ICU. From a number of drugs it is known that they may cause neuropathy. Drugs known to trigger the development of neuropathy include platins, disulfiram, phenytoin, vincristine, amiodarone, hydralazine, perhexiline, metronidazole, fluoroquinolones, nitrofurantoin, thalidomide, isoniazid, or dapsone. Drugs given specifically for COVID-19, which can be made responsible for neuropathy include chloroquine [3], lopinavir [4], and tocilizumab [5]. Thus, we should be told how many of the 11 patients were under a therapy with any of these drugs.

We should also know how the authors explain symmetrical weakness, in the absence of critical ill myopathy, and critical ill neuropathy only in a single patient. Which was the cause of symmetrical weakness in the remaining ten patients?

Overall, this study has a number of shortcomings which should be met before drawing final conclusions. It is crucial to know the history and medication prior to the viral infection, the medication during the ICU treatment, to intensify the search for the underlying cause of multiplex neuropathy, and the CSF findings. Though the authors request detailed neurological assessment of patients with post-COVID-19 neuropathy and symmetric weakness, they did not apply this approach to their patients.